AiPD: Autoinhibited Protein Database

Q16620

Gene name	NTRK2 (TRKB)
Protein name	BDNF/NT-3 growth factors receptor
Names	GP145-TrkB, Trk-B, Neurotrophic tyrosine kinase receptor type 2, TrkB tyrosine kinase, Tropomyosin-related kinase B
Species	Homo sapiens (Human)
KEGG Pathway	hsa:4915
EC number	2.7.10.1: Protein-tyrosine kinases
Protein Class	TYROSINE-PROTEIN KINASE RECEPTOR (PTHR24416)

Descriptions

NTRK2 is a receptor for brain-derived neurotrophic factor (BDNF), and is involved in survival, differentiation, development, and maturation of the central and peripheral nervous system. The autoinhibitory region of NTRK2 is the extracellular juxtamembrane motif (EJM). In the inactivated form, the two intracellular kinase domains (IKDs) are separated by the conformation set by EJM. Deletion of the EJM facilitates dimer formation and increases the amount of preformed dimers.

Autoinhibitory domains (AIDs)

Target domain	538-807 (Protein kinase domain)
Relief mechanism	Partner binding
Assay	Deletion assay

AID

365-430 (Extracellular juxtamembrane motif)

Target domain

538-807 (Protein kinase domain)

Relief mechanism

Partner binding (Binding of MM12 to EJM)

Assay

Deletion assay

Accessory elements

693-718 (Activation loop from InterPro)

Target domain	538-807 (Protein kinase domain)
Relief mechanism
Assay

References

Shen J et al. (2019) "Extracellular Juxtamembrane Motif Critical for TrkB Preformed Dimer and Activation", Cells, 8,

Artim SC et al. (2012) "Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family", The Biochemical journal, 448, 213-20

Uchikawa E et al. (2019) "Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex", eLife, 8,

Nielsen J et al. (2022) "Structural Investigations of Full-Length Insulin Receptor Dynamics and Signalling", Journal of molecular biology, 434, 167458

Chen YS et al. (2021) "Insertion of a synthetic switch into insulin provides metabolite-dependent regulation of hormone-receptor activation", Proceedings of the National Academy of Sciences of the United States of America, 118,

Craddock BP et al. (2007) "Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region", FEBS letters, 581, 3235-40

Autoinhibited structure

Activated structure

9 structures for Q16620

Entry ID	Method	Resolution	Chain	Position	Source
1HCF	X-ray	270 A	X/Y	286-383	PDB
1WWB	X-ray	210 A	X	283-385	PDB
2MFQ	NMR	-	B	497-519	PDB
4ASZ	X-ray	170 A	A	527-822	PDB
4AT3	X-ray	177 A	A	527-822	PDB
4AT4	X-ray	236 A	A	527-822	PDB
4AT5	X-ray	171 A	A	527-822	PDB
5MO9	X-ray	259 A	X	278-426	PDB
AF-Q16620-F1	Predicted				AlphaFoldDB

406 variants for Q16620

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV001266336 rs2058655147	36	C>*	Inborn genetic diseases [ClinVar]	Yes	ClinVar dbSNP
RCV000505546 CA374008545 rs201362502	324	L>M	Neuroblastoma [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs142393662 RCV001263254	427	G>C	Intellectual disability [ClinVar]	Yes	ClinVar dbSNP
RCV000782078 RCV001265761 rs886041091 VAR_080659 CA10602696 RCV000577864	434	Y>C	DEE58; unknown pathological significance Inborn genetic diseases Developmental and epileptic encephalopathy, 58 [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1085308029 RCV000490246 CA374008308	444	G>*	Obesity, hyperphagia, and developmental delay [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000754970 CA374010019 rs777251032	651	S>W	Obesity [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV001262599 CA195815113 rs201044261	655	H>R	Obesity, hyperphagia, and developmental delay [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs1554774973 VAR_080661 CA374010383 RCV000577832	704	T>I	Obesity, hyperphagia, and developmental delay OBHD; unknown pathological significance [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs121434633 CA120116 VAR_065890 RCV000009698	706	Y>C	Obesity, hyperphagia, and developmental delay OBHD; expressed normally on the cell surface; results in markedly impaired ligand-induced phosphorylation as well as impaired downstream MAPK1 phosphorylation [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA374004524 rs1181805012	2	S>L		No	ClinGen gnomAD
rs981883098 CA195738458	5	I>V		No	ClinGen TOPMed
rs76318698 CA195738459	7	W>*		No	ClinGen Ensembl
CA374004558 rs1587817911	7	W>G		No	ClinGen Ensembl
rs1373336521 CA374004573	9	G>R		No	ClinGen TOPMed
rs1421322179 CA374004578	9	G>V		No	ClinGen TOPMed gnomAD
CA374004582 rs1432834509 COSM609480	10	P>H	lung [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1359560976 CA374004581	10	P>S		No	ClinGen gnomAD
rs78936193 RCV001816809 CA5105392 RCV000735072	11	A>S		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA5105393 rs78936193	11	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA5105394 rs777390281	12	M>I		No	ClinGen ExAC gnomAD
rs756957794 CA5105396	15	L>H		No	ClinGen ExAC gnomAD
rs756957794 CA374004612	15	L>P		No	ClinGen ExAC gnomAD
CA374004623 rs1465892427	17	G>R		No	ClinGen Ensembl
rs1172673440 CA374004629	18	F>V		No	ClinGen TOPMed
rs200698390 CA5105398	19	C>F		No	ClinGen ExAC gnomAD
CA5105399 rs772667595	22	V>A		No	ClinGen ExAC gnomAD
CA374004661 rs772667595	22	V>G		No	ClinGen ExAC gnomAD
rs1587818326 CA374004666	23	V>G		No	ClinGen Ensembl
CA5105400 rs78480824	23	V>M		No	ClinGen ExAC gnomAD
rs747519919 CA5105401	24	G>S		No	ClinGen ExAC gnomAD
rs199900277 CA5105402	26	W>R		No	ClinGen 1000Genomes ExAC gnomAD
CA374004688 rs1181332313	27	R>G		No	ClinGen TOPMed gnomAD
CA374004699 rs1587818463	28	A>G		No	ClinGen Ensembl
CA374004703 rs1440777069	29	A>T		No	ClinGen gnomAD
rs1186058354 CA374004711	30	F>S		No	ClinGen TOPMed
rs370304899 CA374004715	31	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs370304899 CA5105405	31	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA5105406 rs143073407	34	T>A		No	ClinGen ExAC TOPMed gnomAD
rs759206123 CA5105407	34	T>M		No	ClinGen ExAC gnomAD
rs759206123 CA374004736	34	T>R		No	ClinGen ExAC gnomAD
rs767325817 CA5105408	38	C>F		No	ClinGen ExAC gnomAD
rs147067960 CA195738460	39	S>R		No	ClinGen ESP
CA5105410 rs760689213	41	S>F		No	ClinGen ExAC TOPMed gnomAD
rs1454412423 CA374004780	41	S>T		No	ClinGen gnomAD
rs76060730 CA195738462	42	R>Q		No	ClinGen Ensembl
rs1420992400 CA374004786	42	R>W		No	ClinGen TOPMed gnomAD
CA374004817 rs1171041569	46	S>N		No	ClinGen gnomAD
CA5105412 rs376605075	46	S>R		No	ClinGen ExAC TOPMed gnomAD
rs1211901247 CA374004813	46	S>R		No	ClinGen TOPMed
CA195738463 rs78200643	47	D>Y		No	ClinGen Ensembl
rs756974214 CA5105413	48	P>L		No	ClinGen ExAC gnomAD
CA374004837 rs1371476425	49	S>F		No	ClinGen gnomAD
CA195738464 rs938587244	51	G>D		No	ClinGen Ensembl
rs200996010 CA195738465	52	I>V		No	ClinGen TOPMed gnomAD
rs778391314 CA5105414	53	V>M		No	ClinGen ExAC TOPMed gnomAD
CA5105416 rs758729728	57	R>I		No	ClinGen ExAC TOPMed gnomAD
CA5105418 rs747571706	58	L>S		No	ClinGen ExAC gnomAD
CA5105419 rs769089926	60	P>H		No	ClinGen ExAC gnomAD
CA195738466 rs915858967	62	S>G		No	ClinGen Ensembl
rs201875843 CA195738469	64	D>E		No	ClinGen 1000Genomes TOPMed
rs781249905 CA5105420	64	D>G		No	ClinGen ExAC gnomAD
rs944995042 CA195738470	66	E>K		No	ClinGen TOPMed gnomAD
CA195738471 rs1045092810	67	N>K		No	ClinGen Ensembl
rs1244676877 CA374004949	67	N>S		No	ClinGen gnomAD
CA5105421 rs748182988	68	I>V		No	ClinGen ExAC gnomAD
CA374004960 rs1168031496	69	T>A		No	ClinGen gnomAD
rs1166326389 CA374004967	70	E>A		No	ClinGen TOPMed
COSM1110669 CA374004964 rs1408094711	70	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1169880026 CA374004973	71	I>V		No	ClinGen gnomAD
COSM1741430 rs201490630 CA195742776	74	A>T	urinary_tract [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs771127404 CA5105444	78	R>M		No	ClinGen ExAC gnomAD
rs775430298 CA374005059	81	I>F		No	ClinGen ExAC TOPMed gnomAD
rs775430298 CA5105445	81	I>V		No	ClinGen ExAC TOPMed gnomAD
rs143970219 CA374005078	83	N>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1487008553 CA374005075	83	N>S		No	ClinGen TOPMed gnomAD
CA374005086 rs1233368130	84	E>D		No	ClinGen TOPMed
CA5105447 rs768737791	85	D>Y		No	ClinGen ExAC gnomAD
CA195742785 rs762914833	87	V>A		No	ClinGen Ensembl
rs923820423 CA195742787	88	E>K		No	ClinGen TOPMed gnomAD
CA374005153 rs1185342057	95	N>D		No	ClinGen gnomAD
CA374005158 rs1367604059	95	N>K		No	ClinGen gnomAD
CA374005178 rs1193996829	97	T>A		No	ClinGen TOPMed
CA195742832 rs1052977316	98	I>V		No	ClinGen TOPMed gnomAD
CA195742834 rs890209390	100	D>G		No	ClinGen TOPMed
rs1445492288 CA374005253	108	H>R		No	ClinGen gnomAD
rs1303772589 CA374005265	110	A>T		No	ClinGen gnomAD
CA5105471 rs772625764	115	S>R		No	ClinGen ExAC
rs202214549 CA195742840	117	L>V		No	ClinGen Ensembl
rs765851371 CA374005331	119	H>L		No	ClinGen ExAC TOPMed gnomAD
rs765851371 CA5105473	119	H>R		No	ClinGen ExAC TOPMed gnomAD
rs200467220 CA5105474	120	I>V		No	ClinGen ExAC TOPMed gnomAD
CA374005357 rs1384751404	121	N>S		No	ClinGen gnomAD
rs758634866 CA5105484	122	F>I		No	ClinGen ExAC TOPMed gnomAD
CA374005374 rs1229434307	124	R>G		No	ClinGen TOPMed gnomAD
CA5105485 rs781137734 COSM1463355	124	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs201256653 CA5105486	128	T>M		No	ClinGen 1000Genomes ExAC gnomAD
CA374005399 rs1317048518	128	T>P		No	ClinGen gnomAD
CA374005407 rs1489559304	129	S>T		No	ClinGen gnomAD
CA374005449 rs1429261165	135	F>L		No	ClinGen gnomAD
rs749146781 CA5105489	136	R>C		No	ClinGen ExAC gnomAD
COSM456172 rs144037140 CA5105490	136	R>H	breast [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA374005459 rs144037140	136	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs773840958 CA5105491	139	D>E		No	ClinGen ExAC gnomAD
CA374005478 rs1371806545	139	D>G		No	ClinGen TOPMed
CA374005475 rs1252318857	139	D>H		No	ClinGen Ensembl
CA5105492 rs150692457	140	L>F		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA5105508 rs778403111	144	I>V		No	ClinGen ExAC gnomAD
rs1203098513 CA374005637	146	V>A		No	ClinGen TOPMed gnomAD
CA195744678 rs201757733	149	P>L		No	ClinGen Ensembl
rs760215602 CA5105512	155	D>G		No	ClinGen ExAC gnomAD
CA374005739 rs1564102310	156	I>V		No	ClinGen Ensembl
rs769121017 CA5105513	161	T>I		No	ClinGen ExAC gnomAD
CA195744687 rs200773017	164	E>V		No	ClinGen TOPMed
rs762413234 CA5105515	166	K>T		No	ClinGen ExAC gnomAD
rs765799040 CA5105516	167	S>T		No	ClinGen ExAC gnomAD
rs76950094 CA5105517	167	S>Y		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA374005874 rs1369331924	168	S>I		No	ClinGen TOPMed
CA5105518 rs371313025	170	D>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA5105519 rs766335528	171	T>A		No	ClinGen ExAC gnomAD
CA195744694 rs913317289	173	D>G		No	ClinGen TOPMed gnomAD
CA374005920 rs1239779612	173	D>N		No	ClinGen gnomAD
CA374005978 rs1564102617	178	N>S		No	ClinGen Ensembl
CA195744698 rs199957207	182	K>E		No	ClinGen gnomAD
CA374006024 rs1156459668	182	K>R		No	ClinGen gnomAD
CA374006030 rs1379145164	183	N>H		No	ClinGen gnomAD
CA5105522 rs563972840	187	A>E		No	ClinGen 1000Genomes ExAC gnomAD
CA374006823 rs764986674	195	G>A		No	ClinGen ExAC TOPMed gnomAD
CA374006821 rs764986674	195	G>D		No	ClinGen ExAC TOPMed gnomAD
CA5105542 rs764986674	195	G>V		No	ClinGen ExAC TOPMed gnomAD
CA195747571 rs773925423	199	A>V		No	ClinGen Ensembl
CA5105543 rs139119122	201	L>M		No	ClinGen ESP ExAC TOPMed
rs1437483265 CA374006901	202	A>D		No	ClinGen gnomAD
CA5105544 rs117250170	203	A>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA5105545 rs117250170	203	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs139913267 CA5105546 COSM1236220	204	P>H	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs139913267 CA195747580	204	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs142190177 CA195747584	205	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs1317085689 CA374006939	206	L>F		No	ClinGen TOPMed
CA5105549 rs747768342	208	V>L		No	ClinGen ExAC TOPMed
CA374007003 rs1334971005	211	G>R		No	ClinGen TOPMed
rs1360196810 CA374007018	212	K>E		No	ClinGen TOPMed gnomAD
CA195747591 rs1016963587	214	I>V		No	ClinGen TOPMed
rs1477448636 CA374007165	223	D>G		No	ClinGen TOPMed gnomAD
CA374007177 rs1194284331	224	P>L		No	ClinGen gnomAD
rs1476700706 CA374007185	225	V>A		No	ClinGen gnomAD
rs1476700706 CA374007184	225	V>G		No	ClinGen gnomAD
CA374007206 rs1169635968	227	N>S		No	ClinGen gnomAD
CA374007227 rs1424756918	228	M>I		No	ClinGen TOPMed
CA5105554 rs774525198	229	Y>H		No	ClinGen ExAC gnomAD
CA374007373 rs1564128887	239	H>L		No	ClinGen Ensembl
CA5105557 rs200807970	240	M>T		No	ClinGen ExAC TOPMed gnomAD
rs767612147 CA5105556	240	M>V		No	ClinGen ExAC TOPMed gnomAD
CA5105568 rs778290134	241	N>S		No	ClinGen ExAC gnomAD
CA374007416 rs1341434594	242	E>K		No	ClinGen gnomAD
CA195747740 rs78101850	243	T>I		No	ClinGen ExAC TOPMed gnomAD
CA5105570 rs78101850	243	T>K		No	ClinGen ExAC TOPMed gnomAD
CA195747742 rs200053780	244	S>G		No	ClinGen Ensembl
CA5105571 rs779338307	244	S>N		No	ClinGen ExAC gnomAD
rs1240437124 CA374007448	247	Q>E		No	ClinGen TOPMed gnomAD
rs1287454889 CA374007451	247	Q>R		No	ClinGen gnomAD
CA5105573 rs772111782	249	S>Y		No	ClinGen ExAC TOPMed gnomAD
CA195747747 rs200869053	251	R>K		No	ClinGen TOPMed
rs1443894759 CA374007481	252	I>L		No	ClinGen gnomAD
rs1236700381 CA374007512	256	S>L		No	ClinGen gnomAD
rs760889003 CA5105575	258	D>E		No	ClinGen ExAC gnomAD
CA195747750 rs200636057	258	D>N		No	ClinGen TOPMed
CA374007543 rs1389555393	261	G>E		No	ClinGen gnomAD
rs138637060 COSM1463378 CA5105576	261	G>R	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC gnomAD
CA374007574 rs1564130459	265	S>F		No	ClinGen Ensembl
CA195747754 rs780082310	267	V>M		No	ClinGen Ensembl
CA195747756 rs997635600	268	A>V		No	ClinGen Ensembl
CA374007605 rs1273333430	270	N>S		No	ClinGen TOPMed
rs1404514232 CA374007617	272	V>I		No	ClinGen TOPMed
CA374007641 rs1564130631	275	D>E		No	ClinGen Ensembl
CA374007635 rs1403591514	275	D>N		No	ClinGen gnomAD
CA5105578 rs762704550	277	D>V		No	ClinGen ExAC gnomAD
rs1332554506 CA374007666	279	V>L		No	ClinGen gnomAD
CA5105579 rs766162328	280	N>I		No	ClinGen ExAC gnomAD
rs766162328 CA195747762	280	N>S		No	ClinGen ExAC gnomAD
rs766162328 CA374007673	280	N>T		No	ClinGen ExAC gnomAD
CA374007676 rs1426549238	281	L>F		No	ClinGen TOPMed
CA195747765 rs202187366	282	T>N		No	ClinGen Ensembl
CA5105582 rs767147256	284	H>R		No	ClinGen ExAC TOPMed gnomAD
rs759501723 CA5105581	284	H>Y		No	ClinGen ExAC gnomAD
rs140359847 CA5105596	288	T>A		No	ClinGen ESP ExAC gnomAD
CA374008127 rs1226874845	290	T>I		No	ClinGen TOPMed
CA195748582 rs200940075	290	T>S		No	ClinGen gnomAD
rs1456574135 CA374008146	293	E>K		No	ClinGen gnomAD
rs1284937999 CA374008275	303	I>L		No	ClinGen TOPMed
CA374008325 rs1429250775	307	V>M		No	ClinGen gnomAD
CA374008350 rs1192714938	309	G>S		No	ClinGen Ensembl
CA5105602 rs763671078	314	A>V		No	ClinGen ExAC gnomAD
CA374008514 rs141580491	320	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA5105605 rs779160638	321	G>R		No	ClinGen ExAC gnomAD
CA195748591 rs886792077	322	A>T		No	ClinGen Ensembl
rs750758088 CA5105606	322	A>V		No	ClinGen ExAC gnomAD
rs200564196 CA5105608	323	I>M		No	ClinGen ExAC gnomAD
rs943748747 CA195748595	323	I>V		No	ClinGen Ensembl
CA5105609 rs201032414	328	K>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA195748602 rs200961252	328	K>R		No	ClinGen Ensembl
rs1489487403 CA374008676	336	V>D		No	ClinGen gnomAD
rs1268292641 CA374008684	337	T>I		No	ClinGen TOPMed gnomAD
rs1268292641 CA374008683	337	T>S		No	ClinGen TOPMed gnomAD
rs192640311 CA5105612	338	N>I		No	ClinGen 1000Genomes ExAC gnomAD
rs1047856 VAR_011973 CA195748608	338	N>Y		No	ClinGen UniProt Ensembl dbSNP
rs774048334 CA5105614	347	Q>H		No	ClinGen ExAC gnomAD
CA374008864 rs1369882959	352	T>P		No	ClinGen gnomAD
CA374008894 rs1360624294	354	M>R		No	ClinGen gnomAD
rs762253055 CA5105616	354	M>V		No	ClinGen ExAC gnomAD
CA5105617 rs775608354	356	N>S		No	ClinGen ExAC gnomAD
rs1323675151 CA374008989	362	I>T		No	ClinGen gnomAD
rs761378488 CA5105621	362	I>V		No	ClinGen ExAC gnomAD
rs1451356116 CA374008991	363	A>T		No	ClinGen TOPMed
CA5105625 rs146616471	377	H>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA5105626 rs148355466	379	M>L		No	ClinGen ESP ExAC gnomAD
CA195748632 rs202086886	384	I>T		No	ClinGen Ensembl
rs183322024 CA5105628	385	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs200996090 COSM456175 CA5105629	386	D>N	breast [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs551310223 CA5105649	387	G>D		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs199505477 CA5105650	389	N>S		No	ClinGen ExAC gnomAD
rs199667706 CA195751862	391	N>S		No	ClinGen 1000Genomes
CA5105651 rs528858919	393	P>S		No	ClinGen 1000Genomes ExAC gnomAD
rs754864774 CA5105673	402	T>A		No	ClinGen ExAC gnomAD
CA5105674 rs780831721	403	A>T		No	ClinGen ExAC gnomAD
CA5105675 rs556985581	404	A>V		No	ClinGen ExAC gnomAD
rs777294894 CA5105677	406	D>G		No	ClinGen ExAC gnomAD
CA374006765 rs1472093753	407	I>F		No	ClinGen gnomAD
CA5105678 rs748744999	408	G>R		No	ClinGen ExAC gnomAD
CA5105680 rs774034569	410	T>N		No	ClinGen ExAC TOPMed gnomAD
rs78629699 CA5105681	411	T>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs78629699 CA5105682	411	T>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA195752634 rs201342791	412	N>D		No	ClinGen gnomAD
CA374006801 rs1299400371	413	R>G		No	ClinGen gnomAD
rs761253022 CA5105684	414	S>N		No	ClinGen ExAC gnomAD
rs368307071 CA5105685	416	E>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs202153392 CA5105686	419	S>P		No	ClinGen ExAC gnomAD
CA374006899 rs1167335341	420	T>I		No	ClinGen TOPMed
rs759743944 CA195752642	421	D>G		No	ClinGen TOPMed gnomAD
rs137873897 CA5105689 COSM1110700	422	V>I	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs142393662 CA5105691	427	G>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs752393508 CA5105692	428	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA195752648 rs958492686	428	R>W		No	ClinGen TOPMed gnomAD
rs1237850077 CA374007013	429	E>K		No	ClinGen gnomAD
rs777735763 CA5105694	430	H>R		No	ClinGen ExAC gnomAD
rs145968424 CA5105693	430	H>Y		No	ClinGen ESP ExAC TOPMed gnomAD
CA5105696 rs756829653	431	L>P		No	ClinGen ExAC
rs200354354 CA195752655	432	S>L		No	ClinGen TOPMed gnomAD
rs372937529 CA5105712	435	A>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs1483049620 CA374008199	436	V>L		No	ClinGen TOPMed
CA5105713 rs757130152	437	V>L		No	ClinGen ExAC gnomAD
rs778403210 CA5105714	438	V>A		No	ClinGen ExAC gnomAD
CA374008224 rs1251903649	438	V>M		No	ClinGen TOPMed
rs1197079255 COSM1490192 CA374008250	440	A>T	breast [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1332713570 CA374008262	440	A>V		No	ClinGen gnomAD
CA5105716 rs758094577	442	V>L		No	ClinGen ExAC gnomAD
rs779625097 CA5105717	445	F>I		No	ClinGen ExAC gnomAD
CA374008337 rs1245199940	446	C>S		No	ClinGen TOPMed
rs746665735 CA5105718	447	L>F		No	ClinGen ExAC gnomAD
CA374008384 rs1252750979	449	V>A		No	ClinGen gnomAD
rs201445439 CA5105720 COSM1110703	449	V>I	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA374008389 rs1286314407	450	M>V		No	ClinGen TOPMed
rs1227694041 CA374008415	452	F>L		No	ClinGen TOPMed
CA374008445 rs1181697709	454	L>R		No	ClinGen gnomAD
CA374008461 rs1482444647	455	K>N		No	ClinGen TOPMed gnomAD
CA195754472 rs2275857	457	A>P		No	ClinGen Ensembl
rs999011148 CA195754474	458	R>G		No	ClinGen TOPMed gnomAD
CA5105722 rs770383737	462	F>S		No	ClinGen ExAC gnomAD
rs149694868 CA5105773	466	G>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs149694868 CA5105774	466	G>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA5105777 rs201028496	470	V>I		No	ClinGen ExAC TOPMed gnomAD
rs75796345 CA195792402	472	S>I		No	ClinGen Ensembl
rs1433723325 CA374005556	473	N>H		No	ClinGen gnomAD
CA195792406 rs892842591	474	D>G		No	ClinGen TOPMed
CA195792414 rs1011244815	477	S>P		No	ClinGen TOPMed
rs757730386 CA5105780	483	H>N		No	ClinGen ExAC gnomAD
rs375893744 CA5105781	484	I>L		No	ClinGen ESP ExAC gnomAD
rs746345297 CA5105782	488	S>N		No	ClinGen ExAC gnomAD
CA374005876 rs1587743298	494	S>L		No	ClinGen Ensembl
CA374005894 rs1437197716	495	E>G		No	ClinGen TOPMed
CA5105785 rs200927720	497	G>V		No	ClinGen ExAC gnomAD
rs199554482 CA195792435	498	P>L		No	ClinGen Ensembl
rs1285574585 CA374005994	501	V>I		No	ClinGen TOPMed gnomAD
CA195792440 rs200871730	502	I>V		No	ClinGen Ensembl
rs201888268 CA195792443	507	K>N		No	ClinGen gnomAD
CA5105786 rs768879622	515	Q>E		No	ClinGen ExAC
rs772901814 CA5105787	518	G>D		No	ClinGen ExAC gnomAD
rs1201764479 CA374006313	519	I>T		No	ClinGen gnomAD
CA5105788 rs749156184	521	N>K		No	ClinGen ExAC gnomAD
rs1201591880 CA374006386	524	L>H		No	ClinGen gnomAD
CA195792454 rs373889692	525	K>N		No	ClinGen gnomAD
CA374006405 rs1414430883	526	P>S		No	ClinGen Ensembl
rs1318112036 CA374006232	532	H>Q		No	ClinGen gnomAD
CA374006253 rs1406295517	534	K>R		No	ClinGen gnomAD
CA5105820 rs763470905	536	H>R		No	ClinGen ExAC gnomAD
rs766917919 CA5105821	538	I>V		No	ClinGen ExAC gnomAD
rs200481866 CA195812924	541	K>E		No	ClinGen Ensembl
rs1075108 CA374006385	545	G>D		No	ClinGen TOPMed
CA195812925 rs1075108 VAR_049715	545	G>V		No	ClinGen UniProt TOPMed dbSNP
rs1281250433 CA374006434	548	A>V		No	ClinGen gnomAD
CA374006510 rs1263542133	558	Y>H		No	ClinGen gnomAD
CA195812928 rs201539451	558	Y>S		No	ClinGen Ensembl
rs781117934 CA195812929	559	N>K		No	ClinGen ExAC TOPMed gnomAD
rs752976453 CA5105825	560	L>F		No	ClinGen ExAC gnomAD
rs756338416 CA374006532	561	C>F		No	ClinGen ExAC gnomAD
rs1483760777 CA374006529	561	C>R		No	ClinGen TOPMed
rs756338416 CA5105826	561	C>Y		No	ClinGen ExAC gnomAD
CA374006535 rs1437034761	562	P>T		No	ClinGen gnomAD
rs1564478478 CA374006542	563	E>Q		No	ClinGen Ensembl
CA5105827 rs778882958	565	D>G		No	ClinGen ExAC gnomAD
rs745611356 CA5105828	568	L>F		No	ClinGen ExAC TOPMed gnomAD
rs1235066441 CA374006601	571	V>A		No	ClinGen TOPMed gnomAD
CA374009133 rs1393774313	576	D>Y		No	ClinGen gnomAD
CA374009189 rs1303737733	577	A>T		No	ClinGen gnomAD
rs1273745094 CA374009206	577	A>V		No	ClinGen TOPMed
rs746983050 CA5105848	578	S>C		No	ClinGen ExAC gnomAD
CA374009226 rs1402829992	578	S>N		No	ClinGen gnomAD
CA374009234 rs1402829992	578	S>T		No	ClinGen gnomAD
CA5105850 rs147652140	582	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs147652140 CA5105849	582	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs183344464 CA195814399	587	R>H		No	ClinGen 1000Genomes gnomAD
rs1564492351 CA374009490	590	E>K		No	ClinGen Ensembl
rs1205052587 CA374009588	597	H>Y		No	ClinGen gnomAD
CA374009652 rs1211018594	601	V>I		No	ClinGen gnomAD
rs202136187 CA5105854	602	K>R		No	ClinGen ExAC TOPMed gnomAD
rs200399260 CA5105856	606	V>I		No	ClinGen ExAC gnomAD
rs200399260 CA5105857	606	V>L		No	ClinGen ExAC gnomAD
rs1194954580 CA374009712	608	V>L		No	ClinGen TOPMed gnomAD
CA374009710 rs1194954580	608	V>M		No	ClinGen TOPMed gnomAD
CA195814401 rs895713202	610	G>D		No	ClinGen TOPMed
rs201553907 CA5105860	611	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs201553907 CA195814402	611	D>Y		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1367316585 CA374009735	612	P>T		No	ClinGen gnomAD
rs1292664958 CA374009742	613	L>F		No	ClinGen gnomAD
CA374009763 rs1385491348	616	V>I		No	ClinGen gnomAD
CA5105861 rs764268451	621	K>R		No	ClinGen ExAC gnomAD
rs552897673 CA5105863	622	H>D		No	ClinGen 1000Genomes ExAC gnomAD
CA374009812 rs1227692441	622	H>L		No	ClinGen gnomAD
rs552897673 CA5105862	622	H>Y		No	ClinGen 1000Genomes ExAC gnomAD
rs754776571 CA5105866	627	K>Q		No	ClinGen ExAC gnomAD
rs1445862129 CA374009887	631	A>T		No	ClinGen gnomAD
CA374009894 rs1374615996	632	H>Y		No	ClinGen gnomAD
CA195815111 rs200114699	637	V>L		No	ClinGen ExAC TOPMed gnomAD
CA5105894 rs200114699	637	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1310111405 CA374009959	642	G>S		No	ClinGen gnomAD
CA5105897 rs201105177	644	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA374009976 rs201105177	644	P>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1564499114 CA374009975	644	P>S		No	ClinGen Ensembl
CA5105898 rs780511969	649	T>A		No	ClinGen ExAC gnomAD
rs747525829 CA5105899	649	T>M		No	ClinGen ExAC gnomAD
rs777251032 CA5105901	651	S>L		No	ClinGen ExAC TOPMed gnomAD
CA374010030 rs1449704490	653	M>L		No	ClinGen TOPMed
rs1011861704 CA195815114	657	A>V		No	ClinGen TOPMed
CA374010084 rs1406280648	661	A>T		No	ClinGen TOPMed
CA374010090 rs1463968979	662	A>T		No	ClinGen gnomAD
CA195815115 rs202111708	662	A>V		No	ClinGen Ensembl
CA374010100 rs1370309853	663	G>A		No	ClinGen gnomAD
CA5105905 rs763175850	664	M>I		No	ClinGen ExAC
CA5105906 rs767304206	665	V>A		No	ClinGen ExAC gnomAD
rs1285612169 CA374010130	668	A>E		No	ClinGen TOPMed gnomAD
rs1285612169 CA374010131	668	A>V		No	ClinGen TOPMed gnomAD
rs760629075 CA5105908	669	S>F		No	ClinGen ExAC gnomAD
rs1224365290 CA374010255	686	E>G		No	ClinGen gnomAD
rs1490499624 CA374010250	686	E>K		No	ClinGen gnomAD
CA374010263 rs1244771562	687	N>S		No	ClinGen gnomAD
CA374010384 rs1564499587	705	D>N		No	ClinGen Ensembl
rs199684178 CA195815118	708	R>T		No	ClinGen Ensembl
rs903676836 CA195830736	710	G>S		No	ClinGen TOPMed
CA374007774 VAR_046520 rs1324578301	718	R>C	a lung carcinoma sample; somatic mutation [UniProt]	No	ClinGen UniProt dbSNP gnomAD
CA5105953 rs767802494	718	R>H		No	ClinGen ExAC gnomAD
CA374007803 rs1276608169	722	P>S		No	ClinGen gnomAD
rs1554788562 RCV000627581	724	S>missing		No	ClinVar dbSNP
rs753056075 CA5105954	725	I>V		No	ClinGen ExAC gnomAD
rs1180233906 CA374007876	732	T>A		No	ClinGen gnomAD
rs367769334 CA5105957	732	T>M		No	ClinGen ESP ExAC gnomAD
rs1170229422 CA374007904	736	V>I		No	ClinGen gnomAD
rs746097417 CA5105960	741	V>I		No	ClinGen ExAC gnomAD
CA374007943 rs1368656393	742	V>M		No	ClinGen gnomAD
rs748028871 CA5105963	745	E>G		No	ClinGen ExAC gnomAD
CA195830759 rs577506861	747	F>L		No	ClinGen 1000Genomes
CA195830768 rs1034634919	758	S>P		No	ClinGen Ensembl
CA5105970 rs767248118	760	N>K		No	ClinGen ExAC gnomAD
CA5105969 rs148990783	760	N>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1164175843 CA374008702	762	V>M		No	ClinGen gnomAD
rs1369955410 CA374008758	765	C>S		No	ClinGen gnomAD
CA374008788 rs1456152062	767	T>S		No	ClinGen gnomAD
rs201491838 CA374008827	770	R>L		No	ClinGen ExAC TOPMed gnomAD
CA5105983 rs201491838	770	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA5105985 rs532184896	774	R>Q		No	ClinGen 1000Genomes ExAC gnomAD
rs201902834 CA5105987	776	R>C		No	ClinGen ExAC TOPMed gnomAD
CA195831011 rs957713208	776	R>H		No	ClinGen TOPMed gnomAD
CA374008915 rs957713208	776	R>L		No	ClinGen TOPMed gnomAD
rs988042143 CA195831013	777	T>M		No	ClinGen TOPMed
CA374008972 rs1242988461	780	Q>L		No	ClinGen gnomAD
rs1265661428 CA374009087	788	G>W		No	ClinGen gnomAD
rs758574086 CA5105995	796	M>I		No	ClinGen ExAC gnomAD
CA195831020 rs758154340	796	M>R		No	ClinGen Ensembl
CA5105994 rs750902920	796	M>V		No	ClinGen ExAC gnomAD
rs200900730 CA5105998	809	N>D		No	ClinGen ExAC TOPMed gnomAD
CA5106000 rs749137113	812	K>E		No	ClinGen ExAC gnomAD
rs926486304 CA195831030	812	K>N		No	ClinGen gnomAD
CA374009546 rs1381902898	813	A>V		No	ClinGen TOPMed gnomAD
rs770827440 CA5106001	815	P>L		No	ClinGen ExAC gnomAD
rs1351530738 CA374009579	816	V>F		No	ClinGen TOPMed gnomAD
CA374009577 rs1351530738	816	V>I		No	ClinGen TOPMed gnomAD
CA374009630 rs1299029308	820	I>V		No	ClinGen gnomAD
CA374009648 rs1229826541	822	G>S		No	ClinGen gnomAD

2 associated diseases with Q16620

[MIM: 617830]: Developmental and epileptic encephalopathy 58 (DEE58)

A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE58 is an autosomal dominant condition characterized by onset of refractory seizures in the first days or months of life. {ECO:0000269|PubMed:29100083}. Note=The disease may be caused by variants affecting the gene represented in this entry.

[MIM: 613886]: Obesity, hyperphagia, and developmental delay (OBHD)

A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language. {ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:27884935, ECO:0000269|PubMed:29100083}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE58 is an autosomal dominant condition characterized by onset of refractory seizures in the first days or months of life. {ECO:0000269|PubMed:29100083}. Note=The disease may be caused by variants affecting the gene represented in this entry.
A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language. {ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:27884935, ECO:0000269|PubMed:29100083}. Note=The disease is caused by variants affecting the gene represented in this entry.

18 regional properties for Q16620

Type	Name	Position	InterPro Accession
domain	Flavodoxin-like	756 - 769	IPR001094-1
domain	Flavodoxin-like	803 - 814	IPR001094-2
domain	Flavodoxin-like	876 - 886	IPR001094-3
domain	Flavodoxin-like	900 - 919	IPR001094-4
domain	Oxidoreductase FAD/NAD(P)-binding	1246 - 1358	IPR001433
domain	PDZ domain	17 - 100	IPR001478
domain	Flavoprotein pyridine nucleotide cytochrome reductase	1027 - 1037	IPR001709-1
domain	Flavoprotein pyridine nucleotide cytochrome reductase	1173 - 1180	IPR001709-2
domain	Flavoprotein pyridine nucleotide cytochrome reductase	1209 - 1218	IPR001709-3
domain	Flavoprotein pyridine nucleotide cytochrome reductase	1245 - 1264	IPR001709-4
domain	Flavoprotein pyridine nucleotide cytochrome reductase	1275 - 1284	IPR001709-5
domain	Flavoprotein pyridine nucleotide cytochrome reductase	1288 - 1299	IPR001709-6
domain	Flavoprotein pyridine nucleotide cytochrome reductase	1320 - 1336	IPR001709-7
domain	Flavoprotein pyridine nucleotide cytochrome reductase	1345 - 1353	IPR001709-8
domain	Sulfite reductase [NADPH] flavoprotein alpha-component-like, FAD-binding	986 - 1214	IPR003097
domain	Nitric oxide synthase, N-terminal	351 - 712	IPR004030
domain	Flavodoxin/nitric oxide synthase	755 - 935	IPR008254
domain	FAD-binding domain, ferredoxin reductase-type	990 - 1237	IPR017927

Functions

		Description
EC Number	2.7.10.1	Protein-tyrosine kinases
Subcellular Localization	Cell membrane ; Single-pass type I membrane protein Endosome membrane ; Single-pass type I membrane protein Early endosome membrane Cell projection, axon Cell projection, dendrite Cytoplasm, perinuclear region Postsynaptic density	Internalized to endosomes upon ligand-binding
PANTHER Family	PTHR24416	TYROSINE-PROTEIN KINASE RECEPTOR
PANTHER Subfamily	PTHR24416:SF136	BDNF_NT-3 GROWTH FACTORS RECEPTOR
PANTHER Protein Class	transmembrane signal receptor
PANTHER Pathway Category	No pathway information available

13 GO annotations of cellular component

Name	Definition
axon	The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter.
axon terminus	Terminal inflated portion of the axon, containing the specialized apparatus necessary to release neurotransmitters. The axon terminus is considered to be the whole region of thickening and the terminal button is a specialized region of it.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dendrite	A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
dendritic spine	A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity.
early endosome	A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways.
early endosome membrane	The lipid bilayer surrounding an early endosome.
integral component of plasma membrane	The component of the plasma membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
perinuclear region of cytoplasm	Cytoplasm situated near, or occurring around, the nucleus.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynaptic density	An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components.
receptor complex	Any protein complex that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
terminal bouton	Terminal inflated portion of the axon, containing the specialized apparatus necessary to release neurotransmitters. The axon terminus is considered to be the whole region of thickening and the terminal bouton is a specialized region of it.

9 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
brain-derived neurotrophic factor binding	Binding to brain-derived neurotrophic factor.
brain-derived neurotrophic factor-activated receptor activity	Combining with a brain-derived neurotrophic factor and transmitting the signal across the plasma membrane to initiate a change in cell activity.
neurotrophin binding	Binding to a neurotrophin, any of a family of growth factors that prevent apoptosis in neurons and promote nerve growth.
neurotrophin receptor activity	Combining with a neurotrophin, any of a family of growth factors that prevent apoptosis in neurons and promote nerve growth, and transmitting the signal to initiate a change in cell activity.
protease binding	Binding to a protease or a peptidase.
protein homodimerization activity	Binding to an identical protein to form a homodimer.
protein serine/threonine/tyrosine kinase activity	Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
transmembrane receptor protein tyrosine kinase activity	Combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction: ATP + a protein-L-tyrosine = ADP + a protein-L-tyrosine phosphate.

39 GO annotations of biological process

Name	Definition
brain-derived neurotrophic factor receptor signaling pathway	The series of molecular signals generated as a consequence of a brain-derived neurotrophic factor receptor binding to one of its physiological ligands.
cellular response to amino acid stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amino acid stimulus. An amino acid is a carboxylic acids containing one or more amino groups.
cellular response to brain-derived neurotrophic factor stimulus	A process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a brain-derived neurotrophic factor stimulus.
cellular response to nerve growth factor stimulus	A process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nerve growth factor stimulus.
central nervous system neuron development	The process whose specific outcome is the progression of a neuron whose cell body is located in the central nervous system, from initial commitment of the cell to a neuronal fate, to the fully functional differentiated neuron.
cerebral cortex development	The progression of the cerebral cortex over time from its initial formation until its mature state. The cerebral cortex is the outer layered region of the telencephalon.
circadian rhythm	Any biological process in an organism that recurs with a regularity of approximately 24 hours.
feeding behavior	Behavior associated with the intake of food.
glutamate secretion	The controlled release of glutamate by a cell. The glutamate is the most abundant excitatory neurotransmitter in the nervous system.
learning	Any process in an organism in which a relatively long-lasting adaptive behavioral change occurs as the result of experience.
long-term synaptic potentiation	A process that modulates synaptic plasticity such that synapses are changed resulting in the increase in the rate, or frequency of synaptic transmission at the synapse.
mechanoreceptor differentiation	The process in which a relatively unspecialized cell acquires specialized features of a mechanoreceptor, a cell specialized to transduce mechanical stimuli and relay that information centrally in the nervous system.
myelination in peripheral nervous system	The process in which neuronal axons and dendrites become coated with a segmented lipid-rich sheath (myelin) to enable faster and more energetically efficient conduction of electrical impulses. The sheath is formed by the cell membranes of Schwann cells in the peripheral nervous system. Adjacent myelin segments are separated by a non-myelinated stretch of axon called a node of Ranvier.
negative regulation of amyloid-beta formation	Any process that stops, prevents or reduces the frequency, rate or extent of amyloid-beta formation.
negative regulation of anoikis	Any process that stops, prevents or reduces the frequency, rate or extent of anoikis.
negative regulation of neuron apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
neuron differentiation	The process in which a relatively unspecialized cell acquires specialized features of a neuron.
neuron migration	The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature.
neuronal action potential propagation	The propagation of an action potential along an axon, away from the soma.
oligodendrocyte differentiation	The process in which a relatively unspecialized cell acquires the specialized features of an oligodendrocyte. An oligodendrocyte is a type of glial cell involved in myelinating the axons of neurons in the central nervous system.
peripheral nervous system neuron development	The process whose specific outcome is the progression of a neuron whose cell body is located in the peripheral nervous system, from initial commitment of the cell to a neuronal fate, to the fully functional differentiated neuron.
positive regulation of axonogenesis	Any process that activates or increases the frequency, rate or extent of axonogenesis.
positive regulation of cell population proliferation	Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of gene expression	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of kinase activity	Any process that activates or increases the frequency, rate or extent of kinase activity, the catalysis of the transfer of a phosphate group, usually from ATP, to a substrate molecule.
positive regulation of MAPK cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade.
positive regulation of neuron projection development	Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
positive regulation of peptidyl-serine phosphorylation	Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-serine.
positive regulation of phosphatidylinositol 3-kinase signaling	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the phosphatidylinositol 3-kinase cascade.
positive regulation of protein phosphorylation	Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of synapse assembly	Any process that activates, maintains or increases the frequency, rate or extent of synapse assembly, the aggregation, arrangement and bonding together of a set of components to form a synapse.
protein autophosphorylation	The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
regulation of GTPase activity	Any process that modulates the rate of GTP hydrolysis by a GTPase.
regulation of protein kinase B signaling	Any process that modulates the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
retinal rod cell development	Development of a rod cell, one of the sensory cells in the eye that reacts to the presence of light. Rod cells contain the photopigment rhodopsin or porphyropsin and are responsible for vision in dim light.
trans-synaptic signaling by BDNF, modulating synaptic transmission	Cell-cell signaling between presynapse and postsynapse, via the vesicular release and reception of brain derived neurotrophic factor (BDNF), that modulates the synaptic transmission properties of the synapse.
trans-synaptic signaling by neuropeptide, modulating synaptic transmission	Cell-cell signaling between presynapse and postsynapse, via the vesicular release and reception of neuropeptide molecules, that modulates the synaptic transmission properties of the synapse.
transmembrane receptor protein tyrosine kinase signaling pathway	The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
vasculogenesis	The differentiation of endothelial cells from progenitor cells during blood vessel development, and the de novo formation of blood vessels and tubes.

67 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q91044	NTRK3	NT-3 growth factor receptor	Gallus gallus (Chicken)	SS
Q91009	NTRK1	High affinity nerve growth factor receptor	Gallus gallus (Chicken)	SS
Q8AXY6	MUSK	Muscle, skeletal receptor tyrosine protein kinase	Gallus gallus (Chicken)	SS
Q91987	NTRK2	BDNF/NT-3 growth factors receptor	Gallus gallus (Chicken)	SS
Q5IS37	NTRK3	NT-3 growth factor receptor	Pan troglodytes (Chimpanzee)	SS
Q24488	Ror	Tyrosine-protein kinase transmembrane receptor Ror	Drosophila melanogaster (Fruit fly)	SS
Q9V6K3	Nrk	Tyrosine-protein kinase transmembrane receptor Ror2	Drosophila melanogaster (Fruit fly)	SS
P07949	RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Homo sapiens (Human)	EV
O15146	MUSK	Muscle, skeletal receptor tyrosine-protein kinase	Homo sapiens (Human)	EV
Q01974	ROR2	Tyrosine-protein kinase transmembrane receptor ROR2	Homo sapiens (Human)	EV
Q01973	ROR1	Inactive tyrosine-protein kinase transmembrane receptor ROR1	Homo sapiens (Human)	PR
Q16832	DDR2	Discoidin domain-containing receptor 2	Homo sapiens (Human)	SS
Q08345	DDR1	Epithelial discoidin domain-containing receptor 1	Homo sapiens (Human)	EV
P04629	NTRK1	High affinity nerve growth factor receptor	Homo sapiens (Human)	EV
Q16288	NTRK3	NT-3 growth factor receptor	Homo sapiens (Human)	SS
P35916	FLT4	Vascular endothelial growth factor receptor 3	Homo sapiens (Human)	SS
P17948	FLT1	Vascular endothelial growth factor receptor 1	Homo sapiens (Human)	SS
P35968	KDR	Vascular endothelial growth factor receptor 2	Homo sapiens (Human)	EV
P29317	EPHA2	Ephrin type-A receptor 2	Homo sapiens (Human)	SS
P21709	EPHA1	Ephrin type-A receptor 1	Homo sapiens (Human)	SS
P54760	EPHB4	Ephrin type-B receptor 4	Homo sapiens (Human)	SS
P29376	LTK	Leukocyte tyrosine kinase receptor	Homo sapiens (Human)	SS
Q9UM73	ALK	ALK tyrosine kinase receptor	Homo sapiens (Human)	EV
P08922	ROS1	Proto-oncogene tyrosine-protein kinase ROS	Homo sapiens (Human)	SS
P14616	INSRR	Insulin receptor-related protein	Homo sapiens (Human)	SS
P08069	IGF1R	Insulin-like growth factor 1 receptor	Homo sapiens (Human)	EV
P06213	INSR	Insulin receptor	Homo sapiens (Human)	EV
P11362	FGFR1	Fibroblast growth factor receptor 1	Homo sapiens (Human)	EV
P21802	FGFR2	Fibroblast growth factor receptor 2	Homo sapiens (Human)	EV
P22455	FGFR4	Fibroblast growth factor receptor 4	Homo sapiens (Human)	SS
P22607	FGFR3	Fibroblast growth factor receptor 3	Homo sapiens (Human)	EV
Q12866	MERTK	Tyrosine-protein kinase Mer	Homo sapiens (Human)	EV
Q04912	MST1R	Macrophage-stimulating protein receptor	Homo sapiens (Human)	EV
P30530	AXL	Tyrosine-protein kinase receptor UFO	Homo sapiens (Human)	PR
Q06418	TYRO3	Tyrosine-protein kinase receptor TYRO3	Homo sapiens (Human)	SS
P08581	MET	Hepatocyte growth factor receptor	Homo sapiens (Human)	EV
P04626	ERBB2	Receptor tyrosine-protein kinase erbB-2	Homo sapiens (Human)	SS
Q15303	ERBB4	Receptor tyrosine-protein kinase erbB-4	Homo sapiens (Human)	SS
P21860	ERBB3	Receptor tyrosine-protein kinase erbB-3	Homo sapiens (Human)	SS
P00533	EGFR	Epidermal growth factor receptor	Homo sapiens (Human)	EV
P34925	RYK	Tyrosine-protein kinase RYK	Homo sapiens (Human)	PR
Q02763	TEK	Angiopoietin-1 receptor	Homo sapiens (Human)	SS
P35590	TIE1	Tyrosine-protein kinase receptor Tie-1	Homo sapiens (Human)	PR
P10721	KIT	Mast/stem cell growth factor receptor Kit	Homo sapiens (Human)	EV
P09619	PDGFRB	Platelet-derived growth factor receptor beta	Homo sapiens (Human)	EV
P07333	CSF1R	Macrophage colony-stimulating factor 1 receptor	Homo sapiens (Human)	SS
P16234	PDGFRA	Platelet-derived growth factor receptor alpha	Homo sapiens (Human)	EV
P36888	FLT3	Receptor-type tyrosine-protein kinase FLT3	Homo sapiens (Human)	EV
Q3UFB7	Ntrk1	High affinity nerve growth factor receptor	Mus musculus (Mouse)	SS
Q61006	Musk	Muscle, skeletal receptor tyrosine-protein kinase	Mus musculus (Mouse)	SS
Q6VNS1	Ntrk3	NT-3 growth factor receptor	Mus musculus (Mouse)	SS
Q9Z138	Ror2	Tyrosine-protein kinase transmembrane receptor ROR2	Mus musculus (Mouse)	SS
Q9Z139	Ror1	Inactive tyrosine-protein kinase transmembrane receptor ROR1	Mus musculus (Mouse)	PR
P15209	Ntrk2	BDNF/NT-3 growth factors receptor	Mus musculus (Mouse)	SS
P24786	NTRK3	NT-3 growth factor receptor	Sus scrofa (Pig)	SS
Q62838	Musk	Muscle, skeletal receptor tyrosine protein kinase	Rattus norvegicus (Rat)	SS
P35739	Ntrk1	High affinity nerve growth factor receptor	Rattus norvegicus (Rat)	SS
Q03351	Ntrk3	NT-3 growth factor receptor	Rattus norvegicus (Rat)	SS
Q63604	Ntrk2	BDNF/NT-3 growth factors receptor	Rattus norvegicus (Rat)	SS
G5EGK5	cam-1	Tyrosine-protein kinase receptor cam-1	Caenorhabditis elegans	SS
P43298	TMK1	Receptor protein kinase TMK1	Arabidopsis thaliana (Mouse-ear cress)	PR
Q8LPS5	SERK5	Somatic embryogenesis receptor kinase 5	Arabidopsis thaliana (Mouse-ear cress)	PR
Q94C77	At4g34220	Receptor protein kinase-like protein At4g34220	Arabidopsis thaliana (Mouse-ear cress)	PR
Q93ZS4	NIK3	Protein NSP-INTERACTING KINASE 3	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9XIC7	SERK2	Somatic embryogenesis receptor kinase 2	Arabidopsis thaliana (Mouse-ear cress)	PR
C0LGX1	At5g65240	Probable LRR receptor-like serine/threonine-protein kinase At5g65240	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9LFG1	At3g53590	Putative leucine-rich repeat receptor-like serine/threonine-protein kinase At3g53590	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MSSWIRWHGP	AMARLWGFCW	LVVGFWRAAF	ACPTSCKCSA	SRIWCSDPSP	GIVAFPRLEP
70	80	90	100	110	120
NSVDPENITE	IFIANQKRLE	IINEDDVEAY	VGLRNLTIVD	SGLKFVAHKA	FLKNSNLQHI
130	140	150	160	170	180
NFTRNKLTSL	SRKHFRHLDL	SELILVGNPF	TCSCDIMWIK	TLQEAKSSPD	TQDLYCLNES
190	200	210	220	230	240
SKNIPLANLQ	IPNCGLPSAN	LAAPNLTVEE	GKSITLSCSV	AGDPVPNMYW	DVGNLVSKHM
250	260	270	280	290	300
NETSHTQGSL	RITNISSDDS	GKQISCVAEN	LVGEDQDSVN	LTVHFAPTIT	FLESPTSDHH
310	320	330	340	350	360
WCIPFTVKGN	PKPALQWFYN	GAILNESKYI	CTKIHVTNHT	EYHGCLQLDN	PTHMNNGDYT
370	380	390	400	410	420
LIAKNEYGKD	EKQISAHFMG	WPGIDDGANP	NYPDVIYEDY	GTAANDIGDT	TNRSNEIPST
430	440	450	460	470	480
DVTDKTGREH	LSVYAVVVIA	SVVGFCLLVM	LFLLKLARHS	KFGMKGPASV	ISNDDDSASP
490	500	510	520	530	540
LHHISNGSNT	PSSSEGGPDA	VIIGMTKIPV	IENPQYFGIT	NSQLKPDTFV	QHIKRHNIVL
550	560	570	580	590	600
KRELGEGAFG	KVFLAECYNL	CPEQDKILVA	VKTLKDASDN	ARKDFHREAE	LLTNLQHEHI
610	620	630	640	650	660
VKFYGVCVEG	DPLIMVFEYM	KHGDLNKFLR	AHGPDAVLMA	EGNPPTELTQ	SQMLHIAQQI
670	680	690	700	710	720
AAGMVYLASQ	HFVHRDLATR	NCLVGENLLV	KIGDFGMSRD	VYSTDYYRVG	GHTMLPIRWM
730	740	750	760	770	780
PPESIMYRKF	TTESDVWSLG	VVLWEIFTYG	KQPWYQLSNN	EVIECITQGR	VLQRPRTCPQ
790	800	810	820
EVYELMLGCW	QREPHMRKNI	KGIHTLLQNL	AKASPVYLDI	LG