AiPD: Autoinhibited Protein Database

Q9UQM7

Gene name	CAMK2A (CAMKA, KIAA0968)
Protein name	Calcium/calmodulin-dependent protein kinase type II subunit alpha
Names	CaM kinase II subunit alpha, CaMK-II subunit alpha
Species	Homo sapiens (Human)
KEGG Pathway	hsa:815
EC number	2.7.11.17: Protein-serine/threonine kinases
Protein Class	SERINE/THREONINE-PROTEIN KINASE (PTHR24347)

Descriptions

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase that is highly abundant in the brain, especially in the postsynaptic density (PSD). CaMKII forms a homomeric or heteromeric dodecamer of four different isoforms (α, β, γ, δ) encoded by four genes (CAMK2A, CAMK2B, CAMK2G, and CAMK2D, respectively), and α and β isoforms are predominant in the brain. In the resting state, the kinase activity of each subunit of CaMKII is inhibited by binding of the regulatory segment of CaMKII to the substrate binding groove of its kinase domain, which is called autoinhibition. When Ca2+-bound calmodulin (Ca2+/CaM) increases upon intracellular Ca2+ elevation, Ca2+/CaM binding to the regulatory segment dissociates the segment from the kinase domain, and within the regulatory segment, Thr286 in CaMKIIα and Thr287 in CaMKIIβ are phosphorylated by adjacent subunits, preventing the segment from returning to the kinase domain. This CaMKII activity is essential for neuronal plasticity and learning.

Autoinhibitory domains (AIDs)

Target domain	13-271 (Protein kinase domain)
Relief mechanism	Ligand binding
Assay	Structural analysis, Mutagenesis experiment

AID

272-302 (autoinhibitory domain)

Target domain

13-271 (Protein kinase domain)

Relief mechanism

Ligand binding (Ca2+-bound calmodulin binding)

Assay

Structural analysis, Mutagenesis experiment

Accessory elements

155-178 (Activation loop from InterPro)

Target domain	13-271 (Protein kinase domain)
Relief mechanism
Assay

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100

Akita T et al. (2018) "De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders", Annals of clinical and translational neurology, 5, 280-296

Yang E et al. (1999) "Structural examination of autoregulation of multifunctional calcium/calmodulin-dependent protein kinase II", The Journal of biological chemistry, 274, 26199-208

Rellos P et al. (2010) "Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation", PLoS biology, 8, e1000426

Özden C et al. (2022) "CaMKII binds both substrates and activators at the active site", Cell reports, 40, 111064

Autoinhibited structure

Activated structure

22 structures for Q9UQM7

Entry ID	Method	Resolution	Chain	Position	Source
2VZ6	X-ray	230 A	A/B	13-302	PDB
3SOA	X-ray	355 A	A	1-474	PDB
5IG3	X-ray	275 A	A/B/C/D/E/F	345-475	PDB
6OF8	X-ray	210 A	A/B/C/D/E/F/G	345-475	PDB
6VZK	X-ray	255 A	A	7-274	PDB
6W4O	EM	480 A	A/B/C/D/E/F/G/I/J/K/L/M/O	7-478	PDB
6W4P	EM	660 A	A/B/C/D/E/F/G/H/I/J/K/L/M	7-478	PDB
6X5G	X-ray	185 A	A	7-274	PDB
6X5Q	X-ray	214 A	A	7-274	PDB
7KL0	X-ray	240 A	A/B	7-274	PDB
7KL1	X-ray	240 A	A/B	7-274	PDB
7KL2	X-ray	256 A	A	7-274	PDB
7REC	X-ray	220 A	A/B/C/D/E/F/G	345-475	PDB
7UIQ	X-ray	311 A	A/B	7-274	PDB
7UIR	X-ray	310 A	A/B	7-274	PDB
7UIS	X-ray	258 A	A	7-274	PDB
7UJP	X-ray	256 A	A/B	7-274	PDB
7UJQ	X-ray	225 A	A/B	7-274	PDB
7UJR	X-ray	195 A	A	7-274	PDB
7UJS	X-ray	275 A	A	7-274	PDB
7UJT	X-ray	210 A	A	7-274	PDB
AF-Q9UQM7-F1	Predicted				AlphaFoldDB

178 variants for Q9UQM7

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1554122526 RCV000577897 CA361754600 VAR_080579 RCV000516156	98	F>S	Intellectual disability Intellectual disability, autosomal dominant 53 MRD53; no effect on protein abundance; decreased autophosphorylation; decreased neuronal migration [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1287121256 RCV000577915 CA361754204 RCV000516151 VAR_080580	109	E>D	Intellectual disability Intellectual disability, autosomal dominant 53 MRD53; no effect on protein abundance; increased autophosphorylation; decreased neuronal migration [ClinVar, UniProt]	Yes	ClinGen ClinVar dbSNP gnomAD UniProt
rs779607303 CA3509897 RCV001251933	110	A>V	Variant assessed as Somatic; 0.0 impact. Intellectual disability, autosomal dominant 53 [NCI-TCGA, ClinVar]	Yes	ClinGen ClinVar ExAC NCI-TCGA dbSNP gnomAD
VAR_080581	112	A>V	MRD53; unknown pathological significance [UniProt]	Yes	UniProt
VAR_080582	138	P>A	MRD53; unknown pathological significance; no effect on protein abundance; no effect on autophosphorylation; no effect on neuronal migration [UniProt]	Yes	UniProt
CA361750749 RCV000577883 RCV000516153 rs1554122129 VAR_080583	183	E>V	Intellectual disability Intellectual disability, autosomal dominant 53 MRD53; increased ubiquitin-mediated proteasomal degradation with a dominant negative effect on wild-type protein; decreased localization to dendritic spines; no effect on holoenzyme assembly; loss of interaction with SHANK3; loss of interaction with GRIN2B; loss of interaction with CACNB2; loss of interaction with LRRC7; loss of interaction with GRM5; decreased protein serine/threonine kinase activity with a dominant negative effect on wild-type protein; decreased autophosphorylation; changed dendritic spine development; decreased neuronal migration [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA129150428 RCV001558478 rs926027867 RCV002470885 VAR_080584 RCV000577918	212	P>L	Intellectual disability Variant assessed as Somatic; impact. Intellectual disability, autosomal dominant 53 MRD53; unknown pathological significance; no effect on protein abundance; no effect on autophosphorylation; no effect on neuronal migration [ClinVar, NCI-TCGA, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl NCI-TCGA dbSNP
rs926027867 VAR_081160 RCV000678211 CA361750093	212	P>Q	Intellectual disability, autosomal dominant 53 MRD53; increased basal autophosphorylation [ClinVar, UniProt]	Yes	ClinGen ClinVar Ensembl dbSNP UniProt
CA248921 RCV000577881 RCV000678212 rs864309606 VAR_080585 RCV000202726	235	P>L	Intellectual disability Intellectual disability, autosomal dominant 53 MRD53; unknown pathological significance; no effect on protein abundance; no effect on autophosphorylation; no effect on neuronal migration [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1554121875 CA361749404 VAR_080586 RCV000516155 RCV000577902	282	H>R	Intellectual disability Intellectual disability, autosomal dominant 53 MRD53; decreased protein abundance; increased autophosphorylation; decreased neuronal migration [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000516152 CA361749377 rs1554121872 RCV000577925 VAR_080587	286	T>P	Intellectual disability Intellectual disability, autosomal dominant 53 MRD53; no effect on protein abundance; loss of autophosphorylation; loss of neuronal migration [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1754406562 RCV001266835	444	P>T	Inborn genetic diseases [ClinVar]	Yes	ClinVar dbSNP
CA361739033 VAR_081161 RCV000678210 rs1554119274	466	H>Y	Intellectual disability, autosomal recessive 63 MRT63; decreased oligomerization [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA3509993 rs757273062	2	A>T		No	ClinGen ExAC gnomAD
rs1373405268 CA361723264	3	T>I		No	ClinGen gnomAD
rs1056874482 CA129116861	8	R>C		No	ClinGen TOPMed
CA3509991 rs764230609	8	R>H		No	ClinGen ExAC gnomAD
rs6861622 CA361723117	10	T>A		No	ClinGen Ensembl
rs1160900025 CA361723102	10	T>M		No	ClinGen TOPMed
rs6861622 CA361723114	10	T>S		No	ClinGen Ensembl
CA129116852 rs928636452	12	E>D		No	ClinGen TOPMed gnomAD
TCGA novel	14	Q>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
COSM1064323 rs1580966945 CA361722927	17	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1202019049 CA361718950	23	A>G		No	ClinGen gnomAD
rs1439139668 CA361718935 COSM298063	25	S>L	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
rs751885208 CA3509969	28	R>*	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA361718920 rs1331999283	28	R>Q		No	ClinGen gnomAD
rs766825548 CA3509968	38	E>K		No	ClinGen ExAC gnomAD
CA361718825 rs1580947248	39	Y>D		No	ClinGen Ensembl
rs1267862122 CA361718776	43	I>V		No	ClinGen TOPMed
rs1356458925 CA361718731	46	T>S		No	ClinGen gnomAD
TCGA novel	47	K>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs202217757 CA129109536	52	R>T		No	ClinGen Ensembl
rs750935357 CA3509948	54	H>L		No	ClinGen ExAC gnomAD
rs761424198 CA3509946	59	R>C	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA3509943 rs544705728	62	R>C	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen 1000Genomes ExAC NCI-TCGA gnomAD
CA129106222 rs867820640	62	R>H		No	ClinGen gnomAD
TCGA novel	64	C>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA361715968 rs1195589386	65	R>H		No	ClinGen TOPMed
CA129102100 rs61732056	74	R>*		No	ClinGen Ensembl
rs61732056 CA129102106	74	R>G		No	ClinGen Ensembl
CA361714523 rs1366605186	75	L>Q		No	ClinGen TOPMed
rs202107716 CA3509921	79	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA361714436 rs1201263122	81	E>*		No	ClinGen gnomAD
rs1480404414 CA361714400	83	G>E		No	ClinGen gnomAD
rs866698307 CA129102081	87	L>P		No	ClinGen Ensembl
TCGA novel	98	F>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	106	Y>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	121	E>G	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA129154210 rs758821296	124	L>V		No	ClinGen Ensembl
CA3509871 rs780817639	134	R>W		No	ClinGen ExAC gnomAD
CA129151677 rs866152886	150	A>V		No	ClinGen Ensembl
CA129151643 rs986491632	151	A>T		No	ClinGen Ensembl
rs745482187 CA3509849	163	V>L		No	ClinGen ExAC
rs1372333506 CA361752268	164	E>D		No	ClinGen gnomAD
rs1755922883 RCV001200176	168	Q>*		No	ClinVar dbSNP
CA3509848 rs778835439	169	A>S		No	ClinGen ExAC gnomAD
CA361752117 rs1422349611	169	A>V		No	ClinGen TOPMed
TCGA novel	170	W>G	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs756158214 CA3509826	191	G>W		No	ClinGen ExAC gnomAD
rs370600720 CA3509824	193	P>A		No	ClinGen ESP ExAC TOPMed gnomAD
TCGA novel	195	D>E	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1462812363 CA361750187	207	L>P		No	ClinGen TOPMed
rs747987338 CA3509790	210	Y>S		No	ClinGen ExAC gnomAD
rs1300146469 CA361750002	217	D>E		No	ClinGen TOPMed
CA129150416 rs11956781	219	H>L		No	ClinGen Ensembl
CA361749979 rs11956781	219	H>P		No	ClinGen Ensembl
rs1185191650 CA361749966	220	R>C	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1425310941 COSM1064319 CA361749963	220	R>H	Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA TOPMed gnomAD
CA361749957 rs1425310941	220	R>L		No	ClinGen TOPMed gnomAD
rs17854002 CA361749912	223	Q>*		No	ClinGen gnomAD
CA129150376 rs17854002	223	Q>K		No	ClinGen gnomAD
CA361749806 rs1236371050	228	G>S		No	ClinGen gnomAD
rs1319168744 CA361749795	229	A>T		No	ClinGen TOPMed gnomAD
CA3509782 rs368023327	231	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
COSM1064318 CA361749737 rs1160671001	234	S>L	Variant assessed as Somatic; 4.641e-05 impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
rs1325334771 CA361749714	238	D>N		No	ClinGen gnomAD
CA3509761 rs751800259	242	P>L		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	255	N>missing	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA361749584 rs1580922542	257	S>P		No	ClinGen Ensembl
rs915686916 CA129149561	260	I>L		No	ClinGen Ensembl
rs1487504062 CA361749559	260	I>M		No	ClinGen gnomAD
CA3509759 rs758925573	261	T>I		No	ClinGen ExAC gnomAD
CA361749541 rs1346541754	264	E>K	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA3509757 rs764807945	265	A>G		No	ClinGen ExAC gnomAD
rs568397508 CA129149541	268	H>R		No	ClinGen Ensembl
CA361749502 rs1331653509	269	P>L		No	ClinGen gnomAD
CA361749498 RCV000760641 rs1562164380	270	W>*		No	ClinGen ClinVar Ensembl dbSNP
CA3509737 rs200216623	274	R>C	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA361749398 rs1171881562	283	R>K		No	ClinGen gnomAD
RCV001090380 rs1755639151	301	G>E		No	ClinVar dbSNP
rs1210191385 CA361748310	303	I>V		No	ClinGen gnomAD
CA361748244 rs1349742423	306	T>M		No	ClinGen gnomAD
CA361748138 rs1449666180	315	G>R	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1158829901 CA361747682	316	G>R		No	ClinGen TOPMed
CA3509693 rs765165346	319	G>E		No	ClinGen ExAC gnomAD
rs55696902 CA3509691	321	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
TCGA novel	324	S>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA361747498 rs375813680	324	S>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1445974036 CA361747492	325	D>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
rs1292054661 CA361745701	331	S>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs770841322 CA129139929	332	E>D		No	ClinGen ExAC gnomAD
CA361745636 rs1350890212	334	T>A		No	ClinGen TOPMed gnomAD
CA361745632 rs1287488367	334	T>I		No	ClinGen TOPMed gnomAD
rs1279296830 CA361745427	342	D>E		No	ClinGen TOPMed
CA129139920 rs1024265518	343	T>A		No	ClinGen TOPMed gnomAD
CA129139917 rs999120588	343	T>N		No	ClinGen TOPMed
rs1345838148 CA361745385	345	V>L		No	ClinGen gnomAD
CA3509582 rs778942662	346	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs745982580 CA3509583	346	R>W	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
TCGA novel	349	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	351	I>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA3509581 rs757512233	351	I>V		No	ClinGen ExAC TOPMed gnomAD
CA361742778 rs1190483281	353	V>L		No	ClinGen gnomAD
CA361742681 rs1440684133	357	L>M		No	ClinGen TOPMed gnomAD
TCGA novel	359	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	360	A>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA361742511 rs1201903749	364	G>E		No	ClinGen gnomAD
TCGA novel	365	D>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1301785267 CA361741197	376	G>D		No	ClinGen gnomAD
rs1408224855 CA361741119	382	P>S		No	ClinGen gnomAD
rs1408224855 CA361741120	382	P>T		No	ClinGen gnomAD
rs1313874797 CA361741112	383	E>Q		No	ClinGen TOPMed
rs764964453 CA3509553	387	N>I		No	ClinGen ExAC gnomAD
CA3509552 rs761351468	393	D>E		No	ClinGen ExAC gnomAD
rs1420436174 CA361740966	395	H>R		No	ClinGen gnomAD
rs753708011 CA3509551	396	R>*	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA361740955 rs1442791113	396	R>Q		No	ClinGen gnomAD
CA361740931 rs1204852152	398	Y>C		No	ClinGen gnomAD
rs763794315 CA3509550	401	N>T		No	ClinGen ExAC gnomAD
CA3509549 rs376699738	402	L>M		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	403	W>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA361740194 rs1161905638	405	R>Q		No	ClinGen gnomAD
rs1362570011 CA361740198	405	R>W	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA3509519 rs772746827	410	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1580891745 CA361740118	412	T>P		No	ClinGen Ensembl
CA361740112 rs1580891738	413	T>P		No	ClinGen Ensembl
rs1269084885 CA361740071	417	P>T		No	ClinGen gnomAD
rs756733402 CA3509516	419	I>F		No	ClinGen ExAC gnomAD
CA361740015 rs1580891693	420	H>P		No	ClinGen Ensembl
rs1311432465 CA361739969	422	M>I		No	ClinGen gnomAD
CA361739947 rs1406491152	424	D>N		No	ClinGen gnomAD
RCV001310532 rs1754415187	425	E>K		No	ClinVar dbSNP
rs907583897 CA129123696	429	I>V		No	ClinGen Ensembl
rs752541567 CA3509512	430	A>T		No	ClinGen ExAC TOPMed gnomAD
CA361739819 rs1266065955	432	I>V		No	ClinGen Ensembl
CA3509511 rs767291853	433	R>C		No	ClinGen ExAC TOPMed gnomAD
rs754962340 CA3509510	433	R>H		No	ClinGen ExAC gnomAD
rs766270888 CA3509508	435	T>M		No	ClinGen ExAC gnomAD
rs760949012 CA3509504	440	A>G		No	ClinGen ExAC gnomAD
CA361739651 rs374924411	440	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs374924411 CA3509505	440	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD
CA129123595 rs199592588	441	G>S		No	ClinGen 1000Genomes
rs772552968 CA3509502	442	G>S		No	ClinGen ExAC TOPMed gnomAD
CA361739558 rs1221317581	445	R>H		No	ClinGen TOPMed
CA361739552 rs1456960358	446	T>A		No	ClinGen TOPMed
TCGA novel	446	T>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA361739551 rs1456960358	446	T>P		No	ClinGen TOPMed
CA3509498 rs748774194	447	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA361739520 rs1580891529	447	A>V		No	ClinGen Ensembl
rs777247730 CA3509497	449	S>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA361739435 rs1580891510	452	T>P		No	ClinGen Ensembl
rs367551385 CA3509495	453	R>C		No	ClinGen ESP ExAC gnomAD
CA3509494 rs780762936	453	R>H		No	ClinGen ExAC gnomAD
CA361739407 rs1382795728	454	V>F		No	ClinGen gnomAD
CA361739412 rs1382795728	454	V>I		No	ClinGen gnomAD
rs1580891481 CA361739370	456	H>P		No	ClinGen Ensembl
CA3509493 rs754732557	457	R>C	Variant assessed as Somatic; 4.647e-05 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs375918851 CA3509492	457	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs577586528 CA361739324	458	R>W		No	ClinGen 1000Genomes ExAC gnomAD
rs1167006357 CA361739218	460	G>D	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA3509489 rs753904024	464	I>V		No	ClinGen ExAC TOPMed gnomAD
rs764264581 CA3509488	465	V>I	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA361738952 rs954139326	468	H>Q		No	ClinGen TOPMed gnomAD
TCGA novel	472	A>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA3509485 rs767783317	472	A>V	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs771394411 CA3509482	475	V>I	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA3509481 rs763490198	477	P>H		No	ClinGen ExAC gnomAD

2 associated diseases with Q9UQM7

[MIM: 617798]: Intellectual developmental disorder, autosomal dominant 53 (MRD53)

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:29560374}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 618095]: Intellectual developmental disorder, autosomal recessive 63 (MRT63)

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT63 patients manifest global developmental delay, severe intellectual disability, and seizures. {ECO:0000269|PubMed:29784083}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:29560374}. Note=The disease is caused by variants affecting the gene represented in this entry.
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT63 patients manifest global developmental delay, severe intellectual disability, and seizures. {ECO:0000269|PubMed:29784083}. Note=The disease is caused by variants affecting the gene represented in this entry.

4 regional properties for Q9UQM7

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	13 - 271	IPR000719
active_site	Serine/threonine-protein kinase, active site	131 - 143	IPR008271
domain	Calcium/calmodulin-dependent protein kinase II, association-domain	346 - 473	IPR013543
binding_site	Protein kinase, ATP binding site	19 - 42	IPR017441

Functions

		Description
EC Number	2.7.11.17	Protein-serine/threonine kinases
Subcellular Localization	Synapse Postsynaptic density Cell projection, dendritic spine Cell projection, dendrite	Postsynaptic lipid rafts
PANTHER Family	PTHR24347	SERINE/THREONINE-PROTEIN KINASE
PANTHER Subfamily	PTHR24347:SF384	CALCIUM_CALMODULIN-DEPENDENT PROTEIN KINASE TYPE II SUBUNIT ALPHA
PANTHER Protein Class	non-receptor serine/threonine protein kinase protein modifying enzyme
PANTHER Pathway Category	Inflammation mediated by chemokine and cytokine signaling pathway CaMK Ionotropic glutamate receptor pathway CaMKII

11 GO annotations of cellular component

Name	Definition
anchoring junction	A cell junction that mechanically attaches a cell (and its cytoskeleton) to neighboring cells or to the extracellular matrix.
calcium- and calmodulin-dependent protein kinase complex	An enzyme complex which in eukaryotes is composed of four different chains: alpha, beta, gamma, and delta. The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits. Catalyzes the phosphorylation of proteins to O-phosphoproteins.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
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.
endocytic vesicle membrane	The lipid bilayer surrounding an endocytic vesicle.
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
neuron projection	A prolongation or process extending from a nerve cell, e.g. an axon or dendrite.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
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.

10 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
calmodulin binding	Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
calmodulin-dependent protein kinase activity	Calmodulin-dependent catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; and ATP + a protein threonine = ADP + protein threonine phosphate.
glutamate receptor binding	Binding to a glutamate receptor.
identical protein binding	Binding to an identical protein or proteins.
kinase activity	Catalysis of the transfer of a phosphate group, usually from ATP, to a substrate molecule.
metal ion binding	Binding to a metal ion.
protein homodimerization activity	Binding to an identical protein to form a homodimer.
protein serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.

18 GO annotations of biological process

Name	Definition
angiotensin-activated signaling pathway	A G protein-coupled receptor signaling pathway initiated by angiotensin II binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
calcium ion transport	The directed movement of calcium (Ca) ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
dendritic spine development	The process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission.
G1/S transition of mitotic cell cycle	The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated.
negative regulation of hydrolase activity	Any process that stops or reduces the rate of hydrolase activity, the catalysis of the hydrolysis of various bonds.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
peptidyl-threonine autophosphorylation	The phosphorylation by a protein of one or more of its own threonine amino acid residues, or a threonine residue on an identical protein.
positive regulation of calcium ion transport	Any process that activates or increases the frequency, rate or extent of the directed movement of calcium ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
positive regulation of cardiac muscle cell apoptotic process	Any process that increases the rate or extent of cardiac cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a cardiac muscle cell and result in its death.
positive regulation of NF-kappaB transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB.
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).
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of endocannabinoid signaling pathway	Any process that modulates the frequency, rate or extent of endocannabinoid signaling pathway.
regulation of mitochondrial membrane permeability involved in apoptotic process	Any regulation of mitochondrial membrane permeability that is involved in apoptotic process.
regulation of neuron migration	Any process that modulates the frequency, rate or extent of neuron migration.
regulation of neuronal synaptic plasticity	A process that modulates neuronal synaptic plasticity, the ability of neuronal synapses to change as circumstances require. They may alter function, such as increasing or decreasing their sensitivity, or they may increase or decrease in actual numbers.
regulation of neurotransmitter secretion	Any process that modulates the frequency, rate or extent of the regulated release of a neurotransmitter from a cell.
response to ischemia	Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a inadequate blood supply.

49 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q3MHJ9	CAMK2B	Calcium/calmodulin-dependent protein kinase type II subunit beta	Bos taurus (Bovine)	SS
Q2HJF7	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	Bos taurus (Bovine)	SS
Q5ZKI0	CAMK2D	Calcium/calmodulin-dependent protein kinase type II delta chain	Gallus gallus (Chicken)	SS
Q24210	CASK	Peripheral plasma membrane protein CASK	Drosophila melanogaster (Fruit fly)	SS
Q00168	CaMKII	Calcium/calmodulin-dependent protein kinase type II alpha chain	Drosophila melanogaster (Fruit fly)	SS
O14936	CASK	Peripheral plasma membrane protein CASK	Homo sapiens (Human)	EV
Q16816	PHKG1	Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform	Homo sapiens (Human)	PR
P15735	PHKG2	Phosphorylase b kinase gamma catalytic chain, liver/testis isoform	Homo sapiens (Human)	PR
Q13554	CAMK2B	Calcium/calmodulin-dependent protein kinase type II subunit beta	Homo sapiens (Human)	EV
Q13555	CAMK2G	Calcium/calmodulin-dependent protein kinase type II subunit gamma	Homo sapiens (Human)	EV
Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	Homo sapiens (Human)	EV
Q9H1R3	MYLK2	Myosin light chain kinase 2, skeletal/cardiac muscle	Homo sapiens (Human)	EV
Q32MK0	MYLK3	Myosin light chain kinase 3	Homo sapiens (Human)	SS
Q86YV6	MYLK4	Myosin light chain kinase family member 4	Homo sapiens (Human)	SS
P11801	PSKH1	Serine/threonine-protein kinase H1	Homo sapiens (Human)	SS
Q6P2M8	PNCK	Calcium/calmodulin-dependent protein kinase type 1B	Homo sapiens (Human)	SS
Q96NX5	CAMK1G	Calcium/calmodulin-dependent protein kinase type 1G	Homo sapiens (Human)	SS
Q8IU85	CAMK1D	Calcium/calmodulin-dependent protein kinase type 1D	Homo sapiens (Human)	SS
Q8NCB2	CAMKV	CaM kinase-like vesicle-associated protein	Homo sapiens (Human)	SS
Q14012	CAMK1	Calcium/calmodulin-dependent protein kinase type 1	Homo sapiens (Human)	EV
O70589	Cask	Peripheral plasma membrane protein CASK	Mus musculus (Mouse)	SS
Q923T9	Camk2g	Calcium/calmodulin-dependent protein kinase type II subunit gamma	Mus musculus (Mouse)	SS
Q6PHZ2	Camk2d	Calcium/calmodulin-dependent protein kinase type II subunit delta	Mus musculus (Mouse)	SS
P28652	Camk2b	Calcium/calmodulin-dependent protein kinase type II subunit beta	Mus musculus (Mouse)	SS
P11798	Camk2a	Calcium/calmodulin-dependent protein kinase type II subunit alpha	Mus musculus (Mouse)	PR
Q95266	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	Sus scrofa (Pig)	SS
P15791	Camk2d	Calcium/calmodulin-dependent protein kinase type II subunit delta	Rattus norvegicus (Rat)	SS
P11730	Camk2g	Calcium/calmodulin-dependent protein kinase type II subunit gamma	Rattus norvegicus (Rat)	SS
P11275	Camk2a	Calcium/calmodulin-dependent protein kinase type II subunit alpha	Rattus norvegicus (Rat)	PR
P54936	lin-2	Protein lin-2	Caenorhabditis elegans	SS
O62305	unc-43	Calcium/calmodulin-dependent protein kinase type II	Caenorhabditis elegans	EV
Q9ZV15	CPK20	Calcium-dependent protein kinase 20	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9SJ61	CPK25	Calcium-dependent protein kinase 25	Arabidopsis thaliana (Mouse-ear cress)	PR
Q06850	CPK1	Calcium-dependent protein kinase 1	Arabidopsis thaliana (Mouse-ear cress)	PR
Q38870	CPK2	Calcium-dependent protein kinase 2	Arabidopsis thaliana (Mouse-ear cress)	PR
Q3E9C0	CPK34	Calcium-dependent protein kinase 34	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9FMP5	CPK17	Calcium-dependent protein kinase 17	Arabidopsis thaliana (Mouse-ear cress)	PR
Q42479	CPK3	Calcium-dependent protein kinase 3	Arabidopsis thaliana (Mouse-ear cress)	PR
Q38872	CPK6	Calcium-dependent protein kinase 6	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9ZSA4	CPK27	Calcium-dependent protein kinase 27	Arabidopsis thaliana (Mouse-ear cress)	PR
Q39016	CPK11	Calcium-dependent protein kinase 11	Arabidopsis thaliana (Mouse-ear cress)	SS
Q38869	CPK4	Calcium-dependent protein kinase 4	Arabidopsis thaliana (Mouse-ear cress)	SS
Q42396	CPK12	Calcium-dependent protein kinase 12	Arabidopsis thaliana (Mouse-ear cress)	SS
Q7XJR9	CPK16	Calcium-dependent protein kinase 16	Arabidopsis thaliana (Mouse-ear cress)	PR
Q1PE17	CPK18	Calcium-dependent protein kinase 18	Arabidopsis thaliana (Mouse-ear cress)	SS
Q38997	KIN10	SNF1-related protein kinase catalytic subunit alpha KIN10	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9FKW4	CPK28	Calcium-dependent protein kinase 28	Arabidopsis thaliana (Mouse-ear cress)	SS
Q6DGS3	camk2d2	Calcium/calmodulin-dependent protein kinase type II delta 2 chain	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q6DEH3	camk2d1	Calcium/calmodulin-dependent protein kinase type II delta 1 chain	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MATITCTRFT	EEYQLFEELG	KGAFSVVRRC	VKVLAGQEYA	AKIINTKKLS	ARDHQKLERE
70	80	90	100	110	120
ARICRLLKHP	NIVRLHDSIS	EEGHHYLIFD	LVTGGELFED	IVAREYYSEA	DASHCIQQIL
130	140	150	160	170	180
EAVLHCHQMG	VVHRDLKPEN	LLLASKLKGA	AVKLADFGLA	IEVEGEQQAW	FGFAGTPGYL
190	200	210	220	230	240
SPEVLRKDPY	GKPVDLWACG	VILYILLVGY	PPFWDEDQHR	LYQQIKAGAY	DFPSPEWDTV
250	260	270	280	290	300
TPEAKDLINK	MLTINPSKRI	TAAEALKHPW	ISHRSTVASC	MHRQETVDCL	KKFNARRKLK
310	320	330	340	350	360
GAILTTMLAT	RNFSGGKSGG	NKKSDGVKES	SESTNTTIED	EDTKVRKQEI	IKVTEQLIEA
370	380	390	400	410	420
ISNGDFESYT	KMCDPGMTAF	EPEALGNLVE	GLDFHRFYFE	NLWSRNSKPV	HTTILNPHIH
430	440	450	460	470
LMGDESACIA	YIRITQYLDA	GGIPRTAQSE	ETRVWHRRDG	KWQIVHFHRS	GAPSVLPH