AiPD: Autoinhibited Protein Database

Q08493

EV SS

Gene name	PDE4C
Protein name	cAMP-specific 3',5'-cyclic phosphodiesterase 4C
Names	DPDE1, PDE21
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5143
EC number	3.1.4.53: Phosphoric diester hydrolases
Protein Class	CYCLIC NUCLEOTIDE PHOSPHODIESTERASE (PTHR11347)

Descriptions

PDE4 encodes for cAMP-specific 3',5'-cyclic phosphodiesterase, involved in the hydrolysis of cAMP and cGMP that plays important roles in many physiological processes. The carboxyl-terminal half of UCR1 interacts with the amino-terminal region of UCR2, and UCR2 domain occludes the active site of PDEase domain.

Autoinhibitory domains (AIDs)

115-174 (UCR1 domain) SS

Target domain	312-641 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain)
Relief mechanism	PTM
Assay

AID

115-174 (UCR1 domain)

Target domain

312-641 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain)

Relief mechanism

PTM (Phosphorylation of residues in UCR1 domain by PKA and ERK)

Assay

Target domain	312-641 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain)
Relief mechanism	PTM
Assay	Split protein assay, Mutagenesis experiment

AID

199-276 (UCR2 domain)

Target domain

312-641 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain)

Relief mechanism

PTM (Phosphorylation of residues in UCR domain by PKA and ERK)

Assay

Split protein assay, Mutagenesis experiment

Accessory elements

No accessory elements

References

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

Houslay MD et al. (2010) "Putting the lid on phosphodiesterase 4", Nature biotechnology, 28, 38-40

Beard MB et al. (2000) "UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions", The Journal of biological chemistry, 275, 10349-58

Burgin AB et al. (2010) "Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety", Nature biotechnology, 28, 63-70

Autoinhibited structure

Activated structure

2 structures for Q08493

Entry ID	Method	Resolution	Chain	Position	Source
2QYM	X-ray	190 A	A	306-663	PDB
AF-Q08493-F1	Predicted				AlphaFoldDB

559 variants for Q08493

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA306169427 rs868562305	2	E>G		No	ClinGen Ensembl
CA404809774 rs1437974889	4	L>M		No	ClinGen TOPMed gnomAD
rs1437974889 CA404809771	4	L>V		No	ClinGen TOPMed gnomAD
rs181170477 CA306169420	5	G>E		No	ClinGen 1000Genomes gnomAD
rs1283809646 CA404809728	7	G>S		No	ClinGen gnomAD
CA404809669 rs1365148263	9	G>A		No	ClinGen TOPMed gnomAD
CA404809671 rs1365148263	9	G>E		No	ClinGen TOPMed gnomAD
rs142521081 CA9308770	12	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs373663195 CA9308769	12	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1333420018 CA404809586	14	S>R		No	ClinGen gnomAD
CA9308768 rs745939492	16	L>F		No	ClinGen ExAC gnomAD
CA9308767 rs781678465	17	S>C		No	ClinGen ExAC gnomAD
rs757687498 CA9308766	17	S>R		No	ClinGen ExAC gnomAD
rs202099292 CA9308765	18	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA306169366 rs202099292	18	R>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9308764 rs370109192	19	S>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA404809439 rs1190331077	20	R>C		No	ClinGen gnomAD
rs1470297635 CA404809427	20	R>L		No	ClinGen TOPMed gnomAD
rs1239511462 CA404809399	21	G>D		No	ClinGen gnomAD
rs894075549 CA306169364	22	R>C		No	ClinGen TOPMed gnomAD
rs1456897271 CA404809382	22	R>H		No	ClinGen TOPMed gnomAD
rs1456897271 CA404809376	22	R>L		No	ClinGen TOPMed gnomAD
CA404809359 rs1429669815	23	H>R		No	ClinGen gnomAD
rs1300313509 CA404809211	28	A>T		No	ClinGen gnomAD
rs1311686793 CA404809170	29	P>A		No	ClinGen gnomAD
CA9308760 rs571659585	29	P>L		No	ClinGen ExAC TOPMed gnomAD
CA9308759 rs571659585	29	P>R		No	ClinGen ExAC TOPMed gnomAD
CA404809088 rs1399556612	31	H>Q		No	ClinGen gnomAD
CA404809048 rs1329396997	32	L>P		No	ClinGen Ensembl
rs760528271 CA9308757	33	W>*		No	ClinGen ExAC gnomAD
CA404808960 rs1357838247	34	R>L		No	ClinGen gnomAD
rs1281406922 CA404808983	34	R>W		No	ClinGen TOPMed gnomAD
rs548025731 CA404808873	36	P>L		No	ClinGen 1000Genomes gnomAD
CA306169328 rs548025731	36	P>R		No	ClinGen 1000Genomes gnomAD
rs1032756619 CA306169327	37	R>L		No	ClinGen gnomAD
rs1032756619 CA404808862	37	R>Q		No	ClinGen gnomAD
rs868153668 CA306169323	38	R>C		No	ClinGen Ensembl
rs1464698739 CA404808836	38	R>L		No	ClinGen TOPMed
CA306169318 rs867886084	39	P>H		No	ClinGen gnomAD
CA404808813 rs867886084	39	P>L		No	ClinGen gnomAD
rs773180505 CA9308756	40	I>M		No	ClinGen ExAC TOPMed gnomAD
CA404808791 rs1183584543	40	I>S		No	ClinGen gnomAD
rs767249358 CA9308755	41	R>H		No	ClinGen ExAC TOPMed gnomAD
rs761626676 CA404808762	42	I>M		No	ClinGen ExAC gnomAD
CA306169309 rs1051800846	42	I>T		No	ClinGen TOPMed gnomAD
rs1238240124 CA404808730	44	Q>*		No	ClinGen gnomAD
rs868472984 CA404808713	45	R>H		No	ClinGen TOPMed gnomAD
rs868472984 CA306169296	45	R>L		No	ClinGen TOPMed gnomAD
CA404808699 rs1568264925	46	F>C		No	ClinGen Ensembl
rs1369567387 CA404808683	47	Y>N		No	ClinGen TOPMed
CA404808665 rs1313499863	48	S>A		No	ClinGen gnomAD
rs770013445 CA9308752	50	P>L		No	ClinGen ExAC TOPMed gnomAD
rs770013445 CA404808637	50	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs902949308 CA306169287	51	D>E		No	ClinGen TOPMed
CA404808630 rs1377660218	51	D>H		No	ClinGen gnomAD
CA404808596 rs1310181629	53	S>F		No	ClinGen TOPMed
CA404808587 rs1230218685	54	A>E		No	ClinGen TOPMed
rs1568264905 CA404808575	55	G>A		No	ClinGen Ensembl
rs776567028 CA9308750	57	R>C		No	ClinGen ExAC gnomAD
CA404808552 rs776567028	57	R>G		No	ClinGen ExAC gnomAD
rs1362777502 CA404808550	57	R>H		No	ClinGen gnomAD
rs200387259 CA9308749	58	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs565453629 CA9308748	61	L>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA404808455 rs778449807	63	P>L		No	ClinGen ExAC TOPMed gnomAD
rs778449807 CA9308747	63	P>R		No	ClinGen ExAC TOPMed gnomAD
CA404808441 rs1255416017	64	R>P		No	ClinGen gnomAD
rs939929358 CA404808426	65	P>L		No	ClinGen TOPMed gnomAD
CA404808430 rs939929358	65	P>Q		No	ClinGen TOPMed gnomAD
CA306169262 rs939929358	65	P>R		No	ClinGen TOPMed gnomAD
CA404808376 rs1214780301	68	R>K		No	ClinGen gnomAD
CA9308745 rs748533036	69	K>N		No	ClinGen ExAC gnomAD
rs778651923 CA9308744	71	R>Q		No	ClinGen ExAC gnomAD
rs147726602 CA9308743	72	L>F		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs147726602 CA306169248	72	L>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA306169218 rs576597879	75	P>A		No	ClinGen 1000Genomes TOPMed gnomAD
CA306169215 rs576597879	75	P>S		No	ClinGen 1000Genomes TOPMed gnomAD
CA404808186 rs1314424064	78	S>F		No	ClinGen gnomAD
CA404808166 rs1395281151	79	C>F		No	ClinGen TOPMed gnomAD
rs542653053 CA9308742	79	C>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA404808168 rs1395281151	79	C>S		No	ClinGen TOPMed gnomAD
CA9308741 rs765777381	80	R>G		No	ClinGen ExAC TOPMed gnomAD
rs765777381 CA306169203	80	R>W		No	ClinGen ExAC TOPMed gnomAD
CA404808136 rs1455946655	81	R>H		No	ClinGen gnomAD
rs1294873659 CA404808147	81	R>S		No	ClinGen gnomAD
CA9308696 rs765003516	82	F>L		No	ClinGen ExAC TOPMed gnomAD
CA9308697 rs752553505	82	F>V		No	ClinGen ExAC gnomAD
rs767684989 CA9308693	86	N>D		No	ClinGen ExAC gnomAD
CA404803936 rs1399398937	86	N>S		No	ClinGen gnomAD
rs1401694596 CA404803888	88	L>H		No	ClinGen gnomAD
rs373661564 CA9308691	89	S>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs369382669 CA404803818	93	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308688 rs775915503	94	A>S		No	ClinGen ExAC gnomAD
CA9308687 rs770179960	94	A>V		No	ClinGen ExAC
CA9308686 rs745495140	97	P>T		No	ClinGen ExAC gnomAD
rs1555824686 CA404803673	102	G>D		No	ClinGen Ensembl
rs146818532 CA306162449	105	R>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs146818532 CA9308684	105	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
COSM1391643 rs746534804 CA306162445	108	Q>*	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs746534804 CA9308683	108	Q>E		No	ClinGen ExAC gnomAD
CA404803546 rs1600083545	109	A>V		No	ClinGen Ensembl
CA9308681 COSM163369 rs758343814	110	P>S	breast [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs553070308 COSM711128 CA9308679	112	P>L	lung [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs998344490 CA306162439	113	H>Y		No	ClinGen Ensembl
CA306162437 rs965598707	114	S>N		No	ClinGen TOPMed
rs767854993 CA404803410	116	R>L		No	ClinGen ExAC TOPMed
rs767854993 CA9308676	116	R>Q		No	ClinGen ExAC TOPMed
rs750626536 CA9308677	116	R>W		No	ClinGen ExAC gnomAD
CA404803402 rs1354369697	117	R>C		No	ClinGen TOPMed gnomAD
rs140364206 CA9308674	117	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA404803393 rs1422636316	118	E>K		No	ClinGen gnomAD
rs151221680 CA9308671	123	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs775909997 CA9308670	123	R>H		No	ClinGen ExAC TOPMed gnomAD
CA306162430 rs893436397	125	D>E		No	ClinGen Ensembl
rs142235928 CA404803220	126	S>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs759923759 CA9308667	127	D>N		No	ClinGen ExAC TOPMed gnomAD
RCV000905789 CA9308665 rs61734285	128	Y>C		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA9308664 VAR_050473 rs10413646	131	S>L		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA404803117 rs1486998721	132	P>L		No	ClinGen TOPMed
CA306162422 rs373560603	132	P>S		No	ClinGen ESP TOPMed
rs772774240 CA9308662	133	K>R		No	ClinGen ExAC gnomAD
rs1311528388 CA404803058	135	M>I		No	ClinGen gnomAD
rs1214304068 CA404803061	135	M>T		No	ClinGen TOPMed
CA9308661 rs771527028	135	M>V		No	ClinGen ExAC gnomAD
rs1390209198 CA404803052	136	S>T		No	ClinGen gnomAD
rs529117552 CA306162415	137	R>G		No	ClinGen 1000Genomes
rs369793065 CA9308660	137	R>Q		No	ClinGen ESP ExAC gnomAD
rs529117552 CA306162414	137	R>W		No	ClinGen 1000Genomes
rs779019900 CA9308659	138	N>K		No	ClinGen ExAC gnomAD
CA404802901 rs1600083073	144	D>A		No	ClinGen Ensembl
CA9308655 rs374792253	144	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs139517384 CA9308656	144	D>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1381665198 CA404802888	145	L>R		No	ClinGen gnomAD
CA404802673 rs1485616725	147	G>A		No	ClinGen gnomAD
CA9308641 rs147388938	149	D>H		No	ClinGen ESP ExAC gnomAD
rs200650372 CA9308640	150	M>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA404802570 rs1219652000	153	T>M		No	ClinGen gnomAD
rs749300533 CA9308638	155	F>S		No	ClinGen ExAC
CA9308622 rs760973090	160	A>V		No	ClinGen ExAC gnomAD
rs1438081953 CA404802345	161	S>N		No	ClinGen gnomAD
rs1332025634 CA404802312	163	R>Q		No	ClinGen gnomAD
rs750056384 CA9308621	163	R>W		No	ClinGen ExAC gnomAD
rs768317307 CA9308617	165	V>I		No	ClinGen ExAC TOPMed gnomAD
CA9308616 rs762961023	166	R>W		No	ClinGen ExAC TOPMed gnomAD
CA9308615 rs775589812	167	S>R		No	ClinGen ExAC gnomAD
CA9308614 rs769590869	170	A>S		No	ClinGen ExAC gnomAD
rs769590869 CA404802150	170	A>T		No	ClinGen ExAC gnomAD
CA404802122 rs745653185	171	A>D		No	ClinGen ExAC gnomAD
CA404802133 rs1459459120	171	A>S		No	ClinGen TOPMed gnomAD
CA404802132 rs1459459120	171	A>T		No	ClinGen TOPMed gnomAD
rs745653185 CA9308613	171	A>V		No	ClinGen ExAC gnomAD
CA9308612 rs772172919	174	R>C		No	ClinGen ExAC gnomAD
CA306161897 rs772172919	174	R>G		No	ClinGen ExAC gnomAD
rs748436307 CA9308610	174	R>L		No	ClinGen ExAC gnomAD
CA9308611 rs772172919	174	R>S		No	ClinGen ExAC gnomAD
CA404802048 rs1231607717	175	Q>P		No	ClinGen gnomAD
CA404802046 rs1231607717	175	Q>R		No	ClinGen gnomAD
rs1346586702 CA404802041	176	Q>E		No	ClinGen TOPMed gnomAD
rs778932770 CA9308609	177	C>R		No	ClinGen ExAC gnomAD
rs868369089 CA306161887	178	L>V		No	ClinGen gnomAD
CA9308608 rs755103310	180	A>V		No	ClinGen ExAC gnomAD
CA404801960 rs780459639	181	A>P		No	ClinGen ExAC gnomAD
CA9308606 rs780459639	181	A>T		No	ClinGen ExAC gnomAD
rs1315082616 CA404801956	181	A>V		No	ClinGen gnomAD
rs370465668 CA9308605	182	K>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1317760101 CA404801846	182	K>N		No	ClinGen gnomAD
rs143206287 CA9308580	183	Q>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA306161745 rs138906054	184	G>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308578 rs138906054	184	G>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA404801811 rs1008223231	185	P>A		No	ClinGen TOPMed gnomAD
rs1187952480 CA404801806	185	P>R		No	ClinGen gnomAD
rs1008223231 CA306161743	185	P>S		No	ClinGen TOPMed gnomAD
CA404801800 rs746422587	186	V>F		No	ClinGen ExAC gnomAD
rs746422587 CA9308577	186	V>I		No	ClinGen ExAC gnomAD
CA9308575 rs757717714	188	N>K		No	ClinGen ExAC gnomAD
CA9308574 rs751215605	189	P>H		No	ClinGen ExAC gnomAD
rs763841329 CA9308572	190	S>L		No	ClinGen ExAC gnomAD
CA9308571 rs757922084	191	S>F		No	ClinGen ExAC gnomAD
rs867333126 CA306161723	191	S>P		No	ClinGen Ensembl
CA404801719 rs757922084	191	S>Y		No	ClinGen ExAC gnomAD
CA306161721 rs1037220069	192	S>G		No	ClinGen TOPMed
CA404801689 rs1197131362	193	N>D		No	ClinGen TOPMed
rs764870579 CA9308569	194	Q>E		No	ClinGen ExAC gnomAD
CA404801661 rs1373278005	194	Q>H		No	ClinGen gnomAD
rs201567736 CA9308568	194	Q>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs191605418 CA9308566	196	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs563886076 CA9308565	197	P>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs755640528 CA9308511	200	D>N		No	ClinGen ExAC gnomAD
rs756943907 CA9308507	202	G>A		No	ClinGen ExAC gnomAD
rs1417935398 CA404801409	203	Q>*		No	ClinGen TOPMed
CA404801411 rs1417935398	203	Q>E		No	ClinGen TOPMed
CA404801375 rs1280123442	205	L>V		No	ClinGen gnomAD
rs754164808 CA9308503	207	L>V		No	ClinGen ExAC TOPMed gnomAD
rs773792449 CA9308500	212	E>K		No	ClinGen ExAC gnomAD
CA404801238 rs1568668664	213	L>V		No	ClinGen Ensembl
rs200889967 CA9308499	216	C>F		No	ClinGen 1000Genomes ExAC gnomAD
rs200889967 CA404801160	216	C>Y		No	ClinGen 1000Genomes ExAC gnomAD
CA404801118 rs1600078137	218	D>G		No	ClinGen Ensembl
rs1433011736 CA404801130	218	D>Y		No	ClinGen gnomAD
CA404801090 rs1401573392	219	Q>H		No	ClinGen gnomAD
CA404801029 rs1177561276	222	T>R		No	ClinGen TOPMed
rs774776753 CA9308497	226	R>W		No	ClinGen ExAC gnomAD
rs1600078055 CA404800908	229	V>G		No	ClinGen Ensembl
rs368457060 CA9308494	229	V>L		No	ClinGen ESP ExAC gnomAD
CA404800884 rs1185323255	230	G>A		No	ClinGen TOPMed gnomAD
CA306161490 rs757669215	231	E>*		No	ClinGen Ensembl
CA404800835 rs1485086531	232	M>V		No	ClinGen gnomAD
rs868023161 CA306161486	234	S>P		No	ClinGen Ensembl
rs751905073 CA306161484	236	K>T		No	ClinGen Ensembl
rs1042552963 CA306161437	239	R>Q		No	ClinGen TOPMed gnomAD
rs745587320 CA9308473	243	R>Q		No	ClinGen ExAC
rs1232413842 CA404799605	243	R>W		No	ClinGen gnomAD
rs1355944334 CA404799601	244	E>Q		No	ClinGen gnomAD
CA306161434 rs998549392	246	T>P		No	ClinGen Ensembl
CA9308470 rs746916844	250	E>K		No	ClinGen ExAC gnomAD
rs777605436 CA9308469	251	T>P		No	ClinGen ExAC gnomAD
CA9308468 rs369131996	253	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308466 rs150688284	253	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9308467 rs150688284	253	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1367476661 CA404799530	255	G>E		No	ClinGen TOPMed
rs1163249842 CA404799533	255	G>R		No	ClinGen gnomAD
rs756405551 CA9308465	257	Q>R		No	ClinGen ExAC gnomAD
CA9308463 rs550397774	260	E>K		No	ClinGen 1000Genomes ExAC gnomAD
CA404799501 rs550397774	260	E>Q		No	ClinGen 1000Genomes ExAC gnomAD
rs1295930514 CA404799474	263	S>F		No	ClinGen TOPMed
CA9308461 rs752034401	264	R>Q		No	ClinGen ExAC gnomAD
CA9308462 rs201545624	264	R>W		No	ClinGen 1000Genomes ExAC gnomAD
CA404799451 rs1306527980	268	D>N		No	ClinGen TOPMed
CA9308443 rs201157838	272	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1600075610 CA404799397	273	V>G		No	ClinGen Ensembl
rs148172085 CA9308441	276	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308439 rs759925889	279	T>A		No	ClinGen ExAC gnomAD
rs765962984 CA9308437	280	A>T		No	ClinGen ExAC gnomAD
rs760437402 CA9308436	283	A>D		No	ClinGen ExAC gnomAD
CA9308435 rs772595376	285	Q>K		No	ClinGen ExAC gnomAD
CA9308434 rs771753014	286	P>S		No	ClinGen ExAC TOPMed gnomAD
CA404799306 rs1568667490	288	S>T		No	ClinGen Ensembl
rs34503849 RCV000883532 CA9308432 VAR_050474	289	R>Q		No	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA9308433 rs201138155	289	R>W		No	ClinGen ExAC TOPMed gnomAD
rs768494960 COSM3937940 CA9308431	294	H>R	oesophagus [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA9308430 rs749047957	295	G>E		No	ClinGen ExAC gnomAD
CA404799257 rs1313040483	296	L>F		No	ClinGen TOPMed gnomAD
CA404799258 rs1313040483	296	L>V		No	ClinGen TOPMed gnomAD
CA306160998 rs940669528	299	S>N		No	ClinGen TOPMed
rs775410699 CA9308429	300	A>S		No	ClinGen ExAC TOPMed gnomAD
CA9308428 rs771052936	301	S>T		No	ClinGen ExAC gnomAD
CA9308427 rs372274542	302	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1253348432 CA404799197	305	A>V		No	ClinGen TOPMed
rs758494391 CA9308425	306	T>A		No	ClinGen ExAC TOPMed gnomAD
CA9308424 rs748615888	306	T>I		No	ClinGen ExAC TOPMed gnomAD
CA404799190 rs1472102857	307	V>L		No	ClinGen gnomAD
rs147234546 CA9308423	308	P>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9308422 rs769889373	309	R>C		No	ClinGen ExAC gnomAD
rs555152018 CA9308421	309	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs368559727 CA9308420	310	F>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308419 rs755694388	311	G>A		No	ClinGen ExAC gnomAD
CA404799169 rs1209463013	311	G>R		No	ClinGen gnomAD
CA404799144 rs1226951987	315	D>N		No	ClinGen gnomAD
CA9308417 rs567898184	316	Q>E		No	ClinGen 1000Genomes ExAC gnomAD
rs751107115 CA9308396	324	L>I		No	ClinGen ExAC gnomAD
CA9308394 rs762775837	326	D>H		No	ClinGen ExAC gnomAD
rs775519312 CA9308393	328	N>D		No	ClinGen ExAC TOPMed gnomAD
CA404799040 rs1421697432	328	N>S		No	ClinGen gnomAD
rs202088570 CA404799016	331	G>*		No	ClinGen 1000Genomes ExAC gnomAD
rs202088570 CA9308391	331	G>R		No	ClinGen 1000Genomes ExAC gnomAD
CA404799009 rs1254109746	332	L>I		No	ClinGen gnomAD
CA404798992 rs1215945039	333	D>A		No	ClinGen TOPMed gnomAD
CA404798986 rs1248875763	333	D>E		No	ClinGen TOPMed
rs879077826 CA306160844	335	F>L		No	ClinGen gnomAD
CA9308389 rs772270728 COSM1219992	338	A>E	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA9308390 rs759381148	338	A>T		No	ClinGen ExAC gnomAD
CA9308388 rs772270728	338	A>V		No	ClinGen ExAC TOPMed gnomAD
CA404798914 rs774386403	340	L>I		No	ClinGen ExAC TOPMed gnomAD
rs768832653 CA9308385	340	L>P		No	ClinGen ExAC gnomAD
CA306160824 rs774386403	340	L>V		No	ClinGen ExAC TOPMed gnomAD
CA404798872 rs1305452225	343	N>S		No	ClinGen gnomAD
rs2229228 CA9308383 VAR_034374	344	R>Q		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_061497 rs11879710 CA9308384	344	R>W		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs769991817 CA9308382	345	P>H		No	ClinGen ExAC TOPMed gnomAD
rs769991817 CA404798849	345	P>L		No	ClinGen ExAC TOPMed gnomAD
CA404798855 rs1293197599	345	P>S		No	ClinGen gnomAD
rs1250775964 CA404798843	346	L>F		No	ClinGen gnomAD
CA404798811 rs1320887946	349	I>V		No	ClinGen TOPMed
CA404798792 rs1372585616	350	I>T		No	ClinGen gnomAD
rs1166806857 CA404798774	352	S>G		No	ClinGen gnomAD
CA9308381 rs746217505	352	S>I		No	ClinGen ExAC gnomAD
CA9308364 rs763102655	356	E>*		No	ClinGen ExAC TOPMed gnomAD
rs554130523 COSM132746 CA9308363	357	R>Q	central_nervous_system [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC gnomAD
rs967694325 CA306160567	357	R>W		No	ClinGen TOPMed gnomAD
CA404798624 rs1600072935	358	D>A		No	ClinGen Ensembl
CA404798604 rs1377514033	359	L>P		No	ClinGen gnomAD
CA404798540 rs1428272715	363	F>C		No	ClinGen TOPMed
rs1183004387 CA404798525	364	Q>*		No	ClinGen TOPMed gnomAD
CA404798519 rs1568666461	364	Q>H		No	ClinGen Ensembl
rs1331999718 CA404798489	366	P>L		No	ClinGen TOPMed
CA404798481 rs1436030527	367	A>V		No	ClinGen TOPMed
rs1273240731 CA404798473	368	D>H		No	ClinGen TOPMed
rs1367525453 COSM993058 CA404798430	371	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed
CA404798420 rs1229193912	372	T>I		No	ClinGen TOPMed
rs1600072772 CA404798426	372	T>P		No	ClinGen Ensembl
CA9308360 rs746415511	373	Y>*		No	ClinGen ExAC gnomAD
rs1600072749 CA404798408	373	Y>S		No	ClinGen Ensembl
rs1261167675 CA404798334	379	G>D		No	ClinGen gnomAD
CA404798337 rs1224584180	379	G>R		No	ClinGen TOPMed
rs746619948 CA9308357	380	H>Y		No	ClinGen ExAC gnomAD
CA9308355 rs199850000	383	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA306160485 rs113176090	384	N>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308354 rs113176090	384	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308352 rs767041794	386	A>T		No	ClinGen ExAC gnomAD
CA9308351 rs753824973	386	A>V		No	ClinGen ExAC gnomAD
CA9308350 rs766115961	387	Y>*		No	ClinGen ExAC gnomAD
rs1568666282 CA404798194	389	N>D		No	ClinGen Ensembl
CA9308349 rs760498191	389	N>S		No	ClinGen ExAC gnomAD
CA9308348 rs751669414	393	A>T		No	ClinGen ExAC gnomAD
CA9308347 rs375881931	394	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308345 COSM1391642 rs374321161	395	D>N	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs760069983 CA9308343	396	V>M		No	ClinGen ExAC TOPMed gnomAD
CA404798101 rs1165436106	397	A>T		No	ClinGen TOPMed
rs761441597 CA306160432	398	Q>P		No	ClinGen Ensembl
CA404798060 rs370618947	400	T>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308342 rs370618947	400	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA306160420 rs1010005720	401	H>L		No	ClinGen gnomAD
CA404798046 rs1010005720	401	H>R		No	ClinGen gnomAD
CA404798050 rs1600072248	401	H>Y		No	ClinGen Ensembl
rs747390836 CA9308340	402	V>E		No	ClinGen ExAC gnomAD
rs773928995 CA306160413	405	A>V		No	ClinGen Ensembl
COSM109526 rs148755672 CA9308339	406	T>M	skin [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs771752706 CA9308338	407	P>A		No	ClinGen ExAC TOPMed gnomAD
rs140868147 CA9308337	407	P>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA9308335 rs754509086	409	L>R		No	ClinGen ExAC TOPMed gnomAD
rs1387020496 CA404797959	410	E>K		No	ClinGen gnomAD
CA404797339 rs1339777187	411	A>P		No	ClinGen TOPMed
CA306160344 rs896397694	411	A>V		No	ClinGen TOPMed
rs755308767 CA9308309	412	V>M		No	ClinGen ExAC TOPMed gnomAD
CA306160331 rs376738010	413	F>S		No	ClinGen ESP TOPMed gnomAD
rs1478916388 CA404797321	414	T>S		No	ClinGen gnomAD
CA306160326 rs987634259	416	L>V		No	ClinGen TOPMed
rs1483985314 CA404797294	418	I>V		No	ClinGen TOPMed
CA404797252 rs1451261269	424	A>V		No	ClinGen gnomAD
rs1200511435 CA404797248	425	S>N		No	ClinGen TOPMed
CA9308306 rs766607057	426	A>T		No	ClinGen ExAC TOPMed gnomAD
rs761224404 CA9308305	426	A>V		No	ClinGen ExAC gnomAD
rs1414674563 CA404797229	428	H>R		No	ClinGen TOPMed
rs200589596 CA9308304	428	H>Y		No	ClinGen 1000Genomes ExAC gnomAD
COSM3362757 rs1273466664 CA404797225	429	D>N	kidney [Cosmic]	No	ClinGen cosmic curated gnomAD
CA9308300 rs768288276	430	V>A		No	ClinGen ExAC gnomAD
CA404797216 rs773939203	430	V>L		No	ClinGen ExAC gnomAD
rs773939203 CA9308301	430	V>M		No	ClinGen ExAC gnomAD
CA404797211 rs1427331818	431	D>N		No	ClinGen gnomAD
rs762629857 CA9308299	437	N>D		No	ClinGen ExAC gnomAD
CA404797157 rs1174232544	439	F>L		No	ClinGen gnomAD
rs151012513 CA9308298	442	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs769207299 CA9308297	443	T>I		No	ClinGen ExAC gnomAD
CA404797125 rs1467687779	444	N>H		No	ClinGen TOPMed
CA9308267 rs756166983	445	S>T		No	ClinGen ExAC gnomAD
CA404797101 rs1209270737	446	E>K		No	ClinGen TOPMed
rs941118492 CA306159846	448	A>V		No	ClinGen Ensembl
CA9308265 rs781403967	449	L>F		No	ClinGen ExAC gnomAD
CA9308264 rs368759869	450	M>I		No	ClinGen ESP ExAC gnomAD
rs752077587 CA306159841 CA9308263	451	Y>*		No	ClinGen ExAC TOPMed gnomAD
rs764378346 CA9308262	452	N>D		No	ClinGen ExAC gnomAD
CA9308260 rs752298553	453	D>A		No	ClinGen ExAC gnomAD
CA404797055 COSM1219993 rs1456454360	453	D>N	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs759273148 CA9308258	454	A>D		No	ClinGen ExAC gnomAD
CA306159823 rs201331426	454	A>T		No	ClinGen 1000Genomes gnomAD
rs199811187 CA9308257	455	S>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs773285462 CA9308254	459	N>K		No	ClinGen ExAC TOPMed gnomAD
rs139503179 CA306159802	460	H>Y		No	ClinGen ESP TOPMed gnomAD
CA404797005 rs1461267900	461	H>Y		No	ClinGen TOPMed
CA404796977 rs1265708350	465	G>D		No	ClinGen gnomAD
CA9308253 rs771951155	468	L>M		No	ClinGen ExAC gnomAD
rs1228408433 CA404796942	471	A>T		No	ClinGen gnomAD
rs1367283206 CA404796936	472	E>Q		No	ClinGen TOPMed gnomAD
rs147372445 CA9308251	473	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA404796910 rs1227130989	475	D>E		No	ClinGen TOPMed
rs781078768 CA9308248	475	D>G		No	ClinGen ExAC TOPMed gnomAD
rs746162922 CA9308249	475	D>N		No	ClinGen ExAC TOPMed gnomAD
CA404796905 rs1459658486	476	I>T		No	ClinGen gnomAD
CA306159777 rs544479457	476	I>V		No	ClinGen 1000Genomes
rs1164172649 CA404796882	479	N>S		No	ClinGen gnomAD
CA9308246 rs747477408	481	S>R		No	ClinGen ExAC
rs200178612 CA9308242	482	A>T		No	ClinGen ExAC TOPMed gnomAD
rs758954948 CA9308241	482	A>V		No	ClinGen ExAC TOPMed gnomAD
CA404796849 rs1187195939	484	Q>R		No	ClinGen gnomAD
rs1449297362 CA404796844	485	R>*		No	ClinGen gnomAD
CA404796841 rs1268523791	485	R>L		No	ClinGen gnomAD
CA404796843 rs1268523791	485	R>Q		No	ClinGen gnomAD
rs1193246479 CA404796836	486	L>R		No	ClinGen TOPMed gnomAD
CA306159744 rs144273719 COSM108433	488	L>P	skin [Cosmic]	No	ClinGen cosmic curated Ensembl
CA306159760 rs111712277	488	L>V		No	ClinGen Ensembl
rs373742607 CA9308240	489	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
COSM1219990 rs1264438482 CA404796818	489	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA404796814 rs1205323853	490	R>G		No	ClinGen TOPMed gnomAD
rs371204175 CA9308239	493	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs754573326 CA9308238	495	M>V		No	ClinGen ExAC TOPMed gnomAD
rs1028440753 CA306158142	496	V>M		No	ClinGen TOPMed gnomAD
CA9308206 rs773268047	497	L>V		No	ClinGen ExAC gnomAD
CA404795676 rs1198642961	500	D>V		No	ClinGen gnomAD
rs1258233511 CA404795683	500	D>Y		No	ClinGen gnomAD
rs748536731 CA9308204	501	M>I		No	ClinGen ExAC gnomAD
rs1482860285 CA404795665	501	M>L		No	ClinGen gnomAD
rs772152394 CA9308205	501	M>T		No	ClinGen ExAC TOPMed gnomAD
rs779504127 CA9308203	504	H>Y		No	ClinGen ExAC gnomAD
CA9308202 rs768851834	507	L>V		No	ClinGen ExAC gnomAD
rs757151451 CA9308200	510	D>N		No	ClinGen ExAC gnomAD
rs552094016 CA9308197	511	L>R		No	ClinGen 1000Genomes
rs979525960 CA306158095	513	T>I		No	ClinGen Ensembl
rs750117516 CA9308196	514	M>T		No	ClinGen ExAC gnomAD
CA404795431 rs1405940951	515	V>A		No	ClinGen TOPMed gnomAD
rs1405940951 CA404795433	515	V>G		No	ClinGen TOPMed gnomAD
CA404795399 rs1339369998	517	T>I		No	ClinGen TOPMed
CA404795332 rs1459099668	521	T>I		No	ClinGen gnomAD
rs1459099668 CA404795334	521	T>R		No	ClinGen gnomAD
rs780785976 CA404795313 COSM322574	522	S>R	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs751406908 CA9308194	523	L>F		No	ClinGen ExAC gnomAD
rs751406908 CA9308193	523	L>I		No	ClinGen ExAC gnomAD
rs764071894 CA9308192	523	L>R		No	ClinGen ExAC gnomAD
CA9308190 rs752486195	524	G>S		No	ClinGen ExAC TOPMed gnomAD
CA404795226 rs1266514698	529	D>V		No	ClinGen gnomAD
CA306158058 rs752357705	529	D>Y		No	ClinGen gnomAD
rs760829283 CA9308187	532	S>C		No	ClinGen ExAC gnomAD
CA404795169 COSM182191 rs1286059404	533	D>N	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA306158050 rs968186165	534	R>*		No	ClinGen TOPMed gnomAD
CA9308185 rs371170617	534	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA404795115 rs1183496503	536	Q>R		No	ClinGen TOPMed
rs148641627 CA9308170	540	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1184550329 CA404793455	542	V>A		No	ClinGen TOPMed
CA9308168 rs767755226	546	D>H		No	ClinGen ExAC TOPMed gnomAD
CA306157325 rs958389244	549	N>T		No	ClinGen Ensembl
rs774480987 CA9308166	550	P>S		No	ClinGen ExAC gnomAD
CA9308165 rs764134639	551	T>A		No	ClinGen ExAC TOPMed gnomAD
rs1456693536 CA404793168	553	P>A		No	ClinGen TOPMed
rs149614671 CA9308162	553	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1335778296 CA404793124	555	P>S		No	ClinGen TOPMed
CA9308160 rs777177447	556	L>R		No	ClinGen ExAC TOPMed gnomAD
CA9308158 rs746699082	557	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA9308157 rs146406381	558	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs757850745 CA9308156	558	R>H		No	ClinGen ExAC TOPMed gnomAD
rs748037751 CA9308155	559	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA404793031 rs1350684351	560	W>R		No	ClinGen gnomAD
rs1028070498 COSM474362 CA306157285	561	T>M	kidney breast [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs754956144 CA404792963	562	D>H		No	ClinGen ExAC gnomAD
CA9308153 rs754956144	562	D>N		No	ClinGen ExAC gnomAD
CA404792919 rs1326213719	563	R>H		No	ClinGen TOPMed
rs753597067 CA9308152	563	R>S		No	ClinGen ExAC gnomAD
CA9308150 rs757483177	568	F>S		No	ClinGen ExAC gnomAD
CA404792808 rs1600054907	568	F>V		No	ClinGen Ensembl
CA404792733 rs1175399970	571	Q>*		No	ClinGen gnomAD
CA404792695 rs1480236852	572	G>E		No	ClinGen gnomAD
CA9308147 rs763152273	574	R>C		No	ClinGen ExAC TOPMed gnomAD
CA9308146 rs775763570	574	R>H		No	ClinGen ExAC TOPMed gnomAD
rs760188691 CA9308144	575	E>K		No	ClinGen ExAC gnomAD
CA9308143 rs777042876	576	R>C		No	ClinGen ExAC gnomAD
rs771214410 CA306157235	576	R>H		No	ClinGen ExAC TOPMed gnomAD
rs771214410 CA9308142	576	R>L		No	ClinGen ExAC TOPMed gnomAD
CA9308140 rs763067347	577	E>D		No	ClinGen ExAC gnomAD
rs547282310 CA9308139	578	S>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA404792473 rs1450169160	580	L>R		No	ClinGen gnomAD
CA306157217 rs867729198	586	C>R		No	ClinGen Ensembl
CA404792341 rs1347981505	586	C>Y		No	ClinGen TOPMed
rs1224655717 CA404792279	589	H>R		No	ClinGen TOPMed
rs779837499 CA9308134	589	H>Y		No	ClinGen ExAC gnomAD
CA9308133 rs755896777	590	T>M		No	ClinGen ExAC gnomAD
CA9308131 rs753643057	593	V>E		No	ClinGen ExAC gnomAD
rs760522234 CA9308129	594	E>D		No	ClinGen ExAC gnomAD
rs764110418 CA9308130	594	E>K		No	ClinGen ExAC gnomAD
rs1183425571 CA404792190	595	K>Q		No	ClinGen TOPMed gnomAD
CA9308128 rs765472933	597	Q>E		No	ClinGen ExAC TOPMed gnomAD
CA9308127 rs760062134	597	Q>H		No	ClinGen ExAC gnomAD
CA9308108 rs754321359	599	G>C		No	ClinGen ExAC TOPMed gnomAD
CA404792071 rs754321359	599	G>S		No	ClinGen ExAC TOPMed gnomAD
CA404792029 rs1291009909	601	I>T		No	ClinGen gnomAD
CA9308107 rs369402107	601	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs567462984 CA9308105	604	I>V		No	ClinGen 1000Genomes ExAC gnomAD
rs1012278746 CA306156895	605	A>P		No	ClinGen gnomAD
CA404791973 rs1012278746	605	A>S		No	ClinGen gnomAD
rs1225263390 CA404791967	606	H>Y		No	ClinGen TOPMed
rs1381382791 CA404791956	607	P>L		No	ClinGen gnomAD
CA404791935 rs1406883866	610	E>D		No	ClinGen gnomAD
rs761395563 CA9308102	612	W>R		No	ClinGen ExAC gnomAD
rs1474100825 CA404791916	613	A>D		No	ClinGen TOPMed gnomAD
rs1474100825 CA404791914	613	A>V		No	ClinGen TOPMed gnomAD
CA404791896 rs1412718375	616	V>A		No	ClinGen gnomAD
rs960606454 CA306156884	617	H>R		No	ClinGen TOPMed
CA9308096 rs745876744	618	P>S		No	ClinGen ExAC TOPMed gnomAD
CA306156872 rs764540611	619	D>E		No	ClinGen Ensembl
rs564073130 CA306156880	619	D>G		No	ClinGen Ensembl
rs776512163 CA9308095	620	A>V		No	ClinGen ExAC TOPMed gnomAD
CA306156861 rs555617927	621	Q>E		No	ClinGen TOPMed gnomAD
CA9308094 rs770853902	621	Q>R		No	ClinGen ExAC gnomAD
CA9308091 rs755300352	624	L>P		No	ClinGen ExAC gnomAD
rs1202246846 CA404791844	625	D>G		No	ClinGen TOPMed
CA404791835 rs1249529810	626	T>M		No	ClinGen gnomAD
CA404791828 rs1312519079	628	E>Q		No	ClinGen gnomAD
rs1302298137 CA404791819	629	D>Y		No	ClinGen gnomAD
rs1600052842 CA404791811	630	N>Y		No	ClinGen Ensembl
rs780245468 CA9308089	631	R>*		No	ClinGen ExAC gnomAD
rs756562245 CA9308088	631	R>Q		No	ClinGen ExAC gnomAD
CA9308087 rs141280746	634	Y>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs1307569696 CA404791776	635	Q>*		No	ClinGen TOPMed
rs966600135 CA306156843	635	Q>H		No	ClinGen TOPMed gnomAD
rs868245603 CA306156838	636	S>I		No	ClinGen gnomAD
CA404791768 rs868245603	636	S>N		No	ClinGen gnomAD
CA9308086 rs767800939	636	S>R		No	ClinGen ExAC TOPMed gnomAD
CA9308084 rs751972854	640	R>*		No	ClinGen ExAC TOPMed gnomAD
rs763707510 CA9308083	640	R>Q		No	ClinGen ExAC gnomAD
rs868304717 CA306156794	642	P>L		No	ClinGen Ensembl
COSM417693 CA306156787 rs373558260	643	S>*	urinary_tract [Cosmic]	No	ClinGen cosmic curated ESP TOPMed
CA306156791 rs373558260	643	S>L		No	ClinGen ESP TOPMed
COSM246503 CA404791705 rs1178986156	646	T>I	prostate [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA9308082 rs762738383	647	N>D		No	ClinGen ExAC TOPMed gnomAD
CA9308081 rs774852899	648	P>R		No	ClinGen ExAC gnomAD
rs1227198416 CA404791696	648	P>T		No	ClinGen TOPMed
CA9308079 COSM438961 rs759324714	649	E>K	breast [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs770802497 CA306156761	650	R>L		No	ClinGen ExAC TOPMed gnomAD
rs770802497 CA9308077	650	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs776743379 CA9308078	650	R>W		No	ClinGen ExAC TOPMed gnomAD
CA404791665 rs1568659417	651	D>N		No	ClinGen Ensembl
CA9308074 rs768755672	652	G>R		No	ClinGen ExAC TOPMed gnomAD
rs148119555 CA9308073	654	D>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs1282883028 CA404791616	655	R>G		No	ClinGen gnomAD
CA404791582 rs1381580421	657	Q>*		No	ClinGen TOPMed gnomAD
rs375292128 CA9308071	659	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA404791548 rs1232171429	659	E>V		No	ClinGen Ensembl
CA306156739 rs371324110	660	L>P		No	ClinGen ESP gnomAD
rs929451280 CA306156722	661	T>I		No	ClinGen TOPMed
CA9308070 rs149096279	661	T>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9308069 rs551540885	662	L>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1320115157 CA404791441	668	E>K		No	ClinGen TOPMed
rs751921667 CA9308067	670	E>D		No	ClinGen ExAC gnomAD
rs1454935702 CA404791389	670	E>G		No	ClinGen gnomAD
rs1159402423 CA404791395	670	E>Q		No	ClinGen gnomAD
CA9308066 rs535422150	672	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1038151777 CA9308064	674	E>D		No	ClinGen TOPMed
CA9308063 rs201098229	676	G>R		No	ClinGen 1000Genomes ExAC gnomAD
CA404791213 rs1361088467	678	E>K		No	ClinGen TOPMed
rs764614889 CA9308060	679	T>I		No	ClinGen ExAC gnomAD
rs764614889 CA404791183	679	T>K		No	ClinGen ExAC gnomAD
rs1262811829 CA404791164	681	L>S		No	ClinGen gnomAD
CA9308059 rs759109164	684	E>K		No	ClinGen ExAC gnomAD
rs1259046143 CA404791115	685	A>D		No	ClinGen gnomAD
CA9308058 rs753446946	688	L>S		No	ClinGen ExAC gnomAD
CA306156650 rs948840153	691	T>S		No	ClinGen TOPMed gnomAD
rs916015043 CA306156648	692	E>Q		No	ClinGen TOPMed gnomAD
rs7259700 CA9308057	694	L>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs773127645 CA9308055	698	A>D		No	ClinGen ExAC gnomAD
CA404790960 rs878971994	699	G>R		No	ClinGen TOPMed gnomAD
CA306156626 rs878971994	699	G>S		No	ClinGen TOPMed gnomAD
CA404790937 rs1382233578	700	P>L		No	ClinGen gnomAD
CA306156622 rs779902922	702	P>L		No	ClinGen Ensembl
rs927854764 CA306156614	703	G>R		No	ClinGen TOPMed
rs1406784122 CA404790907	704	D>N		No	ClinGen gnomAD
CA9308052 rs371890883	704	D>V		No	ClinGen ExAC TOPMed gnomAD
rs769710762 CA9308051	706	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1443881924 CA404790861	708	D>N		No	ClinGen TOPMed gnomAD
rs781318531 CA9308049	709	N>S		No	ClinGen ExAC gnomAD
CA404790830 rs1194981417	710	Q>*		No	ClinGen TOPMed gnomAD
CA404790833 rs1194981417	710	Q>K		No	ClinGen TOPMed gnomAD
rs1448972249 CA404790817	711	R>G		No	ClinGen gnomAD
rs771418461 CA9308048	711	R>K		No	ClinGen ExAC gnomAD

No associated diseases with Q08493

4 regional properties for Q08493

Type	Name	Position	InterPro Accession
domain	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	312 - 641	IPR002073
domain	HD/PDEase domain	385 - 569	IPR003607
conserved_site	3'5'-cyclic nucleotide phosphodiesterase, conserved site	428 - 439	IPR023174
domain	Phosphodiesterase 4 upstream conserved regions (UCR)	152 - 268	IPR040844

Functions

		Description
EC Number	3.1.4.53	Phosphoric diester hydrolases
Subcellular Localization	Cell projection, cilium
PANTHER Family	PTHR11347	CYCLIC NUCLEOTIDE PHOSPHODIESTERASE
PANTHER Subfamily	PTHR11347:SF135	CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE 4C
PANTHER Protein Class	phosphodiesterase
PANTHER Pathway Category	No pathway information available

5 GO annotations of cellular component

Name	Definition
cilium	A specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface and of some cytoplasmic parts. Each cilium is largely bounded by an extrusion of the cytoplasmic (plasma) membrane, and contains a regular longitudinal array of microtubules, anchored to a basal body.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extracellular space	That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
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.
perinuclear region of cytoplasm	Cytoplasm situated near, or occurring around, the nucleus.

3 GO annotations of molecular function

Name	Definition
3',5'-cyclic-AMP phosphodiesterase activity	Catalysis of the reaction: 3',5'-cyclic AMP + H2O = AMP + H+.
3',5'-cyclic-nucleotide phosphodiesterase activity	Catalysis of the reaction: a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate.
metal ion binding	Binding to a metal ion.

2 GO annotations of biological process

Name	Definition
cAMP catabolic process	The chemical reactions and pathways resulting in the breakdown of the nucleotide cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate).
signal transduction	The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.

34 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q28156	PDE5A	cGMP-specific 3',5'-cyclic phosphodiesterase	Bos taurus (Bovine)	SS
P23439	PDE6B	Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta	Bos taurus (Bovine)	PR
P52731	PDE6C	Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'	Gallus gallus (Chicken)	PR
H2QL32	PDE9A	High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A	Pan troglodytes (Chimpanzee)	PR
Q9VJ79	Pde11	Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11	Drosophila melanogaster (Fruit fly)	SS
Q9W4T4	dnc	3',5'-cyclic-AMP phosphodiesterase, isoform I	Drosophila melanogaster (Fruit fly)	SS
O60658	PDE8A	High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A	Homo sapiens (Human)	PR
P27815	PDE4A	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (Human)	EV SS
Q07343	PDE4B	cAMP-specific 3',5'-cyclic phosphodiesterase 4B	Homo sapiens (Human)	EV SS
Q08499	PDE4D	cAMP-specific 3',5'-cyclic phosphodiesterase 4D	Homo sapiens (Human)	EV
O76083	PDE9A	High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A	Homo sapiens (Human)	PR
P54750	PDE1A	Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A	Homo sapiens (Human)	PR
Q9Y233	PDE10A	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Homo sapiens (Human)	PR
Q9HCR9	PDE11A	Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A	Homo sapiens (Human)	SS
P35913	PDE6B	Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta	Homo sapiens (Human)	PR
P51160	PDE6C	Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'	Homo sapiens (Human)	PR
O76074	PDE5A	cGMP-specific 3',5'-cyclic phosphodiesterase	Homo sapiens (Human)	EV
P23440	Pde6b	Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta	Mus musculus (Mouse)	PR
O89084	Pde4a	3',5'-cyclic-AMP phosphodiesterase 4A	Mus musculus (Mouse)	SS
O70628	Pde9a	High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A	Mus musculus (Mouse)	PR
Q8CG03	Pde5a	cGMP-specific 3',5'-cyclic phosphodiesterase	Mus musculus (Mouse)	SS
Q8CA95	Pde10a	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Mus musculus (Mouse)	PR
P0C1Q2	Pde11a	Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A	Mus musculus (Mouse)	SS
Q01063	Pde4d	3',5'-cyclic-AMP phosphodiesterase 4D	Mus musculus (Mouse)	SS
Q3UEI1	Pde4c	cAMP-specific 3',5'-cyclic phosphodiesterase 4C	Mus musculus (Mouse)	PR
Q8QZV1	Pde9a	High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A	Rattus norvegicus (Rat)	PR
P14646	Pde4b	cAMP-specific 3',5'-cyclic phosphodiesterase 4B	Rattus norvegicus (Rat)	SS
Q8VID6	Pde11a	Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A	Rattus norvegicus (Rat)	SS
O54735	Pde5a	cGMP-specific 3',5'-cyclic phosphodiesterase	Rattus norvegicus (Rat)	SS
P54748	Pde4a	3',5'-cyclic-AMP phosphodiesterase 4A	Rattus norvegicus (Rat)	SS
Q9QYJ6	Pde10a	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Rattus norvegicus (Rat)	PR
P14270	Pde4d	cAMP-specific 3',5'-cyclic phosphodiesterase 4D	Rattus norvegicus (Rat)	PR
P14644	Pde4c	cAMP-specific 3',5'-cyclic phosphodiesterase 4C	Rattus norvegicus (Rat)	PR
Q22000	pde-4	Probable 3',5'-cyclic phosphodiesterase pde-4	Caenorhabditis elegans	PR

10	20	30	40	50	60
MENLGVGEGA	EACSRLSRSR	GRHSMTRAPK	HLWRQPRRPI	RIQQRFYSDP	DKSAGCRERD
70	80	90	100	110	120
LSPRPELRKS	RLSWPVSSCR	RFDLENGLSC	GRRALDPQSS	PGLGRIMQAP	VPHSQRRESF
130	140	150	160	170	180
LYRSDSDYEL	SPKAMSRNSS	VASDLHGEDM	IVTPFAQVLA	SLRTVRSNVA	ALARQQCLGA
190	200	210	220	230	240
AKQGPVGNPS	SSNQLPPAED	TGQKLALETL	DELDWCLDQL	ETLQTRHSVG	EMASNKFKRI
250	260	270	280	290	300
LNRELTHLSE	TSRSGNQVSE	YISRTFLDQQ	TEVELPKVTA	EEAPQPMSRI	SGLHGLCHSA
310	320	330	340	350	360
SLSSATVPRF	GVQTDQEEQL	AKELEDTNKW	GLDVFKVAEL	SGNRPLTAII	FSIFQERDLL
370	380	390	400	410	420
KTFQIPADTL	ATYLLMLEGH	YHANVAYHNS	LHAADVAQST	HVLLATPALE	AVFTDLEILA
430	440	450	460	470	480
ALFASAIHDV	DHPGVSNQFL	INTNSELALM	YNDASVLENH	HLAVGFKLLQ	AENCDIFQNL
490	500	510	520	530	540
SAKQRLSLRR	MVIDMVLATD	MSKHMNLLAD	LKTMVETKKV	TSLGVLLLDN	YSDRIQVLQN
550	560	570	580	590	600
LVHCADLSNP	TKPLPLYRQW	TDRIMAEFFQ	QGDRERESGL	DISPMCDKHT	ASVEKSQVGF
610	620	630	640	650	660
IDYIAHPLWE	TWADLVHPDA	QDLLDTLEDN	REWYQSKIPR	SPSDLTNPER	DGPDRFQFEL
670	680	690	700	710
TLEEAEEEDE	EEEEEGEETA	LAKEALELPD	TELLSPEAGP	DPGDLPLDNQ	RT