AiPD: Autoinhibited Protein Database

Q9UN37

Gene name	VPS4A
Protein name	Vacuolar protein sorting-associated protein 4A
Names	Protein SKD2, VPS4-1, hVPS4
Species	Homo sapiens (Human)
KEGG Pathway	hsa:27183
EC number	3.6.4.6: Acting on ATP; involved in cellular and subcellular movement
Protein Class	AAA DOMAIN-CONTAINING (PTHR23074)

Descriptions

VPS4 proteins are AAA+ ATPases required to form multivesicular bodies, release viral particles, and complete cytokinesis. VPS4 proteins act by disassembling ESCRT-III heteropolymers during or after their proposed function in membrane scission. Deleting the N-terminal MIT domain and adjacent linker from VPS4A increases both basal and liposome-enhanced ATPase activity, indicating that these elements play a role in autoinhibiting VPS4A until it encounters ESCRT-III polymers. The interactions between acidic ESCRT-III residues and sequences in VPS4A, in particular in the linker connecting the MIT and AAA+ domains, are involved in regulating the intrinsic autoinhibition of the enzyme.

Autoinhibitory domains (AIDs)

Target domain	159-295 (AAA+ domain)
Relief mechanism	Partner binding
Assay	Deletion assay, Mutagenesis experiment

AID

100-112 (MIT-AAA+ linker)

Target domain

159-295 (AAA+ domain)

Relief mechanism

Partner binding (Interaction between VPS4A and the C-terminal fragments of ESCRT-III proteins)

Assay

Deletion assay, Mutagenesis experiment

Accessory elements

No accessory elements

References

Merrill SA et al. (2010) "Activation of human VPS4A by ESCRT-III proteins reveals ability of substrates to relieve enzyme autoinhibition", The Journal of biological chemistry, 285, 35428-38

Autoinhibited structure

Activated structure

4 structures for Q9UN37

Entry ID	Method	Resolution	Chain	Position	Source
1YXR	NMR	-	A	1-77	PDB
2JQ9	NMR	-	A	1-84	PDB
2K3W	NMR	-	A	1-84	PDB
AF-Q9UN37-F1	Predicted				AlphaFoldDB

267 variants for Q9UN37

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV001374867 rs1965431981 RCV001290972	28	A>V	CIMDAG SYNDROME Syndromic congenital hemolytic and dyserythropoietic anemia [ClinVar]	Yes	ClinVar dbSNP
RCV001290971 RCV001374866 rs1965484288	203	G>E	CIMDAG SYNDROME Syndromic congenital hemolytic and dyserythropoietic anemia [ClinVar]	Yes	ClinVar dbSNP
RCV001374865 RCV001290980 rs1965484443	206	E>K	CIMDAG SYNDROME [ClinVar]	Yes	ClinVar dbSNP
rs1965499910 RCV001374864 RCV001290979	284	R>G	CIMDAG SYNDROME [ClinVar]	Yes	ClinVar dbSNP
RCV001374863 RCV001290978 RCV001290970 rs1965499910	284	R>W	CIMDAG SYNDROME Syndromic congenital hemolytic and dyserythropoietic anemia [ClinVar]	Yes	ClinVar dbSNP
CA396461375 rs1180031926	2	T>A		No	ClinGen TOPMed
CA283325607 rs868005614	3	T>K		No	ClinGen Ensembl
CA396461475 rs1367024931	5	T>I		No	ClinGen gnomAD
rs1471164840 CA396461503	7	Q>K		No	ClinGen gnomAD
rs776846579 CA8132972	10	I>S		No	ClinGen ExAC TOPMed gnomAD
CA8132971 rs776846579	10	I>T		No	ClinGen ExAC TOPMed gnomAD
CA8132975 rs757227102	18	E>K		No	ClinGen ExAC gnomAD
rs767515591 CA8132977	19	E>D		No	ClinGen ExAC TOPMed gnomAD
CA396463548 rs1490853450	22	A>T		No	ClinGen gnomAD
COSM972871 CA8132983 rs748705794	26	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA396463686 rs748705794	26	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA396463724 rs1406826311	27	E>A		No	ClinGen gnomAD
rs1037382453 CA283329243	30	R>Q		No	ClinGen TOPMed gnomAD
CA283329242 rs376416470	30	R>W		No	ClinGen Ensembl
rs1365684070 CA396463818	33	Q>E		No	ClinGen gnomAD
rs771264354 CA8132987	33	Q>R		No	ClinGen ExAC gnomAD
rs776771864 CA8132988	34	H>L		No	ClinGen ExAC gnomAD
CA8132989 rs759795974	35	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1597211605 CA396463901	36	V>G		No	ClinGen Ensembl
CA396464033 rs1300178956	41	H>R		No	ClinGen gnomAD
rs763089299 CA8132992	41	H>Y		No	ClinGen ExAC gnomAD
CA283329281 rs947704641 COSM1232396	42	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA396464234 rs1456630141	45	Y>F		No	ClinGen gnomAD
rs1343361238 CA396464285	48	H>R		No	ClinGen TOPMed
rs1337229075 CA396464302	49	S>N		No	ClinGen gnomAD
CA8133026 rs769996046	50	D>N		No	ClinGen ExAC gnomAD
COSM1379231 rs908061852 CA283329539	52	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs1296422320 CA396464402	54	E>D		No	ClinGen TOPMed
rs1332900353 CA396464388	54	E>K		No	ClinGen TOPMed
rs1287016570 CA396464413	55	S>N		No	ClinGen gnomAD
rs1420303551 CA396464442	57	R>*		No	ClinGen gnomAD
CA396464452 rs1265429882	57	R>L		No	ClinGen gnomAD
rs1359842430 CA396464485	60	C>S		No	ClinGen TOPMed
CA8133030 rs199747574	61	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA396464546 rs1254993121	66	R>G		No	ClinGen TOPMed gnomAD
rs1254993121 CA396464548	66	R>W		No	ClinGen TOPMed gnomAD
CA283329566 rs755682902	68	E>K		No	ClinGen TOPMed gnomAD
CA8133033 rs776363177	73	Y>C		No	ClinGen ExAC gnomAD
rs1177045672 CA396464667	74	L>F		No	ClinGen gnomAD
rs759385403 CA8133034	75	R>Q		No	ClinGen ExAC gnomAD
rs1464321715 CA396464702	77	K>E		No	ClinGen TOPMed gnomAD
rs570971398 CA8133036	81	G>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA8133037 rs532302590	83	K>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA396464930 rs1278441821	84	P>A		No	ClinGen TOPMed
CA8133038 rs763641951	86	K>Q		No	ClinGen ExAC gnomAD
rs1349912753 CA396465025	87	E>D		No	ClinGen gnomAD
rs1597211732 CA396465010	87	E>Q		No	ClinGen Ensembl
CA8133039 rs200710053	88	N>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA8133040 rs373232218	88	N>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1218123219 CA396465064	89	Q>*		No	ClinGen TOPMed
CA396465140 rs1341256116	92	G>S		No	ClinGen TOPMed
CA396466951 rs1451042598	98	D>E		No	ClinGen gnomAD
CA396466959 rs1186940332	99	S>G		No	ClinGen gnomAD
rs1389707025 CA396466963	99	S>N		No	ClinGen gnomAD
rs951587565 CA283332000	102	D>N		No	ClinGen gnomAD
CA8133060 rs766932017	103	N>S		No	ClinGen ExAC gnomAD
CA8133061 rs375698468	104	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA8133063 rs766947194	106	K>R		No	ClinGen ExAC gnomAD
rs1351781114 CA396467303	115	G>D		No	ClinGen gnomAD
CA8133120 rs771844822	117	V>I		No	ClinGen ExAC TOPMed gnomAD
rs746652806 CA8133122	118	V>M		No	ClinGen ExAC TOPMed gnomAD
rs770600511 CA8133123	120	E>Q		No	ClinGen ExAC gnomAD
rs1303373176 CA396467349	122	P>L		No	ClinGen TOPMed
rs776254647 CA396467356	123	N>K		No	ClinGen ExAC gnomAD
rs1436282512 CA396467354	123	N>S		No	ClinGen TOPMed
CA396467363 rs1368547594	124	I>T		No	ClinGen TOPMed
CA283332469 rs1026275809	125	R>Q		No	ClinGen TOPMed
rs372187571 CA283332461	125	R>W		No	ClinGen TOPMed gnomAD
CA396467385 rs1482085728	128	D>N		No	ClinGen gnomAD
rs1257405012 CA396467405	131	G>R		No	ClinGen TOPMed
CA396467427 rs1424893027	134	G>E		No	ClinGen gnomAD
CA396467430 rs1432290814	135	A>T		No	ClinGen gnomAD
CA396467442 rs1371906754	136	K>N		No	ClinGen gnomAD
rs1427194974 CA396467452	138	A>T		No	ClinGen gnomAD
CA8133132 rs762002494	147	I>T		No	ClinGen ExAC gnomAD
rs1340139234 CA396468153	155	G>C		No	ClinGen gnomAD
CA396468216 rs1246570108	155	G>V		No	ClinGen gnomAD
CA396468240 rs1463301230	156	K>N		No	ClinGen TOPMed gnomAD
CA396468267 rs1187519834	157	R>H		No	ClinGen gnomAD
COSM1379232 CA8133155 rs536870010	161	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA8133157 rs758329744	162	G>E		No	ClinGen ExAC gnomAD
CA396468467 rs867659456	167	G>R		No	ClinGen gnomAD
CA283333231 rs867659456	167	G>R		No	ClinGen gnomAD
CA8133161 rs375403355	168	P>R		No	ClinGen ESP ExAC gnomAD
CA8133162 rs745531182	172	G>E		No	ClinGen ExAC gnomAD
rs779594017 CA8133164	175	Y>*		No	ClinGen ExAC gnomAD
rs866376451 CA283333266	177	A>T		No	ClinGen Ensembl
CA8133165 rs748698446	179	A>V		No	ClinGen ExAC
CA283333287 rs573192094	180	V>M		No	ClinGen TOPMed
CA8133167 rs149990111	181	A>V		No	ClinGen 1000Genomes ExAC gnomAD
rs1449940946 CA396468911	185	N>I		No	ClinGen gnomAD
CA8133171 rs773370042	196	D>N		No	ClinGen ExAC gnomAD
CA8133170 rs773370042	196	D>Y		No	ClinGen ExAC gnomAD
rs1236375735 CA396469269	198	M>I		No	ClinGen gnomAD
RCV000996295 CA396469307 rs1597213310	200	K>E		No	ClinGen ClinVar Ensembl dbSNP
rs776790995 CA8133173	200	K>R		No	ClinGen ExAC TOPMed gnomAD
rs764131541 CA8133175	204	E>G		No	ClinGen ExAC gnomAD
rs1404698023 CA396469430	205	S>G		No	ClinGen gnomAD
CA396469472 rs1412978413	205	S>R		No	ClinGen gnomAD
CA8133206 rs778099042	209	V>G		No	ClinGen ExAC gnomAD
rs1160061571 CA396469848	209	V>I		No	ClinGen TOPMed
CA396469861 rs1386510680	210	K>E		No	ClinGen gnomAD
rs747403949 CA8133207	211	N>K		No	ClinGen ExAC gnomAD
rs781532708 CA8133209	214	E>D		No	ClinGen ExAC gnomAD
rs770050243 CA8133211	219	H>R		No	ClinGen ExAC gnomAD
CA396469996 rs1267161514	219	H>Y		No	ClinGen TOPMed gnomAD
CA283334331 rs369640885	220	K>R		No	ClinGen ESP
rs1173654957 CA396470060	222	S>C		No	ClinGen TOPMed
rs1260256729 CA396470077	223	I>T		No	ClinGen TOPMed
rs1567423979 CA396470122	226	I>V		No	ClinGen Ensembl
CA8133214 rs772052880	229	V>M		No	ClinGen ExAC TOPMed gnomAD
rs374250970 CA8133217	233	C>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs776308848 CA396470232	234	G>R		No	ClinGen ExAC gnomAD
rs776308848 CA8133218	234	G>W		No	ClinGen ExAC gnomAD
rs759163393 CA8133219	236	R>*		No	ClinGen ExAC gnomAD
rs764817590 CA8133220	236	R>Q		No	ClinGen ExAC gnomAD
RCV000436732 rs1057520199	240	E>missing		No	ClinVar dbSNP
CA283334372 rs940324553	242	E>D		No	ClinGen TOPMed
CA8133223 rs764672905	244	A>T		No	ClinGen ExAC TOPMed gnomAD
rs751994747 CA8133224	245	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA396470340 rs1360667538	245	R>W		No	ClinGen gnomAD
rs968258094 CA283334394 COSM264664	251	F>L	large_intestine [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1191807696 CA396470443	254	Q>H		No	ClinGen gnomAD
rs1232567036 CA396470455	255	M>I		No	ClinGen gnomAD
rs1261254269 CA396470454	255	M>R		No	ClinGen gnomAD
CA283334418 rs920494012	255	M>V		No	ClinGen TOPMed
CA8133251 rs755129371	258	V>M		No	ClinGen ExAC gnomAD
rs1314687585 CA396470559	260	N>H		No	ClinGen gnomAD
rs1433482899 CA396470566	260	N>S		No	ClinGen gnomAD
CA396470611 rs1439899728	264	G>R		No	ClinGen gnomAD
CA396470621 rs1597213951	265	T>P		No	ClinGen Ensembl
CA396470650 rs1221187575	268	L>V		No	ClinGen gnomAD
CA396470741 rs1229301691	275	W>*		No	ClinGen gnomAD
rs573646046 CA283334888	275	W>L		No	ClinGen Ensembl
CA8133257 rs769562853	279	S>L		No	ClinGen ExAC gnomAD
rs1489646110 CA396470857	281	I>M		No	ClinGen gnomAD
rs1392812787 CA396470893	284	R>K		No	ClinGen gnomAD
rs1393426741 CA396472122	288	R>*		No	ClinGen TOPMed gnomAD
rs1457982028 CA396472126	288	R>Q		No	ClinGen gnomAD
rs1420999003 CA396472155	290	Y>H		No	ClinGen TOPMed gnomAD
rs768197783 CA8133282	292	P>H		No	ClinGen ExAC
CA396472249 rs1430036338	294	P>L		No	ClinGen gnomAD
CA396472264 rs1382020505	295	E>G		No	ClinGen gnomAD
rs1330193814 CA396472281	296	E>A		No	ClinGen gnomAD
CA396472293 rs1208974573	296	E>D		No	ClinGen gnomAD
rs1208974573 CA396472295	296	E>D		No	ClinGen gnomAD
rs1272972505 CA396472278	296	E>K		No	ClinGen gnomAD
CA396472316 rs896113006	297	A>G		No	ClinGen TOPMed gnomAD
CA283337926 rs896113006	297	A>V		No	ClinGen TOPMed gnomAD
CA8133285 rs771707990 COSM1379233	299	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs370027890 CA8133287	300	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs953227769 CA283337949	301	Q>H		No	ClinGen TOPMed gnomAD
CA396472425 rs1472757773	302	M>I		No	ClinGen TOPMed gnomAD
rs766947312 CA8133288	302	M>L		No	ClinGen ExAC gnomAD
rs766947312 CA396472409	302	M>V		No	ClinGen ExAC gnomAD
CA396472462 rs532354829	304	R>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs759875196 CA283337953	304	R>P		No	ClinGen ExAC TOPMed gnomAD
CA8133290 rs759875196	304	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA8133289 rs532354829	304	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1334991308 CA396472500	305	L>F		No	ClinGen TOPMed gnomAD
CA396472498 rs1334991308	305	L>F		No	ClinGen TOPMed gnomAD
rs199701300 CA8133292	308	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA8133293 COSM972873 rs377128919	309	S>N	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA396472628 rs1230689648	310	T>N		No	ClinGen gnomAD
CA396472617 rs1597214178	310	T>P		No	ClinGen Ensembl
rs750409239 CA8133295	311	P>A		No	ClinGen ExAC TOPMed
rs756067870 CA396472652	311	P>H		No	ClinGen ExAC TOPMed gnomAD
CA8133296 rs756067870	311	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1466452481 CA396472668	312	H>R		No	ClinGen TOPMed
rs1221995501 CA396472664	312	H>Y		No	ClinGen gnomAD
rs779976530 CA8133297	313	N>H		No	ClinGen ExAC gnomAD
rs188288592 CA8133298	313	N>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA396472700 rs1278735127	314	L>F		No	ClinGen gnomAD
rs1443596563 CA396472719	315	T>K		No	ClinGen TOPMed gnomAD
rs1443596563 CA396472717	315	T>M		No	ClinGen TOPMed gnomAD
rs1256643940 CA396472757	316	D>G		No	ClinGen TOPMed gnomAD
CA396472796 rs1472869139	318	N>D		No	ClinGen gnomAD
CA283338002 rs372620820	321	E>D		No	ClinGen ESP
rs865827898 CA283337995	321	E>K		No	ClinGen TOPMed gnomAD
CA396472982 rs1427360079	324	R>Q		No	ClinGen gnomAD
rs747774322 CA8133301	324	R>W		No	ClinGen ExAC TOPMed gnomAD
CA8133302 rs375640414	326	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs775731726 CA283338044	327	E>G		No	ClinGen gnomAD
rs1412189505 CA396473051	328	G>D		No	ClinGen gnomAD
rs1231243780 CA396473050	328	G>S		No	ClinGen TOPMed
rs1567424390 CA396473173	334	I>F		No	ClinGen Ensembl
rs1349435819 CA396473187	335	S>G		No	ClinGen gnomAD
CA396473208 rs1231515684	336	I>V		No	ClinGen gnomAD
COSM1232395 CA8133308 rs765629568	338	V>M	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA396473270 rs1197436525	339	R>W		No	ClinGen gnomAD
CA396473319 rs1436944581	341	S>F		No	ClinGen gnomAD
CA283338132 rs905326386	342	L>P		No	ClinGen TOPMed
rs868652529 CA283338151	345	P>S		No	ClinGen Ensembl
CA8133312 rs751643808	348	K>N		No	ClinGen ExAC gnomAD
CA396473425 rs1390838429	349	V>M		No	ClinGen gnomAD
CA396473446 rs1432190785	350	Q>H		No	ClinGen gnomAD
CA396473441 rs1179363591	350	Q>R		No	ClinGen TOPMed
rs1166620879 CA396473468	351	S>L		No	ClinGen TOPMed gnomAD
rs1325925985 CA396473501	353	T>I		No	ClinGen gnomAD
CA396473522 rs1438218215	354	H>R		No	ClinGen gnomAD
rs1372807260 CA396473511	354	H>Y		No	ClinGen gnomAD
CA283338220 rs550359468	356	K>R		No	ClinGen ExAC gnomAD
CA8133315 rs550359468	356	K>T		No	ClinGen ExAC gnomAD
CA283338225 rs896152486	357	K>R		No	ClinGen TOPMed gnomAD
CA396473629 rs896152486	357	K>T		No	ClinGen TOPMed gnomAD
rs758206091 CA8133336	358	V>A		No	ClinGen ExAC gnomAD
CA8133335 rs752541856	358	V>L		No	ClinGen ExAC gnomAD
CA8133340 rs372786596	361	P>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA8133342 rs201855530	363	R>C		No	ClinGen ExAC TOPMed gnomAD
CA8133343 rs377166999	363	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs769005950 CA8133346	366	P>S		No	ClinGen ExAC TOPMed gnomAD
CA8133345 rs769005950	366	P>T		No	ClinGen ExAC TOPMed gnomAD
CA396474045 rs1213659992	368	M>I		No	ClinGen gnomAD
CA396474054 rs1256093452	369	M>T		No	ClinGen gnomAD
CA8133348 rs375833582	370	I>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA396474115 rs1183409179	374	L>Q		No	ClinGen gnomAD
CA396474135 rs1204048605	376	P>T		No	ClinGen TOPMed
rs564060765 CA283339707	377	C>S		No	ClinGen Ensembl
CA283339710 rs1025387872	378	S>L		No	ClinGen TOPMed
rs1362710787 CA396474184	380	G>A		No	ClinGen gnomAD
CA8133351 rs760608398	380	G>R		No	ClinGen ExAC TOPMed gnomAD
CA396474194 rs1307739542	381	D>G		No	ClinGen TOPMed
CA396474188 rs1314159891	381	D>N		No	ClinGen TOPMed gnomAD
rs1314159891 CA396474192	381	D>Y		No	ClinGen TOPMed gnomAD
rs762905489 CA8133354	383	G>E		No	ClinGen ExAC gnomAD
CA8133353 rs752664707	383	G>R		No	ClinGen ExAC gnomAD
CA8133355 rs763947616	384	A>T		No	ClinGen ExAC gnomAD
CA396474227 rs369539490	385	M>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA8133356 rs369539490	385	M>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA396474238 rs1312983074	386	E>D		No	ClinGen gnomAD
rs372824425 CA8133358	387	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs372824425 CA8133357	387	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs755566234 CA396474277	391	D>E		No	ClinGen ExAC gnomAD
rs184892976 CA8133359	391	D>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs780605736 CA8133361	392	V>I		No	ClinGen ExAC TOPMed gnomAD
CA396474291 rs1462633219	394	G>W		No	ClinGen TOPMed
CA396474309 rs1454441865	396	K>N		No	ClinGen gnomAD
CA8133363 rs769059309	397	L>V		No	ClinGen ExAC gnomAD
rs763376764 CA8133364	398	L>S		No	ClinGen ExAC gnomAD
CA396474336 rs1356495435	401	V>M		No	ClinGen TOPMed
CA396474352 rs1434050871	403	C>S		No	ClinGen gnomAD
rs1356077523 CA396474362	404	M>I		No	ClinGen gnomAD
CA396474357 rs1195674825	404	M>V		No	ClinGen Ensembl
rs1457503175 CA396474947	405	S>L		No	ClinGen gnomAD
CA396474962 rs1304085099	407	M>I		No	ClinGen TOPMed
rs768719182 CA8133394	407	M>V		No	ClinGen ExAC TOPMed gnomAD
CA396474971 rs1201479350	409	R>Q		No	ClinGen gnomAD
CA396474970 rs1193076012	409	R>W		No	ClinGen TOPMed gnomAD
rs772967508 CA8133398	412	A>T		No	ClinGen ExAC gnomAD
rs879221481 CA283341752	414	T>I		No	ClinGen TOPMed gnomAD
rs879221481 CA396474999	414	T>N		No	ClinGen TOPMed gnomAD
CA396475003 rs1438154375	415	R>Q		No	ClinGen gnomAD
CA396475017 rs1187048520	417	T>M		No	ClinGen TOPMed
rs753353693 CA8133401	420	A>V		No	ClinGen ExAC TOPMed gnomAD
rs375090646 CA8133403	421	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs1268233174 CA396475044	422	D>N		No	ClinGen gnomAD
CA396475109 rs1275351896	431	E>*		No	ClinGen gnomAD
rs1049040611 CA283341783	431	E>D		No	ClinGen gnomAD
CA8133405 rs758833717	432	D>G		No	ClinGen ExAC gnomAD
rs1340758447 CA396475149	436	E>D		No	ClinGen TOPMed
rs1423358966 CA396475146	436	E>G		No	ClinGen gnomAD
CA396475155 rs1475705740	437	S>T		No	ClinGen gnomAD

1 associated diseases with Q9UN37

[MIM: 619273]: CIMDAG syndrome (CIMDAG)

An autosomal dominant syndrome characterized by global developmental delay, severely impaired intellectual development, poor or absent speech, microcephaly, growth retardation, poor motor skills with inability to walk, hypotonia and spasticity, and cataracts. Cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination are apparent on brain imaging. Affected individuals show hematologic abnormalities mostly consistent with congenital dyserythropoietic anemia. {ECO:0000269|PubMed:33186543, ECO:0000269|PubMed:33186545, ECO:0000269|PubMed:33460484}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Without disease ID

An autosomal dominant syndrome characterized by global developmental delay, severely impaired intellectual development, poor or absent speech, microcephaly, growth retardation, poor motor skills with inability to walk, hypotonia and spasticity, and cataracts. Cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination are apparent on brain imaging. Affected individuals show hematologic abnormalities mostly consistent with congenital dyserythropoietic anemia. {ECO:0000269|PubMed:33186543, ECO:0000269|PubMed:33186545, ECO:0000269|PubMed:33460484}. Note=The disease may be caused by variants affecting the gene represented in this entry.

7 regional properties for Q9UN37

Type	Name	Position	InterPro Accession
domain	AAA+ ATPase domain	159 - 295	IPR003593
domain	ATPase, AAA-type, core	163 - 293	IPR003959
conserved_site	ATPase, AAA-type, conserved site	265 - 284	IPR003960
domain	MIT domain	2 - 80	IPR007330
domain	Spastin/Vps4, C-terminal	374 - 434	IPR015415
domain	AAA ATPase, AAA+ lid domain	316 - 350	IPR041569
domain	Vacuolar protein sorting-associated protein 4, MIT domain	4 - 79	IPR045253

Functions

		Description
EC Number	3.6.4.6	Acting on ATP; involved in cellular and subcellular movement
Subcellular Localization	Late endosome membrane ; Peripheral membrane protein Midbody Cytoplasm, cytoskeleton, spindle	Membrane-associated in the prevacuolar endosomal compartment Localizes to the midbody of dividing cells, interaction with ZFYVE19/ANCHR mediates retention at midbody (PubMed:24814515) Localized in two distinct rings on either side of the Flemming body
PANTHER Family	PTHR23074	AAA DOMAIN-CONTAINING
PANTHER Subfamily	PTHR23074:SF177	VACUOLAR PROTEIN SORTING-ASSOCIATED PROTEIN 4A
PANTHER Protein Class	cytoskeletal protein non-motor microtubule binding protein
PANTHER Pathway Category	No pathway information available

17 GO annotations of cellular component

Name	Definition
centrosome	A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
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.
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.
endosome	A vacuole to which materials ingested by endocytosis are delivered.
endosome membrane	The lipid bilayer surrounding an endosome.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
Flemming body	A cell part that is the central region of the midbody characterized by a gap in alpha-tubulin staining. It is a dense structure of antiparallel microtubules from the central spindle in the middle of the intercellular bridge.
late endosome	A prelysosomal endocytic organelle differentiated from early endosomes by lower lumenal pH and different protein composition. Late endosomes are more spherical than early endosomes and are mostly juxtanuclear, being concentrated near the microtubule organizing center.
late endosome membrane	The lipid bilayer surrounding a late endosome.
lysosome	A small lytic vacuole that has cell cycle-independent morphology found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions.
midbody	A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis.
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.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
spindle pole	Either of the ends of a spindle, where spindle microtubules are organized; usually contains a microtubule organizing center and accessory molecules, spindle microtubules and astral microtubules.
vacuolar membrane	The lipid bilayer surrounding the vacuole and separating its contents from the cytoplasm of the cell.

6 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
ATP hydrolysis activity	Catalysis of the reaction: ATP + H2O = ADP + H+ phosphate. ATP hydrolysis is used in some reactions as an energy source, for example to catalyze a reaction or drive transport against a concentration gradient.
protein C-terminus binding	Binding to a protein C-terminus, the end of a peptide chain at which the 1-carboxyl function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
protein disaggregase activity	An ATP-dependent molecular chaperone activity that mediates the solubilization of ordered protein aggregates.
protein domain specific binding	Binding to a specific domain of a protein.
protein-containing complex binding	Binding to a macromolecular complex.

34 GO annotations of biological process

Name	Definition
abscission	The controlled shedding of a body part.
actomyosin contractile ring contraction	The process of an actomyosin ring getting smaller in diameter, in the context of cytokinesis that takes place as part of a cell cycle.
cell division	The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.
cytoskeleton-dependent cytokinesis	A cytokinesis that involves the function of a set of proteins that are part of the microfilament or microtubule cytoskeleton.
endosomal transport	The directed movement of substances mediated by an endosome, a membrane-bounded organelle that carries materials enclosed in the lumen or located in the endosomal membrane.
endosomal vesicle fusion	The homotypic fusion of endocytic vesicles to form or add to an early endosome.
ESCRT complex disassembly	The disaggregation of an ESCRT complex into its constituent components.
ESCRT III complex disassembly	The disaggregation of an ESCRT III complex into its constituent components.
intracellular cholesterol transport	The directed movement of cholesterol, cholest-5-en-3-beta-ol, within cells.
late endosomal microautophagy	The autophagy process by which cytosolic proteins targeted for degradation are tagged with a chaperone and are directly transferred into and degraded in a late endosomal compartment.
macroautophagy	The major inducible pathway for the general turnover of cytoplasmic constituents in eukaryotic cells, it is also responsible for the degradation of active cytoplasmic enzymes and organelles during nutrient starvation. Macroautophagy involves the formation of double-membrane-bounded autophagosomes which enclose the cytoplasmic constituent targeted for degradation in a membrane-bounded structure. Autophagosomes then fuse with a lysosome (or vacuole) releasing single-membrane-bounded autophagic bodies that are then degraded within the lysosome (or vacuole). Some types of macroautophagy, e.g. pexophagy, mitophagy, involve selective targeting of the targets to be degraded.
midbody abscission	The process by which the midbody, the cytoplasmic bridge that connects the two prospective daughter cells, is severed at the end of mitotic cytokinesis, resulting in two separate daughter cells.
mitotic cytokinesis checkpoint signaling	A signaling process that contributes to a mitotic cell cycle checkpoint that detects a defect in cytokinesis and prevents further rounds of nuclear division until cytokinesis is completed.
mitotic metaphase plate congression	The cell cycle process in which chromosomes are aligned at the metaphase plate, a plane halfway between the poles of the mitotic spindle, during mitosis.
mitotic nuclear membrane reassembly	The mitotic cell cycle process involving ESCRTIII that results in reformation of the nuclear envelope after mitotic nuclear division. In organisms undergoing closed mitosis this involves resealing or 'repair' of the nuclear envelope in the nuclear bridge.
multivesicular body assembly	The aggregation, arrangement and bonding together of a set of components to form a multivesicular body, a type of late endosome in which regions of the limiting endosomal membrane invaginate to form internal vesicles; membrane proteins that enter the internal vesicles are sequestered from the cytoplasm.
negative regulation of cytokinesis	Any process that stops, prevents, or reduces the frequency, rate or extent of the division of the cytoplasm of a cell, and its separation into two daughter cells.
nuclear envelope organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the nuclear envelope.
nuclear membrane reassembly	The reformation of the nuclear membranes following their breakdown in the context of a normal process.
nucleus organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the nucleus.
positive regulation of exosomal secretion	Any process that activates or increases the frequency, rate or extent of exosomal secretion.
positive regulation of viral budding via host ESCRT complex	Any process that activates or increases the frequency, rate or extent of viral budding via host ESCRT complex.
protein targeting to lysosome	The process of directing proteins towards the lysosome using signals contained within the protein.
regulation of protein localization	Any process that modulates the frequency, rate or extent of any process in which a protein is transported to, or maintained in, a specific location.
regulation of protein localization to plasma membrane	Any process that modulates the frequency, rate or extent of protein localization to plasma membrane.
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	The chemical reactions and pathways resulting in the breakdown of a protein or peptide covalently tagged with ubiquitin, via the multivesicular body (MVB) sorting pathway; ubiquitin-tagged proteins are sorted into MVBs, and delivered to a lysosome/vacuole for degradation.
ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	The chemical reactions and pathways resulting in the breakdown of a protein or peptide, via the multivesicular body (MVB) sorting pathway; proteins are sorted into MVBs, and delivered to a lysosome/vacuole for degradation. This process is independent of ubiquitination.
vacuole organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a vacuole.
vesicle budding from membrane	The evagination of a membrane, resulting in formation of a vesicle.
vesicle uncoating	A protein depolymerization process that results in the disassembly of vesicle coat proteins.
vesicle-mediated transport	A cellular transport process in which transported substances are moved in membrane-bounded vesicles; transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. The process begins with a step that directs a substance to the forming vesicle, and includes vesicle budding and coating. Vesicles are then targeted to, and fuse with, an acceptor membrane.
viral budding from plasma membrane	A viral budding that starts with formation of a membrane curvature in the host plasma membrane.
viral budding via host ESCRT complex	Viral budding which uses a host ESCRT protein complex, or complexes, to mediate the budding process.
viral release from host cell	The dissemination of mature viral particles from the host cell, e.g. by cell lysis or the budding of virus particles from the cell membrane.

13 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P52917	VPS4	Vacuolar protein sorting-associated protein 4	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
Q0VD48	VPS4B	Vacuolar protein sorting-associated protein 4B	Bos taurus (Bovine)	SS
O75351	VPS4B	Vacuolar protein sorting-associated protein 4B	Homo sapiens (Human)	PR
O75449	KATNA1	Katanin p60 ATPase-containing subunit A1	Homo sapiens (Human)	PR
Q9UBP0	SPAST	Spastin	Homo sapiens (Human)	PR
A6NCM1	IQCA1L	IQ and AAA domain-containing protein 1-like	Homo sapiens (Human)	PR
Q86XH1	IQCA1	Dynein regulatory complex protein 11	Homo sapiens (Human)	PR
Q6PIW4	FIGNL1	Fidgetin-like protein 1	Homo sapiens (Human)	PR
P46467	Vps4b	Vacuolar protein sorting-associated protein 4B	Mus musculus (Mouse)	PR
Q8VEJ9	Vps4a	Vacuolar protein sorting-associated protein 4A	Mus musculus (Mouse)	PR
Q793F9	Vps4a	Vacuolar protein sorting-associated protein 4A	Rattus norvegicus (Rat)	PR
D0FH76	VPS4	Vacuolar protein sorting-associated protein 4	Bombyx mori (Silk moth)	SS
Q9ZNT0	SKD1	Protein SUPPRESSOR OF K(+) TRANSPORT GROWTH DEFECT 1	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MTTSTLQKAI	DLVTKATEED	KAKNYEEALR	LYQHAVEYFL	HAIKYEAHSD	KAKESIRAKC
70	80	90	100	110	120
VQYLDRAEKL	KDYLRSKEKH	GKKPVKENQS	EGKGSDSDSE	GDNPEKKKLQ	EQLMGAVVME
130	140	150	160	170	180
KPNIRWNDVA	GLEGAKEALK	EAVILPIKFP	HLFTGKRTPW	RGILLFGPPG	TGKSYLAKAV
190	200	210	220	230	240
ATEANNSTFF	SVSSSDLMSK	WLGESEKLVK	NLFELARQHK	PSIIFIDEVD	SLCGSRNENE
250	260	270	280	290	300
SEAARRIKTE	FLVQMQGVGN	NNDGTLVLGA	TNIPWVLDSA	IRRRFEKRIY	IPLPEEAARA
310	320	330	340	350	360
QMFRLHLGST	PHNLTDANIH	ELARKTEGYS	GADISIIVRD	SLMQPVRKVQ	SATHFKKVCG
370	380	390	400	410	420
PSRTNPSMMI	DDLLTPCSPG	DPGAMEMTWM	DVPGDKLLEP	VVCMSDMLRS	LATTRPTVNA
430
DDLLKVKKFS	EDFGQES