AiPD: Autoinhibited Protein Database

Q96M94

Gene name	KLHL15 (KIAA1677)
Protein name	Kelch-like protein 15
Names
Species	Homo sapiens (Human)
KEGG Pathway	hsa:80311
EC number
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

234-307 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

234-307 (Predicted disordered autoinhibitory region)

Target domain

Relief mechanism

Assay

cis-regPred

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

Autoinhibited structure

Activated structure

1 structures for Q96M94

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q96M94-F1	Predicted				AlphaFoldDB

156 variants for Q96M94

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1929447820 RCV001253263	73	H>D	Intellectual disability, X-linked 103 [ClinVar]	Yes	ClinVar dbSNP
RCV001028104 CA412596472 rs1602008532	131	E>K	Intellectual disability, X-linked 103 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV001329419 rs1929031015	237	K>M	Intellectual disability, X-linked 103 [ClinVar]	Yes	ClinVar dbSNP
CA412592860 rs1195344747 RCV001329420	274	R>C	Variant assessed as Somatic; 0.0 impact. Intellectual disability, X-linked 103 [NCI-TCGA, ClinVar]	Yes	ClinGen ClinVar NCI-TCGA TOPMed dbSNP gnomAD
RCV000241532 rs1929024034	394	Y>missing	Intellectual disability, X-linked 103 [ClinVar]	Yes	ClinVar dbSNP
TCGA novel	2	A>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10370601 rs767545496	4	D>V		No	ClinGen ExAC gnomAD
CA10370600 rs755056333	5	V>M		No	ClinGen ExAC gnomAD
CA10370596 rs776335640	14	D>N	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA327676098 rs938645004	16	S>T		No	ClinGen Ensembl
rs760646483 CA10370594	19	A>D		No	ClinGen ExAC gnomAD
CA10370593 rs775569198	29	L>S		No	ClinGen ExAC gnomAD
TCGA novel	33	V>A	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA412597142 rs1263976152	37	I>V		No	ClinGen gnomAD
CA412597089 rs1230288479	43	Q>H		No	ClinGen TOPMed
TCGA novel	56	F>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	61	T>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10370589 rs770527810	64	M>T		No	ClinGen ExAC
TCGA novel	81	G>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA327676093 rs1030467290	85	V>I		No	ClinGen Ensembl
TCGA novel	88	F>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10370583 rs755040003	91	Y>C		No	ClinGen ExAC TOPMed gnomAD
rs751659147 CA10370582	94	I>T		No	ClinGen ExAC gnomAD
rs1351096157 CA412596707	97	S>N		No	ClinGen TOPMed
rs145973085 CA10370579	101	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA327676092 rs1007541087	102	H>D		No	ClinGen gnomAD
TCGA novel	103	E>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA412596586 rs1437021505	114	I>T		No	ClinGen TOPMed
rs904799490 CA327676091	121	C>F		No	ClinGen Ensembl
CA10370577 rs760556757	124	L>F		No	ClinGen ExAC gnomAD
TCGA novel	124	L>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA412596383 rs1450213628	136	I>V		No	ClinGen gnomAD
CA412596269 rs762473984	143	F>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs188398180 CA10370570	144	G>S	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen 1000Genomes ExAC NCI-TCGA TOPMed gnomAD
rs1323704658 COSM1119406 CA412596254	145	V>I	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA10370568 rs748571216	148	E>K	Variant assessed as Somatic; 6.248e-05 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs769194076 CA412596077	155	D>E		No	ClinGen ExAC gnomAD
rs201181072 CA10370565	156	T>A		No	ClinGen ExAC TOPMed gnomAD
CA10370564 rs779952638	156	T>I		No	ClinGen ExAC TOPMed gnomAD
RCV000584841 rs758506007 CA10370563	158	L>M		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA412596031 rs1602008449	161	N>S		No	ClinGen Ensembl
rs752578893 CA10370559	173	S>F		No	ClinGen ExAC TOPMed gnomAD
CA412595918 rs1569267820	174	Y>C		No	ClinGen Ensembl
CA412595908 rs1459413363	175	L>V		No	ClinGen TOPMed gnomAD
rs1388918646 CA412595880	177	F>L		No	ClinGen TOPMed
rs985055222 CA327676088	178	E>*		No	ClinGen Ensembl
TCGA novel	178	E>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs985055222 RCV000520503 CA412595867	178	E>Q		No	ClinGen ClinVar Ensembl dbSNP
rs374408726 CA10370557	188	H>Y		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA412595693 rs1381741169	190	S>I		No	ClinGen TOPMed
CA412595687 rs1280171506	191	R>G		No	ClinGen gnomAD
rs1371021277 CA412595621	195	I>T		No	ClinGen TOPMed
CA10370554 rs762540184	195	I>V		No	ClinGen ExAC gnomAD
CA10370553 rs772839798	199	E>K		No	ClinGen ExAC gnomAD
TCGA novel	206	R>Q	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	217	T>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	218	I>M	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1406867861 CA412595321	218	I>V		No	ClinGen gnomAD
rs1210802281 CA412595296	221	N>S		No	ClinGen TOPMed
CA412595246 rs1336250388	228	T>S		No	ClinGen gnomAD
CA10370548 rs747404400	232	V>I		No	ClinGen ExAC gnomAD
rs1187981910 CA412593267	246	R>Q		No	ClinGen gnomAD
rs948817983 CA327674472	249	R>H		No	ClinGen TOPMed
CA10370533 rs749977545	251	E>D		No	ClinGen ExAC gnomAD
rs1486371427 CA412593209	251	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1369986909 COSM3939926 CA412593168	253	D>E	oesophagus [Cosmic]	No	ClinGen cosmic curated TOPMed
rs764850590 CA10370532	253	D>H		No	ClinGen ExAC gnomAD
rs1158367893 CA412593063	261	N>H		No	ClinGen TOPMed
rs1416583841 CA412593055	261	N>S		No	ClinGen gnomAD
rs756377419 CA10370530	263	H>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs756377419 CA412593036	263	H>Y		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1472166249 CA412592935	269	D>E		No	ClinGen gnomAD
rs1242218223 CA412592884	272	S>*		No	ClinGen gnomAD
rs1487106316 CA412592857	274	R>H		No	ClinGen gnomAD
rs1262129861 CA412592836	275	I>M		No	ClinGen gnomAD
rs1395684575 CA412592760	280	P>L		No	ClinGen TOPMed
rs1395684575 CA412592762	280	P>Q		No	ClinGen TOPMed
rs752673552 CA10370529	284	V>I		No	ClinGen 1000Genomes ExAC gnomAD
rs1337443452 CA412592684	285	F>L		No	ClinGen TOPMed
TCGA novel	292	S>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs761155111 CA10370528	293	M>V		No	ClinGen ExAC gnomAD
CA412592370 rs1355665750	304	P>S		No	ClinGen gnomAD
rs897844390 CA327674471	308	W>R		No	ClinGen Ensembl
rs1278925427 CA412592239	311	E>G		No	ClinGen gnomAD
CA10370526 rs772671945	324	I>V		No	ClinGen ExAC TOPMed gnomAD
rs774522260 CA10370524	325	V>I	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs771164671 CA10370523	326	N>H		No	ClinGen ExAC gnomAD
rs1419520930 CA412592037	326	N>S		No	ClinGen gnomAD
CA10370522 rs749454178	339	P>S		No	ClinGen ExAC gnomAD
rs911830115 CA327674467	341	G>D		No	ClinGen Ensembl
CA412591902 rs1471514413	346	S>A		No	ClinGen TOPMed
TCGA novel	355	R>E	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10370517 rs758413801	357	N>S		No	ClinGen ExAC gnomAD
CA10370516 rs750386599	358	S>C		No	ClinGen ExAC gnomAD
rs376144826 CA10370515	360	L>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs1259986349 CA412600252	361	Q>E		No	ClinGen gnomAD
TCGA novel CA412600245 rs1173796323	361	Q>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA ClinGen TOPMed
rs1220543432 CA412600228	363	A>T		No	ClinGen TOPMed gnomAD
TCGA novel	364	D>missing	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs756768743 CA10370514	364	D>G		No	ClinGen ExAC gnomAD
TCGA novel	373	A>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs760913970 CA10370511	377	I>V		No	ClinGen ExAC gnomAD
rs1233931213 CA412600091	381	I>V		No	ClinGen gnomAD
CA412600077 rs1408458279	383	A>T		No	ClinGen TOPMed
rs975790215 CA327674464	384	V>I	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
rs775002758 CA10370507	396	T>A		No	ClinGen ExAC
CA412599937 rs1481864772	403	N>S		No	ClinGen TOPMed
CA10370504 rs180839888	404	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1422731651 CA412599904	407	E>V		No	ClinGen gnomAD
TCGA novel	411	P>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs55868044 CA10370501	422	T>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA10370499 rs745742831	427	K>N		No	ClinGen ExAC gnomAD
CA412599758 rs1456463390	428	L>W		No	ClinGen gnomAD
rs755741023 CA10370494	445	V>L		No	ClinGen ExAC TOPMed gnomAD
CA412599648 rs755741023	445	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1013084607 CA327674458	451	E>G		No	ClinGen Ensembl
CA412599559 rs1445245390	457	R>Q		No	ClinGen gnomAD
CA10370492 rs767855623 COSM356256	466	N>H	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs958902418 CA327674456	466	N>S		No	ClinGen gnomAD
CA10370491 rs759992404 COSM1582905	467	C>Y	meninges [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA327674455 rs112761724	471	K>R		No	ClinGen Ensembl
CA412599446 rs1273637960	473	K>N		No	ClinGen TOPMed
CA412599382 rs1304968521	482	K>E		No	ClinGen TOPMed
rs767061464 CA10370489	483	M>V		No	ClinGen ExAC gnomAD
CA327674453 rs146866972 RCV001280745	487	N>S		No	ClinGen ClinVar ESP TOPMed dbSNP
rs894583289 CA327674452	488	G>S		No	ClinGen TOPMed
CA16609548 rs1060499748 RCV000454336	492	V>I		No	ClinGen ClinVar Ensembl dbSNP
CA10370484 rs776726742	496	V>D		No	ClinGen ExAC
rs1354803960 CA412599214	506	S>F		No	ClinGen gnomAD
CA327674449 rs202247762	510	P>S		No	ClinGen Ensembl
TCGA novel	513	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs778787688 CA10370481	514	V>L		No	ClinGen ExAC TOPMed gnomAD
rs1397237829 CA412599151	516	N>D		No	ClinGen gnomAD
CA412599148 rs1376402704	516	N>S		No	ClinGen gnomAD
rs1192792019 CA412599143	517	P>A		No	ClinGen TOPMed
rs749203211 CA10370479	518	E>Q		No	ClinGen ExAC gnomAD
CA10370478 rs777296343	529	P>L		No	ClinGen ExAC gnomAD
TCGA novel	538	T>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10370475 rs780766102	540	L>Q		No	ClinGen ExAC gnomAD
rs1601994465 CA412598862	542	K>N		No	ClinGen Ensembl
rs776669453 CA327674446	558	D>N		No	ClinGen Ensembl
rs1181456733 CA412598560	565	P>L		No	ClinGen gnomAD
CA10370473 rs201695883	565	P>T		No	ClinGen ESP ExAC gnomAD
rs978027257 CA327674445	566	D>E		No	ClinGen TOPMed
rs1349865266 CA412598535	567	E>G		No	ClinGen TOPMed
CA412598528 rs1265719492	568	N>D		No	ClinGen gnomAD
rs763508042 CA10370471 CA412598498	569	K>N		No	ClinGen ExAC TOPMed gnomAD
rs765298160 CA10370469	577	R>Q		No	ClinGen ExAC gnomAD
TCGA novel	581	K>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1400172518 CA412598215	591	H>D		No	ClinGen gnomAD
rs1399128377 CA412598183	595	Y>C		No	ClinGen gnomAD
CA412598168 rs1391242971	597	L>R		No	ClinGen gnomAD
rs1456358617 CA412598166	598	D>N		No	ClinGen gnomAD
CA10370463 rs770741932	601	R>S		No	ClinGen ExAC gnomAD
rs1340998246 CA412598122	602	R>C		No	ClinGen TOPMed
rs749182065 CA10370462	603	C>*		No	ClinGen ExAC gnomAD

1 associated diseases with Q96M94

[MIM: 300982]: Intellectual developmental disorder, X-linked 103 (XLID103)

A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:24817631, ECO:0000269|PubMed:25644381}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Without disease ID

A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:24817631, ECO:0000269|PubMed:25644381}. Note=The disease may be caused by variants affecting the gene represented in this entry.

6 regional properties for Q96M94

Type	Name	Position	InterPro Accession
domain	BTB/POZ domain	23 - 128	IPR000210
repeat	Kelch repeat type 1	328 - 426	IPR006652-1
repeat	Kelch repeat type 1	427 - 592	IPR006652-2
domain	BTB/Kelch-associated	133 - 237	IPR011705
domain	Kelch-like protein 15, BTB/POZ domain	1 - 137	IPR030597
domain	Kelch-like protein 15, BACK domain	128 - 235	IPR047030

Functions

		Description
EC Number
Subcellular Localization	Nucleus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

2 GO annotations of cellular component

Name	Definition
Cul3-RING ubiquitin ligase complex	A ubiquitin ligase complex in which a cullin from the Cul3 subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by a BTB-domain-containing protein.
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.

1 GO annotations of molecular function

Name	Definition
ubiquitin ligase-substrate adaptor activity	The binding activity of a molecule that brings together a ubiquitin ligase and its substrate. Usually mediated by F-box BTB/POZ domain proteins.

4 GO annotations of biological process

Name	Definition
negative regulation of double-strand break repair via homologous recombination	Any process that stops, prevents, or reduces the frequency, rate or extent of double-strand break repair via homologous recombination.
nuclear protein quality control by the ubiquitin-proteasome system	The chemical reactions and pathways resulting in the breakdown of misfolded proteins via a mechanism in which the proteins are transported to the nucleus for ubiquitination, and then targeted to proteasomes for degradation.
protein ubiquitination	The process in which one or more ubiquitin groups are added to a protein.
ubiquitin-dependent protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein.

1 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q5ZJU2	KLHL15	Kelch-like protein 15	Gallus gallus (Chicken)	PR

10	20	30	40	50	60
MAGDVEGFCS	SIHDTSVSAG	FRALYEEGLL	LDVTLVIEDH	QFQAHKALLA	TQSDYFRIMF
70	80	90	100	110	120
TADMRERDQD	KIHLKGLTAT	GFSHVLQFMY	YGTIELSMNT	VHEILQAAMY	VQLIEVVKFC
130	140	150	160	170	180
CSFLLAKICL	ENCAEIMRLL	DDFGVNIEGV	REKLDTFLLD	NFVPLMSRPD	FLSYLSFEKL
190	200	210	220	230	240
MSYLDNDHLS	RFPEIELYEA	VQSWLRHDRR	RWRHTDTIIQ	NIRFCLMTPT	SVFEKVKTSE
250	260	270	280	290	300
FYRYSRQLRY	EVDQALNYFQ	NVHQQPLLDM	KSSRIRSAKP	QTTVFRGMIG	HSMVNSKILL
310	320	330	340	350	360
LKKPRVWWEL	EGPQVPLRPD	CLAIVNNFVF	LLGGEELGPD	GEFHASSKVF	RYDPRQNSWL
370	380	390	400	410	420
QMADMSVPRS	EFAVGVIGKF	IYAVAGRTRD	ETFYSTERYD	ITNDKWEFVD	PYPVNKYGHE
430	440	450	460	470	480
GTVLNNKLFI	TGGITSSSTS	KQVCVFDPSK	EGTIEQRTRR	TQVVTNCWEN	KSKMNYARCF
490	500	510	520	530	540
HKMISYNGKL	YVFGGVCVIL	RASFESQGCP	STEVYNPETD	QWTILASMPI	GRSGHGVTVL
550	560	570	580	590	600
DKQIMVLGGL	CYNGHYSDSI	LTFDPDENKW	KEDEYPRMPC	KLDGLQVCNL	HFPDYVLDEV

RRCN