KLHL15

Summary

KLHL15 (kelch like family member 15, HGNC:29347) is a protein-coding gene on chromosome Xp22.11, encoding Kelch-like protein 15 (Q96M94). Substrate-specific adapter for CUL3 E3 ubiquitin-protein ligase complex.

This gene encodes a member of the kelch-like family of proteins that share a common domain structure consisting of an N-terminal broad-complex, tramtrack, bric-a-brac/poxvirus and zinc finger domain and C-terminal kelch repeat motifs. The encoded protein may be involved in protein ubiquitination and cytoskeletal organization.

Source: NCBI Gene 80311 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, X-linked 103 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 147 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_030624

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29347
Approved symbol	KLHL15
Name	kelch like family member 15
Location	Xp22.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1677
Ensembl gene	ENSG00000174010
Ensembl biotype	protein_coding
OMIM	300980
Entrez	80311

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000328046, ENST00000684871, ENST00000685367, ENST00000689334, ENST00000692681, ENST00000693269, ENST00000934049, ENST00000972024

RefSeq mRNA: 1 — MANE Select: NM_030624 NM_030624

CCDS: CCDS35217

Canonical transcript exons

ENST00000328046 — 4 exons

Exon	Start	End
ENSE00001198431	24024857	24025058
ENSE00001198437	24027140	24027186
ENSE00001321570	23983720	23989030
ENSE00001422972	24005989	24006700

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 95.09.

Top tissues by expression

248 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	95.09	gold quality
secondary oocyte	CL:0000655	92.40	gold quality
endothelial cell	CL:0000115	90.35	gold quality
corpus epididymis	UBERON:0004359	88.91	gold quality
oocyte	CL:0000023	88.62	gold quality
caput epididymis	UBERON:0004358	87.96	gold quality
cartilage tissue	UBERON:0002418	87.42	gold quality
tibia	UBERON:0000979	87.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.21	gold quality
adult organism	UBERON:0007023	86.19	gold quality
parietal pleura	UBERON:0002400	84.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.88	gold quality
cauda epididymis	UBERON:0004360	83.72	gold quality
bone marrow	UBERON:0002371	82.90	gold quality
tibialis anterior	UBERON:0001385	82.78	silver quality
mucosa of stomach	UBERON:0001199	82.73	gold quality
epithelial cell of pancreas	CL:0000083	82.45	silver quality
pigmented layer of retina	UBERON:0001782	81.98	gold quality
palpebral conjunctiva	UBERON:0001812	81.90	gold quality
Brodmann (1909) area 23	UBERON:0013554	81.84	gold quality
superficial temporal artery	UBERON:0001614	81.75	gold quality
middle temporal gyrus	UBERON:0002771	81.48	gold quality
deltoid	UBERON:0001476	81.15	gold quality
right adrenal gland cortex	UBERON:0035827	80.99	gold quality
islet of Langerhans	UBERON:0000006	80.84	gold quality
germinal epithelium of ovary	UBERON:0001304	80.23	gold quality
adrenal gland	UBERON:0002369	79.54	gold quality
oviduct epithelium	UBERON:0004804	79.22	gold quality
cortical plate	UBERON:0005343	79.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.18	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

301 targeting KLHL15, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Literature-anchored findings (GeneRIF, showing 4)

• KLHL15 (KIAA1677) binds Cul3 (PMID:14528312)
• KLHL15 can interact with the PP2A/B’beta heterotrimer, it only degrades B’beta, thus promoting exchange with other regulatory subunits. (PMID:23135275)
• Study identifies the KLHL15 as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. (PMID:27561354)
• Genetic vulnerabilities upon inhibition of DNA damage response. (PMID:34320214)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl15	ENSDARG00000001930
mus_musculus	Klhl15	ENSMUSG00000043929
rattus_norvegicus	Klhl15	ENSRNOG00000006515

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), KLHL5 (ENSG00000109790), BACH2 (ENSG00000112182), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), IVNS1ABP (ENSG00000116679), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch-like protein 15 — Q96M94 (reviewed: Q96M94)

All UniProt accessions (3): Q96M94, A0A8I5QJW5, V9HWF1

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter for CUL3 E3 ubiquitin-protein ligase complex. Acts as an adapter for CUL3 to target the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits. Acts as an adapter for CUL3 to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR).

Subunit / interactions. Homodimer. Dimerization does not affect PPP2R5B-binding, but is required for its proteasomal degradation. Interacts with CUL3. Directly interacts with PPP2R5B; this interaction leads to PPP2R5B proteasomal degradation. Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation. Interacts with PACMP micropeptide; interaction prevents ubiquitination and degradation of RBBP8/CtIP.

Subcellular location. Nucleus.

Disease relevance. Intellectual developmental disorder, X-linked 103 (XLID103) [MIM:300982] 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. The disease may be caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (1): NP_085127* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR006652	Kelch_1	Repeat
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR017096	BTB-kelch_protein	Family
IPR030597	BTB_POZ_KLHL15	Domain
IPR047030	KLHL15_BACK	Domain

Pfam: PF00651, PF01344, PF07707

UniProt features (19 total): mutagenesis site 10, repeat 5, domain 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96M94-F1	91.35	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (10):

Position	Phenotype
72–75	no effect on ppp2r5b-binding, nor on homodimerization, but loss of cul3 recruitment to the klhl15/ppp2r5b complex and im
132	decreased interaction with cul3, especially with the neddylated form of cul3.
136	decreased interaction with cul3, especially with the neddylated form of cul3.
318	impaired ppp2r5b-binding and proteasomal degradation.
335–337	impaired ppp2r5b-binding and proteasomal degradation.
371	impaired ppp2r5b-binding and proteasomal degradation.
386	decreased interaction with rbbp8 and complete loss of nuclear localization, found exclusively in the cytoplasm.
552	decreased interaction with rbbp8 and increased dna-end resection and homologous recombination frequency following dna do
32	impaired homodimerization and ppp2r5b proteasomal degradation. no effect on ppp2r5b-binding.
45	no effect on homodimerization, ppp2r5b-binding, nor on ppp2r5b proteasomal degradation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, MODULE_97, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_182, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS

GO Biological Process (4): ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), nuclear protein quality control by the ubiquitin-proteasome system (GO:0071630), negative regulation of double-strand break repair via homologous recombination (GO:2000042)

GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), Cul3-RING ubiquitin ligase complex (GO:0031463)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
protein quality control for misfolded or incompletely synthesized proteins	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
cellular response to misfolded protein	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
enzyme-substrate adaptor activity	1
binding	1
intracellular membrane-bounded organelle	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL15	RBBP8	Q99708	643
KLHL15	CUL3	Q13618	578
KLHL15	APOO	Q9BUR5	545
KLHL15	IL1RAPL1	Q9NZN1	488
KLHL15	LAS1L	Q9Y4W2	461
KLHL15	SHISA4	Q96DD7	458
KLHL15	LRRC40	Q9H9A6	452
KLHL15	ACOT9	Q9Y305	452
KLHL15	MNMIP1	A4FU49	449
KLHL15	ZBTB2	Q8N680	447
KLHL15	PCYT1B	Q9Y5K3	445
KLHL15	AAMDC	Q9H7C9	439
KLHL15	RLIM	Q9NVW2	438
KLHL15	LEPROTL1	O95214	422
KLHL15	NABP2	Q9BQ15	413

IntAct

130 interactions, top by confidence:

A	B	Type	Score
PABIR1	PPP2R1A	psi-mi:“MI:0914”(association)	0.880
PAAT	CLTC	psi-mi:“MI:0914”(association)	0.740
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
NUDCD3	KLHL15	psi-mi:“MI:0915”(physical association)	0.670
KLHL15	CACNB1	psi-mi:“MI:0914”(association)	0.640
CUL3	ENC1	psi-mi:“MI:0914”(association)	0.640
KLHL15	TOR1AIP1	psi-mi:“MI:0914”(association)	0.640
TNS2	YWHAB	psi-mi:“MI:2364”(proximity)	0.570
COPS5	KLHL18	psi-mi:“MI:0914”(association)	0.530
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
CER1	POTEF	psi-mi:“MI:0914”(association)	0.530
KPTN	EIF4G3	psi-mi:“MI:0914”(association)	0.530
C2orf68	PIR	psi-mi:“MI:0914”(association)	0.530
SAMD7	GAPDHS	psi-mi:“MI:0914”(association)	0.530
CAVIN1	ZZEF1	psi-mi:“MI:0914”(association)	0.530
TOR1AIP1	AIFM1	psi-mi:“MI:0914”(association)	0.530
POMC	AMD1	psi-mi:“MI:0914”(association)	0.530
ACP5	KLHL15	psi-mi:“MI:0914”(association)	0.530
FAM161B	KLHL15	psi-mi:“MI:0914”(association)	0.530

BioGRID (170): KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS)

ESM2 similar proteins: A2AAX3, A2AUC9, B3DIV9, D2HEW7, D3ZA50, D3ZZC3, E9QJ30, G3X9X1, O14682, O35709, O60662, Q08BL9, Q0D2A9, Q1LYM6, Q2TBA0, Q2WGJ6, Q3B7M1, Q4KLM4, Q53GT1, Q56A24, Q5EB39, Q5RCQ9, Q5RDY3, Q5RGB8, Q5U504, Q5U575, Q5ZJU2, Q66HD2, Q6DEL7, Q6DFF7, Q6GQU2, Q6NYM1, Q6Q7X9, Q6TFL4, Q6V595, Q8BRG6, Q8BWA5, Q8CA72, Q8IY47, Q8N4N3

Diamond homologs: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829, O88282, O88939, O93567, O95365, P24278, P41182, P41183, P52739, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2T9Z7, Q3B725, Q3B7N9, Q3SWU4

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
KLHL15	“down-regulates quantity by destabilization”	PPP2R5B	binding
KLHL15	“up-regulates activity”	“Cullin 3-RBX1-Skp1”	binding
KLHL15	“down-regulates quantity by destabilization”	RBBP8	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cargo recognition for clathrin-mediated endocytosis	7	8.3×	7e-03
Neddylation	10	5.4×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	5	36.9×	7e-05
protein neddylation	6	33.2×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

147 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	72
Likely benign	24
Benign	4

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
254657	NC_000023.10:g.24020361_24042839del	Pathogenic
254658	NM_030624.3(KLHL15):c.1179del (p.Tyr394fs)	Pathogenic
3340655	NM_030624.3(KLHL15):c.1105C>T (p.Arg369Cys)	Pathogenic
402161	NM_030624.3(KLHL15):c.1474G>A (p.Val492Ile)	Likely pathogenic

SpliceAI

956 predictions. Top by Δscore:

Variant	Effect	Δscore
X:23987979:TGTAA:T	donor_gain	1.0000
X:24005984:CTAA:C	donor_loss	1.0000
X:24005985:TAA:T	donor_loss	1.0000
X:24005986:AAC:A	donor_loss	1.0000
X:24005988:C:CG	donor_loss	1.0000
X:24005988:CCTT:C	donor_gain	1.0000
X:24006696:ATCAC:A	acceptor_gain	1.0000
X:24006697:TCAC:T	acceptor_gain	1.0000
X:24006698:CAC:C	acceptor_gain	1.0000
X:24006698:CACC:C	acceptor_gain	1.0000
X:24006699:AC:A	acceptor_gain	1.0000
X:24006700:CC:C	acceptor_gain	1.0000
X:24006701:C:CA	acceptor_loss	1.0000
X:24006701:C:CC	acceptor_gain	1.0000
X:24024852:CGTA:C	donor_loss	1.0000
X:24024853:GTA:G	donor_loss	1.0000
X:24024854:TAC:T	donor_loss	1.0000
X:24024855:A:AG	donor_loss	1.0000
X:23989029:ACCTA:A	acceptor_loss	0.9900
X:23989031:C:CC	acceptor_gain	0.9900
X:23989031:CTA:C	acceptor_loss	0.9900
X:23989032:T:C	acceptor_loss	0.9900
X:24006697:TCACC:T	acceptor_gain	0.9900
X:24006698:CACCT:C	acceptor_gain	0.9900
X:24006699:ACC:A	acceptor_gain	0.9900
X:24006700:CCTGG:C	acceptor_gain	0.9900
X:24006701:C:A	acceptor_gain	0.9900
X:24006701:C:T	acceptor_gain	0.9900
X:24006702:T:A	acceptor_loss	0.9900
X:24006702:T:G	acceptor_gain	0.9900

AlphaMissense

4028 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:23988026:C:A	W570C	1.000
X:23988026:C:G	W570C	1.000
X:23988027:C:G	W570S	1.000
X:23988028:A:G	W570R	1.000
X:23988028:A:T	W570R	1.000
X:23988048:A:G	F563S	1.000
X:23988054:A:G	L561P	1.000
X:23988090:C:A	G549V	1.000
X:23988090:C:T	G549D	1.000
X:23988091:C:G	G549R	1.000
X:23988093:C:A	G548V	1.000
X:23988093:C:T	G548E	1.000
X:23988094:C:G	G548R	1.000
X:23988094:C:T	G548R	1.000
X:23988170:C:A	W522C	1.000
X:23988170:C:G	W522C	1.000
X:23988171:C:G	W522S	1.000
X:23988172:A:G	W522R	1.000
X:23988172:A:T	W522R	1.000
X:23988193:A:C	Y515D	1.000
X:23988252:C:A	G495V	1.000
X:23988252:C:T	G495D	1.000
X:23988253:C:A	G495C	1.000
X:23988253:C:G	G495R	1.000
X:23988255:C:A	G494V	1.000
X:23988255:C:T	G494D	1.000
X:23988295:G:C	H481D	1.000
X:23988296:A:C	F480L	1.000
X:23988296:A:T	F480L	1.000
X:23988298:A:G	F480L	1.000

dbSNP variants (sampled 300 via entrez): RS1000070461 (X:24028683 T>C), RS1000086699 (X:24019122 T>G), RS1000221113 (X:24007984 A>G), RS1000266028 (X:23986822 T>C), RS1000299986 (X:24023049 A>T), RS1000326245 (X:23998251 G>A), RS1000356201 (X:24008952 T>C), RS1000373068 (X:24022811 C>A,G), RS1000401823 (X:24015555 G>C), RS1000443825 (X:23997429 C>T), RS1000568640 (X:24014165 G>A), RS1000628528 (X:24025929 C>G), RS1000705948 (X:24020851 G>A,T), RS1001121069 (X:23999898 A>G), RS1001138685 (X:24013955 G>A)

Disease associations

OMIM: gene MIM:300980 | disease phenotypes: MIM:300982

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked 103	Strong	X-linked

Mondo (1): intellectual disability, X-linked 103 (MONDO:0010508)

Orphanet (0):

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000054	Micropenis
HP:0000154	Wide mouth
HP:0000280	Coarse facial features
HP:0000463	Anteverted nares
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001419	X-linked recessive inheritance
HP:0002126	Polymicrogyria
HP:0004279	Short palm
HP:0006956	Lateral ventricle dilatation
HP:0008689	Bilateral cryptorchidism
HP:0031936	Delayed ability to walk

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004093_12	Prostate-specific antigen levels	1.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation	3
sodium arsenite	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
bisphenol A	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	affects expression	1
ferrous chloride	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Naled	affects expression	1
Phthalic Acids	decreases methylation	1
Potassium Chloride	decreases response to substance, increases expression	1
Silver	increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.