TSPAN7

Summary

TSPAN7 (tetraspanin 7, HGNC:11854) is a protein-coding gene on chromosome Xp11.4, encoding Tetraspanin-7 (P41732). May be involved in cell proliferation and cell motility.

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. This gene is associated with X-linked cognitive disability and neuropsychiatric diseases such as Huntington’s chorea, fragile X syndrome and myotonic dystrophy.

Source: NCBI Gene 7102 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, X-linked 58 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 151 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 10
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004615

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11854
Approved symbol	TSPAN7
Name	tetraspanin 7
Location	Xp11.4
Locus type	gene with protein product
Status	Approved
Aliases	DXS1692E, TALLA-1, A15, CD231
Ensembl gene	ENSG00000156298
Ensembl biotype	protein_coding
OMIM	300096
Entrez	7102

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000286824, ENST00000378482, ENST00000419600, ENST00000471410, ENST00000475216, ENST00000480976, ENST00000488893, ENST00000494037, ENST00000899436, ENST00000899437, ENST00000899438, ENST00000899439, ENST00000899440, ENST00000899441, ENST00000899442, ENST00000922419, ENST00000949526

RefSeq mRNA: 1 — MANE Select: NM_004615 NM_004615

CCDS: CCDS14248

Canonical transcript exons

ENST00000378482 — 8 exons

Exon	Start	End
ENSE00001851361	38687939	38688918
ENSE00003468331	38671376	38671450
ENSE00003495853	38674221	38674316
ENSE00003499086	38681204	38681287
ENSE00003543305	38687599	38687674
ENSE00003557911	38666121	38666309
ENSE00003662647	38561542	38561627
ENSE00003694102	38675705	38675860

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.67.

FANTOM5 (CAGE): breadth broad, TPM avg 34.4495 / max 1567.9343, expressed in 764 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195938	29.6855	722
195937	4.1061	524
195943	0.2250	52
195944	0.2052	43
195940	0.1303	14
195942	0.0694	34
195941	0.0154	6
195939	0.0127	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caudate nucleus	UBERON:0001873	99.67	gold quality
nucleus accumbens	UBERON:0001882	99.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.64	gold quality
prefrontal cortex	UBERON:0000451	99.63	gold quality
putamen	UBERON:0001874	99.61	gold quality
right frontal lobe	UBERON:0002810	99.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.56	gold quality
cerebellar cortex	UBERON:0002129	99.55	gold quality
cerebellar hemisphere	UBERON:0002245	99.55	gold quality
frontal pole	UBERON:0002795	99.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.54	gold quality
frontal cortex	UBERON:0001870	99.53	gold quality
cerebellum	UBERON:0002037	99.53	gold quality
frontal lobe	UBERON:0016525	99.53	gold quality
postcentral gyrus	UBERON:0002581	99.51	gold quality
paraflocculus	UBERON:0005351	99.51	gold quality
cingulate cortex	UBERON:0003027	99.45	gold quality
superior frontal gyrus	UBERON:0002661	99.44	gold quality
anterior cingulate cortex	UBERON:0009835	99.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.44	gold quality
parietal lobe	UBERON:0001872	99.43	gold quality
amygdala	UBERON:0001876	99.43	gold quality
neocortex	UBERON:0001950	99.39	gold quality
cerebellar vermis	UBERON:0004720	99.38	gold quality
Ammon’s horn	UBERON:0001954	99.35	gold quality
telencephalon	UBERON:0001893	99.27	gold quality
cerebral cortex	UBERON:0000956	99.26	gold quality
temporal lobe	UBERON:0001871	99.07	gold quality
middle frontal gyrus	UBERON:0002702	99.06	gold quality
hypothalamus	UBERON:0001898	99.05	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	3403.23
E-HCAD-11	yes	484.50
E-MTAB-10287	yes	79.56
E-MTAB-10553	yes	59.65
E-HCAD-1	yes	44.12
E-HCAD-35	yes	42.75
E-GEOD-134144	yes	41.93
E-GEOD-84465	yes	28.10
E-MTAB-5061	yes	25.74
E-MTAB-8410	yes	24.03
E-GEOD-81547	yes	20.22
E-HCAD-9	yes	17.83
E-CURD-112	yes	10.70
E-MTAB-9067	yes	7.96
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, FOXO3

miRNA regulators (miRDB)

71 targeting TSPAN7, 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-513B-5P	99.99	69.96	2150
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3185	99.99	68.12	1959
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-4796-5P	99.34	70.06	810

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 17)

• The role of TMSF2 in mental retardation (PMID:14735593)
• coding mutations in TSPAN7 are not associated with our cohort of autism patients (PMID:19339915)
• associated with spermatozoa (PMID:19535787)
• The interaction of VP26 with tetraspanin-7 plays an essential role in normal HSV-1 replication. (PMID:20630051)
• Studies indicate that The thymus leukemia (TL) antigen and CD8alphaalpha are interacting surface molecules that are expressed at the frontline of the mucosal immune system. (PMID:20850477)
• TM4SF2 was identified as a putative antigenic target in Wegener’s granulomatosis (PMID:20951001)
• Loss of TSPAN7 is associated with metastasis in clear-cell renal cell carcinoma. (PMID:22213152)
• This study identified that TSPAN7 as a key molecule for the functional maturation of dendritic spines via PICK1 and ampa receptor trafficking. (PMID:22445342)
• Elevated TSPAN7 may be associated with better outcomes for multiple myeloma patients. (PMID:25637218)
• These results disclosed a previously uncharacterized role of TSPAN7 in the regulation of the expression and functional activity of DRD2 by postendocytic trafficking. (PMID:28223337)
• The role of TSPAN7 in immune system response to HIV-1 is reviewed. TSPAN7 appears to be a positive regulator of actin nucleation and stabilization, through the ARP2/3 complex. By doing so, TSPAN7 limits HIV-1 endocytosis and maintains viral particles on actin-rich dendrites for an efficient transfer toward T lymphocytes. (PMID:28620031)
• Dendritic Cell Maturation Regulates TSPAN7 Function in HIV-1 Transfer to CD4(+) T Lymphocytes. (PMID:32181159)
• Autoimmunity to tetraspanin-7 in type 1 diabetes. (PMID:32314012)
• Tetraspanin 7 and its closest paralog tetraspanin 6: membrane organizers with key functions in brain development, viral infection, innate immunity, diabetes and cancer. (PMID:32468130)
• Loss of tetraspanin-7 expression reduces pancreatic beta-cell exocytosis Ca[2+] sensitivity but has limited effect on systemic metabolism. (PMID:36264270)
• New insights into the role of tetraspanin 6, 7, and 8 in physiology and pathology. (PMID:39031113)
• Unveiling the unique role of TSPAN7 across tumors: a pan-cancer study incorporating retrospective clinical research and bioinformatic analysis. (PMID:39175035)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspan7	ENSDARG00000008407
mus_musculus	Tspan7	ENSMUSG00000058254
rattus_norvegicus	Tspan7	ENSRNOG00000003229
rattus_norvegicus	LOC102551255	ENSRNOG00000049257

Paralogs (32): TSPAN6 (ENSG00000000003), CD9 (ENSG00000010278), TSPAN9 (ENSG00000011105), TSPAN17 (ENSG00000048140), TSPAN32 (ENSG00000064201), CD82 (ENSG00000085117), TSPAN15 (ENSG00000099282), CD37 (ENSG00000104894), UPK1A (ENSG00000105668), TSPAN12 (ENSG00000106025), TSPAN13 (ENSG00000106537), TSPAN14 (ENSG00000108219), CD81 (ENSG00000110651), TSPAN11 (ENSG00000110900), PRPH2 (ENSG00000112619), UPK1B (ENSG00000114638), TSPAN1 (ENSG00000117472), TSPAN8 (ENSG00000127324), TSPAN16 (ENSG00000130167), TSPAN2 (ENSG00000134198), CD63 (ENSG00000135404), TSPAN31 (ENSG00000135452), TSPAN3 (ENSG00000140391), CD53 (ENSG00000143119), ROM1 (ENSG00000149489), TSPAN18 (ENSG00000157570), TSPAN33 (ENSG00000158457), TSPAN5 (ENSG00000168785), CD151 (ENSG00000177697), TSPAN10 (ENSG00000182612), TSPAN4 (ENSG00000214063), TSPAN19 (ENSG00000231738)

Protein

Protein identifiers

Tetraspanin-7 — P41732 (reviewed: P41732)

Alternative names: Cell surface glycoprotein A15, Membrane component chromosome X surface marker 1, T-cell acute lymphoblastic leukemia-associated antigen 1, Transmembrane 4 superfamily member 2

All UniProt accessions (5): P41732, B4DDG0, F8WC96, F8WF47, F8WF53

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in cell proliferation and cell motility.

Subunit / interactions. (Microbial infection) Interacts with herpes simplex virus 1 (HHV-1) UL35.

Subcellular location. Membrane.

Tissue specificity. Not solely expressed in T-cells. Expressed in acute myelocytic leukemia cells of some patients.

Disease relevance. Intellectual developmental disorder, X-linked 58 (XLID58) [MIM:300210] 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 intellectual disability, while syndromic intellectual disability presents with associated physical, neurological and/or psychiatric manifestations. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the tetraspanin (TM4SF) family.

RefSeq proteins (1): NP_004606* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000301	Tetraspanin_animals	Family
IPR008952	Tetraspanin_EC2_sf	Homologous_superfamily
IPR018499	Tetraspanin/Peripherin	Family
IPR018503	Tetraspanin_CS	Conserved_site
IPR048232	TSN6/7_LEL	Domain

Pfam: PF00335

UniProt features (19 total): topological domain 5, glycosylation site 5, transmembrane region 4, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41732-F1	89.18	0.76

Functional residue map

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

Glycosylation sites (5): 54, 155, 158, 177, 188

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors

MSigDB gene sets: 276 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, ATF_B, VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_169, RORA1_01, MODULE_64, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, CREBP1_Q2, TGACCTY_ERR1_Q2, AP2_Q3, COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP, AAAYRNCTG_UNKNOWN, LA_MEN1_TARGETS, RODWELL_AGING_KIDNEY_NO_BLOOD_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Hemostasis	1
Trafficking of AMPA receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPAN7	PICK1	Q9NRD5	749
TSPAN7	HSPA5	P11021	662
TSPAN7	TSPAN32	Q96QS1	582
TSPAN7	OPHN1	O60890	533
TSPAN7	ITGB1	P05556	526
TSPAN7	IGSF3	O75054	524
TSPAN7	CD81	P18582	509
TSPAN7	IL1RAPL1	Q9NZN1	505
TSPAN7	ATF6	P18850	485
TSPAN7	SDCBP2	Q9H190	471
TSPAN7	SLC30A10	Q6XR72	470
TSPAN7	SDCBP	O00560	470
TSPAN7	SLC30A8	Q8IWU4	446
TSPAN7	GDI1	P31150	441
TSPAN7	ARHGEF6	Q15052	437

IntAct

35 interactions, top by confidence:

A	B	Type	Score
TSPAN7	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
TSPAN7	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
TSPAN7	GPR152	psi-mi:“MI:0915”(physical association)	0.560
TSPAN7	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
TSPAN7	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	CCR2	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	CCR9	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	DRD2	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	BUD31	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	GNRHR	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	GPR35	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	HTR4	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	CHRM4	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	OXTR	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	SMO	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	CACNA1A	psi-mi:“MI:0915”(physical association)	0.370
CREB3	TSPAN7	psi-mi:“MI:0915”(physical association)	0.370
PLD5	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
TSC22D3	VPS37C	psi-mi:“MI:0914”(association)	0.350
RBL1	TSPAN7	psi-mi:“MI:0915”(physical association)	0.000
	TSPAN7	psi-mi:“MI:0915”(physical association)	0.000
TSPAN7	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
TSPAN7	FAM209A	psi-mi:“MI:0915”(physical association)	0.000
TSPAN7	GPR152	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): TSPAN7 (Two-hybrid), TSPAN7 (Affinity Capture-MS), TSPAN7 (Two-hybrid), TSPAN7 (Affinity Capture-MS), TSPAN7 (Two-hybrid), TSPAN7 (Two-hybrid), GPR152 (Two-hybrid), LHFPL5 (Two-hybrid), TSPAN7 (Two-hybrid), TSPAN7 (Two-hybrid), TSPAN7 (Two-hybrid), TSPAN7 (Two-hybrid), TSPAN7 (Two-hybrid), TSPAN7 (Two-hybrid), TSPAN7 (Two-hybrid)

ESM2 similar proteins: O43657, O46101, O60635, O70352, O70401, O75508, P08962, P0C672, P19331, P19397, P27591, P27701, P28648, P34285, P40237, P41731, P41732, P91799, Q11098, Q22495, Q24188, Q26499, Q28709, Q2KIS9, Q32KU6, Q3MHK4, Q3T0S3, Q4R3L1, Q4R7W6, Q55CV4, Q55CV5, Q55CV7, Q55CW7, Q58DM3, Q5RAS5, Q5RC27, Q5REK8, Q5WRN1, Q60771, Q61451

Diamond homologs: A1L157, B0BM39, B5X3I6, O14817, O35566, O43657, O60636, O70401, O75954, P08962, P19397, P21926, P24485, P27701, P30409, P30932, P40239, P40240, P40241, P41731, P41732, P48509, P61170, P61171, Q06AA5, Q0VC33, Q28709, Q2KIS9, Q32KU6, Q3ZBH3, Q568Y5, Q58CY8, Q58DM3, Q5RAP3, Q5RAS5, Q61451, Q62283, Q6DCQ3, Q7YQK9, Q7YQL0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TSPAN7	“down-regulates quantity”	DRD2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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
Class A/1 (Rhodopsin-like receptors)	8	29.7×	8e-09
GPCR ligand binding	8	25.7×	1e-08
Signaling by GPCR	8	16.0×	3e-07
GPCR downstream signalling	7	15.2×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
G protein-coupled receptor signaling pathway	7	9.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	60
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
11629	NM_004615.4(TSPAN7):c.652G>T (p.Gly218Ter)	Pathogenic
11631	NM_004615.4(TSPAN7):c.572_573del (p.Val191fs)	Pathogenic
1164055	NM_004615.4(TSPAN7):c.289del (p.Leu97fs)	Pathogenic
4813576	NM_004615.4(TSPAN7):c.492C>A (p.Tyr164Ter)	Pathogenic
688550	GRCh37/hg19 Xp11.4(chrX:38438500-38619112)x0	Pathogenic
3767244	NM_004615.4(TSPAN7):c.271-1G>T	Likely pathogenic

SpliceAI

1985 predictions. Top by Δscore:

Variant	Effect	Δscore
X:38561626:GG:G	donor_gain	1.0000
X:38561627:GG:G	donor_gain	1.0000
X:38561628:G:GG	donor_gain	1.0000
X:38666115:TTTCA:T	acceptor_loss	1.0000
X:38666116:TTCA:T	acceptor_loss	1.0000
X:38666116:TTCAG:T	acceptor_loss	1.0000
X:38666117:TCAG:T	acceptor_loss	1.0000
X:38666117:TCAGA:T	acceptor_loss	1.0000
X:38666118:CAG:C	acceptor_loss	1.0000
X:38666118:CAGAT:C	acceptor_loss	1.0000
X:38666119:A:C	acceptor_loss	1.0000
X:38671370:TTTCA:T	acceptor_loss	1.0000
X:38671371:TTCAG:T	acceptor_loss	1.0000
X:38671372:TCAGT:T	acceptor_loss	1.0000
X:38671373:CAGTA:C	acceptor_loss	1.0000
X:38671374:A:AG	acceptor_gain	1.0000
X:38671374:A:G	acceptor_loss	1.0000
X:38671375:G:GA	acceptor_gain	1.0000
X:38671375:G:GC	acceptor_gain	1.0000
X:38671375:GT:G	acceptor_gain	1.0000
X:38671375:GTA:G	acceptor_gain	1.0000
X:38671375:GTAT:G	acceptor_gain	1.0000
X:38671448:GAG:G	donor_gain	1.0000
X:38671451:G:GA	donor_loss	1.0000
X:38671451:GTGA:G	donor_loss	1.0000
X:38671452:T:A	donor_loss	1.0000
X:38671453:GAGTA:G	donor_loss	1.0000
X:38674217:A:AG	acceptor_gain	1.0000
X:38674218:T:G	acceptor_gain	1.0000
X:38674218:TAG:T	acceptor_loss	1.0000

AlphaMissense

1635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:38675740:G:C	W159C	1.000
X:38675740:G:T	W159C	1.000
X:38666127:G:A	G30R	0.999
X:38666127:G:C	G30R	0.999
X:38666127:G:T	G30W	0.999
X:38666128:G:A	G30E	0.999
X:38666148:G:A	G37R	0.999
X:38666148:G:C	G37R	0.999
X:38666149:G:A	G37E	0.999
X:38666224:T:A	L62H	0.999
X:38666235:G:C	G66R	0.999
X:38666236:G:A	G66D	0.999
X:38671413:T:C	L103P	0.999
X:38671419:C:A	A105D	0.999
X:38671421:G:C	G106R	0.999
X:38671422:G:A	G106D	0.999
X:38671431:G:A	G109E	0.999
X:38675738:T:A	W159R	0.999
X:38675738:T:C	W159R	0.999
X:38681208:G:A	C201Y	0.999
X:38681270:G:A	G222R	0.999
X:38681270:G:C	G222R	0.999
X:38681271:G:A	G222E	0.999
X:38687605:G:C	G230R	0.999
X:38666224:T:C	L62P	0.998
X:38666229:G:A	G64R	0.998
X:38666229:G:C	G64R	0.998
X:38666230:G:A	G64E	0.998
X:38666256:G:C	G73R	0.998
X:38666257:G:A	G73D	0.998

dbSNP variants (sampled 300 via entrez): RS1000057916 (X:38677452 G>C), RS1000193440 (X:38563765 A>G), RS1000220556 (X:38596952 TGAA>T), RS1000250687 (X:38579265 G>A), RS1000264204 (X:38573356 C>G), RS1000329420 (X:38622967 T>C), RS1000380862 (X:38612849 C>G), RS1000391119 (X:38564202 C>T), RS1000429400 (X:38590757 A>C), RS1000435295 (X:38673666 C>A), RS1000440974 (X:38633229 T>G), RS1000519118 (X:38603598 G>C), RS1000523755 (X:38593868 C>A), RS1000527334 (X:38660914 G>A), RS1000562479 (X:38667162 G>A,C)

Disease associations

OMIM: gene MIM:300096 | disease phenotypes: MIM:300210, MIM:309530

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked 58	Definitive	X-linked
non-syndromic X-linked intellectual disability	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
non-syndromic X-linked intellectual disability	Moderate	XL

Mondo (4): intellectual disability, X-linked 58 (MONDO:0010266), non-syndromic X-linked intellectual disability (MONDO:0019181), primary ovarian failure (MONDO:0005387), intellectual disability (MONDO:0001071)

Orphanet (3): X-linked non-syndromic intellectual disability (Orphanet:777), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000322	Short philtrum
HP:0000545	Myopia
HP:0000639	Nystagmus
HP:0000689	Dental malocclusion
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001419	X-linked recessive inheritance
HP:0001792	Small nail

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002407_379	White blood cell count	8.000000e-09

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C564566	Mental Retardation, X-Linked 58 (supp.)
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	7
sodium arsenite	increases expression, affects acetylation, affects methylation, decreases expression	4
Cadmium Chloride	increases abundance, increases expression	3
monomethylarsonous acid	affects acetylation, affects methylation, increases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Diethylhexyl Phthalate	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
lead acetate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	affects cotreatment, increases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	increases methylation	1
lead chloride	increases expression, affects cotreatment	1
nickel sulfate	decreases expression	1
cadmium sulfate	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
NSC 689534	increases expression, affects binding	1
(+)-JQ1 compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF