intellectual disability, X-linked 58

Summary

intellectual disability, X-linked 58 (MONDO:0010266) is a disease caused by TSPAN7 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TSPAN7 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 58
Mondo ID	MONDO:0010266
MeSH	C564566
OMIM	300210
DOID	DOID:0112024
UMLS	C1846174
MedGen	337526
GARD	0022670
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 58, X-linked recessive · intellectual disability, X-linked 58 · intellectual disability, X-linked type 58 · mental retardation, X-linked 58 · mental retardation, X-linked type 58 · MRX58 · non-syndromic X-linked intellectual disability caused by mutation in TSPAN7 · TSPAN7 non-syndromic X-linked intellectual disability

Data availability: 11 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › non-syndromic X-linked intellectual disability › intellectual disability, X-linked 58

Related subtypes (51): intellectual disability, X-linked 23, intellectual disability, X-linked 20, intellectual disability, X-linked 14, intellectual disability, X-linked 50, intellectual disability, X-linked 21, intellectual disability, X-linked 72, intellectual disability, X-linked 53, intellectual disability, X-linked 73, intellectual disability, X-linked 42, intellectual disability, X-linked 63, intellectual disability, X-linked, with or without seizures, ARX-related, intellectual disability, X-linked 2, intellectual disability, X-linked 81, intellectual disability, X-linked 46, intellectual disability, X-linked 77, intellectual disability, X-linked 45, intellectual disability, X-linked 84, intellectual disability, X-linked 82, intellectual disability, X-linked 30, intellectual disability, X-linked 91, intellectual disability, X-linked 93, chromosome Xp11.22 duplication syndrome, intellectual disability, X-linked 95, intellectual disability, X-linked 96, intellectual disability, X-linked 97, intellectual disability, X-linked 19, intellectual disability, X-linked 89, intellectual disability, X-linked 41, intellectual disability, X-linked 90, intellectual disability, X-linked 92, intellectual disability, X-linked 88, intellectual disability, X-linked 99, intellectual disability, X-linked 100, intellectual disability, X-linked 101, intellectual disability, X-linked 102, intellectual disability, X-linked 61, intellectual disability, X-linked 103, intellectual disability, X-linked 104, intellectual disability, X-linked 105, intellectual disability, X-linked 1, methylmalonic acidemia with homocystinuria, type cblX, FRAXE intellectual disability, intellectual disability, X-linked 9, intellectual developmental disorder, X-linked 108, intellectual disability, X-linked 106, intellectual disability, X-linked 107, intellectual developmental disorder, X-linked 110, intellectual developmental disorder, X-linked 111, intellectual developmental disorder, X-linked 112, intellectual developmental disorder, X-linked 113, intellectual developmental disorder, X-linked 114

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 not provided, 1 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
11629	NM_004615.4(TSPAN7):c.652G>T (p.Gly218Ter)	TSPAN7	Pathogenic	no assertion criteria provided
11631	NM_004615.4(TSPAN7):c.572_573del (p.Val191fs)	TSPAN7	Pathogenic	no assertion criteria provided
1164055	NM_004615.4(TSPAN7):c.289del (p.Leu97fs)	TSPAN7	Pathogenic	no assertion criteria provided
4813576	NM_004615.4(TSPAN7):c.492C>A (p.Tyr164Ter)	TSPAN7	Pathogenic	criteria provided, single submitter
3767244	NM_004615.4(TSPAN7):c.271-1G>T	TSPAN7	Likely pathogenic	criteria provided, single submitter
11630	NM_004615.4(TSPAN7):c.515C>A (p.Pro172His)	TSPAN7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683623	NM_004615.4(TSPAN7):c.248G>C (p.Gly83Ala)	TSPAN7	Uncertain significance	criteria provided, single submitter
4076278	NM_004615.4(TSPAN7):c.626T>C (p.Met209Thr)	TSPAN7	Uncertain significance	criteria provided, single submitter
130644	NM_004615.4(TSPAN7):c.237T>C (p.Ala79=)	TSPAN7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
95155	NM_004615.3(TSPAN7):c.-15_-13delCCG	TSPAN7	Benign	criteria provided, multiple submitters, no conflicts
1327408	GRCh37/hg19 Xp11.4(chrX:38480090-38634614)x3	TSPAN7	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TSPAN7	Definitive	X-linked	intellectual disability, X-linked 58	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSPAN7	Orphanet:777	X-linked non-syndromic intellectual disability

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TSPAN7	HGNC:11854	ENSG00000156298	P41732	Tetraspanin-7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSPAN7	Tetraspanin-7	May be involved in cell proliferation and cell motility.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSPAN7	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
dorsolateral prefrontal cortex	1
nucleus accumbens	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSPAN7	281	broad	marker	caudate nucleus, nucleus accumbens, dorsolateral prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSPAN7	1,218

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPAN7	P41732	89.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Trafficking of GluR2-containing AMPA receptors	1	671.8×	0.003	TSPAN7
Cell surface interactions at the vascular wall	1	95.2×	0.011	TSPAN7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSPAN7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TSPAN7

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TSPAN7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.