TSPAN7

Chr XXLR

tetraspanin 7

Also known as: A15, CCG-B7, CD231, DXS1692E, MRX58, MXS1, TALLA-1, TM4SF2

The protein is a cell surface glycoprotein that regulates neurite outgrowth and complexes with integrins to mediate signal transduction events controlling cell development, activation, growth and motility. Mutations cause X-linked intellectual developmental disorder with onset in early childhood. The gene shows moderate constraint against loss-of-function variants (pLI 0.75, LOEUF 0.54) and follows X-linked recessive inheritance.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 58MIM #300210
XLR
0
Active trials
7
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.54
LOEUF
LOF
Mechanism· G2P
Clinical SummaryTSPAN7
🧬
Gene-Disease Validity (ClinGen)
non-syndromic X-linked intellectual disability · XLModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.746
Z-score 2.45
OE 0.11 (0.040.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.91Z-score
OE missense 0.47 (0.370.60)
48 obs / 102.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.040.54)
00.351.4
Missense OE0.47 (0.370.60)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 1 / 8.9Missense obs/exp: 48 / 102.2Syn Z: -0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTSPAN7-related intellectual developmental disorderLOFXLR
DN
0.6358th %ile
GOF
0.6930th %ile
LOF
0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TSPAN7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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