TSPAN7

Chr X

tetraspanin 7

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

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. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.54
Clinical SummaryTSPAN7
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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.
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ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 31 VUS of 110 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.11 (0.040.54)
00.351.4
Missense OE?0.47 (0.370.60)
00.61.4
Synonymous OE?1.04
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

This gene — mechanism propensity

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

110 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS31
Likely Benign5
Benign1
Conflicting1
4
Pathogenic
1
Likely Pathogenic
31
VUS
5
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
0
0
4
Likely Pathogenic
1
0
0
0
1
VUS
3
23
5
0
31
Likely Benign
0
2
1
2
5
Benign
0
0
0
1
1
Conflicting
1
Total8256343

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

68 pathogenic / likely-pathogenic (of 107) ClinVar copy-number / structural variants overlap TSPAN7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

TSPAN7 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →