TSPAN3

Chr 15

tetraspanin 3

Also known as: TM4-A, TM4SF8, TSPAN-3

NCBI Gene: 10099 ENSG00000140391 UniProt: O60637

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. The use of alternate polyadenylation sites has been found for this gene. Multiple alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Dec 2009]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.060

Z-score 2.12

OE 0.34 (0.17–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.81Z-score

OE missense 0.56 (0.46–0.68)

73 obs / 131.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.17–0.77)

0≤0.351.4

Missense OE?0.56 (0.46–0.68)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 4 / 11.9Missense obs/exp: 73 / 131.2Syn Z: -0.42

Background carrier burden — how many people carry a rare variant somewhere in TSPAN3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 460

263 rare PASS variants

Rare truncating (LoF)

1 in 7,400

30 rare PASS variants

Rare synonymous (reference)

1 in 590

135 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TSPAN3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 480	1 in 7,000
South Asian	~43k	1 in 260	1 in 7,700
Remaining (unassigned)	~30k	1 in 320	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,100	≈ 1 in 12,000
Admixed American	~22k	1 in 280	≈ 1 in 22,000
African / African American	~21k	1 in 280	≈ 1 in 6,400
East Asian	~20k	1 in 1,200	none seen
Ashkenazi Jewish	~13k	1 in 1,400	≈ 1 in 5,400
Middle Eastern	~2,884	1 in 350	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.