TM4SF1

Chr 3

transmembrane 4 L six family member 1

Also known as: H-L6, L6, M3S1, TAAL6

NCBI Gene: 4071 ENSG00000169908 UniProt: P30408 OMIM: 191155

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 antigen and is highly expressed in different carcinomas. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.07

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.002

Z-score 1.40

OE 0.54 (0.30–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.86–1.17)

115 obs / 114.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.54 (0.30–1.07)

0≤0.351.4

Missense OE?1.00 (0.86–1.17)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 6 / 11.0Missense obs/exp: 115 / 114.6Syn Z: 0.13

Background carrier burden — how many people carry a rare variant somewhere in TM4SF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

278 rare PASS variants

Rare truncating (LoF)

1 in 2,400

51 rare PASS variants

Rare synonymous (reference)

1 in 590

111 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TM4SF1. 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 220	1 in 3,900
South Asian	~43k	1 in 200	1 in 620
Remaining (unassigned)	~30k	1 in 230	1 in 2,200
European (Finnish)	~27k	1 in 1,700	1 in 4,400
Admixed American	~22k	1 in 240	1 in 1,200
African / African American	~21k	1 in 260	1 in 2,300
East Asian	~20k	1 in 370	1 in 1,700
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	1 in 140	none seen

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.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓