TM4SF4

Chr 3

transmembrane 4 L six family member 4

Also known as: ILTMP, il-TMP

NCBI Gene: 7104 ENSG00000169903 UniProt: P48230 OMIM: 606567

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 that can regulate cell proliferation.[provided by RefSeq, Mar 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.62

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.62LOEUF

pLI 0.000

Z-score 0.02

OE 0.99 (0.62–1.62)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.18Z-score

OE missense 1.05 (0.90–1.22)

123 obs / 117.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.99 (0.62–1.62)

0≤0.351.4

Missense OE?1.05 (0.90–1.22)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 11 / 11.1Missense obs/exp: 123 / 117.5Syn Z: -1.11

Background carrier burden — how many people carry a rare variant somewhere in TM4SF4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

275 rare PASS variants

Rare truncating (LoF)

1 in 1,300

49 rare PASS variants

Rare synonymous (reference)

1 in 270

120 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TM4SF4. 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 170	1 in 1,200
South Asian	~43k	1 in 130	1 in 2,100
Remaining (unassigned)	~30k	1 in 150	1 in 1,100
European (Finnish)	~27k	1 in 1,100	≈ 1 in 13,000
Admixed American	~22k	1 in 310	1 in 500
African / African American	~21k	1 in 130	1 in 3,300
East Asian	~20k	1 in 140	1 in 830
Ashkenazi Jewish	~13k	1 in 930	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 360	≈ 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.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 5.? see exons ↓