TM4SF18

Chr 3

transmembrane 4 L six family member 18

Also known as: L6D

NCBI Gene: 116441 ENSG00000163762 UniProt: Q96CE8

Predicted to be active in membrane. [provided by Alliance of Genome Resources, Jul 2025]

Research

Predicted to be active in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.60

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.60LOEUF

pLI 0.000

Z-score 0.20

OE 0.93 (0.56–1.60)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.03 (0.89–1.21)

112 obs / 108.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.93 (0.56–1.60)

0≤0.351.4

Missense OE?1.03 (0.89–1.21)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 9 / 9.7Missense obs/exp: 112 / 108.3Syn Z: 0.19

Background carrier burden — how many people carry a rare variant somewhere in TM4SF18?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

275 rare PASS variants

Rare truncating (LoF)

1 in 1,800

40 rare PASS variants

Rare synonymous (reference)

1 in 230

95 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TM4SF18. 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 260	1 in 3,800
South Asian	~43k	1 in 180	1 in 680
Remaining (unassigned)	~30k	1 in 120	1 in 440
European (Finnish)	~27k	1 in 1,300	none seen
Admixed American	~22k	1 in 160	1 in 1,500
African / African American	~21k	1 in 130	1 in 3,100
East Asian	~20k	1 in 360	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 210	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): 4 of 5 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 5.? see exons ↓