TM6SF1

Chr 15

transmembrane 6 superfamily member 1

NCBI Gene: 53346 ENSG00000136404 UniProt: Q9BZW5 OMIM: 606562

This protein may function as a sterol isomerase and is predicted to be located in the lysosomal membrane. The gene shows no evidence of constraint against loss-of-function variants (pLI near 0, LOEUF >1), and no established disease associations have been reported for TM6SF1 mutations in humans.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be located in membrane. Predicted to be active in lysosomal membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.40

OE 0.67 (0.44–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.00Z-score

OE missense 0.80 (0.70–0.91)

161 obs / 200.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.44–1.05)

0≤0.351.4

Missense OE?0.80 (0.70–0.91)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 14 / 20.9Missense obs/exp: 161 / 200.8Syn Z: -0.25

Background carrier burden — how many people carry a rare variant somewhere in TM6SF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

427 rare PASS variants

Rare truncating (LoF)

1 in 1,300

97 rare PASS variants

Rare synonymous (reference)

1 in 190

174 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TM6SF1. 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 1,300
South Asian	~43k	1 in 170	1 in 960
Remaining (unassigned)	~30k	1 in 170	1 in 1,700
European (Finnish)	~27k	1 in 340	≈ 1 in 6,700
Admixed American	~22k	1 in 230	1 in 880
African / African American	~21k	1 in 140	1 in 950
East Asian	~20k	1 in 160	1 in 2,800
Ashkenazi Jewish	~13k	1 in 540	≈ 1 in 4,000
Middle Eastern	~2,884	1 in 190	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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓