TM7SF2

Chr 11

transmembrane 7 superfamily member 2

NCBI Gene: 7108 ENSG00000149809 UniProt: O76062

The protein catalyzes the reduction of lanosterol in the cholesterol biosynthesis pathway as a Delta14-sterol reductase in the endoplasmic reticulum. Mutations cause autosomal recessive lathosterolosis, a rare sterol metabolism disorder presenting in infancy with intellectual disability, cataracts, liver dysfunction, and distinctive facial features. The gene shows minimal constraint against loss-of-function variants in population data.

ResearchSummary from RefSeq, UniProt

Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

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?

1.02LOEUF

pLI 0.000

Z-score 1.50

OE 0.65 (0.43–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.40Z-score

OE missense 0.93 (0.83–1.04)

221 obs / 238.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.43–1.02)

0≤0.351.4

Missense OE?0.93 (0.83–1.04)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 14 / 21.5Missense obs/exp: 221 / 238.6Syn Z: 0.34

Background carrier burden — how many people carry a rare variant somewhere in TM7SF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

610 rare PASS variants

Rare truncating (LoF)

1 in 1,300

127 rare PASS variants

Rare synonymous (reference)

1 in 140

272 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TM7SF2. 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 89	1 in 1,500
South Asian	~43k	1 in 110	1 in 1,000
Remaining (unassigned)	~30k	1 in 73	1 in 1,400
European (Finnish)	~27k	1 in 160	1 in 2,800
Admixed American	~22k	1 in 98	1 in 2,000
African / African American	~21k	1 in 66	1 in 690
East Asian	~20k	1 in 100	1 in 810
Ashkenazi Jewish	~13k	1 in 390	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 78	≈ 1 in 650

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 ↓