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

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.05

Clinical Summary— TM6SF1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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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

This gene — mechanism propensity

0.77top 25%

GOF

0.6248th %ile

LOF

0.2385th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.