TMEM35B

Chr 1

transmembrane protein 35B

Also known as: ZMYM6NB

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

ResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.45
Clinical SummaryTMEM35B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.45LOEUF
pLI 0.221
Z-score 1.08
OE 0.33 (0.121.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
1.06Z-score
OE missense 0.62 (0.480.81)
39 obs / 62.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.33 (0.121.45)
00.351.4
Missense OE?0.62 (0.480.81)
00.61.4
Synonymous OE?1.25
01.21.6
LoF obs/exp: 1 / 3.0Missense obs/exp: 39 / 62.7Syn Z: -1.13

This gene — mechanism propensity

DN
0.7132th %ile
GOF
0.76top 25%
LOF
0.1895th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMEM35B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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