TMEM35B

Chr 1

transmembrane protein 35B

Also known as: ZMYM6NB

TMEM35B encodes a protein predicted to be located in cellular membranes, though its specific function remains unclear. Mutations in this gene have been associated with neurodevelopmental disorders, but the clinical phenotype and inheritance pattern are not well-established based on current data. The gene shows moderate constraint against loss-of-function variants.

ResearchSummary from RefSeq
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 OE0.33 (0.121.45)
00.351.4
Missense OE0.62 (0.480.81)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 1 / 3.0Missense obs/exp: 39 / 62.7Syn Z: -1.13
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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →