TMEM35A

Chr X

transmembrane protein 35A

Also known as: NACHO, TMEM35, TUF-1

TMEM35A encodes a molecular chaperone that mediates proper assembly and functional expression of nicotinic acetylcholine receptors throughout the brain, facilitating their folding, assembly, and surface trafficking. Mutations cause autosomal recessive intellectual developmental disorder with seizures and language delay. The gene shows moderate constraint against loss-of-function variants, affecting critical neurotransmitter receptor function in the developing nervous system.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.85
LOEUF
GOF
Mechanism· predicted
Clinical SummaryTMEM35A
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.66) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.85LOEUF
pLI 0.659
Z-score 1.73
OE 0.00 (0.000.85)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
1.07Z-score
OE missense 0.64 (0.500.82)
45 obs / 70.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.85)
00.351.4
Missense OE0.64 (0.500.82)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 0 / 3.5Missense obs/exp: 45 / 70.2Syn Z: 0.59
DN
0.5967th %ile
GOF
0.6832th %ile
LOF
0.3551th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

TMEM35A · 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 →