TMEM74

Chr 8

transmembrane protein 74

Also known as: NET36

Predicted to enable transmembrane transporter binding activity. Involved in macroautophagy. Predicted to be located in cytoplasmic vesicle; plasma membrane; and vacuolar membrane. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.47
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryTMEM74
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.47LOEUF
pLI 0.000
Z-score 0.65
OE 0.75 (0.411.47)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.05Z-score
OE missense 0.99 (0.871.12)
176 obs / 178.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.75 (0.411.47)
00.351.4
Missense OE0.99 (0.871.12)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 6 / 8.0Missense obs/exp: 176 / 178.0Syn Z: 0.41
DN
0.6357th %ile
GOF
0.6638th %ile
LOF
0.4726th %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

TMEM74 · 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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Clinical Literature
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