TMEM273

Chr 10

transmembrane protein 273

Also known as: C10orf128

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

0
Active trials
1
Pubs (1 yr)
59
P/LP submissions
P/LP missense
1.44
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryTMEM273
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 31 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.44LOEUF
pLI 0.006
Z-score 0.84
OE 0.64 (0.311.44)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.64Z-score
OE missense 1.23 (1.021.49)
74 obs / 60.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.64 (0.311.44)
00.351.4
Missense OE1.23 (1.021.49)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 4 / 6.3Missense obs/exp: 74 / 60.1Syn Z: -0.34
DN
0.77top 25%
GOF
0.79top 25%
LOF
0.2873th %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

100 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic21
VUS31
38
Pathogenic
21
Likely Pathogenic
31
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
38
Likely Pathogenic
21
VUS
31
Likely Benign
0
Benign
0
Total90

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TMEM273 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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