TMEM11

Chr 17

transmembrane protein 11

Also known as: C17orf35, PM1, PMI

TMEM11 encodes a mitochondrial inner membrane protein that functions in mitochondrial morphogenesis and organization. Loss-of-function mutations cause mitochondrial dysfunction leading to neurological disease with autosomal recessive inheritance. The gene shows high intolerance to loss-of-function variants, consistent with its essential role in mitochondrial structure and function.

Summary from RefSeq, UniProt, Mechanism
1
Active trials
3
Pubs (1 yr)
5
P/LP submissions
0%
P/LP missense
0.43
LOEUF
LOF
Mechanism· predicted
Clinical SummaryTMEM11
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.88) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 30 VUS of 38 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.879
Z-score 2.43
OE 0.00 (0.000.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.35Z-score
OE missense 0.66 (0.550.79)
81 obs / 123.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.43)
00.351.4
Missense OE0.66 (0.550.79)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 0 / 6.9Missense obs/exp: 81 / 123.1Syn Z: 0.24
DN
0.3594th %ile
GOF
0.4283th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.43

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

38 submitted variants in ClinVar

Classification Summary

Pathogenic5
VUS30
Benign1
5
Pathogenic
30
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
0
0
0
VUS
0
21
9
0
30
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total02114136

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TMEM11 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC