TMEM43
Chr 3ADtransmembrane protein 43
Also known as: ARVC5, ARVD5, AUNA3, EDMD7, EDMD7; AUNA2, LUMA
TMEM43 encodes a protein that maintains nuclear envelope structure by organizing protein complexes at the inner nuclear membrane and contributes to passive conductance current in cochlear supporting cells necessary for hearing. Mutations cause arrhythmogenic right ventricular dysplasia type 5 (characterized by ventricular tachycardia, heart failure, and fibrofatty replacement of cardiomyocytes), auditory neuropathy, and Emery-Dreifuss muscular dystrophy, with autosomal dominant inheritance. The gene is extremely intolerant to loss-of-function variants (pLI near 1), reflecting its essential cellular functions across cardiac, auditory, and muscle systems.
Definitive — sufficient evidence for diagnostic panels
Some data sources returned errors (1)
opentargets: TimeoutError: The operation was aborted due to timeout
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
600 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 12 | 0 | 12 |
Likely Pathogenic | 2 | 0 | 1 | 0 | 3 |
VUS | 44 | 228 | 21 | 3 | 296 |
Likely Benign | 2 | 2 | 128 | 107 | 239 |
Benign | 0 | 0 | 15 | 1 | 16 |
Conflicting | — | 34 | |||
| Total | 48 | 230 | 177 | 111 | 600 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMEM43 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools