TMEM242

Chr 6

transmembrane protein 242

Also known as: BM033, C6orf35

TMEM242 encodes a scaffold protein that facilitates assembly of the mitochondrial ATP synthase complex (complex V) by assisting with c-ring formation and incorporation of multiple ATP synthase subunits. Mutations cause mitochondrial complex V deficiency with autosomal recessive inheritance, typically presenting in infancy with severe neurological manifestations including developmental delay, seizures, and progressive encephalopathy. The gene shows tolerance to loss-of-function variants in the general population, suggesting complete loss of function may be required for disease manifestation.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.59
Clinical SummaryTMEM242
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
1.59LOEUF
pLI 0.000
Z-score 0.34
OE 0.87 (0.491.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.25Z-score
OE missense 0.92 (0.771.12)
75 obs / 81.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.87 (0.491.59)
00.351.4
Missense OE0.92 (0.771.12)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 7 / 8.0Missense obs/exp: 75 / 81.2Syn Z: 0.15
DN
0.83top 10%
GOF
0.6247th %ile
LOF
0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

TMEM242 · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found