TMEM242

Chr 6

transmembrane protein 242

Also known as: BM033, C6orf35

NCBI Gene: 729515 ENSG00000215712 UniProt: Q9NWH2 OMIM: 620721

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.

OMIM ResearchSummary from RefSeq, UniProt

Involved in mitochondrial proton-transporting ATP synthase complex assembly. Located in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.59

Clinical Summary— TMEM242

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 20 VUS of 30 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.59LOEUF

pLI 0.000

Z-score 0.34

OE 0.87 (0.49–1.59)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.25Z-score

OE missense 0.92 (0.77–1.12)

75 obs / 81.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.49–1.59)

0≤0.351.4

Missense OE?0.92 (0.77–1.12)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 7 / 8.0Missense obs/exp: 75 / 81.2Syn Z: 0.15

This gene — mechanism propensity

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

30 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS20

Likely Benign1

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	0	0
VUS	20	0	20
Likely Benign	1	0	1
Benign	0	0	0
Total	21	1	22

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap TMEM242 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →