TMEM70

Chr 8AR

transmembrane protein 70

Also known as: MC5DN2

NCBI Gene: 54968 ENSG00000175606 UniProt: Q9BUB7 OMIM: 612418

The protein is a mitochondrial inner membrane protein involved in the biogenesis of mitochondrial ATP synthase (complex V). Mutations cause autosomal recessive mitochondrial complex V deficiency, typically presenting as neonatal mitochondrial encephalocardiomyopathy due to ATP synthase deficiency.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene likely encodes a mitochondrial membrane protein. The encoded protein may play a role in biogenesis of mitochondrial ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalocardiomyopathy due to ATP synthase deficiency. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.921 OMIM phenotype

Clinical Summary— TMEM70

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

41 unique Pathogenic / Likely Pathogenic· 173 VUS of 396 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — TMEM70

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.029

Z-score 1.75

OE 0.40 (0.20–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.13Z-score

OE missense 0.97 (0.84–1.12)

139 obs / 143.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.20–0.92)

0≤0.351.4

Missense OE?0.97 (0.84–1.12)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 4 / 9.9Missense obs/exp: 139 / 143.4Syn Z: -0.55

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTMEM70-related mitochondrial complex V (ATP synthase) deficiency, nuclearLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.74top 25%

GOF

0.5072th %ile

LOF

0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

396 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic20

VUS173

Likely Benign131

Benign29

Conflicting17

Pathogenic

Likely Pathogenic

173

VUS

131

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	19	0	2	0	21
Likely Pathogenic	16	3	1	0	20
VUS	6	134	31	2	173
Likely Benign	1	3	39	88	131
Benign	0	6	23	0	29
Conflicting	—				17
Total	42	146	96	90	391

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap TMEM70 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →