TMEM70

Chr 8

transmembrane protein 70

Also known as: MC5DN2

NCBI Gene: 54968 ENSG00000175606 UniProt: Q9BUB7

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMitochondrial complex V deficiency, nuclear type 2

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in TMEM70?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

369 rare PASS variants

Rare truncating (LoF)

1 in 890

61 rare PASS variants

Rare synonymous (reference)

1 in 320

157 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TMEM70; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 310	1 in 770
South Asian	~43k	1 in 180	1 in 5,400
Remaining (unassigned)	~30k	1 in 230	1 in 1,300
European (Finnish)	~27k	1 in 740	1 in 1,700
Admixed American	~22k	1 in 200	1 in 1,400
African / African American	~21k	1 in 170	1 in 1,600
East Asian	~20k	1 in 120	1 in 2,400
Ashkenazi Jewish	~13k	1 in 340	none seen
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓