TMEM126A

Chr 11AR

transmembrane protein 126A

Also known as: OPA7

NCBI Gene: 84233 ENSG00000171202 UniProt: Q9H061 OMIM: 612988

This mitochondrial membrane protein functions as a chaperone for cotranslational protein quality control and is required for assembly of the ND4 module of mitochondrial complex I. Mutations cause optic atrophy 7, which follows autosomal recessive inheritance and primarily affects the visual system through mitochondrial dysfunction.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a mitochondrial membrane protein of unknown function. Defects in this gene are a cause of optic atrophy type 7 (OPA7). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Optic atrophy 7MIM #612989

UniProtOptic atrophy 7 with or without auditory neuropathy

Clinical highlights

Gene–disease validity (ClinGen)

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

1.33

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.002

Z-score 0.95

OE 0.63 (0.33–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.57Z-score

OE missense 1.16 (1.00–1.35)

118 obs / 101.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.63 (0.33–1.33)

0≤0.351.4

Missense OE?1.16 (1.00–1.35)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 5 / 7.9Missense obs/exp: 118 / 101.9Syn Z: 0.08

Background carrier burden — how many people carry a rare variant somewhere in TMEM126A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

262 rare PASS variants

Rare truncating (LoF)

1 in 3,700

49 rare PASS variants

Rare synonymous (reference)

1 in 880

69 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM126A. 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 290	1 in 4,100
South Asian	~43k	1 in 200	1 in 7,200
Remaining (unassigned)	~30k	1 in 210	1 in 3,800
European (Finnish)	~27k	1 in 590	1 in 3,300
Admixed American	~22k	1 in 180	1 in 2,000
African / African American	~21k	1 in 170	1 in 940
East Asian	~20k	1 in 360	1 in 940
Ashkenazi Jewish	~13k	1 in 500	none seen
Middle Eastern	~2,884	1 in 260	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): 3 of 4 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 4.? see exons ↓