TMEM223

Chr 11

transmembrane protein 223

Also known as: Mrx15

NCBI Gene: 79064 ENSG00000168569 UniProt: A0PJW6 OMIM: 620434

The protein stimulates translation of MT-CO1 mRNA and participates in early assembly steps of cytochrome c oxidase complex IV in mitochondria. Mutations cause autosomal recessive mitochondrial complex IV deficiency with early-onset neurological manifestations. The gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables mitochondrial ribosome binding activity. Involved in mitochondrial respiratory chain complex IV assembly. Located in mitochondrion. Is active in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.81

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.000

Z-score -0.20

OE 1.09 (0.61–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.47Z-score

OE missense 1.12 (0.97–1.30)

129 obs / 114.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.09 (0.61–1.81)

0≤0.351.4

Missense OE?1.12 (0.97–1.30)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 7 / 6.4Missense obs/exp: 129 / 114.9Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in TMEM223?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

398 rare PASS variants

Rare truncating (LoF)

1 in 370

77 rare PASS variants

Rare synonymous (reference)

1 in 290

158 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TMEM223; 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 140	1 in 1,600
South Asian	~43k	1 in 91	1 in 460
Remaining (unassigned)	~30k	1 in 110	1 in 770
European (Finnish)	~27k	1 in 300	1 in 1,300
Admixed American	~22k	1 in 120	1 in 1,500
African / African American	~21k	1 in 110	1 in 480
East Asian	~20k	1 in 180	1 in 560
Ashkenazi Jewish	~13k	1 in 1,300	none seen
Middle Eastern	~2,884	1 in 110	1 in 530

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓