MICOS13

Chr 19AR

mitochondrial contact site and cristae organizing system subunit 13

Also known as: C19orf70, MIC12, MIC13, P117, QIL1

NCBI Gene: 125988 ENSG00000174917 UniProt: Q5XKP0 OMIM: 616658

The MICOS13 protein is a component of the MICOS complex that maintains mitochondrial inner membrane architecture and cristae junction formation, which are essential for proper oxidative phosphorylation. Mutations cause combined oxidative phosphorylation deficiency 37, inherited in an autosomal recessive pattern. This gene appears to tolerate loss-of-function variants relatively well in the population (low constraint), suggesting that biallelic mutations are required for disease manifestation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in cristae formation. Located in mitochondrial crista junction. Part of MICOS complex. Implicated in combined oxidative phosphorylation deficiency 37. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 37MIM #618329

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2023

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.63

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.63LOEUF

pLI 0.001

Z-score 0.43

OE 0.81 (0.42–1.63)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.10Z-score

OE missense 1.04 (0.85–1.26)

69 obs / 66.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.81 (0.42–1.63)

0≤0.351.4

Missense OE?1.04 (0.85–1.26)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 5 / 6.2Missense obs/exp: 69 / 66.7Syn Z: 0.53

Background carrier burden — how many people carry a rare variant somewhere in MICOS13?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 370

215 rare PASS variants

Rare truncating (LoF)

1 in 2,400

50 rare PASS variants

Rare synonymous (reference)

1 in 1,400

81 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MICOS13. 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 420	1 in 2,900
South Asian	~43k	1 in 290	1 in 800
Remaining (unassigned)	~30k	1 in 420	1 in 1,800
European (Finnish)	~27k	≈ 1 in 8,100	1 in 5,000
Admixed American	~22k	1 in 380	1 in 2,100
African / African American	~21k	1 in 270	1 in 1,500
East Asian	~20k	1 in 390	1 in 1,200
Ashkenazi Jewish	~13k	≈ 1 in 13,000	none seen
Middle Eastern	~2,884	1 in 270	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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓