MIEF2

Chr 17AR

mitochondrial elongation factor 2

Also known as: COXPD49, D3B, MID49, SMCR7

NCBI Gene: 125170 ENSG00000177427 UniProt: Q96C03 OMIM: 615498

The protein is a mitochondrial outer membrane protein that regulates mitochondrial organization by recruiting dynamin-related protein 1 (DNM1L) to promote mitochondrial fission. Mutations cause combined oxidative phosphorylation deficiency 49, which follows autosomal recessive inheritance. The gene is located within the Smith-Magenis syndrome region on chromosome 17.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an outer mitochondrial membrane protein that functions in the regulation of mitochondrial morphology. It can directly recruit the fission mediator dynamin-related protein 1 (Drp1) to the mitochondrial surface. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Combined oxidative phosphorylation deficiency 49MIM #619024

Clinical highlights

Gene–disease validity (ClinGen)

Limited · mitochondrial disease · AR · ClinGen 2025

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.83

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.016

Z-score 1.99

OE 0.40 (0.21–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.51Z-score

OE missense 0.92 (0.83–1.01)

269 obs / 293.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.21–0.83)

0≤0.351.4

Missense OE?0.92 (0.83–1.01)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 5 / 12.7Missense obs/exp: 269 / 293.7Syn Z: 0.57

Background carrier burden — how many people carry a rare variant somewhere in MIEF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

765 rare PASS variants

Rare truncating (LoF)

1 in 310

83 rare PASS variants

Rare synonymous (reference)

1 in 130

264 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MIEF2. 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 49	1 in 290
South Asian	~43k	1 in 55	1 in 470
Remaining (unassigned)	~30k	1 in 40	1 in 340
European (Finnish)	~27k	1 in 140	1 in 460
Admixed American	~22k	1 in 53	1 in 320
African / African American	~21k	1 in 39	1 in 1,600
East Asian	~20k	1 in 52	1 in 2,500
Ashkenazi Jewish	~13k	1 in 160	none seen
Middle Eastern	~2,884	1 in 42	≈ 1 in 720

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 ↓