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…

GOFmechanismARLOEUF 0.831 OMIM phenotype

Clinical Summary— MIEF2

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 103 VUS of 128 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.5574th %ile

GOF

0.6833th %ile

LOF

0.2777th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

128 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS103

Likely Benign23

Benign1

Pathogenic

103

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	1	102	0	0	103
Likely Benign	1	18	1	3	23
Benign	0	1	0	0	1
Total	3	121	1	3	128

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

116 pathogenic / likely-pathogenic (of 122) ClinVar copy-number / structural variants overlap MIEF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →