MIEF2

Chr 17AR

mitochondrial elongation factor 2

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

Mitochondrial outer membrane protein involved in the regulation of mitochondrial organization (PubMed:29361167). It is required for mitochondrial fission and promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface independently of the mitochondrial fission FIS1 and MFF proteins. Regulates DNM1L GTPase activity

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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Some data sources returned errors (1)

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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.