MIEF2

Chr 17AR

mitochondrial elongation factor 2

Also known as: COXPD49, D3B, MID49, SMCR7

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismARLOEUF 0.831 OMIM phenotype
Clinical SummaryMIEF2
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.016
Z-score 1.99
OE 0.40 (0.210.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.51Z-score
OE missense 0.92 (0.831.01)
269 obs / 293.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.210.83)
00.351.4
Missense OE0.92 (0.831.01)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 5 / 12.7Missense obs/exp: 269 / 293.7Syn Z: 0.57
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MIEF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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