MFF

Chr 2AR

mitochondrial fission factor

Also known as: C2orf33, EMPF2, GL004

The MFF protein recruits dynamin-1-like protein to mitochondria and peroxisomes to promote fission of these organelles. Biallelic mutations cause autosomal recessive encephalopathy due to defective mitochondrial and peroxisomal fission. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.567), and the disorder primarily affects the central nervous system through disrupted cellular organelle dynamics.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.571 OMIM phenotype
Clinical SummaryMFF
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.065
Z-score 3.02
OE 0.29 (0.160.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.44Z-score
OE missense 0.91 (0.811.03)
187 obs / 204.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.160.57)
00.351.4
Missense OE0.91 (0.811.03)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 6 / 20.9Missense obs/exp: 187 / 204.9Syn Z: 0.89
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMFF-related encephalopathy due to defective mitochondrial and peroxisomal fissionLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.77top 25%
GOF
0.5759th %ile
LOF
0.3841th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MFF · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗