MFF

Chr 2AR

mitochondrial fission factor

NCBI Gene: 56947ENSG00000168958UniProt: Q9GZY8

Plays a role in mitochondrial and peroxisomal fission (PubMed:18353969, PubMed:23530241, PubMed:24196833). Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface (PubMed:23530241). May be involved in regulation of synaptic vesicle membrane dynamics by recruitment of DNM1L to clathrin-containing vesicles (By similarity)

Primary Disease Associations & Inheritance

Encephalopathy due to defective mitochondrial and peroxisomal fission 2MIM #617086
AR
230
ClinVar variants
37
Pathogenic / LP
0.07
pLI score
2
Active trials
Clinical Summary— MFF
🧬
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.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 94 VUS of 230 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.57LOEUF
pLI 0.065
Z-score 3.02
OE 0.29 (0.16–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.44Z-score
OE missense 0.91 (0.81–1.03)
187 obs / 204.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.16–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.81–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 6 / 20.9Missense obs/exp: 187 / 204.9Syn Z: 0.89

ClinVar Variant Classifications

230 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic9
VUS94
Likely Benign54
Benign42
Conflicting3
28
Pathogenic
9
Likely Pathogenic
94
VUS
54
Likely Benign
42
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
25
0
28
Likely Pathogenic
7
0
2
0
9
VUS
1
84
9
0
94
Likely Benign
0
4
29
21
54
Benign
0
3
38
1
42
Conflicting
—3
Total119110322230

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

View 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.

Gene2Phenotype Curations

MFF-related encephalopathy due to defective mitochondrial and peroxisomal fission

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Encephalopathy due to defective mitochondrial and peroxisomal fission 2

MIM #617086

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MFF
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mitochondrial elongation impairs breast cancer metastasis.
Minarrieta L et al.·Sci Adv
2024
Disruption of cTnT-Mediated Sarcomere-Mitochondrial Communication Results in Dilated Cardiomyopathy.
Ye L et al.·Circulation
2025
Targeting DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling.
Li X et al.·J Exp Clin Cancer Res
2024Functional
Tethering ATG16L1 or LC3 induces targeted autophagic degradation of protein aggregates and mitochondria.
Mei L et al.·Autophagy
2023
The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn(2+) trafficking.
Song Y et al.·Autophagy
2024
Regulator of calcineurin 1 deletion attenuates mitochondrial dysfunction and apoptosis in acute kidney injury through JNK/Mff signaling pathway.
Xiao JJ et al.·Cell Death Dis
2022
Sirtuins: Research advances on the therapeutic role in acute kidney injury.
Huang C et al.·Phytomedicine
2022
Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease.
Sandholm N et al.·Diabetologia
2022Meta-analysis
Mitochondrial fission factor drives an actionable metabolic vulnerability in multiple myeloma.
Cantafio MEG et al.·Haematologica
2025
Metal fume fever among galvanized welders.
Wardhana et al.·Acta Med Indones
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Environmental ciprofloxacin triggers pregnancy loss: senescence-driven miscarriage via TRIM21-mediated MFF degradation.
Sun 孙义 Y et al.·EBioMedicine
2026🔓 Open Access
Targeting MFF succinylation: a novel therapeutic strategy for premature ovarian insufficiency by restoring mitochondrial dynamics in granulosa cells.
Cao Y et al.·J Ovarian Res
2026
The new modified four-factor functional frailty index (mFF-4) in colorectal surgery: A retrospective cohort study.
Agathis AZ et al.·Surgery
2026Cohort
Anti-inflammatory gut immune modulation induced by direct-fed endospores of bacteriostatic lipopeptide-producing Bacillus velezensis MFF 2.2 and B. subtilis TC12 in BALB/c mice: A first step toward a probiotic additive to prevent post-weaning diarrhea.
Di Giácomo AL et al.·Res Vet Sci
2026
MFF-ClassificationNet: CNN-Transformer Hybrid with Multi-Feature Fusion for Breast Cancer Histopathology Classification.
Wang X et al.·Biosensors (Basel)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Facioscapulohumeral Muscular Dystrophy 1

Study to Evaluate the Efficacy and Safety of Satralizumab in FSHD1

ACTIVE NOT RECRUITING
NCT06222827Phase PHASE2Centre Hospitalier Universitaire de NiceStarted 2024-01-24
Satralizumab Prefilled SyringePlacebo Comparator
Charcot-Marie-Tooth Disease Type 4J

Study of Intrathecal ELP-02 for Charcot-Marie-Tooth Disease Type 4J (CMT4J)

NOT YET RECRUITING
NCT07447557Phase PHASE1, PHASE2Elpida Therapeutics SPCStarted 2026-04
ELP-02

External Resources

Links to major genomics databases and tools