MFF

mitochondrial fission factor

Basic information

Region (hg38): 2:227325150-227357833

Previous symbols: [ "C2orf33" ]

Links

ENSG00000168958 ∙ NCBI:56947 ∙ OMIM:614785 ∙ HGNC:24858 ∙ Uniprot:Q9GZY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• encephalopathy due to defective mitochondrial and peroxisomal fission 2 (Definitive), mode of inheritance: AR
• encephalopathy due to defective mitochondrial and peroxisomal fission 2 (Strong), mode of inheritance: AR
• encephalopathy due to mitochondrial and peroxisomal fission defect (Moderate), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy due to defective mitochondrial and peroxisomal fission 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	22499341; 26783368; 32181496

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MFF gene.

• Encephalopathy due to defective mitochondrial and peroxisomal fission 2 (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MFF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				14	2	16
missense			48	3		51
nonsense	1					1
start loss						0
frameshift	2					2
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			3	3	1	7
non coding		3	1	23	39	66
Total	3	4	50	40	41

Highest pathogenic variant AF is 0.00000657

Variants in MFF

This is a list of pathogenic ClinVar variants found in the MFF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-227325204-C-T			Benign (Jul 22, 2019)
2-227325269-C-A			Benign (Jun 23, 2018)
2-227325286-C-G			Benign (Jun 29, 2018)
2-227325328-C-A			Benign (Jul 22, 2019)
2-227325435-T-C			Benign (Jun 29, 2018)
2-227325534-GC-G			Benign (Oct 23, 2019)
2-227327507-A-AAGT			Benign (Jun 11, 2018)
2-227327572-C-G			Benign (Jul 22, 2019)
2-227328648-T-G			Benign (Jun 23, 2018)
2-227328689-GCT-G		not specified	Likely benign (Feb 12, 2016)
2-227328780-T-A		not specified	Likely benign (Feb 14, 2017)
2-227329738-G-A		not specified	Likely benign (Jul 20, 2016)
2-227329764-A-T		not specified	Benign (Dec 02, 2015)
2-227329764-AG-TT		not specified	Benign (Jan 31, 2024)
2-227329765-G-T		not specified	Benign (Dec 02, 2015)
2-227329767-G-T		Inborn genetic diseases	Likely benign (Jul 12, 2022)
2-227329782-A-AG		Encephalopathy due to defective mitochondrial and peroxisomal fission 2	Likely pathogenic (Mar 29, 2024)
2-227329783-G-A		Inborn genetic diseases	Uncertain significance (Jul 24, 2022)
2-227329784-G-A			Likely pathogenic (Apr 28, 2023)
2-227329785-T-G		Encephalopathy due to defective mitochondrial and peroxisomal fission 2	Likely pathogenic (Mar 29, 2024)
2-227329793-A-G		MFF-related disorder	Likely benign (Dec 03, 2019)
2-227329797-T-G		not specified	Likely benign (Jun 03, 2016)
2-227329854-G-A			Benign (Jun 23, 2018)
2-227329923-T-TA			Benign (Aug 10, 2019)
2-227329923-T-TAA			Benign (Aug 10, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MFF	protein_coding	protein_coding	ENST00000353339	9	32684

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0654	0.934	125666	0	82	125748	0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.445	187	205	0.913	0.0000121	2189
Missense in Polyphen		58	68.317	0.84898		807
Synonymous	0.885	61	70.5	0.866	0.00000399	694
Loss of Function	3.02	6	20.9	0.287	0.00000132	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000338	0.000335
Ashkenazi Jewish	0.000608	0.000595
East Asian	0.000164	0.000163
Finnish	0.000280	0.000277
European (Non-Finnish)	0.000225	0.000220
Middle Eastern	0.000164	0.000163
South Asian	0.00103	0.000980
Other	0.000502	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in mitochondrial and peroxisomal fission. Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface. May be involved in regulation of synaptic vesicle membrane dynamics by recruitment of DNM1L to clathrin-containing vesicles. {ECO:0000269|PubMed:18353969, ECO:0000269|PubMed:23530241}.

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.864
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.54

Haploinsufficiency Scores

• pHI: 0.210
• hipred: Y
• hipred_score: 0.529
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0480

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Mff
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: mitochondrial fission;release of cytochrome c from mitochondria;protein targeting to mitochondrion;mitochondrial fusion;regulation of mitochondrion organization;peroxisome fission;mitochondrial fragmentation involved in apoptotic process;protein homooligomerization;mitochondrion morphogenesis;positive regulation of mitochondrial fission;positive regulation of release of cytochrome c from mitochondria;positive regulation of protein targeting to membrane;regulation of peroxisome organization
• Cellular component: mitochondrion;mitochondrial outer membrane;peroxisome;synaptic vesicle;cell junction;integral component of mitochondrial membrane
• Molecular function: protein binding;protein homodimerization activity