MFN1

mitofusin 1

Basic information

Region (hg38): 3:179347708-179394936

Links

ENSG00000171109 ∙ NCBI:55669 ∙ OMIM:608506 ∙ HGNC:18262 ∙ Uniprot:Q8IWA4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MFN1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MFN1 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						0
missense			26			26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	26	0	0

Variants in MFN1

This is a list of pathogenic ClinVar variants found in the MFN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-179348881-C-G		not specified	Uncertain significance (Jun 30, 2023)
3-179351987-T-C		not specified	Uncertain significance (Apr 24, 2024)
3-179352019-G-A		not specified	Uncertain significance (Nov 08, 2022)
3-179362421-C-T		not specified	Uncertain significance (Mar 03, 2022)
3-179364361-G-A		not specified	Uncertain significance (Nov 22, 2021)
3-179365149-G-A			not provided (-)
3-179367443-G-A		not specified	Uncertain significance (Aug 02, 2023)
3-179367521-G-A		not specified	Uncertain significance (Jul 19, 2023)
3-179368062-G-T		not specified	Uncertain significance (Apr 13, 2022)
3-179375223-T-C		not specified	Uncertain significance (Jul 27, 2021)
3-179375306-A-G		not specified	Uncertain significance (Dec 01, 2022)
3-179375310-G-T		not specified	Uncertain significance (Aug 10, 2021)
3-179375319-A-G		not specified	Uncertain significance (Jun 02, 2024)
3-179377356-A-G		not specified	Uncertain significance (Jun 06, 2023)
3-179377365-G-A		not specified	Uncertain significance (Sep 13, 2023)
3-179377402-G-A		not specified	Uncertain significance (Aug 13, 2021)
3-179378356-A-C		not specified	Uncertain significance (Jan 03, 2024)
3-179378386-G-A		not specified	Uncertain significance (Mar 21, 2023)
3-179378410-G-A		not specified	Uncertain significance (Sep 17, 2021)
3-179378630-A-T		not specified	Uncertain significance (Nov 18, 2022)
3-179378650-A-G		not specified	Uncertain significance (Dec 06, 2021)
3-179378681-A-G		not specified	Uncertain significance (Jan 16, 2024)
3-179378743-C-G		not specified	Uncertain significance (Nov 17, 2022)
3-179378759-T-G		not specified	Uncertain significance (Jan 24, 2023)
3-179385618-C-T		not specified	Uncertain significance (Sep 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MFN1	protein_coding	protein_coding	ENST00000471841	17	47240

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.51e-10	0.994	125693	0	54	125747	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	313	380	0.824	0.0000187	4872
Missense in Polyphen		80	119.92	0.66714		1635
Synonymous	1.87	108	136	0.796	0.00000676	1378
Loss of Function	2.58	22	39.5	0.557	0.00000202	493

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000536	0.000520
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000276	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000277	0.000246
Middle Eastern	0.000276	0.000272
South Asian	0.000233	0.000229
Other	0.000330	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:12475957, PubMed:12759376, PubMed:27920125, PubMed:28114303). Membrane clustering requires GTPase activity (PubMed:27920125). It may involve a major rearrangement of the coiled coil domains (PubMed:27920125, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:12475957, PubMed:12759376). Overexpression induces the formation of mitochondrial networks (in vitro) (PubMed:12759376). Has low GTPase activity (PubMed:27920125, PubMed:28114303). {ECO:0000269|PubMed:12475957, ECO:0000269|PubMed:12759376, ECO:0000269|PubMed:27920125, ECO:0000269|PubMed:28114303}.
• Pathway: Mitophagy - animal - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Factors involved in megakaryocyte development and platelet production;Pink/Parkin Mediated Mitophagy;Mitophagy;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.237
• rvis_EVS: -0.25
• rvis_percentile_EVS: 36.07

Haploinsufficiency Scores

• pHI: 0.828
• hipred: Y
• hipred_score: 0.503
• ghis: 0.651

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.979

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mfn1
• Phenotype: growth/size/body region phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype

Gene ontology

• Biological process: mitochondrial fusion;macroautophagy;GTP metabolic process;mitochondrion localization;mitochondrial membrane fusion
• Cellular component: mitochondrion;mitochondrial outer membrane;integral component of membrane;intrinsic component of mitochondrial outer membrane;integral component of mitochondrial outer membrane;outer mitochondrial membrane protein complex
• Molecular function: GTPase activity;protein binding;GTP binding