MFN1

protein-coding

mitofusin 1

Gene summary

The protein encoded by this gene is a mediator of mitochondrial fusion. This protein and mitofusin 2 are homologs of the Drosophila protein fuzzy onion (Fzo). They are mitochondrial membrane proteins that interact with each other to facilitate mitochondrial targeting. [provided by RefSeq, Jul 2008]

MANE transcript

NM_033540.3

Inheritance

—

ClinVar variants

U:94B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr3:179,347,709-179,394,936

External References & Databases

Ensembl (ENSG00000171109)

Transcript & Mutation Effects

hg38 • Region Span ~47.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MFN1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 83

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033540.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar			3
missense			86 clinvar	2 clinvar		88
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	94	2	0	96

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033540.3	RefSeq	NP_284941.2	17	MANE Select
ENST00000471841.6	Ensembl	ENSP00000420617.1	17	MANE Select
ENST00000263969.10	Ensembl	ENSP00000263969.5	17	Standard
ENST00000263969.9	Ensembl	ENSP00000263969.5	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

mitochondrial fusion
macroautophagy
GTP metabolic process
mitochondrion localization
mitochondrial membrane fusion

Molecular Function

GTPase activity
protein binding
GTP binding

Cellular Component

mitochondrion
mitochondrial outer membrane
integral component of membrane
intrinsic component of mitochondrial outer membrane
integral component of mitochondrial outer membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000471841
Coding exons: 17
Length: 47240
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 54
Defined: 125747
p: 0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	313	380	0.824	0.0000187	4872
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00039	0.00037	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00028	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00025	rare
South Asian	0.00023	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.237
RVIS EVS: -0.25
RVIS percentile EVS: 36.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.979

Gene Damage Prediction

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