MYOF

protein-coding

myoferlin, the group of Ferlin family

Gene summary

Mutations in dysferlin, a protein associated with the plasma membrane, can cause muscle weakness that affects both proximal and distal muscles. The protein encoded by this gene is a type II membrane protein that is structurally similar to dysferlin. It is a member of the ferlin family and associates with both plasma and nuclear membranes. The protein contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. Two transcript variants encoding different isoforms have been found for this gene. Other possible variants have been detected, but their full-length nature has not been determined. [provided by RefSeq, Dec 2008]

Previous symbols:

FER1L3

MANE transcript

NM_013451.4

Inheritance

ClinVar variants

P:2U:349B:57

Top phenotype

Angioedema, hereditary, 7

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr10:93,306,429-93,482,334

External References & Databases

Ensembl (ENSG00000138119)

Transcript & Mutation Effects

hg38 • Region Span ~175.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

angioedema, hereditary, 7LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0025713

Submitter: Labcorp Genetics (formerly Invitae)

angioedema, hereditary, 7LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0025713

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Angioedema, hereditary, 7AD

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: The condition can involved episodes of angioedema, and medical management may be beneficial

Refs: 32542751

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYOF variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 334

not providedTotal: 48

MYOF-related disorderTotal: 29

Angioedema, hereditary, 7Total: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013451.4. 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			5 clinvar	26 clinvar	3 clinvar	34
missense	1 clinvar	1 clinvar	326 clinvar	22 clinvar	5 clinvar	355
nonsense			5 clinvar	1 clinvar		6
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	1	1	349	49	8	408

Highest pathogenic variant AF is 0.000016728438

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013451.4	RefSeq	NP_038479.1	54	MANE Select
ENST00000359263.9	Ensembl	ENSP00000352208.4	54	MANE Select
NM_133337.3	RefSeq	NP_579899.1	53	Standard
ENST00000358334.9	Ensembl	ENSP00000351094.5	53	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aryl Hydrocarbon Receptor Pathway
Nuclear Receptors Meta-Pathway
Hepatitis C and Hepatocellular Carcinoma
Signaling events mediated by VEGFR1 and VEGFR2

Biological Process

plasma membrane repair
glycerol metabolic process
muscle contraction
myoblast fusion
blood circulation

Molecular Function

protein binding
phospholipid binding

Cellular Component

nuclear envelope
plasma membrane
caveola
integral component of membrane
cytoplasmic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359263
Coding exons: 54
Length: 175889
Individuals with no LoFs: 124357
Homozygous LoFs: 2
Heterozygous LoFs: 690
Defined: 125049
p: 0.00277

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.112	1156	1.17e+3	0.991	0.0000666	13537
Missense (PolyPhen)		439	456.57	0.96152		5398
Synonymous	0.279	430	437	0.983	0.0000265	3880
Loss of Function	2.49	101	132	0.766	0.00000743	1448

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0037	0.0037	notable
Latino/Admixed American	0.0031	0.0030	notable
Ashkenazi Jewish	0.0046	0.0046	notable
East Asian	0.0027	0.0027	notable
Finnish	0.0011	0.0011	notable
European (Non-Finnish)	0.0022	0.0022	notable
South Asian	0.0048	0.0048	notable
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium/phospholipid-binding protein that plays a role in the plasmalemma repair mechanism of endothelial cells that permits rapid resealing of membranes disrupted by mechanical stress. Involved in endocytic recycling. Implicated in VEGF signal transduction by regulating the levels of the receptor KDR (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

LoFtool: 0.0903
RVIS EVS: -0.44
RVIS percentile EVS: 24.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.517

Gene Damage Prediction

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