MYO1F

protein-coding

myosin IF, the group of Myosin heavy chains, class I

Gene summary

Myosins are molecular motors that use the energy from ATP hydrolysis to generate force on actin filaments. The protein encoded by this gene is an unconventional myosin that may be involved in the intracellular movement of membrane-enclosed compartments. There is evidence to suggest that mutations in this gene can result in hearing loss. [provided by RefSeq, Jan 2017]

MANE transcript

NM_012335.4

Inheritance

ClinVar variants

U:195B:59

Top phenotype

MYO1F-related disorder

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr19:8,517,463-8,577,442

External References & Databases

Ensembl (ENSG00000142347)

Transcript & Mutation Effects

hg38 • Region Span ~60.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nonsyndromic genetic hearing lossNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0019497

Submitter: ClinGen

*MYO1F* was first associated with autosomal dominant nonsyndromic hearing loss in 2009 (Zadro et al., PMID: 19027848). At least 6 unique missense variants have been reported in 7 individuals in 2 publications (PMIDs: 19027848, 22938506), however none of the reported variants has convincing evidence of pathogenicity i.e. all were missense variants that either had a high MAF in gnomAD v4., no family history of hearing loss and/or segregations, or the variant was present in unaffected family members. This gene-disease relationship is supported by expression in the murine inner ear (PMID:12486594). In summary, the relationship between *MYO1F* and autosomal dominant nonsyndromic hearing loss has been disputed. More evidence is needed to either support or refute the role *MYO1F* plays in this disease. This gene-disease pair was originally evaluated by the ClinGen Hearing Loss GCEP on 06/06/2017 as per SOP v5. It was reevaluated on 10/31/2024 using SOP v11. As a result of this reevaluation, this record underwent a review to be consistent with SOP v11. There has been no new evidence published since the last curation.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYO1F variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 196

not providedTotal: 93

MYO1F-related disorderTotal: 26

Bilateral sensorineural hearing impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012335.4. 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			4 clinvar	28 clinvar	9 clinvar	41
missense			184 clinvar	19 clinvar	3 clinvar	206
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	195	47	12	254

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012335.4	RefSeq	NP_036467.2	28	MANE Select
ENST00000644032.2	Ensembl	ENSP00000494550.1	28	MANE Select
NM_001348355.2	RefSeq	NP_001335284.1	28	Standard
NM_001440609.1	RefSeq	NP_001427538.1	28	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process

Molecular Function

motor activity
actin binding
calmodulin binding
ATP binding

Cellular Component

unconventional myosin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338257
Coding exons: 28
Length: 56788
Individuals with no LoFs: 125247
Homozygous LoFs: 0
Heterozygous LoFs: 69
Defined: 125316
p: 0.000275

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.76	582	714	0.815	0.0000502	7206
Missense (PolyPhen)		154	235.27	0.65458		2421
Synonymous	-0.122	297	294	1.01	0.0000224	2121
Loss of Function	4.84	24	66.6	0.360	0.00000404	671

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00045	0.00044	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.201

Intolerance Scores

LoFtool: 0.114
RVIS EVS: -1.83
RVIS percentile EVS: 2.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.939

Gene Damage Prediction

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