MYO1C

protein-coding

myosin IC, the group of Myosin heavy chains, class I|B-WICH chromatin-remodelling complex subunits

Gene summary

This gene encodes a member of the unconventional myosin protein family, which are actin-based molecular motors. The protein is found in the cytoplasm, and one isoform with a unique N-terminus is also found in the nucleus. The nuclear isoform associates with RNA polymerase I and II and functions in transcription initiation. The mouse ortholog of this protein also functions in intracellular vesicle transport to the plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. The related gene myosin IE has been referred to as myosin IC in the literature, but it is a distinct locus on chromosome 19. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001080779.2

Inheritance

ClinVar variants

U:208B:54

Top phenotype

autosomal dominant nonsyndromic hearing loss

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr17:1,464,186-1,492,686

External References & Databases

Ensembl (ENSG00000197879)

Transcript & Mutation Effects

hg38 • Region Span ~28.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant nonsyndromic hearing lossNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0019587

Submitter: ClinGen

The MYO1C gene has been associated with autosomal dominant nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 6/26/2018. This association was made using case-level data only. Multiple missense variants have been reported in humans by Zadro et al. 2009, however each of these variants is present in high frequency in gnomAD. The loss-of-function variants reported by Ji et al. 2014 have no family history information or functional evidence to prove variant impact. In summary, there is convincing evidence disputing the association between autosomal dominant nonsyndromic hearing loss. More evidence is needed to either support or refute the role MYO1C plays in this disease. This classification was approved by the ClinGen Hearing Loss Working Group on 6/26/2018.

autosomal dominant nonsyndromic hearing lossSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019587

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYO1C variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 197

not providedTotal: 87

MYO1C-related disorderTotal: 21

Meniere diseaseTotal: 7

Anophthalmia-microphthalmia syndromeTotal: 1

Miller Dieker syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080779.2. 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	30 clinvar	5 clinvar	38
missense			190 clinvar	13 clinvar	6 clinvar	209
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			14 clinvar			14
Total	0	0	208	43	11	262

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080779.2	RefSeq	NP_001074248.1	32	MANE Select
ENST00000648651.1	Ensembl	ENSP00000496954.1	32	MANE Select
NM_001080950.2	RefSeq	NP_001074419.1	32	Standard
NM_001363855.1	RefSeq	NP_001350784.1	32	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
myo1cb	Danio rerio	Structure: pronephric glomerular basement membrane Quality: increased thickness abnormal

Gene / Model

Organism

Observed Phenotype

myo1cb

Danio rerio

Structure: pronephric glomerular basement membrane

Quality: increased thickness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin Signaling
B-WICH complex positively regulates rRNA expression
Positive epigenetic regulation of rRNA expression
Epigenetic regulation of gene expression
Gene expression (Transcription)

Biological Process

protein targeting
protein targeting to membrane
vesicle transport along actin filament
positive regulation of cell migration
positive regulation of actin filament polymerization

Molecular Function

microfilament motor activity
signaling receptor binding
protein binding
calmodulin binding
ATP binding

Cellular Component

stress fiber
nuclear pore
nucleoplasm
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359786
Coding exons: 32
Length: 28715
Individuals with no LoFs: 125672
Homozygous LoFs: 0
Heterozygous LoFs: 76
Defined: 125748
p: 0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.637	703	657	1.07	0.0000483	6858
Missense (PolyPhen)		276	259.2	1.0648		2704
Synonymous	-3.63	352	275	1.28	0.0000203	2087
Loss of Function	3.70	34	66.6	0.511	0.00000387	702

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00016	0.00014	rare
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.00037	0.00033	rare
Other	0.00049	0.00049	rare

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. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes. {ECO:0000269|PubMed:24636949}.;

Recessive Scores

pRec: 0.212

Intolerance Scores

LoFtool: 0.0331
RVIS EVS: -1.11
RVIS percentile EVS: 6.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.724

Gene Damage Prediction

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