MYO1C

Chr 17

myosin IC

Also known as: MMI-beta, MMIb, MyoIC, NMI, myr2

NCBI Gene: 4641 ENSG00000197879 UniProt: O00159

This gene encodes an unconventional myosin that functions as an actin-based molecular motor with ATPase activity, involved in intracellular vesicle transport, glucose transporter recycling, and serving as a component of the hair cell adaptation-motor complex in inner ear sensory cells. Mutations cause autosomal recessive nonsyndromic hearing loss, typically presenting in childhood. The gene shows high constraint against loss-of-function variants, indicating its critical importance for normal cellular function.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.68

Clinical Summary— MYO1C

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ADDisputed

Disputed — evidence questions this relationship

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

185 VUS of 398 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.000

Z-score 3.70

OE 0.51 (0.39–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.64Z-score

OE missense 1.07 (1.00–1.14)

703 obs / 657.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.51 (0.39–0.68)

0≤0.351.4

Missense OE?1.07 (1.00–1.14)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 34 / 66.6Missense obs/exp: 703 / 657.1Syn Z: -3.63

This gene — mechanism propensity

0.74top 25%

GOF

0.72top 25%

LOF

0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

398 submitted variants in ClinVar

ClinVar

Classification Summary

VUS185

Likely Benign78

Benign96

Conflicting1

185

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	183	1	0	185
Likely Benign	0	12	35	31	78
Benign	0	8	79	9	96
Conflicting	—				1
Total	1	203	115	40	360

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

109 pathogenic / likely-pathogenic (of 125) ClinVar copy-number / structural variants overlap MYO1C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →