MYO1C

Summary

MYO1C (myosin IC, HGNC:7597) is a protein-coding gene on chromosome 17p13.3, encoding Unconventional myosin-Ic (O00159). Myosins are actin-based motor molecules with ATPase activity.

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.

Source: NCBI Gene 4641 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant nonsyndromic hearing loss (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 445 total
• MANE Select transcript: NM_001080779

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7597
Approved symbol	MYO1C
Name	myosin IC
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	myr2, NMI, MyoIC
Ensembl gene	ENSG00000197879
Ensembl biotype	protein_coding
OMIM	606538
Entrez	4641

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 14 protein_coding, 7 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000361007, ENST00000545534, ENST00000570490, ENST00000570984, ENST00000571615, ENST00000571851, ENST00000572615, ENST00000573198, ENST00000573853, ENST00000573961, ENST00000574308, ENST00000574341, ENST00000575011, ENST00000575158, ENST00000575335, ENST00000575864, ENST00000576822, ENST00000646049, ENST00000648446, ENST00000648651, ENST00000904706, ENST00000934819, ENST00000969312, ENST00000969313

RefSeq mRNA: 4 — MANE Select: NM_001080779 NM_001080779, NM_001080950, NM_001363855, NM_033375

CCDS: CCDS11003, CCDS42226, CCDS45562, CCDS86556

Canonical transcript exons

ENST00000648651 — 32 exons

Exon	Start	End
ENSE00000770105	1478616	1478735
ENSE00001198974	1467480	1467577
ENSE00001199012	1470621	1470689
ENSE00001199034	1474812	1474858
ENSE00001199040	1474938	1475032
ENSE00001199046	1477505	1477596
ENSE00001199055	1478087	1478192
ENSE00001199058	1478410	1478492
ENSE00001199090	1482861	1483059
ENSE00001199094	1483610	1483725
ENSE00001199100	1467242	1467341
ENSE00001934540	1464186	1465752
ENSE00002373976	1468403	1468496
ENSE00002380165	1482478	1482558
ENSE00002424611	1468253	1468308
ENSE00003505584	1484148	1484303
ENSE00003542315	1479592	1479705
ENSE00003549184	1471071	1471147
ENSE00003566419	1467840	1467910
ENSE00003578811	1472123	1472228
ENSE00003583437	1470175	1470334
ENSE00003583955	1477891	1477971
ENSE00003596589	1471223	1471336
ENSE00003602861	1474610	1474690
ENSE00003632263	1479431	1479502
ENSE00003640996	1471907	1472024
ENSE00003642134	1470435	1470519
ENSE00003660811	1469531	1469614
ENSE00003664583	1467988	1468123
ENSE00003692646	1480706	1480885
ENSE00003790755	1480527	1480625
ENSE00003834258	1492413	1492686

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.4493 / max 343.6480, expressed in 1777 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163709	15.8695	1706
163713	7.2142	1685
163717	2.9548	595
163712	1.5016	911
163710	1.2524	891
163716	0.2291	112
163715	0.2247	31
163711	0.1653	70
163714	0.0328	5
163708	0.0049	1

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	98.61	gold quality
tibial nerve	UBERON:0001323	98.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.50	gold quality
popliteal artery	UBERON:0002250	98.46	gold quality
tibial artery	UBERON:0007610	98.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.41	gold quality
lower esophagus	UBERON:0013473	98.39	gold quality
mucosa of stomach	UBERON:0001199	98.37	gold quality
buccal mucosa cell	CL:0002336	98.35	gold quality
right coronary artery	UBERON:0001625	98.33	gold quality
aorta	UBERON:0000947	98.28	gold quality
sural nerve	UBERON:0015488	98.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.26	gold quality
omental fat pad	UBERON:0010414	98.25	gold quality
adipose tissue	UBERON:0001013	98.24	gold quality
peritoneum	UBERON:0002358	98.23	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.23	gold quality
stromal cell of endometrium	CL:0002255	98.22	gold quality
olfactory bulb	UBERON:0002264	98.18	gold quality
upper lobe of left lung	UBERON:0008952	98.15	gold quality
ascending aorta	UBERON:0001496	98.11	gold quality
thoracic aorta	UBERON:0001515	98.10	gold quality
apex of heart	UBERON:0002098	98.05	gold quality
body of uterus	UBERON:0009853	98.04	gold quality
left uterine tube	UBERON:0001303	97.97	gold quality
descending thoracic aorta	UBERON:0002345	97.97	gold quality
blood vessel layer	UBERON:0004797	97.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.92	gold quality
endocervix	UBERON:0000458	97.90	gold quality
transverse colon	UBERON:0001157	97.90	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	15.39
E-ANND-3	yes	10.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting MYO1C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-424-5P	99.89	71.90	2641

Literature-anchored findings (GeneRIF, showing 33)

• NM1 cooperates with a chromatin remodelling complex containing WSTF (Williams syndrome transcription factor) and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A member 5 protein (SNF2h). (PMID:16514417)
• WSTF-SNF2h-NM1 forms a platform in transcription while providing chromatin remodeling (PMID:16603771)
• Sensing molecular tension is crucial for a wide array of cellular processes. Myosin I dramatically alters its motile properties in response to tension. (PMID:18599791)
• identification of 6 heterozygous missense mutations in MYO1C and additional 5 heterozygous missense mutations in MYO1F in bilateral sensorineural hearing loss (PMID:19027848)
• NM1 facilitates maturation and accompanies export-competent preribosomal subunits to the nuclear pore complex, thus modulating export. (PMID:19729515)
• Myo1c plays a critical role in the translocation of Neph1 complexes in podocytes. Myo1c’s ability to interact with membranes, F-actin, Neph1, and nephrin indicates that it actively contributes to the dynamic organization of the filtration slit. (PMID:21402783)
• Myo1c regulates lipid raft recycling to control cell spreading, migration and Salmonella invasion. (PMID:22328521)
• This is the first report demonstrating that Myo1c is an important mediator of VEGF-induced VEGFR2 delivery to the cell surface and plays a role in angiogenic signaling. (PMID:23262137)
• Both nucleolar localization signals are functional and necessary for nucleolar localization of specifically myosin IC isoform B. (PMID:23438938)
• These results suggest a unique structural role for NM1 in which the interaction with SNF2h stabilizes B-WICH at the gene promoter and facilitates recruitment of the HAT PCAF (PMID:23555303)
• myosin 1c manipulations lead to loss of the actin filaments and to similar endoplasmic reticulum phenotype as observed after actin depolymerization. (PMID:24523293)
• The structural context and the chemical environment of Myo1c mutations that are involved in sensorineural hearing loss in humans are described and their impact on motor function is discussed. (PMID:24636949)
• The relationship between MYO1C and KAT6B suggests that the two are interacting in chromatin remodelling for gene expression in human masseter muscle. This is the nuclear myosin1 (NM1) function of MYO1C. (PMID:24698832)
• NM1 phosphorylation by GSK3beta blocks NM1 ubiquitination by UBR5 and degradation by the proteasome, leads to NM1 association with the chromatin and promotes rDNA transcription activation at G1. (PMID:24901984)
• Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway (PMID:25551774)
• Myo1c significantly increases the frequency of kinesin-1-driven microtubule-based runs that begin at actin/microtubule intersections. The actin-binding protein tropomyosin 2 abolishes Myo1c-specific effects on both run initiation and run termination. (PMID:25660542)
• Study presents structural demonstration of a cargo protein, Neph1, attached to Myo1c, providing novel insights into the role of Myo1c in intracellular movements of this critical slit diaphragm protein. (PMID:27044863)
• The results establish a mechanistic connection between the calcium regulation of the motor function of myosin IC in the cytoplasm and the induction of its import into the nucleus. (PMID:27192697)
• In glioblastoma 1321 N1 cells, we recently identified Myo1c as a new interactor of SHIP2. SHIP2 localization at lamellipodia and ruffles is impaired in Myo1c depleted cells. In the absence of Myo1c, N1 cells tend to associate to form clusters. (PMID:27246739)
• Upon DNA damage, an increase in the levels of chromatin bound motor protein nuclear myosin 1 (NM1) ensues, which appears to be functionally linked to Upsilon-H2AX signaling. (PMID:27365048)
• Overexpression of MYO1C is associated with gastric cancer. (PMID:27468717)
• Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B. (PMID:27716847)
• NTR(35), which harbors the R21G mutation, was unable to confer MYO1C(35)-like kinetic behavior. Thus, the NTRs affect the specific nucleotide-binding properties of MYO1C isoforms, adding to their kinetic diversity. We propose that this level of fine-tuning within MYO1C broadens its adaptability within cells. (PMID:28893906)
• E2 and NM1 associate via their N-terminal domains and this interaction is ATP dependent. (PMID:29179037)
• MYO1C stabilizes actin at the Golgi complex, facilitating the arrival of incoming transport carriers at the Golgi. (PMID:30872458)
• Isolation and identification in human blood serum of the proteins possessing the ability to bind with 48 kDa form of unconventional myosin 1c and their possible diagnostic and prognostic value. (PMID:33201534)
• Myosin 1C isoform A is a novel candidate diagnostic marker for prostate cancer. (PMID:34019593)
• SH3BGRL3 binds to myosin 1c in a calcium dependent manner and modulates migration in the MDA-MB-231 cell line. (PMID:34380438)
• Elevation of truncated (48 kDa) form of unconventional myosin 1C in blood serum correlates with severe Covid-19. (PMID:36736950)
• m[6]A-modified circRNA MYO1C participates in the tumor immune surveillance of pancreatic ductal adenocarcinoma through m[6]A/PD-L1 manner. (PMID:36781839)
• RAB31 in glioma-derived endothelial cells promotes glioma cell invasion via extracellular vesicle-mediated enrichment of MYO1C. (PMID:37953466)
• Recessive variants in MYO1C as a potential novel cause of proteinuric kidney disease. (PMID:38904753)
• A noncanonical E3 ubiquitin ligase RNF41-mediated MYO1C stability promotes prostate cancer metastasis by inducing actin remodeling. (PMID:39112516)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	myo1cb	ENSDARG00000061579
mus_musculus	Myo1c	ENSMUSG00000017774
rattus_norvegicus	Myo1c	ENSRNOG00000004072

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), MYH2 (ENSG00000125414), MYO1B (ENSG00000128641), MYO5C (ENSG00000128833), CGNL1 (ENSG00000128849), MYH8 (ENSG00000133020), MYH10 (ENSG00000133026), MYH11 (ENSG00000133392), MYO18B (ENSG00000133454), CCDC102A (ENSG00000135736), MYO1G (ENSG00000136286), MYO7A (ENSG00000137474), MYO1F (ENSG00000142347), CGN (ENSG00000143375), TMF1 (ENSG00000144747), MYH15 (ENSG00000144821), MYO10 (ENSG00000145555), CCDC102B (ENSG00000150636), MYO1E (ENSG00000157483), CCDC158 (ENSG00000163749), MYO1A (ENSG00000166866), MYO5B (ENSG00000167306), MYO7B (ENSG00000169994), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535)

Protein

Protein identifiers

Unconventional myosin-Ic — O00159 (reviewed: O00159)

Alternative names: Myosin I beta

All UniProt accessions (6): O00159, F5H6E2, I3L2C3, I3L3F5, I3L3Y6, I3L501

UniProt curated annotations — full annotation on UniProt →

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. Involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation.

Subunit / interactions. Interacts (via its IQ motifs) with CABP1 and CIB1; the interaction with CABP1 and CIB1 is calcium-dependent. Interacts (via tail domain) with PLEKHB1 (via PH domain); the interaction is not affected by the presence or absence of calcium and CALM. Interacts with POLR1A. Interacts with POLR2A. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Interacts (via its IQ motifs) with CALM; this precludes interaction with YWHAB. Interacts with YWHAB; this precludes interaction with CALM. Interacts with RPS6. Interacts with actin. Interacts with LLPH. Interacts with GLUT4. Interacts (via its IQ motifs) with SH3BGRL3; the interaction is dependent on calcium and takes place at membrane ruffles.

Subcellular location. Cytoplasm. Nucleus. Cell cortex. Cell projection. Stereocilium membrane. Cytoplasmic vesicle. Ruffle membrane Nucleus. Nucleoplasm. Nucleolus.

Post-translational modifications. Isoform 2 contains a N-acetylmethionine at position 1.

Domain organisation. Binds directly to large unilamellar vesicles (LUVs) containing phosphatidylinositol 4,5-bisphosphate (PIP2) or inositol 1,4,5-trisphosphate (InsP3). The PIP2-binding site corresponds to the myosin tail domain (PH-like) present in its tail domain.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.

Isoforms (3)

UniProt ID	Names	Canonical?
O00159-1	1, A	yes
O00159-2	2, C
O00159-3	3, B, Nuclear myosin 1, NM1, NMI

RefSeq proteins (4): NP_001074248, NP_001074419, NP_001350784, NP_203693 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR001609	Myosin_head_motor_dom-like	Domain
IPR010926	Myosin_TH1	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036072	MYSc_Myo1	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00063, PF00612, PF06017

UniProt features (88 total): helix 31, strand 22, sequence conflict 10, modified residue 7, domain 4, binding site 4, splice variant 2, sequence variant 2, mutagenesis site 2, turn 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4BYF	X-RAY DIFFRACTION	2.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00159-F1	84.56	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 88; 96; 139–148; 192–196

Post-translational modifications (7): 383, 408, 486, 536, 864, 1041, 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
736	abolishes interaction with ywhab.
736	increases affinity for ywhab.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-199991	Membrane Trafficking
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-9658195	Leishmania infection
R-HSA-9659379	Sensory processing of sound
R-HSA-9664407	Parasite infection
R-HSA-9664417	Leishmania phagocytosis
R-HSA-9709957	Sensory Perception
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 710 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_VESICLE_LOCALIZATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_MACROPHAGE_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, BECKER_TAMOXIFEN_RESISTANCE_UP, MODULE_45, GOBP_APICAL_JUNCTION_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_PROTEIN_TARGETING, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE

GO Biological Process (15): chromatin remodeling (GO:0006338), protein targeting to membrane (GO:0006612), endocytosis (GO:0006897), actin filament organization (GO:0007015), actin filament-based movement (GO:0030048), vesicle transport along actin filament (GO:0030050), positive regulation of cell migration (GO:0030335), vascular endothelial growth factor signaling pathway (GO:0038084), positive regulation of transcription by RNA polymerase I (GO:0045943), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of transcription by RNA polymerase III (GO:0045945), cellular response to type II interferon (GO:0071346), positive regulation of protein targeting to membrane (GO:0090314), positive regulation of cellular response to insulin stimulus (GO:1900078), regulation of bicellular tight junction assembly (GO:2000810)

GO Molecular Function (10): microfilament motor activity (GO:0000146), signaling receptor binding (GO:0005102), calmodulin binding (GO:0005516), ATP binding (GO:0005524), small GTPase binding (GO:0031267), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (29): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), microvillus (GO:0005902), brush border (GO:0005903), cell cortex (GO:0005938), basal plasma membrane (GO:0009925), actin cytoskeleton (GO:0015629), membrane (GO:0016020), lateral plasma membrane (GO:0016328), unconventional myosin complex (GO:0016461), nuclear body (GO:0016604), cytoplasmic vesicle membrane (GO:0030659), filamentous actin (GO:0031941), ruffle membrane (GO:0032587), membrane raft (GO:0045121), phagocytic vesicle (GO:0045335), stereocilium membrane (GO:0060171), extracellular exosome (GO:0070062), B-WICH complex (GO:0110016), nucleus (GO:0005634), actin filament (GO:0005884), myosin complex (GO:0016459), cytoplasmic vesicle (GO:0031410), stereocilium (GO:0032420), cell projection (GO:0042995), plasma membrane bounded cell projection (GO:0120025)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Sensory processing of sound	2
Membrane Trafficking	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Leishmania phagocytosis	1
Positive epigenetic regulation of rRNA expression	1
Immune System	1
Vesicle-mediated transport	1
Innate Immune System	1
Disease	1
Parasitic Infection Pathways	1
Sensory Perception	1
Leishmania infection	1
Parasite infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
positive regulation of DNA-templated transcription	3
positive regulation of cellular process	2
protein binding	2
nuclear lumen	2
intracellular membraneless organelle	2
cytoplasm	2
cell periphery	2
chromatin organization	1
protein targeting	1
establishment of protein localization to membrane	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
actin filament-based process	1
actin filament-based movement	1
actin filament-based transport	1
vesicle cytoskeletal trafficking	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to vascular endothelial growth factor stimulus	1
regulation of transcription by RNA polymerase I	1
transcription by RNA polymerase I	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
regulation of transcription by RNA polymerase III	1
transcription by RNA polymerase III	1
response to type II interferon	1
cellular response to cytokine stimulus	1
protein targeting to membrane	1
regulation of protein targeting to membrane	1
positive regulation of establishment of protein localization	1
cellular response to insulin stimulus	1
positive regulation of response to stimulus	1
regulation of cellular response to insulin stimulus	1

Protein interactions and networks

STRING

1224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYO1C	MYO1B	O43795	758
MYO1C	A0A0A6YYL4	A0A0A6YYL4	674
MYO1C	ACTB	P02570	659
MYO1C	POTEF	A5A3E0	588
MYO1C	DYNLL1	P63167	549
MYO1C	CARMIL1	Q5VZK9	532
MYO1C	SLC2A4	P14672	468
MYO1C	CABP5	Q9NP86	440
MYO1C	PTEN	P60484	439
MYO1C	KDM1A	O60341	424
MYO1C	MYO1D	O94832	395
MYO1C	CAV1	Q03135	392
MYO1C	KRT1	P04264	388
MYO1C	ESR1	P03372	335
MYO1C	MYO1E	Q12965	314

IntAct

181 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
TWF1	MYO1C	psi-mi:“MI:0914”(association)	0.530
MYO1C	TMOD1	psi-mi:“MI:0914”(association)	0.530
MYO1C	CALM3	psi-mi:“MI:0915”(physical association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
SHC1	BCR/ABL fusion	psi-mi:“MI:0914”(association)	0.460
ESR1		psi-mi:“MI:0914”(association)	0.460
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
	MYO1C	psi-mi:“MI:0407”(direct interaction)	0.440
MYO1C		psi-mi:“MI:0915”(physical association)	0.400
MYO1C	POLR1E	psi-mi:“MI:0403”(colocalization)	0.370
PYCARD	MYO1C	psi-mi:“MI:0914”(association)	0.350
SUN2	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (555): MYO1C (Affinity Capture-MS), MYO1C (Affinity Capture-MS), MYO1C (Affinity Capture-MS), MYO1C (Affinity Capture-MS), CBL (Two-hybrid), MYO1C (Affinity Capture-MS), MYO1C (Affinity Capture-MS), MYO1C (Affinity Capture-Western), RRN3 (Affinity Capture-Western), ACTA1 (Affinity Capture-Western), POLR1B (Affinity Capture-Western), MYO1C (Affinity Capture-Western), MYO1C (Reconstituted Complex), ACTG1 (Affinity Capture-MS), ACTN4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JXT6, A0JMK5, A6QLT4, A7MB43, A7YW45, G5EBH0, G5ED68, O00159, O13819, P10687, P10894, P25455, P29074, P51432, Q01970, Q13496, Q13613, Q15111, Q27966, Q32NH8, Q3USB7, Q4R5M3, Q52KU6, Q5EB32, Q5F452, Q5R6F6, Q5R9S3, Q5ZLA6, Q62688, Q63355, Q6AXQ4, Q6TEL0, Q8CIG8, Q8K394, Q8VE11, Q92002, Q96EF0, Q96QG7, Q99JE6, Q9NQ66

Diamond homologs: A0MP03, A1C4A5, A1DBH2, A2R5J1, A3LYL7, A4RE77, A5DKH0, A5E4A8, A5PF48, A6SED8, A6ZMG6, A6ZZJ1, A7EK16, A7TDZ8, A8N2Y6, A8PWF6, B0CRJ3, B0I1T2, B0Y9Q4, D3ZJP6, E7F9L8, E9Q634, F1PRN2, F4HWY6, F4I5Q6, F4IUG9, F4IVR7, F4JM19, F4K5J1, K7U9N8, O00159, O00160, O43795, O88329, O94832, P0CP00, P0CP01, P10568, P10569, P19706

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
DNM2	up-regulates	MYO1C	binding
MYO1C	“form complex”	“B-WICH complex”	binding
GSK3B	“up-regulates activity”	MYO1C	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Tie2 Signaling	5	26.6×	3e-04
VEGFR2 mediated cell proliferation	5	25.3×	3e-04
Downstream signal transduction	6	20.2×	2e-04
FCERI mediated MAPK activation	5	15.3×	1e-03
Signaling by CSF1 (M-CSF) in myeloid cells	5	15.3×	1e-03
RET signaling	6	13.8×	7e-04
Signaling by FGFR1 in disease	5	13.0×	2e-03
Signaling by RAF1 mutants	5	12.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
G2/M transition of mitotic cell cycle	5	11.2×	6e-03
insulin receptor signaling pathway	6	9.6×	5e-03
Ras protein signal transduction	6	8.9×	5e-03
obsolete positive regulation of NF-kappaB transcription factor activity	6	8.9×	5e-03
protein autophosphorylation	7	7.3×	5e-03
protein phosphorylation	10	4.9×	5e-03
intracellular signal transduction	14	3.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

445 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	220
Likely benign	77
Benign	91

Top pathogenic / likely-pathogenic (0)

SpliceAI

5758 predictions. Top by Δscore:

Variant	Effect	Δscore
17:1467337:TGATG:T	acceptor_gain	1.0000
17:1467338:GATG:G	acceptor_gain	1.0000
17:1467340:TG:T	acceptor_gain	1.0000
17:1467342:C:CC	acceptor_gain	1.0000
17:1467474:CCTCA:C	donor_loss	1.0000
17:1467475:CTCAC:C	donor_loss	1.0000
17:1467478:A:AC	donor_gain	1.0000
17:1467478:A:C	donor_loss	1.0000
17:1467478:ACCTG:A	donor_gain	1.0000
17:1467479:C:CC	donor_gain	1.0000
17:1467479:CCTG:C	donor_gain	1.0000
17:1467479:CCTGC:C	donor_gain	1.0000
17:1467482:G:A	donor_gain	1.0000
17:1467573:TCTCC:T	acceptor_gain	1.0000
17:1467574:CTCC:C	acceptor_gain	1.0000
17:1467574:CTCCC:C	acceptor_gain	1.0000
17:1467575:TCC:T	acceptor_gain	1.0000
17:1467575:TCCCT:T	acceptor_gain	1.0000
17:1467576:CC:C	acceptor_gain	1.0000
17:1467576:CCC:C	acceptor_gain	1.0000
17:1467577:CC:C	acceptor_gain	1.0000
17:1467578:C:CC	acceptor_gain	1.0000
17:1467578:CTGG:C	acceptor_loss	1.0000
17:1467587:C:CT	acceptor_gain	1.0000
17:1467587:C:T	acceptor_gain	1.0000
17:1467588:A:T	acceptor_gain	1.0000
17:1467835:GGCAC:G	donor_loss	1.0000
17:1467836:GCAC:G	donor_loss	1.0000
17:1467837:CACCT:C	donor_loss	1.0000
17:1467838:ACC:A	donor_loss	1.0000

AlphaMissense

6941 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:1472151:G:C	C625W	1.000
17:1477928:A:G	L482P	1.000
17:1478171:A:C	N439K	1.000
17:1478171:A:T	N439K	1.000
17:1478430:A:C	F425L	1.000
17:1478430:A:T	F425L	1.000
17:1478432:A:G	F425L	1.000
17:1478443:T:A	D421V	1.000
17:1478443:T:G	D421A	1.000
17:1480809:C:G	R235P	1.000
17:1482515:C:A	R197M	1.000
17:1482517:G:C	S196R	1.000
17:1482517:G:T	S196R	1.000
17:1482519:T:G	S196R	1.000
17:1482529:G:C	N192K	1.000
17:1482529:G:T	N192K	1.000
17:1482551:C:T	G185E	1.000
17:1482973:C:T	G145D	1.000
17:1482988:C:T	G140E	1.000
17:1484179:A:G	L67P	1.000
17:1467564:A:G	L994P	0.999
17:1467887:C:G	D974H	0.999
17:1467897:G:C	S970R	0.999
17:1467897:G:T	S970R	0.999
17:1467899:T:G	S970R	0.999
17:1468103:T:A	K927N	0.999
17:1468103:T:G	K927N	0.999
17:1468110:A:T	V925D	0.999
17:1471942:A:C	F662L	0.999
17:1471942:A:T	F662L	0.999

dbSNP variants (sampled 300 via entrez): RS1000102327 (17:1492333 C>A,G,T), RS1000209079 (17:1469270 G>A,C), RS1000578774 (17:1468199 C>A,T), RS1000607892 (17:1471455 G>A,C,T), RS1000703050 (17:1475454 C>A), RS1000731893 (17:1471007 G>A,T), RS1000780973 (17:1483810 A>C,G), RS1000835320 (17:1486862 C>T), RS1000927948 (17:1480002 C>A,T), RS1001086956 (17:1490223 C>A,T), RS1001160876 (17:1491679 C>G,T), RS1001163819 (17:1483999 G>A), RS1001261091 (17:1479175 A>G), RS1001394818 (17:1488129 G>A,T), RS1001421857 (17:1488718 G>A)

Disease associations

OMIM: gene MIM:606538 | disease phenotypes: MIM:156000, MIM:247200

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Disputed	AD

Mondo (3): Meniere disease (MONDO:0007972), Miller-Dieker lissencephaly syndrome (MONDO:0009532), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (3): Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Miller-Dieker syndrome (Orphanet:531), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008575	Meniere Disease	C09.218.568.217.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases methylation, affects expression, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	2
Cadmium	increases palmitoylation, decreases expression, decreases reaction, increases abundance	2
Doxorubicin	affects expression, decreases expression	2
Smoke	decreases expression	2
Valproic Acid	increases methylation, affects expression, decreases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, increases expression, affects cotreatment	1
decabromobiphenyl ether	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
nivalenol	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
entinostat	increases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

31 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT04674735	PHASE1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT04218123	PHASE2/PHASE3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	PHASE1/PHASE2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	EARLY_PHASE1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	RECRUITING	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?
NCT04935970	Not specified	UNKNOWN	Metabolic Disorders and Vertigo
NCT05322538	Not specified	NOT_YET_RECRUITING	Menier’s Disease - Bone Density Study
NCT05328895	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT05424302	Not specified	RECRUITING	Effect of Peripheral Vestibular Disease Location on Outcomes Following Home-based Virtual Reality Vestibular Therapy
NCT05582148	Not specified	UNKNOWN	Meniere Disease and Hearing Aids
NCT05844657	Not specified	COMPLETED	Comprehensive Evaluation in Patients With Meniere’s Disease
NCT05960786	Not specified	COMPLETED	Treating the Symptoms of Vertigo in a Real-world Setting Using the OtoBand
NCT06278129	Not specified	UNKNOWN	Evaluation of the Diagnostic and Prognostic Efficacy of MRI in Acute Sensorineural Hearing Loss and Ménière’s Disease
NCT06544590	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT07272473	Not specified	RECRUITING	Effects of Cervical Mobilization on Dizziness, Balance, and Joint Position Sense in Patients With Meniere’s Disease