MYH14

Summary

MYH14 (myosin heavy chain 14, HGNC:23212) is a protein-coding gene on chromosome 19q13.33, encoding Myosin-14 (Q7Z406). Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.

This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79784 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant nonsyndromic hearing loss 4A (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,584 total — 16 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001145809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23212
Approved symbol	MYH14
Name	myosin heavy chain 14
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13881, KIAA2034, MHC16, MYH17
Ensembl gene	ENSG00000105357
Ensembl biotype	protein_coding
OMIM	608568
Entrez	79784

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000376970, ENST00000425460, ENST00000595016, ENST00000596571, ENST00000597072, ENST00000598205, ENST00000599920, ENST00000642316, ENST00000642980, ENST00000646861, ENST00000910081, ENST00000910082, ENST00000943710, ENST00000943711, ENST00000943712, ENST00000943713

RefSeq mRNA: 3 — MANE Select: NM_001145809 NM_001077186, NM_001145809, NM_024729

CCDS: CCDS46151, CCDS54295, CCDS59411

Canonical transcript exons

ENST00000642316 — 43 exons

Exon	Start	End
ENSE00000899930	50223247	50223349
ENSE00000900047	50249650	50249823
ENSE00000900051	50250515	50250688
ENSE00000900060	50252639	50252753
ENSE00001059505	50261475	50261635
ENSE00001059523	50281594	50281842
ENSE00001059524	50263312	50263420
ENSE00001125256	50286482	50286694
ENSE00001125499	50268161	50268367
ENSE00001125505	50266877	50267008
ENSE00001125634	50210363	50210770
ENSE00001190531	50257299	50257486
ENSE00001337745	50272560	50272731
ENSE00001399835	50255220	50255318
ENSE00001408221	50271849	50271972
ENSE00001616058	50224154	50224177
ENSE00001724497	50259144	50259265
ENSE00001780190	50260646	50260715
ENSE00003538273	50309005	50309177
ENSE00003549367	50301661	50301869
ENSE00003553804	50307049	50307157
ENSE00003572578	50290887	50291048
ENSE00003596943	50289436	50289648
ENSE00003644341	50293564	50293687
ENSE00003663681	50293233	50293321
ENSE00003684771	50292261	50292389
ENSE00003713514	50271409	50271546
ENSE00003717649	50226903	50226966
ENSE00003722218	50230525	50230623
ENSE00003723064	50280231	50280383
ENSE00003725518	50278083	50278289
ENSE00003726655	50280037	50280141
ENSE00003730737	50217615	50217771
ENSE00003732887	50276757	50276901
ENSE00003733339	50223083	50223110
ENSE00003734450	50275991	50276203
ENSE00003736830	50248987	50249139
ENSE00003743055	50244242	50244337
ENSE00003745853	50225585	50225677
ENSE00003748715	50231930	50232070
ENSE00003754209	50247004	50247122
ENSE00003829360	50309640	50310540
ENSE00003897919	50203622	50203671

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 98.85.

FANTOM5 (CAGE): breadth broad, TPM avg 8.9435 / max 360.0010, expressed in 651 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177126	4.3132	608
177127	3.8970	436
177125	0.5920	16
177128	0.1413	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.85	gold quality
ileal mucosa	UBERON:0000331	98.54	gold quality
gastrocnemius	UBERON:0001388	97.39	gold quality
lower esophagus mucosa	UBERON:0035834	96.99	gold quality
skin of leg	UBERON:0001511	96.13	gold quality
skin of abdomen	UBERON:0001416	95.90	gold quality
apex of heart	UBERON:0002098	95.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.57	gold quality
muscle of leg	UBERON:0001383	95.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.15	gold quality
esophagus mucosa	UBERON:0002469	94.01	gold quality
minor salivary gland	UBERON:0001830	93.58	gold quality
zone of skin	UBERON:0000014	93.51	gold quality
tibialis anterior	UBERON:0001385	93.39	silver quality
left lobe of thyroid gland	UBERON:0001120	93.17	gold quality
right lobe of thyroid gland	UBERON:0001119	93.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.01	gold quality
nasal cavity epithelium	UBERON:0005384	92.94	gold quality
heart left ventricle	UBERON:0002084	92.81	gold quality
cervix squamous epithelium	UBERON:0006922	92.77	silver quality
muscle organ	UBERON:0001630	92.64	gold quality
mouth mucosa	UBERON:0003729	92.52	gold quality
sural nerve	UBERON:0015488	92.50	gold quality
cardiac ventricle	UBERON:0002082	92.35	gold quality
thyroid gland	UBERON:0002046	91.92	gold quality
diaphragm	UBERON:0001103	91.74	silver quality
right uterine tube	UBERON:0001302	91.64	gold quality
saliva-secreting gland	UBERON:0001044	91.47	gold quality
transverse colon	UBERON:0001157	91.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.28	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	48.67
E-ANND-3	yes	12.04
E-CURD-53	no	199.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting MYH14, 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-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-6738-3P	99.03	67.14	1326

Literature-anchored findings (GeneRIF, showing 23)

• mutational screening in a large series of 300 hearing-impaired patients from Italy, Spain, and Belgium and in a German kindred linked to DFNA4 (PMID:15015131)
• mutations and alternative splicing alter the enzymatic and motile activity of nonmuscle myosins II-B and II-C (PMID:15845534)
• data do not support the involvement of MYH14 in cleft lip and palate among the Italian population (PMID:18471249)
• One SNP in PCDH15 (rs7095441) and two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. (PMID:19183343)
• the alternatively spliced isoform of non-muscle myosin II-C is not regulated by myosin light chain phosphorylation (PMID:19240025)
• Mutation in MYH14 gene can cause dominant non-syndromic hearing impairment in Asian population, suggesting that MYH14 gene can be a disease-causing gene of Chinese patients with hearing impairment. (PMID:20533261)
• data identify CEACAM16 as an alpha-tectorin-interacting protein that concentrates at the point of attachment of the TM to the stereocilia and, when mutated, results in ADNSHL at the DFNA4 locus (PMID:21368133)
• kinetic and functional characterization of the motor domains of human nonmuscle myosin-2C isoforms (PMID:21478157)
• A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14 (PMID:21480433)
• the alterations of the MYH14 gene may contribute to Myotonic dystrophy type 1 molecular pathogenesis. (PMID:21872659)
• Results support the hypothesis that there is another DFNA gene upstream of the MYH14 gene and it may be linked to the DFNA4 locus. (PMID:23273769)
• The data show that although NM IIA and IIB form filaments with similar properties, NM IIC forms filaments that are less well suited to roles such as tension maintenance within the cell. (PMID:24072716)
• phosphorylation of human cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice (PMID:26124132)
• This is the first identification of mutations in MYH14 as a cause of Anorectal malformations. (PMID:28191911)
• By reporting two novel variants of MYH14, we suggest that the present study extends the phenotypic spectrum of autosomal dominant MYH14 variants to include nonsyndromic, severe-to-profound hearing loss with prelingual onset. (PMID:28221712)
• confirm faster ADP release from R694N actomyosin mutant, but is not as dramatic as the difference of kinetics of ADP release in the alpha and beta isoforms. (PMID:30654937)
• a truncation mutation in the cMLCK gene p.Pro639Valfs*15 can be associated with significant impairment of MLC2v phosphorylation and possibly with development of DCM, although a larger study of DCM patients is required to determine the prevalence of this mutation and further strengthen its association with disease development. (PMID:30690923)
• We describe the third family carrying the R941L mutation in MYH14, and demonstrate that the R941L mutation impairs non-muscle myosin protein function. To better understand the molecular basis of the peripheral neuropathy phenotype associated with the R941L mutation, which has been hindered by the fact that NMIIC is largely uncharacterized, we have established a previously unrecognized biological role for NMIIC in mediatin (PMID:31231018)
• A novel MYH14 mutation in a Chinese family with autosomal dominant nonsyndromic hearing loss. (PMID:32711451)
• Mutations in myosin S2 alter cardiac myosin-binding protein-C interaction in hypertrophic cardiomyopathy in a phosphorylation-dependent manner. (PMID:34051236)
• Distinct roles of nonmuscle myosin II isoforms for establishing tension and elasticity during cell morphodynamics. (PMID:34374341)
• Prevalence and Clinical Characteristics of Hearing Loss Caused by MYH14 Variants. (PMID:34681017)
• Identification of novel MYH14 variants in families with autosomal dominant sensorineural hearing loss. (PMID:38352997)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	myh14	ENSDARG00000073732
mus_musculus	Myh14	ENSMUSG00000030739
rattus_norvegicus	Myh14	ENSRNOG00000020014

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), 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), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Myosin-14 — Q7Z406 (reviewed: Q7Z406)

Alternative names: Myosin heavy chain 14, Myosin heavy chain, non-muscle IIc, Non-muscle myosin heavy chain IIc

All UniProt accessions (4): A0A2R8Y454, A0A2R8Y4C3, Q7Z406, M0QY43

UniProt curated annotations — full annotation on UniProt →

Function. Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.

Subunit / interactions. Myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).

Tissue specificity. High levels of expression are found in brain (highest in corpus callosum), heart, kidney, liver, lung, small intestine, colon and skeletal muscle. Expression is low in organs composed mainly of smooth muscle, such as aorta, uterus and urinary bladder. No detectable expression is found in thymus, spleen, placenta and lymphocytes.

Disease relevance. Deafness, autosomal dominant, 4A (DFNA4A) [MIM:600652] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Peripheral neuropathy, myopathy, hoarseness, and hearing loss (PNMHH) [MIM:614369] A complex phenotype of progressive peripheral neuropathy and distal myopathy, with later onset of hoarseness and hearing loss. Affected individuals develop distal muscle weakness at a mean age of 10.6 years, followed by progressive atrophy of these muscles. The lower limbs are more severely affected than the upper limbs, and the muscle weakness first affects anterior leg muscles and later posterior leg muscles. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q7Z406-1	1	yes
Q7Z406-2	2
Q7Z406-4	4
Q7Z406-5	5
Q7Z406-6	6

RefSeq proteins (3): NP_001070654, NP_001139281, NP_079005 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR001609	Myosin_head_motor_dom-like	Domain
IPR002928	Myosin_tail	Domain
IPR004009	SH3_Myosin	Domain
IPR008989	Myosin_S1_N	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00063, PF01576, PF02736

UniProt features (105 total): helix 32, strand 21, sequence variant 11, turn 7, modified residue 7, sequence conflict 7, region of interest 6, splice variant 5, domain 3, compositionally biased region 2, initiator methionine 1, chain 1, coiled-coil region 1, binding site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5I4E	X-RAY DIFFRACTION	2.25
5JLH	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z406-F1	74.84	0.17

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 (1): 198–205

Post-translational modifications (7): 2, 60, 1194, 1969, 1980, 1983, 1989

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-5625900	RHO GTPases activate CIT
R-HSA-5627117	RHO GTPases Activate ROCKs
R-HSA-5627123	RHO GTPases activate PAKs
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-373755	Semaphorin interactions
R-HSA-400685	Sema4D in semaphorin signaling
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 229 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, CCAWYNNGAAR_UNKNOWN, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, KEGG_TIGHT_JUNCTION, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_SKELETAL_MUSCLE_CONTRACTION, RODRIGUES_NTN1_TARGETS_DN, MODULE_331, KEGG_VIRAL_MYOCARDITIS, AP1_Q4_01, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_CONTRACTION

GO Biological Process (10): mitotic cytokinesis (GO:0000281), skeletal muscle contraction (GO:0003009), mitochondrion organization (GO:0007005), skeletal muscle tissue development (GO:0007519), sensory perception of sound (GO:0007605), regulation of cell shape (GO:0008360), neuronal action potential (GO:0019228), actin filament-based movement (GO:0030048), actomyosin structure organization (GO:0031032), vocalization behavior (GO:0071625)

GO Molecular Function (8): microfilament motor activity (GO:0000146), calmodulin binding (GO:0005516), ATP binding (GO:0005524), 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 (14): stress fiber (GO:0001725), cytoplasm (GO:0005737), cytosol (GO:0005829), brush border (GO:0005903), membrane (GO:0016020), myosin II complex (GO:0016460), growth cone (GO:0030426), myosin filament (GO:0032982), actomyosin (GO:0042641), extracellular exosome (GO:0070062), myosin II filament (GO:0097513), myosin complex (GO:0016459), axon (GO:0030424), supramolecular fiber (GO:0099512)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
RHO GTPase Effectors	4
Axon guidance	2
EPH-Ephrin signaling	1
Sema4D in semaphorin signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Semaphorin interactions	1
Nervous system development	1
Developmental Biology	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
myosin complex	2
actin cytoskeleton	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
striated muscle contraction	1
musculoskeletal movement	1
organelle organization	1
striated muscle tissue development	1
skeletal muscle organ development	1
sensory perception of mechanical stimulus	1
regulation of cell morphogenesis	1
regulation of biological quality	1
action potential	1
transmission of nerve impulse	1
actin filament-based process	1
actin cytoskeleton organization	1
behavior	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
actin binding	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
cytoskeletal protein binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular anatomical structure	1
cytoplasm	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
site of polarized growth	1

Protein interactions and networks

STRING

1172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYH14	MRPS12	O15235	939
MYH14	BAX	P55269	748
MYH14	GJB2	P29033	705
MYH14	CEACAM16	Q2WEN9	585
MYH14	DMPK	Q09013	583
MYH14	COG3	Q96JB2	502
MYH14	KCNQ4	P56696	461
MYH14	TECTA	O75443	448
MYH14	DMKN	Q6E0U4	418
MYH14	CIB2	O75838	407
MYH14	CDH23	Q9H251	403
MYH14	PNPT1	Q8TCS8	394
MYH14	KARS1	Q15046	393
MYH14	HBB	P02023	392
MYH14	OTOA	Q7RTW8	392

IntAct

129 interactions, top by confidence:

A	B	Type	Score
CHUK	IKBKB	psi-mi:“MI:0914”(association)	0.960
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
MYL6	MYH9	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
MYL6	MYL6B	psi-mi:“MI:0914”(association)	0.530
S100A4	OIP5	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
	AP3D1	psi-mi:“MI:0914”(association)	0.460
	MYL12B	psi-mi:“MI:0914”(association)	0.460
TRPM7	MYH14	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
TRPM6	MYH14	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
EPHA6	HGS	psi-mi:“MI:0914”(association)	0.420

BioGRID (268): MYH14 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), MYH14 (Affinity Capture-MS), DNMT1 (Affinity Capture-MS), ECH1 (Affinity Capture-MS), ABCD3 (Affinity Capture-MS), SRI (Affinity Capture-MS), SSR3 (Affinity Capture-MS), NUP155 (Affinity Capture-MS)

ESM2 similar proteins: A4II46, A4Q9F4, B2RTY4, C9J798, E1BPK6, E7EZG2, E7F3F0, F4K0A6, O43795, O70293, O88910, O88954, O94806, O95267, P42694, P46735, P97711, Q05096, Q13368, Q13459, Q15139, Q3LAC4, Q5R6F6, Q5SV80, Q5XIS9, Q62101, Q63358, Q69ZK0, Q6DFV5, Q6NYU2, Q6Y5D8, Q6ZQ82, Q70Z35, Q7Z406, Q8AVG0, Q8BZ03, Q8C170, Q8K1Y2, Q8N9B8, Q8TCU6

Diamond homologs: A2AQP0, A7E2Y1, F1PT61, F4I507, F4I5Q6, F4IVR7, G3UW82, K7U9N8, O08638, O14157, O94477, P02563, P02564, P02565, P02566, P02567, P04461, P05659, P05661, P08799, P08964, P10587, P11055, P12844, P12845, P12847, P12882, P12883, P13533, P13535, P13538, P13539, P13540, P13541, P13542, P14105, P19524, P21271, P24733, P32492

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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
RHO GTPases activate PAKs	6	31.1×	6e-06
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	29.7×	6e-06
Tie2 Signaling	5	28.6×	8e-05
Downstream signal transduction	6	21.8×	4e-05
Signaling by FGFR1 in disease	6	16.7×	1e-04
FCERI mediated MAPK activation	5	16.5×	6e-04
Signaling by CSF1 (M-CSF) in myeloid cells	5	16.5×	6e-04
Signaling by SCF-KIT	6	14.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1584 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	12
Uncertain significance	810
Likely benign	354
Benign	185

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1073575	NM_001145809.2(MYH14):c.979del (p.Leu327fs)	Pathogenic
1185649	NM_001145809.2(MYH14):c.5990del (p.Thr1997fs)	Pathogenic
1454721	NM_001145809.2(MYH14):c.1304_1305del (p.Val435fs)	Pathogenic
2117681	NM_001145809.2(MYH14):c.3598dup (p.Arg1200fs)	Pathogenic
2135075	NM_001145809.2(MYH14):c.5452_5458del (p.Arg1818fs)	Pathogenic
2196	NM_001145809.2(MYH14):c.20C>A (p.Ser7Ter)	Pathogenic
2198	NM_001145809.2(MYH14):c.2299C>A (p.Arg767Ser)	Pathogenic
2796747	NM_001145809.2(MYH14):c.2518C>T (p.Arg840Ter)	Pathogenic
2830002	NM_001145809.2(MYH14):c.4390C>T (p.Gln1464Ter)	Pathogenic
2892776	NM_001145809.2(MYH14):c.3153_3160del (p.Asn1052fs)	Pathogenic
2984879	NM_001145809.2(MYH14):c.1261C>T (p.Arg421Ter)	Pathogenic
30739	NM_001145809.2(MYH14):c.2921G>T (p.Arg974Leu)	Pathogenic
3250385	NM_001145809.2(MYH14):c.1368C>G (p.Tyr456Ter)	Pathogenic
3629635	NM_001145809.2(MYH14):c.3721_3722del (p.Leu1241fs)	Pathogenic
4769573	NM_001145809.2(MYH14):c.1534C>T (p.Gln512Ter)	Pathogenic
4797050	NM_001145809.2(MYH14):c.3301dup (p.Leu1101fs)	Pathogenic
1012461	NM_001145809.2(MYH14):c.1955del (p.Gly652fs)	Likely pathogenic
1469926	NM_001145809.2(MYH14):c.2424+1G>A	Likely pathogenic
1708295	NM_001145809.2(MYH14):c.4609del (p.Arg1537fs)	Likely pathogenic
2505164	NM_001145809.2(MYH14):c.571G>C (p.Asp191His)	Likely pathogenic
2860825	NM_001145809.2(MYH14):c.3171+1G>T	Likely pathogenic
3250384	NM_001145809.2(MYH14):c.587G>T (p.Cys196Phe)	Likely pathogenic
3250386	NM_001145809.2(MYH14):c.693+1G>A	Likely pathogenic
3345034	NM_001145809.2(MYH14):c.4741del (p.Val1581fs)	Likely pathogenic
3777223	NM_001145809.2(MYH14):c.571G>T (p.Asp191Tyr)	Likely pathogenic
3779986	NM_001145809.2(MYH14):c.1831-1G>A	Likely pathogenic
4081521	NM_001145809.2(MYH14):c.4889_4890del (p.Leu1630fs)	Likely pathogenic
4739060	NM_001145809.2(MYH14):c.4752+1G>A	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

13087 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50210534:T:A	W57R	1.000
19:50210534:T:C	W57R	1.000
19:50210665:C:A	N100K	1.000
19:50210665:C:G	N100K	1.000
19:50210739:T:C	L125P	1.000
19:50223277:C:A	N207K	1.000
19:50223277:C:G	N207K	1.000
19:50225604:T:C	L238P	1.000
19:50226924:T:C	F270L	1.000
19:50226925:T:C	F270S	1.000
19:50226926:T:A	F270L	1.000
19:50226926:T:G	F270L	1.000
19:50249111:T:C	L477P	1.000
19:50249114:A:C	D478A	1.000
19:50249114:A:T	D478V	1.000
19:50249125:T:C	F482L	1.000
19:50249127:T:A	F482L	1.000
19:50249127:T:G	F482L	1.000
19:50249696:T:C	L502P	1.000
19:50252660:T:A	W610R	1.000
19:50252660:T:C	W610R	1.000
19:50257460:T:C	C695R	1.000
19:50259181:T:C	L716P	1.000
19:50261515:G:A	G781E	1.000
19:50261557:T:C	L795P	1.000
19:50261569:G:C	R799P	1.000
19:50210536:G:C	W57C	0.999
19:50210536:G:T	W57C	0.999
19:50210558:T:C	F65L	0.999
19:50210560:C:A	F65L	0.999

dbSNP variants (sampled 300 via entrez): RS1000006308 (19:50230712 G>A,C,T), RS1000015431 (19:50301007 T>C), RS1000034809 (19:50245333 T>G), RS1000088203 (19:50228920 C>G,T), RS1000094409 (19:50295916 G>A), RS1000117485 (19:50307585 T>C), RS1000125552 (19:50274117 A>C,G), RS1000128336 (19:50213188 A>G), RS1000135779 (19:50245681 A>G), RS1000166525 (19:50262295 C>T), RS1000183614 (19:50201808 G>A), RS1000307439 (19:50307074 G>A,T), RS1000312045 (19:50261385 G>A,C), RS1000321633 (19:50250355 C>A), RS1000335009 (19:50296379 A>G)

Disease associations

OMIM: gene MIM:608568 | disease phenotypes: MIM:614369, MIM:600652, MIM:124900, MIM:156000, MIM:192350, MIM:118220

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss 4A	Definitive	Autosomal dominant
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome	Strong	Autosomal dominant
nonsyndromic genetic hearing loss	Moderate	Autosomal dominant
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	Moderate	AD

Mondo (13): peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (MONDO:0013711), autosomal dominant nonsyndromic hearing loss 4A (MONDO:0010915), hearing loss disorder (MONDO:0005365), autosomal dominant nonsyndromic hearing loss (MONDO:0019587), Meniere disease (MONDO:0007972), dilated cardiomyopathy (MONDO:0005021), motor peripheral neuropathy (MONDO:0002316), axonal neuropathy (MONDO:0004183), peripheral neuropathy (MONDO:0005244), sensorineural hearing loss disorder (MONDO:0020678), nonsyndromic genetic hearing loss (MONDO:0019497), VACTERL/vater association (MONDO:0008642), Charcot-Marie-Tooth disease (MONDO:0015626)

Orphanet (7): MYH14-related peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (Orphanet:397744), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Dilated cardiomyopathy (Orphanet:217604), Rare non-syndromic genetic deafness (Orphanet:87884), VACTERL/VATER association (Orphanet:887), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0001644	Dilated cardiomyopathy
HP:0000407	Sensorineural hearing impairment

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001687_6	Disc degeneration (lumbar)	5.000000e-06
GCST002726_60	Glucose homeostasis traits	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006833	glucose effectiveness measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008575	Meniere Disease	C09.218.568.217.500
C563460	Deafness, Autosomal Dominant 4 (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105888 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,159 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3989868	TUCATINIB	4	3,159

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.73	Kd	188	nM	TUCATINIB

PubChem BioAssay actives

1 with measured affinity, of 216 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Tucatinib	1425080: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1880	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, affects cotreatment	2
sodium arsenite	affects methylation, increases expression	2
bisphenol S	increases expression, increases methylation	2
Resveratrol	affects cotreatment, decreases expression	2
Arsenic	affects methylation, decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
Cadmium	increases palmitoylation, increases expression, decreases reaction, increases abundance	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
arsenite	affects binding, decreases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
abrine	increases expression	1
prothioconazole	increases expression	1
bisphenol AF	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Cannabinoids	affects methylation, increases abundance	1
Coumestrol	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991793	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound