MYH15

Summary

MYH15 (myosin heavy chain 15, HGNC:31073) is a protein-coding gene on chromosome 3q13.13, encoding Myosin-15 (Q9Y2K3). Muscle contraction.

Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle.

Source: NCBI Gene 22989 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 355 total — 1 likely-pathogenic
• MANE Select transcript: NM_014981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31073
Approved symbol	MYH15
Name	myosin heavy chain 15
Location	3q13.13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1000
Ensembl gene	ENSG00000144821
Ensembl biotype	protein_coding
OMIM	609929
Entrez	22989

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000273353, ENST00000478998, ENST00000495753, ENST00000689784, ENST00000693548

RefSeq mRNA: 1 — MANE Select: NM_014981 NM_014981

CCDS: CCDS43127

Canonical transcript exons

ENST00000693548 — 41 exons

Exon	Start	End
ENSE00000967285	108470698	108470847
ENSE00000967286	108470042	108470212
ENSE00000967336	108405338	108405453
ENSE00000967337	108399075	108399267
ENSE00000967338	108398637	108398840
ENSE00000967339	108394031	108394156
ENSE00000967340	108391760	108391930
ENSE00000967341	108388970	108389074
ENSE00000967342	108384687	108384782
ENSE00001009919	108463111	108463243
ENSE00001075186	108380368	108381559
ENSE00001075210	108499455	108499482
ENSE00001075215	108498052	108498145
ENSE00001075218	108501712	108501855
ENSE00001075232	108500118	108500274
ENSE00001075235	108383595	108383729
ENSE00001159592	108464638	108464814
ENSE00001176551	108505723	108505829
ENSE00001201089	108486423	108486526
ENSE00001201092	108493114	108493177
ENSE00001201096	108495780	108495872
ENSE00001201118	108485091	108485229
ENSE00001300520	108492500	108492595
ENSE00001301115	108476397	108476515
ENSE00003467550	108459362	108459449
ENSE00003477788	108430832	108430922
ENSE00003486042	108421088	108421214
ENSE00003514434	108414232	108414428
ENSE00003518800	108460300	108460367
ENSE00003519276	108456766	108456883
ENSE00003563284	108444640	108444895
ENSE00003575860	108455736	108455859
ENSE00003577178	108454006	108454142
ENSE00003616347	108441018	108441260
ENSE00003628957	108410583	108410932
ENSE00003630605	108428492	108428881
ENSE00003633714	108439737	108439913
ENSE00003662618	108437554	108437699
ENSE00003668157	108416812	108416930
ENSE00003679695	108408280	108408404
ENSE00003938311	108510443	108510596

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 87.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0729 / max 59.5286, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43671	0.0729	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	87.45	gold quality
frontal pole	UBERON:0002795	87.29	gold quality
middle frontal gyrus	UBERON:0002702	85.36	gold quality
endometrium epithelium	UBERON:0004811	82.29	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.53	gold quality
Brodmann (1909) area 10	UBERON:0013541	69.65	gold quality
cranial nerve II	UBERON:0000941	65.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.77	gold quality
rectum	UBERON:0001052	62.96	gold quality
spinal cord	UBERON:0002240	62.60	gold quality
prefrontal cortex	UBERON:0000451	62.09	gold quality
cingulate cortex	UBERON:0003027	62.00	gold quality
anterior cingulate cortex	UBERON:0009835	61.90	gold quality
amygdala	UBERON:0001876	61.33	gold quality
mucosa of transverse colon	UBERON:0004991	60.49	gold quality
cerebellar vermis	UBERON:0004720	59.85	silver quality
putamen	UBERON:0001874	59.63	gold quality
corpus callosum	UBERON:0002336	59.51	gold quality
nucleus accumbens	UBERON:0001882	59.18	gold quality
hypothalamus	UBERON:0001898	58.77	gold quality
caudate nucleus	UBERON:0001873	58.64	gold quality
substantia nigra	UBERON:0002038	58.48	gold quality
neocortex	UBERON:0001950	57.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	57.02	gold quality
right frontal lobe	UBERON:0002810	56.95	gold quality
frontal cortex	UBERON:0001870	56.78	gold quality
midbrain	UBERON:0001891	56.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	56.41	gold quality
telencephalon	UBERON:0001893	56.02	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting MYH15, 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-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-664A-3P	99.22	71.08	2696

Literature-anchored findings (GeneRIF, showing 5)

• MYH15, the ortholog of the ventricular MYH of frogs and birds, is selectively expressed at the transcript level in the extraocular muscles. (PMID:19948655)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• MYH15 expression is significantly downregulated in human masticatory mucosa during wound healing (PMID:28005267)
• This is the first study to report the association of MYH15 gene polymorphisms with asthma. Polymorphisms of rs9288876, rs7635009, and rs1454197 altered transcriptional regulation of MYH15 and may be functional variants conferring susceptibility to asthma (PMID:30906771)
• Rare variants in MYH15 represent a likely genetic risk factor for amyotrophic lateral sclerosis. Furthermore, MYH15 could modulate the toxicity of dipeptides produced from expanded G4C2 repeat. (PMID:30985904)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	myh7ba	ENSDARG00000076075
mus_musculus	Myh15	ENSMUSG00000092009
rattus_norvegicus	Myh15	ENSRNOG00000061038

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), 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-15 — Q9Y2K3 (reviewed: Q9Y2K3)

Alternative names: Myosin heavy chain 15

All UniProt accessions (3): Q9Y2K3, A0A8I5KXJ3, A0A8I5KYE8

UniProt curated annotations — full annotation on UniProt →

Function. Muscle contraction.

Subunit / interactions. Muscle 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).

Subcellular location. Cytoplasm. Myofibril.

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.

RefSeq proteins (1): NP_055796* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001609	Myosin_head_motor_dom-like	Domain
IPR002928	Myosin_tail	Domain
IPR004009	SH3_Myosin	Domain
IPR008989	Myosin_S1_N	Homologous_superfamily
IPR014751	XRCC4-like_C	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00063, PF01576, PF02736

UniProt features (14 total): sequence variant 5, domain 3, region of interest 2, chain 1, coiled-coil region 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2K3-F1	74.58	0.08

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): 176–183

Post-translational modifications (1): 127

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, KEGG_TIGHT_JUNCTION, KEGG_VIRAL_MYOCARDITIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, GOMF_ACTIN_BINDING, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOCC_MYOSIN_FILAMENT, GOCC_MYOSIN_II_COMPLEX, GOMF_CYTOSKELETAL_PROTEIN_BINDING, GOMF_MICROFILAMENT_MOTOR_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_ISOMERASE_ACTIVITY, GOBP_SENSORY_SYSTEM_DEVELOPMENT

GO Biological Process (1): extraocular skeletal muscle development (GO:0002074)

GO Molecular Function (7): 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)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), myosin II complex (GO:0016460), myofibril (GO:0030016), myosin filament (GO:0032982), myosin complex (GO:0016459)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
myosin complex	2
skeletal muscle tissue development	1
camera-type eye development	1
skeletal muscle organ development	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
intracellular anatomical structure	1
cytoplasm	1
contractile muscle fiber	1
supramolecular fiber	1
actin cytoskeleton	1
protein-containing complex	1

Protein interactions and networks

STRING

1312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYH15	WHRN	Q9P202	692
MYH15	EPS8	Q12929	596
MYH15	MICAL1	Q8TDZ2	486
MYH15	LRCOL1	A6NCL2	462
MYH15	UNC45B	Q8IWX7	384
MYH15	NYAP1	Q6ZVC0	373
MYH15	A6NFB4	A6NFB4	356
MYH15	KIF6	Q6ZMV9	355
MYH15	TNNI1	P19237	354
MYH15	PIGX	Q8TBF5	350
MYH15	ERICH4	A6NGS2	348
MYH15	UTP3	Q9NQZ2	341
MYH15	MYOZ2	Q9NPC6	327
MYH15	CDH23	Q9H251	319
MYH15	MUTYH	Q9UIF7	313

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MYH15	RRBP1	psi-mi:“MI:0915”(physical association)	0.400
MYH15	PDIA4	psi-mi:“MI:0915”(physical association)	0.400
MYH15	H2AZ1	psi-mi:“MI:0915”(physical association)	0.400
FLOT1	MYH15	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MYL12B	EFCAB7	psi-mi:“MI:0914”(association)	0.350
MFGE8	MYH7B	psi-mi:“MI:0914”(association)	0.350
MRPS23	MYH7B	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): ACTN1 (Co-fractionation), ACTN3 (Co-fractionation), ACTN4 (Co-fractionation), ATP2B2 (Co-fractionation), MYH15 (Proximity Label-MS), MYH15 (Proximity Label-MS), MYH15 (Proximity Label-MS), MYH15 (Proximity Label-MS), MYH15 (Affinity Capture-MS), MYH15 (Affinity Capture-MS), MYH15 (Affinity Capture-MS), MYH15 (Affinity Capture-MS), MYH15 (Affinity Capture-MS), MYH15 (Affinity Capture-MS), MYH15 (Affinity Capture-MS)

ESM2 similar proteins: A2AQP0, A5PF48, A7E2Y1, F1PT61, F4IUG9, F4JM19, O08638, P02563, P02564, P02566, P02567, P08799, P10568, P11055, P12844, P12845, P12847, P12883, P13533, P13539, P13540, P13541, P24733, P35749, P49824, P79293, P97479, Q02566, Q076A3, Q076A4, Q076A5, Q13402, Q23979, Q29P71, Q29RW1, Q60LV4, Q8MJU9, Q8MJV0, Q8N1T3, Q90339

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	271
Likely benign	33
Benign	25

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3780514	NM_014981.3(MYH15):c.4736+2592_4736+2593del	Likely pathogenic

SpliceAI

6373 predictions. Top by Δscore:

Variant	Effect	Δscore
3:108391758:AC:A	donor_gain	1.0000
3:108391759:CC:C	donor_gain	1.0000
3:108391793:C:CA	donor_gain	1.0000
3:108391794:C:A	donor_gain	1.0000
3:108391927:CTGC:C	acceptor_gain	1.0000
3:108391928:TGC:T	acceptor_gain	1.0000
3:108391931:C:CC	acceptor_gain	1.0000
3:108391931:CTAG:C	acceptor_loss	1.0000
3:108394028:CAC:C	donor_loss	1.0000
3:108394029:A:AC	donor_gain	1.0000
3:108394029:A:T	donor_loss	1.0000
3:108394030:C:CA	donor_loss	1.0000
3:108394030:C:CC	donor_gain	1.0000
3:108394030:CCT:C	donor_gain	1.0000
3:108394081:C:CT	donor_gain	1.0000
3:108394153:TGTT:T	acceptor_gain	1.0000
3:108394157:C:CC	acceptor_gain	1.0000
3:108394158:T:G	acceptor_loss	1.0000
3:108398662:T:A	donor_gain	1.0000
3:108398671:T:TA	donor_gain	1.0000
3:108398841:C:CC	acceptor_gain	1.0000
3:108398841:C:CG	acceptor_loss	1.0000
3:108398842:T:C	acceptor_loss	1.0000
3:108399071:ATACC:A	donor_loss	1.0000
3:108399072:TACCT:T	donor_loss	1.0000
3:108399073:A:AG	donor_loss	1.0000
3:108399074:CCTT:C	donor_loss	1.0000
3:108405341:A:C	donor_gain	1.0000
3:108405356:T:TA	donor_gain	1.0000
3:108408193:T:TA	donor_gain	1.0000

AlphaMissense

12828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:108463222:A:G	W605R	0.990
3:108463222:A:T	W605R	0.990
3:108470710:A:C	F477L	0.964
3:108470710:A:T	F477L	0.964
3:108470712:A:G	F477L	0.964
3:108463237:A:C	Y600D	0.953
3:108495780:A:C	F257L	0.953
3:108495780:A:T	F257L	0.953
3:108495782:A:G	F257L	0.953
3:108464792:A:G	L546P	0.950
3:108485166:C:G	A367P	0.943
3:108485138:A:G	F376S	0.941
3:108470193:A:G	L488P	0.938
3:108464738:A:G	L564P	0.933
3:108486492:G:C	F322L	0.932
3:108486492:G:T	F322L	0.932
3:108486494:A:G	F322L	0.932
3:108485165:G:T	A367D	0.928
3:108470207:A:C	N483K	0.926
3:108470207:A:T	N483K	0.926
3:108485137:A:C	F376L	0.924
3:108485137:A:T	F376L	0.924
3:108485139:A:G	F376L	0.924
3:108495822:A:C	F243L	0.924
3:108495822:A:T	F243L	0.924
3:108495824:A:G	F243L	0.924
3:108463220:C:A	W605C	0.921
3:108463220:C:G	W605C	0.921
3:108492534:G:C	F299L	0.919
3:108492534:G:T	F299L	0.919

dbSNP variants (sampled 300 via entrez): RS1000004530 (3:108542761 T>C), RS1000020229 (3:108397581 T>A), RS1000043817 (3:108510674 A>G), RS1000114856 (3:108534024 A>C), RS1000141067 (3:108468029 G>A), RS1000148453 (3:108437403 A>G), RS1000196779 (3:108551504 A>G), RS1000204224 (3:108547833 C>T), RS1000205656 (3:108398379 T>C), RS1000252845 (3:108403868 GCTCTA>G), RS1000294682 (3:108540316 C>T), RS1000322447 (3:108528081 G>A,C), RS1000333490 (3:108384205 A>G), RS1000335941 (3:108539140 A>G), RS1000340362 (3:108481427 G>A)

Disease associations

OMIM: gene MIM:609929 | disease phenotypes: MIM:615760

GenCC curated gene-disease

Mondo (1): diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome (MONDO:0014335)

Orphanet (1): Diffuse cerebral and cerebellar atrophy-intractable seizures-progressive microcephaly syndrome (Orphanet:404437)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001378_7	Hemostatic factors and hematological phenotypes	5.000000e-06
GCST002724_17	Airway responsiveness in chronic obstructive pulmonary disease	4.000000e-06
GCST005316_138	Intelligence (MTAG)	1.000000e-08
GCST005316_139	Intelligence (MTAG)	7.000000e-09
GCST006922_10	Regular attendance at a religious group	8.000000e-12
GCST009575_3	Lifetime anxiety disorder	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004503	hematological measurement
EFO:0006897	airway responsiveness measurement
EFO:0004337	intelligence
EFO:0009592	social interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
NSC 689534	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Pesticides	affects methylation	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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