MYO1H

Summary

MYO1H (myosin IH, HGNC:13879) is a protein-coding gene on chromosome 12q24.11, encoding Unconventional myosin-Ih (Q8N1T3). Myosins are actin-based motor molecules with ATPase activity. It is a selective cancer dependency (DepMap: 13.9% of cell lines).

Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization; actin filament-based movement; and endocytosis. Predicted to be part of myosin complex. Predicted to be active in several cellular components, including actin cytoskeleton; microvillus; and plasma membrane. Implicated in congenital central hypoventilation syndrome.

Source: NCBI Gene 283446 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital central hypoventilation syndrome (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 20
• Clinical variants (ClinVar): 216 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 36
• Cancer dependency (DepMap): dependent in 13.9% of screened cell lines
• MANE Select transcript: NM_001101421

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13879
Approved symbol	MYO1H
Name	myosin IH
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ37587
Ensembl gene	ENSG00000174527
Ensembl biotype	protein_coding
OMIM	614636
Entrez	283446

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 retained_intron, 1 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000310903, ENST00000457826, ENST00000542268, ENST00000542883, ENST00000543960

RefSeq mRNA: 1 — MANE Select: NM_001101421 NM_001101421

CCDS: CCDS53826

Canonical transcript exons

ENST00000310903 — 32 exons

Exon	Start	End
ENSE00002203253	109415526	109415620
ENSE00002206689	109409963	109410068
ENSE00002208895	109396384	109396582
ENSE00002223000	109435037	109435113
ENSE00002230748	109420981	109421027
ENSE00002240029	109424748	109424828
ENSE00002240781	109432897	109433010
ENSE00002246423	109436488	109436556
ENSE00002252257	109427469	109427586
ENSE00002252848	109439631	109439790
ENSE00002263366	109425946	109426051
ENSE00002275345	109411894	109411985
ENSE00002279382	109438536	109438620
ENSE00002284445	109407794	109407913
ENSE00002292902	109409557	109409624
ENSE00002302635	109401093	109401272
ENSE00002304712	109447159	109448379
ENSE00002314950	109393331	109393446
ENSE00002324136	109410688	109410768
ENSE00002347308	109397732	109397812
ENSE00003470213	109442217	109442272
ENSE00003475272	109347900	109347972
ENSE00003483156	109444213	109444283
ENSE00003512944	109405922	109406035
ENSE00003528123	109443514	109443649
ENSE00003567167	109445513	109445612
ENSE00003590164	109444432	109444529
ENSE00003600342	109441615	109441708
ENSE00003629210	109403982	109404080
ENSE00003644315	109388683	109388844
ENSE00003647876	109406789	109406860
ENSE00003682448	109440744	109440827

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 82.52.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.52	gold quality
secondary oocyte	CL:0000655	79.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.93	gold quality
mucosa of stomach	UBERON:0001199	68.62	gold quality
smooth muscle tissue	UBERON:0001135	66.28	gold quality
right lobe of thyroid gland	UBERON:0001119	66.19	gold quality
left testis	UBERON:0004533	65.50	gold quality
descending thoracic aorta	UBERON:0002345	64.70	gold quality
right testis	UBERON:0004534	64.43	gold quality
left lobe of thyroid gland	UBERON:0001120	64.40	gold quality
testis	UBERON:0000473	63.95	gold quality
gall bladder	UBERON:0002110	63.88	gold quality
esophagus mucosa	UBERON:0002469	63.87	gold quality
oocyte	CL:0000023	63.81	gold quality
thoracic aorta	UBERON:0001515	63.50	gold quality
ectocervix	UBERON:0012249	63.39	gold quality
ascending aorta	UBERON:0001496	63.30	gold quality
rectum	UBERON:0001052	62.97	gold quality
ganglionic eminence	UBERON:0004023	62.85	gold quality
aorta	UBERON:0000947	62.83	gold quality
ventricular zone	UBERON:0003053	62.79	gold quality
thyroid gland	UBERON:0002046	62.76	gold quality
esophagus	UBERON:0001043	62.67	gold quality
tibial artery	UBERON:0007610	62.57	gold quality
popliteal artery	UBERON:0002250	62.56	gold quality
upper lobe of left lung	UBERON:0008952	62.40	gold quality
apex of heart	UBERON:0002098	62.39	gold quality
left coronary artery	UBERON:0001626	62.10	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.97	gold quality
lower esophagus	UBERON:0013473	61.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.64

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• can contribute to mandibular prognathism (PMID:22196185)
• The single nucleotide polymorphism rs3825393 of the MYO1H gene showed a statistically significant association with mandibular retrognathism (PMID:27131252)
• MYO1H is an important gene in CO2 sensitivity and respiratory control and has been associated with a rare recessive form of congenital central hypoventilation. (PMID:28779001)
• A nonsynonymous common variant of MYO1H rs3825393, C>T, p.Pro1001Leu, was identified to be significantly associated with MP. (PMID:29986156)
• ACTN3 and MYO1H are associated with sagittal and vertical craniofacial skeletal patterns in Brazilian populations. (PMID:30366217)
• Relationship of the rs10850110 and rs11611277 polymorphisms of the MYO1H gene with non-syndromic mandibular prognathism in the Iranian population. (PMID:33448167)
• MYO1H is a novel candidate gene for autosomal dominant pure hereditary spastic paraplegia. (PMID:35704118)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	myo1ha	ENSDARG00000061968
danio_rerio	myo1hb	ENSDARG00000078603
mus_musculus	Myo1h	ENSMUSG00000066952
rattus_norvegicus	Myo1h	ENSRNOG00000047191

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), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Unconventional myosin-Ih — Q8N1T3 (reviewed: Q8N1T3)

Alternative names: Myosin-1H

All UniProt accessions (2): A0A140TA25, S4R387

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.

Disease relevance. Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction (CCHS2) [MIM:619482] An autosomal recessive form of congenital central hypoventilation syndrome, a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular, lung or cardiac disease, or an identifiable brainstem lesion. CCHS2 is characterized by shallow breathing and apneic spells apparent in the neonatal period. Some patients have other features of autonomic dysfunction, including bladder dysfunction, sinus bradycardia, and temperature dysregulation. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be due to intron retention.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N1T3-1	1	yes
Q8N1T3-2	2
Q8N1T3-3	3

RefSeq proteins (1): NP_001094891* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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, PF06017

UniProt features (17 total): domain 4, splice variant 4, sequence variant 3, chain 1, sequence conflict 1, helix 1, region of interest 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6MBM	SOLUTION NMR
8EB1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N1T3-F1	84.77	0.26

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): 105–112

Post-translational modifications (1): 365

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 156 (showing top): RNGTGGGC_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOMF_ACTIN_BINDING, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS, GOCC_MICROVILLUS, GOCC_ACTIN_BASED_CELL_PROJECTION, GOBP_ACTIN_FILAMENT_BASED_MOVEMENT, chr12q24, GOMF_CYTOSKELETAL_PROTEIN_BINDING

GO Biological Process (3): endocytosis (GO:0006897), actin filament organization (GO:0007015), actin filament-based movement (GO:0030048)

GO Molecular Function (6): microfilament motor activity (GO:0000146), 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), actin filament (GO:0005884), plasma membrane (GO:0005886), microvillus (GO:0005902), actin cytoskeleton (GO:0015629), myosin complex (GO:0016459)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin cytoskeleton	2
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
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	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
cellular anatomical structure	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
actin filament bundle	1
actin-based cell projection	1
cytoskeleton	1
protein-containing complex	1

Protein interactions and networks

STRING

640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYO1H	MATN1	P21941	509
MYO1H	KIAA1210	Q9ULL0	485
MYO1H	PHOX2B	Q99453	451
MYO1H	EPB41	P11171	434
MYO1H	SSX2IP	Q9Y2D8	402
MYO1H	OR1J4	Q8NGS1	400
MYO1H	ACTN3	Q08043	371
MYO1H	C1orf167	Q5SNV9	368
MYO1H	TMC2	Q8TDI7	360
MYO1H	LTBP2	Q14767	352
MYO1H	LTBP3	Q9NS15	352
MYO1H	PLXNA2	O75051	350
MYO1H	ATP2B2	Q01814	345
MYO1H	TXLNG	Q9NUQ3	337
MYO1H	ADAMTS1	Q9UHI8	336

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0MP03, A3LYL7, A5DKH0, A5PF48, A6ZMG6, E7F9L8, E9Q634, F1PRN2, F4I460, F4JM19, O00159, O00160, O08638, O88329, O94832, P10568, P10587, P11055, P35748, P35749, P70248, P97479, Q01989, Q04439, Q076A3, Q12965, Q13402, Q17LW0, Q17R14, Q23979, Q27966, Q29P71, Q5SYD0, Q5ZLA6, Q62774, Q62812, Q63355, Q63356, Q63357, Q6BUQ2

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	180
Likely benign	13
Benign	6

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1210289	NM_001101421.4(MYO1H):c.2572del (p.Arg858fs)	Pathogenic
4292641	NM_001101421.4(MYO1H):c.2427G>A (p.Trp809Ter)	Likely pathogenic
4688041	NM_001101421.4(MYO1H):c.263del (p.Val88fs)	Likely pathogenic

SpliceAI

4929 predictions. Top by Δscore:

Variant	Effect	Δscore
12:109388841:A:AG	donor_gain	1.0000
12:109388845:G:GG	donor_gain	1.0000
12:109403976:CAACA:C	acceptor_loss	1.0000
12:109403979:CA:C	acceptor_loss	1.0000
12:109403980:A:AG	acceptor_gain	1.0000
12:109403980:A:C	acceptor_loss	1.0000
12:109403980:AG:A	acceptor_gain	1.0000
12:109403981:G:GG	acceptor_gain	1.0000
12:109403981:GG:G	acceptor_gain	1.0000
12:109403981:GGGT:G	acceptor_gain	1.0000
12:109403981:GGGTC:G	acceptor_gain	1.0000
12:109404078:GAG:G	donor_gain	1.0000
12:109404079:AGGTA:A	donor_loss	1.0000
12:109404080:GGTA:G	donor_loss	1.0000
12:109404081:G:GA	donor_loss	1.0000
12:109404082:T:A	donor_loss	1.0000
12:109405913:T:G	acceptor_gain	1.0000
12:109405920:A:AG	acceptor_gain	1.0000
12:109405921:G:GG	acceptor_gain	1.0000
12:109406784:T:G	acceptor_gain	1.0000
12:109407789:TTCA:T	acceptor_loss	1.0000
12:109407791:CA:C	acceptor_loss	1.0000
12:109407792:A:AG	acceptor_gain	1.0000
12:109407792:AG:A	acceptor_gain	1.0000
12:109407792:AGGT:A	acceptor_gain	1.0000
12:109407793:G:GA	acceptor_gain	1.0000
12:109407793:G:GT	acceptor_loss	1.0000
12:109407793:GG:G	acceptor_gain	1.0000
12:109407793:GGT:G	acceptor_gain	1.0000
12:109407793:GGTG:G	acceptor_gain	1.0000

AlphaMissense

6855 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000656 (12:109334881 C>G,T), RS1000010009 (12:109312797 T>A,G), RS1000013803 (12:109439461 C>G,T), RS1000041859 (12:109418507 G>A), RS1000050816 (12:109378031 T>C), RS1000058819 (12:109407681 G>A), RS1000109837 (12:109319657 A>G), RS1000153497 (12:109371026 T>A), RS1000172971 (12:109318359 A>G), RS1000179407 (12:109442054 A>G), RS1000187556 (12:109410839 G>A), RS1000206568 (12:109308504 G>A), RS1000239936 (12:109359536 G>A), RS1000241810 (12:109328577 C>T), RS1000271985 (12:109368043 T>C)

Disease associations

OMIM: gene MIM:614636 | disease phenotypes: MIM:619482

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital central hypoventilation syndrome	Supportive	Autosomal dominant
central hypoventilation syndrome, congenital, 2, and autonomic dysfunction	Limited	Autosomal recessive

Mondo (2): central hypoventilation syndrome, congenital, 2, and autonomic dysfunction (MONDO:0030537), (MONDO:0008852)

Orphanet (0):

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000545	Myopia
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001688	Sinus bradycardia
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002091	Restrictive ventilatory defect
HP:0002093	Respiratory insufficiency
HP:0002104	Apnea
HP:0002251	Aganglionic megacolon
HP:0002270	Abnormality of the autonomic nervous system
HP:0002571	Achalasia
HP:0002650	Scoliosis
HP:0002791	Hypoventilation
HP:0002808	Kyphosis
HP:0003005	Ganglioneuroma
HP:0003006	Neuroblastoma
HP:0003623	Neonatal onset
HP:0005968	Temperature instability
HP:0006747	Ganglioneuroblastoma
HP:0011471	Gastrostomy tube feeding in infancy
HP:0011951	Aspiration pneumonia
HP:0011968	Feeding difficulties

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000805_11	HDL cholesterol	3.000000e-06
GCST005082_6	Bipolar disorder lithium response (categorical) or schizophrenia	3.000000e-08
GCST005337_21	Headache	8.000000e-09
GCST007387_10	Insomnia symptoms (never/rarely vs. sometimes/usually)	1.000000e-07
GCST007388_50	Insomnia symptoms (never/rarely vs. usually)	1.000000e-09
GCST007709_306	General factor of neuroticism	5.000000e-09
GCST007709_307	General factor of neuroticism	2.000000e-08
GCST010134_6	Non-oily fish consumption	6.000000e-11
GCST010135_11	Oily fish consumption	6.000000e-11
GCST010135_3	Oily fish consumption	7.000000e-17
GCST010140_3	Pork consumption	6.000000e-11
GCST010140_47	Pork consumption	7.000000e-17
GCST010142_62	Fish- and plant-related diet	4.000000e-13
GCST010142_83	Fish- and plant-related diet	4.000000e-08
GCST010142_87	Fish- and plant-related diet	2.000000e-19
GCST010142_94	Fish- and plant-related diet	5.000000e-13
GCST010242_477	HDL cholesterol levels	1.000000e-35
GCST012111_9	Worry too long after an embarrassing experience	1.000000e-09
GCST012114_17	Sociability score	7.000000e-09
GCST012355_9	Depression	1.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007876	insomnia measurement
EFO:0007660	neuroticism measurement
EFO:0008111	diet measurement
EFO:0009589	worry measurement
EFO:0009592	social interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7959663	Efficacy	3	lithium	Bipolar Disorder

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7959663	MYO1H	3	0.00	1	lithium
rs7952909	MYO1H		0.00	0

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Phthalic Acids	increases methylation	1
Rotenone	decreases expression	1
Smoke	increases expression	1

Clinical trials (associated diseases)

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