MYH9

Summary

MYH9 (myosin heavy chain 9, HGNC:7579) is a protein-coding gene on chromosome 22q12.3, encoding Myosin-9 (P35579). Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. It is a selective cancer dependency (DepMap: 52.2% of cell lines).

This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness.

Source: NCBI Gene 4627 — RefSeq curated summary.

At a glance

• Gene–disease (curated): macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 27
• Clinical variants (ClinVar): 1,918 total — 23 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 10 cancer types
• Cancer dependency (DepMap): dependent in 52.2% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002473

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7579
Approved symbol	MYH9
Name	myosin heavy chain 9
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	NMMHCA, NMHC-II-A, MHA, FTNS, EPSTS
Ensembl gene	ENSG00000100345
Ensembl biotype	protein_coding
OMIM	160775
Entrez	4627

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 23 protein_coding, 14 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000216181, ENST00000401701, ENST00000456729, ENST00000459960, ENST00000463027, ENST00000472210, ENST00000473022, ENST00000475726, ENST00000477189, ENST00000486218, ENST00000495928, ENST00000685187, ENST00000685191, ENST00000685708, ENST00000685801, ENST00000687820, ENST00000687922, ENST00000688137, ENST00000690244, ENST00000691109, ENST00000691296, ENST00000691687, ENST00000692930, ENST00000859030, ENST00000859031, ENST00000859032, ENST00000859033, ENST00000859034, ENST00000859035, ENST00000859036, ENST00000859037, ENST00000927178, ENST00000927179, ENST00000955562, ENST00000955563, ENST00000955564, ENST00000955565, ENST00000955566, ENST00000955567, ENST00000955568

RefSeq mRNA: 1 — MANE Select: NM_002473 NM_002473

CCDS: CCDS13927

Canonical transcript exons

ENST00000216181 — 41 exons

Exon	Start	End
ENSE00000653602	36284093	36284265
ENSE00000653608	36286718	36286846
ENSE00000653611	36289085	36289297
ENSE00001230540	36281280	36282785
ENSE00001314674	36288252	36288413
ENSE00001329819	36285865	36285953
ENSE00001597083	36306414	36306607
ENSE00001600096	36320220	36320363
ENSE00001603176	36300851	36301057
ENSE00001629888	36288727	36288939
ENSE00001634111	36296843	36297014
ENSE00001644119	36302568	36302676
ENSE00001648504	36295505	36295717
ENSE00001650829	36294932	36295076
ENSE00001653408	36314145	36314318
ENSE00001658129	36305033	36305102
ENSE00001678567	36316517	36316669
ENSE00001700027	36312049	36312222
ENSE00001704867	36303995	36304155
ENSE00001707705	36301534	36301665
ENSE00001711381	36291986	36292234
ENSE00001718677	36341370	36341526
ENSE00001724650	36319540	36319635
ENSE00001732475	36293329	36293481
ENSE00001737793	36300127	36300264
ENSE00001756791	36294092	36294298
ENSE00001776228	36309282	36309396
ENSE00001779938	36305930	36306051
ENSE00001789650	36298919	36299042
ENSE00001789675	36293759	36293863
ENSE00001874129	36387807	36387967
ENSE00002732339	36348904	36349255
ENSE00003460212	36285121	36285329
ENSE00003468029	36318207	36318325
ENSE00003470888	36327461	36327488
ENSE00003480606	36320798	36320896
ENSE00003496557	36284403	36284511
ENSE00003604645	36326568	36326661
ENSE00003649564	36322429	36322521
ENSE00003668819	36321758	36321821
ENSE00003673428	36285658	36285781

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 347.3925 / max 2574.6598, expressed in 1828 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193940	305.0562	1827
193941	32.5344	1817
193932	3.1722	1253
193913	1.1395	616
193904	1.0241	608
193902	0.7303	439
193884	0.7214	391
193905	0.6564	380
193883	0.5232	247
193918	0.4114	216

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.57	gold quality
ascending aorta	UBERON:0001496	99.57	gold quality
thoracic aorta	UBERON:0001515	99.57	gold quality
descending thoracic aorta	UBERON:0002345	99.54	gold quality
right coronary artery	UBERON:0001625	99.51	gold quality
aorta	UBERON:0000947	99.46	gold quality
popliteal artery	UBERON:0002250	99.43	gold quality
tibial artery	UBERON:0007610	99.43	gold quality
body of uterus	UBERON:0009853	99.33	gold quality
artery	UBERON:0001637	99.32	gold quality
colonic epithelium	UBERON:0000397	99.24	gold quality
right lung	UBERON:0002167	99.24	gold quality
left coronary artery	UBERON:0001626	99.23	gold quality
upper lobe of left lung	UBERON:0008952	99.12	gold quality
upper lobe of lung	UBERON:0008948	98.96	gold quality
left uterine tube	UBERON:0001303	98.89	gold quality
sural nerve	UBERON:0015488	98.88	gold quality
mucosa of stomach	UBERON:0001199	98.87	gold quality
coronary artery	UBERON:0001621	98.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.83	gold quality
monocyte	CL:0000576	98.79	gold quality
omental fat pad	UBERON:0010414	98.76	gold quality
ectocervix	UBERON:0012249	98.76	gold quality
endocervix	UBERON:0000458	98.75	gold quality
granulocyte	CL:0000094	98.72	gold quality
peritoneum	UBERON:0002358	98.72	gold quality
leukocyte	CL:0000738	98.70	gold quality
mononuclear cell	CL:0000842	98.68	gold quality
lower esophagus	UBERON:0013473	98.68	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.68	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	37.27
E-GEOD-125970	yes	22.50
E-MTAB-9543	yes	19.75
E-MTAB-8410	yes	19.31
E-HCAD-10	yes	15.74
E-MTAB-9801	yes	8.17
E-GEOD-83139	yes	7.25
E-GEOD-137537	yes	6.64
E-ENAD-27	yes	6.22
E-MTAB-6108	no	299.41
E-CURD-112	no	1.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CTNNB1	Activation

Upstream regulators (CollecTRI, top): IRF2, PITX2, RUNX1, TFE3, TFEC, USF1, USF2

miRNA regulators (miRDB)

140 targeting MYH9, 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-190A-3P	100.00	80.35	5520
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-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AN	99.97	70.91	2817

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 52.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• mutations cause a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes; hence, the name “MYHIIA syndrome” is proposed to encompass all of these disorders (PMID:11590545)
• mutation in epstein syndrome (PMID:11935325)
• Motor protein nonmuscle myosin heavy chain-IIA and CXCR$ colocalize at the leading edge of migrating T lymphocytes, together with filamentous actin and myosin light chain. (PMID:12421915)
• A major role is indicated for the NMMHC-IIA abnormality in the pathogenesis of leukocyte, platelet, and kidney defects in Fechtner syndrome. (PMID:12500226)
• A single base pair transition in MYH9, resulting in an amino acid substitution D1424N, is responsible for macrothrombocytopenia and hearing loss in the kindred under study. (PMID:12621333)
• The Asp1424Asn mutation in the MYH9 gene causes the May-Hegglin anomaly, Fechtner syndrome, Sebastian syndrome, & Epstein syndrome, which result from a highly unstable protein & failure to reorganize the megakaryocyte cytoskeleton for platelet production. (PMID:12649151)
• MYH9 gene is implicated in May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome and Epstein syndrome which are autosomal dominant macrothrombocytopenias. (PMID:12792306)
• In a case of anaplastic large cell lymphoma, a portion of MYH9 is found to be fused to the ALK gene in a novel chromosomal abnormality, t(2;22)(p23;q11.2). (PMID:12800156)
• Myosin heavy polypeptide 9 (MYH9) colocalizes with actin stress fibers in mammalian cells. (PMID:14706930)
• sCD163-NMMHCA complexes were present in activated T lymphocytes after incubation with shed sCD163 (PMID:15479433)
• Here targeted gene disruption was performed to understand fundamental as well as pathological role of the gene for NMMHCA, MYH9. (PMID:15555549)
• Two cleavage sites on NMHC-A, Asp-1153 and Asp-1948, at which it is cleaved during apoptosis, were determined. (PMID:15749830)
• Casein kinase 2 phosphorylation of the myosin-IIA heavy chain protects against Ca2+-regulated S100 family member MTS1-induced filament disassembly and inhibition of assembly of nonmuscle myosin-IIA filaments. (PMID:15865432)
• Haploinsufficiency of NMMHC-IIA in megakaryocytic lineage is the mechanism of macrothrombocytopenia consequent to MYH9 mutations, whereas in granulocytes a dominant-negative effect of mutant allele is involved in the formation of inclusion bodies. (PMID:16162639)
• VEGF, extracellular matrix, and intracellular motor protein MyH9 are all essential for the novel function of nucleolin in angiogenesis. (PMID:16403913)
• Results suggest that MYH9 mediates the binding of oviductal glycoprotein to human sperm. (PMID:16567366)
• Mutation of MYH9 gene exists in cases of Chinese MYH9-related disease. In the two families, the point mutation was located in exon 38(G5521A), and the transference rule of the MYH9 gene mutation is corresponding with clinical phenotype distribution. (PMID:16806139)
• myosin IIA and IIB isoforms are regulated by different signaling pathways to perform distinct cellular activities (PMID:17020881)
• Patients carrying R702 mutations had significantly larger platelets than those with other MYH9 mutations (PMID:17241369)
• Myosin IIA negatively regulates cell migration and maintains a balance between the actomyosin and microtubule systems by regulating microtubule dynamics. (PMID:17310241)
• MIIA plays a role in CXCR4 endocytosis, which involves its dynamic association with beta-arrestin and highlights the role of endogenous MIIA as a regulator of CXCR4 internalization and, therefore, the onset of SDF-1alpha signaling. (PMID:17327270)
• Pairwise and multilocus haplotype analyses identified linkage disequilibrium between polymorphism alleles at the MYH9 locus and the disease. (PMID:17337617)
• direct platelet myosin IIA participation in internal contraction (PMID:17488351)
• These observations support a direct role for myosin-IIA heavy-chain phosphorylation in mediating motility and chemotaxis. (PMID:17567956)
• MyosinIIa contractility is required for maintenance of platelet structure during spreading on collagen and contributes to thrombus stability (PMID:17645784)
• myosin IIA is required for a critical step between NK immunological synapse formation and granule exocytosis (PMID:17875677)
• An MYH9 human disease model in flies. (PMID:17901043)
• subjects with mutations in the motor domain present with severe thrombocytopenia and develop nephritis and deafness before the age of 40, while those with mutations in the tail domain have a much lower risk of complications and higher platelet counts (PMID:18059020)
• show the differential expression of mutant NMMHC-IIA and postulate that cell-specific regulation mechanisms function in MYH9 disorders (PMID:18192507)
• during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion (PMID:18195072)
• first report of a large deletion of the MYH9 gene leading to the development of MYH9 disorders (PMID:18284620)
• The effects of MYH9-siRNA-induced suppression underline the critical role of NMHC-IIA in maintenance of cell shape and adhesion. (PMID:18330899)
• On both RBCs and microbeads, human CD47 potently inhibits phagocytosis as does direct inhibition of myosin. CD47-SIRPalpha interaction initiates a dephosphorylation cascade directed in part at phosphotyrosine in myosin. (PMID:18332220)
• TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the alpha-helical tail of the myosin IIA heavy chain (PMID:18394644)
• The genes MYH9 might be vulnerability genes for neuropsychologically defined subgroups of schizophrenic patients. (PMID:18571626)
• Expression of full-length human NMHC-IIA and -IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms (PMID:18697221)
• The highest LOD score was found in chromosomal region 22q12.2-12.3 and the total linkage area spans over 20 cM; this region contains the MYH9 gene, which is expressed in the developing palate. (PMID:18716610)
• proplatelet formation in human megakaryocytes undergoes a complex spatio-temporal regulation orchestrated by adhesive proteins, GPIb-IX-V and myosin IIA (PMID:18752571)
• Genetic variation at the MYH9 locus is associated with nondiabetic end-stage kidney diseases. (PMID:18794854)
• Genetic variation at the MYH9 locus substantially explains the increased burden of focal segmental glomerulosclerosis and hypertensive end-stage kidney diseases. (PMID:18794856)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	myh9b	ENSDARG00000001014
danio_rerio	myh9a	ENSDARG00000063295
		ENSDARG00000112168
mus_musculus	Myh9	ENSMUSG00000022443
rattus_norvegicus	Myh9	ENSRNOG00000049236

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

Protein

Protein identifiers

Myosin-9 — P35579 (reviewed: P35579)

Alternative names: Cellular myosin heavy chain, type A, Myosin heavy chain 9, Myosin heavy chain, non-muscle IIa, Non-muscle myosin heavy chain A, Non-muscle myosin heavy chain IIa

All UniProt accessions (6): P35579, A0A8I5KU92, A0A8I5KWT8, A0A8I5KYI1, B1AH99, Q5BKV1

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. Required for cortical actin clearance prior to oocyte exocytosis. Promotes cell motility in conjunction with S100A4. During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10. (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B.

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). Interacts with RASIP1. Interacts with DDR1. Interacts with PDLIM2. Interacts with SVIL. Interacts with HTRA3. Interacts with Myo7a. Interacts with CFAP95. Interacts with LIMCH1; independently of the integration of MYH9 into the myosin complex. Interacts with RAB3A. Interacts with ZBED4. Interacts with S100A4; this interaction increases cell motility. (Microbial infection) Interacts with herpes simplex virus 1/HHV-1 envelope glycoprotein B.

Subcellular location. Cytoplasm. Cytoskeleton. Cell cortex. Cytoplasmic vesicle. Secretory vesicle. Cortical granule. Cell membrane Cell membrane.

Tissue specificity. In the kidney, expressed in the glomeruli. Also expressed in leukocytes.

Post-translational modifications. ISGylated. Ubiquitination.

Disease relevance. Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (MATINS) [MIM:155100] An autosomal dominant disorder characterized by thrombocytopenia, giant platelets and Dohle body-like inclusions in peripheral blood leukocytes with variable ultrastructural appearance. Some affected individuals lack leukocyte inclusion bodies on classic staining of peripheral blood smears. Alport syndrome-like features of nephritis, hearing loss, and eye abnormalities are present in some patients. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant, 17 (DFNA17) [MIM:603622] A form of deafness characterized by progressive high frequency hearing impairment and cochleosaccular degeneration. The disease is caused by variants affecting the gene represented in this entry. Subjects with mutations in the motor domain of MYH9 present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. The clinical course of patients with mutations in the four most frequently affected residues of MYH9 (responsible for 70% of MYH9-related cases) were evaluated. Mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. Genetic variations in MYH9 are associated with non-diabetic end stage renal disease (ESRD).

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 (2)

UniProt ID	Names	Canonical?
P35579-1	1	yes
P35579-2	2

RefSeq proteins (1): NP_002464* (*=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
IPR036305	RGS_sf	Homologous_superfamily
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00063, PF01576, PF02736

UniProt features (85 total): modified residue 29, sequence variant 24, sequence conflict 11, region of interest 5, compositionally biased region 3, domain 3, splice variant 2, strand 2, helix 2, initiator methionine 1, chain 1, coiled-coil region 1, binding site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
4CFQ	X-RAY DIFFRACTION	1.37
4CFR	X-RAY DIFFRACTION	1.4
4ETO	X-RAY DIFFRACTION	1.54
3ZWH	X-RAY DIFFRACTION	1.94
9IHL	X-RAY DIFFRACTION	2.02
9SYU	ELECTRON MICROSCOPY	2.98
9SZR	ELECTRON MICROSCOPY	6.3
2LNK	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35579-F1	76.42	0.16

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): 174–181

Post-translational modifications (29): 2, 8, 11, 102, 299, 435, 613, 628, 754, 850, 860, 975, 1024, 1114, 1234, 1249, 1357, 1392, 1404, 1410 …

Function

Pathways and Gene Ontology

Reactome pathways

40 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-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-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-9662834	CD163 mediating an anti-inflammatory response
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
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-5653656	Vesicle-mediated transport
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5663205	Infectious disease
R-HSA-9658195	Leishmania infection

MSigDB gene sets: 555 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GGGACCA_MIR133A_MIR133B, GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOCC_SECRETORY_GRANULE, GOBP_SPINDLE_LOCALIZATION

GO Biological Process (37): meiotic spindle organization (GO:0000212), angiogenesis (GO:0001525), in utero embryonic development (GO:0001701), establishment of T cell polarity (GO:0001768), plasma membrane repair (GO:0001778), membrane protein ectodomain proteolysis (GO:0006509), phagocytosis, engulfment (GO:0006911), integrin-mediated signaling pathway (GO:0007229), myoblast fusion (GO:0007520), regulation of cell shape (GO:0008360), protein transport (GO:0015031), actin cytoskeleton organization (GO:0030036), actin filament-based movement (GO:0030048), platelet formation (GO:0030220), monocyte differentiation (GO:0030224), actomyosin structure organization (GO:0031032), lysosome localization (GO:0032418), cytokinetic process (GO:0032506), uropod organization (GO:0032796), endodermal cell differentiation (GO:0035987), blood vessel endothelial cell migration (GO:0043534), regulated exocytosis (GO:0045055), symbiont entry into host cell (GO:0046718), leukocyte migration (GO:0050900), establishment of meiotic spindle localization (GO:0051295), cytoplasmic actin-based contraction involved in cell motility (GO:0060327), cortical granule exocytosis (GO:0060471), platelet aggregation (GO:0070527), negative regulation of actin filament severing (GO:1903919), positive regulation of protein processing in phagocytic vesicle (GO:1903923), regulation of plasma membrane repair (GO:1905684), cell morphogenesis (GO:0000902), cytoskeleton organization (GO:0007010), cell adhesion (GO:0007155), regulation of actin filament-based process (GO:0032970), cell motility (GO:0048870), cell-cell adhesion (GO:0098609)

GO Molecular Function (17): microfilament motor activity (GO:0000146), virus receptor activity (GO:0001618), RNA binding (GO:0003723), cytoskeletal motor activity (GO:0003774), actin binding (GO:0003779), integrin binding (GO:0005178), calmodulin binding (GO:0005516), ATP binding (GO:0005524), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein-membrane adaptor activity (GO:0043495), ADP binding (GO:0043531), cadherin binding (GO:0045296), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (36): stress fiber (GO:0001725), ruffle (GO:0001726), immunological synapse (GO:0001772), uropod (GO:0001931), nucleus (GO:0005634), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), spindle (GO:0005819), actomyosin contractile ring (GO:0005826), cytosol (GO:0005829), plasma membrane (GO:0005886), brush border (GO:0005903), adherens junction (GO:0005912), focal adhesion (GO:0005925), cytoplasmic side of plasma membrane (GO:0009898), cell surface (GO:0009986), actin cytoskeleton (GO:0015629), membrane (GO:0016020), myosin II complex (GO:0016460), nuclear body (GO:0016604), cell leading edge (GO:0031252), neuromuscular junction (GO:0031594), cleavage furrow (GO:0032154), myosin filament (GO:0032982), protein-containing complex (GO:0032991), actomyosin (GO:0042641), cortical granule (GO:0060473), extracellular exosome (GO:0070062), myosin II filament (GO:0097513), cytoskeleton (GO:0005856), cell cortex (GO:0005938), COP9 signalosome (GO:0008180), myosin complex (GO:0016459), cortical cytoskeleton (GO:0030863), cytoplasmic vesicle (GO:0031410), supramolecular fiber (GO:0099512)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
RHO GTPase Effectors	4
Sensory processing of sound	2
Membrane Trafficking	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
EPH-Ephrin signaling	1
Sema4D in semaphorin signaling	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Leishmania phagocytosis	1
Signaling by ALK in cancer	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein binding	3
anatomical structure formation involved in morphogenesis	2
actin filament-based process	2
protein-containing complex binding	2
cell adhesion molecule binding	2
adenyl ribonucleotide binding	2
plasma membrane bounded cell projection	2
plasma membrane	2
intracellular membrane-bounded organelle	2
cytoplasm	2
intracellular membraneless organelle	2
spindle organization	1
meiotic cell cycle	1
meiotic cell cycle process	1
blood vessel morphogenesis	1
chordate embryonic development	1
establishment of lymphocyte polarity	1
T cell activation	1
plasma membrane organization	1
wound healing	1
membrane protein proteolysis	1
phagocytosis	1
plasma membrane invagination	1
cell surface receptor signaling pathway	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
regulation of cell morphogenesis	1
regulation of biological quality	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cytoskeleton organization	1
myeloid cell differentiation	1
platelet morphogenesis	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
actin cytoskeleton organization	1
vacuolar localization	1
cytokinesis	1

Protein interactions and networks

STRING

4156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYH9	APOL1	O14791	898
MYH9	ACTN4	O43707	840
MYH9	S100A4	P26447	824
MYH9	MYL12B	O14950	809
MYH9	MYL6	P16475	737
MYH9	TPM4	P07226	719
MYH9	ACTN1	P12814	693
MYH9	COL4A3	Q01955	685
MYH9	FLNA	P21333	678
MYH9	USP6	P35125	673
MYH9	COL4A4	P53420	664
MYH9	WAS	P42768	646
MYH9	ACTG1	P02571	645
MYH9	NPHS1	O60500	636
MYH9	INF2	Q27J81	636

IntAct

347 interactions, top by confidence:

A	B	Type	Score
S100A4	MYH9	psi-mi:“MI:0407”(direct interaction)	0.950
MYH9	S100A4	psi-mi:“MI:0407”(direct interaction)	0.950
S100A4	MYH9	psi-mi:“MI:0915”(physical association)	0.950
MYH9	S100A4	psi-mi:“MI:0915”(physical association)	0.950
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MYH9	S100P	psi-mi:“MI:0407”(direct interaction)	0.680
S100P	MYH9	psi-mi:“MI:0407”(direct interaction)	0.680
MYH9	S100P	psi-mi:“MI:0915”(physical association)	0.680
OS9	HSP90B1	psi-mi:“MI:0914”(association)	0.640
S	MYH9	psi-mi:“MI:2364”(proximity)	0.640
S	MYH9	psi-mi:“MI:0915”(physical association)	0.640
MYH9	S	psi-mi:“MI:0915”(physical association)	0.640
S	MYH9	psi-mi:“MI:0403”(colocalization)	0.640

BioGRID (1030): MYH9 (Affinity Capture-MS), MYH9 (Affinity Capture-MS), MYH9 (Affinity Capture-MS), MYH9 (Biochemical Activity), MYH9 (Affinity Capture-MS), MYH9 (Affinity Capture-MS), MYH9 (Affinity Capture-MS), MYH9 (Affinity Capture-MS), MYH9 (Affinity Capture-Western), MYH9 (Affinity Capture-MS), MYH9 (Affinity Capture-MS), MYH9 (Co-fractionation), MYH9 (Co-fractionation), SRSF5 (Co-fractionation), SSB (Co-fractionation)

ESM2 similar proteins: A0MP03, A4RE77, A8N2Y6, B0CRJ3, E1BPK6, O08638, P02563, P02564, P10587, P11055, P12847, P12883, P13538, P13540, P13541, P13542, P14105, P35579, P35580, P35748, P35749, P49824, P79293, Q01989, Q02566, Q076A6, Q076A7, Q1DLP2, Q258K2, Q27991, Q29122, Q5ZLA6, Q61879, Q62812, Q63862, Q64331, Q8MJU9, Q8MJV1, Q8VDD5, Q91Z83

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

15 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	MYH9	phosphorylation
TFE3	“up-regulates quantity by expression”	MYH9	“transcriptional regulation”
TFEC	“up-regulates quantity by expression”	MYH9	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	MYH9	“transcriptional regulation”
USF2	“up-regulates quantity by expression”	MYH9	“transcriptional regulation”
DLC1	“down-regulates activity”	MYH9	binding
MYH9	“up-regulates quantity by expression”	CTNNB1	“transcriptional regulation”
MYH9	“up-regulates activity”	“RNA Polymerase II”	binding
SPC25	“up-regulates activity”	MYH9	binding
RIOK1	“up-regulates activity”	MYH9	phosphorylation
S100A4	“down-regulates activity”	MYH9	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 158 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
TAK1-dependent IKK and NF-kappa-B activation	5	14.4×	3e-03
NIK–>noncanonical NF-kB signaling	6	13.2×	1e-03
Dectin-1 mediated noncanonical NF-kB signaling	6	12.4×	2e-03
Hh mutants are degraded by ERAD	5	11.7×	4e-03
SCF-beta-TrCP mediated degradation of Emi1	5	11.4×	4e-03
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	5	11.4×	4e-03
Activation of NF-kappaB in B cells	6	11.4×	2e-03
Interleukin-1 signaling	9	10.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	6	17.2×	1e-03
endothelial cell migration	5	16.1×	6e-03
actin filament organization	8	7.4×	6e-03
positive regulation of canonical NF-kappaB signal transduction	9	5.1×	1e-02

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 10 cancer types — BCC, BLCA, BRCA, COADREAD, ESCA, HNSC, NBL, NSCLC, OVT, STOMACH.

Clinical variants and AI predictions

ClinVar

1918 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	33
Uncertain significance	676
Likely benign	595
Benign	200

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028020	NM_002473.6(MYH9):c.97T>C (p.Trp33Arg)	Pathogenic
1275758	NM_002473.6(MYH9):c.5822del (p.Asp1941fs)	Pathogenic
14072	NM_002473.6(MYH9):c.5797C>T (p.Arg1933Ter)	Pathogenic
14074	NM_002473.6(MYH9):c.3493C>T (p.Arg1165Cys)	Pathogenic
14076	NM_002473.6(MYH9):c.4270G>C (p.Asp1424His)	Pathogenic
14077	NM_002473.6(MYH9):c.3464C>T (p.Thr1155Ile)	Pathogenic
14078	NM_002473.6(MYH9):c.2104C>T (p.Arg702Cys)	Pathogenic
14080	NM_002473.6(MYH9):c.5821del (p.Asp1941fs)	Pathogenic
14085	NM_002473.6(MYH9):c.3195_3215dup (p.Gln1068_Leu1074dup)	Pathogenic
14086	NM_002473.6(MYH9):c.228_245del (p.Asn76_Ser81del)	Pathogenic
164432	NM_002473.6(MYH9):c.4546G>T (p.Val1516Leu)	Pathogenic
1677397	NM_002473.6(MYH9):c.2501_2508dup (p.Leu837fs)	Pathogenic
1684410	NM_002473.6(MYH9):c.5773del (p.Asp1925fs)	Pathogenic
1703779	NM_002473.6(MYH9):c.5765+2T>C	Pathogenic
2000225	NM_002473.6(MYH9):c.2104C>G (p.Arg702Gly)	Pathogenic
3068367	NM_002473.6(MYH9):c.4271A>C (p.Asp1424Ala)	Pathogenic
3250387	NM_002473.6(MYH9):c.2163T>G (p.Tyr721Ter)	Pathogenic
38965	NM_002473.6(MYH9):c.3494G>T (p.Arg1165Leu)	Pathogenic
4537177	NM_002473.6(MYH9):c.250del (p.Glu84fs)	Pathogenic
4542444	NM_002473.6(MYH9):c.5833G>T (p.Glu1945Ter)	Pathogenic
4542445	NM_002473.6(MYH9):c.5769del (p.Asp1925fs)	Pathogenic
623110	NM_002473.6(MYH9):c.5770_5779del (p.Gly1924fs)	Pathogenic
627409	NM_002473.6(MYH9):c.99G>C (p.Trp33Cys)	Pathogenic
1338501	NM_002473.6(MYH9):c.4271A>T (p.Asp1424Val)	Likely pathogenic
14084	NM_002473.6(MYH9):c.3195_3215del (p.Gln1068_Leu1074del)	Likely pathogenic
1679093	NM_002473.6(MYH9):c.2482T>C (p.Trp828Arg)	Likely pathogenic
1684327	NM_002473.6(MYH9):c.284C>T (p.Ala95Val)	Likely pathogenic
1684413	NM_002473.6(MYH9):c.4272C>A (p.Asp1424Glu)	Likely pathogenic
1684415	NM_002473.6(MYH9):c.3486G>T (p.Arg1162Ser)	Likely pathogenic
1685380	NM_002473.6(MYH9):c.2129A>C (p.Asn710Thr)	Likely pathogenic

SpliceAI

6730 predictions. Top by Δscore:

Variant	Effect	Δscore
22:36282781:CGCGC:C	acceptor_gain	1.0000
22:36282783:CGC:C	acceptor_gain	1.0000
22:36282786:C:CA	acceptor_loss	1.0000
22:36282786:C:CC	acceptor_gain	1.0000
22:36282793:C:CT	acceptor_gain	1.0000
22:36284087:GCTCA:G	donor_gain	1.0000
22:36284088:CTCA:C	donor_gain	1.0000
22:36284089:TCA:T	donor_gain	1.0000
22:36284090:CACC:C	donor_gain	1.0000
22:36284091:A:AC	donor_gain	1.0000
22:36284091:A:C	donor_gain	1.0000
22:36284091:A:T	donor_loss	1.0000
22:36284092:C:CA	donor_loss	1.0000
22:36284092:C:CC	donor_gain	1.0000
22:36284092:C:G	donor_gain	1.0000
22:36284261:TCGGC:T	acceptor_gain	1.0000
22:36284262:CGGC:C	acceptor_gain	1.0000
22:36284262:CGGCC:C	acceptor_gain	1.0000
22:36284263:GGC:G	acceptor_gain	1.0000
22:36284264:GC:G	acceptor_gain	1.0000
22:36284264:GCCTG:G	acceptor_loss	1.0000
22:36284265:CC:C	acceptor_gain	1.0000
22:36284266:C:CC	acceptor_gain	1.0000
22:36284266:C:CG	acceptor_loss	1.0000
22:36284383:TGCCC:T	donor_gain	1.0000
22:36284400:CA:C	donor_gain	1.0000
22:36284401:A:AT	donor_loss	1.0000
22:36284407:T:TA	donor_gain	1.0000
22:36284414:A:AC	donor_gain	1.0000
22:36284415:C:CC	donor_gain	1.0000

AlphaMissense

12999 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:36288785:C:G	R1571P	1.000
22:36288830:A:G	L1556P	1.000
22:36288854:A:G	L1548P	1.000
22:36295559:A:G	L1144P	1.000
22:36295568:A:G	L1141P	1.000
22:36301023:A:G	L889P	1.000
22:36301652:A:G	L838P	1.000
22:36301655:A:G	L837P	1.000
22:36302583:C:A	W828C	1.000
22:36302583:C:G	W828C	1.000
22:36302585:A:G	W828R	1.000
22:36302585:A:T	W828R	1.000
22:36302586:C:A	W827C	1.000
22:36302586:C:G	W827C	1.000
22:36302588:A:G	W827R	1.000
22:36302588:A:T	W827R	1.000
22:36302592:C:A	W825C	1.000
22:36302592:C:G	W825C	1.000
22:36302594:A:G	W825R	1.000
22:36302594:A:T	W825R	1.000
22:36304061:C:G	R775P	1.000
22:36304073:A:G	L771P	1.000
22:36304099:G:C	F762L	1.000
22:36304099:G:T	F762L	1.000
22:36304101:A:G	F762L	1.000
22:36304115:C:A	G757V	1.000
22:36304115:C:T	G757D	1.000
22:36304116:C:G	G757R	1.000
22:36304121:C:G	R755P	1.000
22:36305063:G:C	F733L	1.000

dbSNP variants (sampled 300 via entrez): RS1000000683 (22:36376772 T>C,G), RS1000001931 (22:36340236 G>C), RS1000059535 (22:36388153 G>C), RS1000102401 (22:36381391 C>T), RS1000113855 (22:36351884 A>C), RS1000122842 (22:36306136 A>G), RS1000184082 (22:36299267 A>G), RS1000185663 (22:36340897 T>C), RS1000194047 (22:36370878 G>A), RS1000201714 (22:36346261 T>C), RS1000269554 (22:36309445 G>A), RS1000273830 (22:36376978 G>A), RS1000362352 (22:36372299 G>A), RS1000363599 (22:36366051 G>A), RS1000390224 (22:36301352 C>T)

Disease associations

OMIM: gene MIM:160775 | disease phenotypes: MIM:153640, MIM:155100, MIM:600208, MIM:605249, MIM:603622, MIM:603266, MIM:156000, MIM:153840, MIM:310400, MIM:609376, MIM:236250, MIM:220290, MIM:607197, MIM:602089

GenCC curated gene-disease

Disease	Classification	Inheritance
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss	Definitive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss 17	Definitive	Autosomal dominant
May-Hegglin anomaly	Strong	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
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss	Definitive	AD

Mondo (23): macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (MONDO:0015912), hearing loss disorder (MONDO:0005365), autosomal dominant nonsyndromic hearing loss 17 (MONDO:0011350), type 1 diabetes mellitus 17 (MONDO:0011302), thrombocytopenia (MONDO:0002049), Meniere disease (MONDO:0007972), kidney disorder (MONDO:0005240), focal segmental glomerulosclerosis (MONDO:0100313), vitelliform macular dystrophy 1 (MONDO:0007933), X-linked myotubular myopathy (MONDO:0010683), cataract 35 (MONDO:0012260), homocystinuria due to methylene tetrahydrofolate reductase deficiency (MONDO:0009353), kidney failure (MONDO:0001106), proteinuria (MONDO:0003634), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (21): MYH9-related syndromic thrombocytopenia (Orphanet:182050), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare genetic deafness (Orphanet:96210), Adult-onset foveomacular vitelliform dystrophy (Orphanet:99000), X-linked centronuclear myopathy (Orphanet:596), Early onset non-syndromic cataract (Orphanet:91492), Early-onset nuclear cataract (Orphanet:98991), Early-onset partial cataract (Orphanet:98992), Early-onset zonular cataract (Orphanet:98995), Homocystinuria due to methylene tetrahydrofolate reductase deficiency (Orphanet:395), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Atypical hemolytic uremic syndrome (Orphanet:2134), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Epstein syndrome (Orphanet:1019), Fechtner syndrome (Orphanet:1984)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000077	Abnormality of the kidney
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000112	Nephropathy
HP:0000123	Nephritis
HP:0000132	Menorrhagia
HP:0000407	Sensorineural hearing impairment
HP:0000421	Epistaxis
HP:0000978	Bruising susceptibility
HP:0001658	Myocardial infarction
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0001902	Giant platelets
HP:0001905	Congenital thrombocytopenia
HP:0001977	Abnormal thrombosis
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003010	Prolonged bleeding time
HP:0003577	Congenital onset
HP:0003621	Juvenile onset
HP:0004406	Spontaneous, recurrent epistaxis
HP:0004866	Impaired ADP-induced platelet aggregation
HP:0005101	High-frequency hearing impairment
HP:0007819	Presenile cataracts
HP:0008148	Impaired epinephrine-induced platelet aggregation
HP:0008264	Neutrophil inclusion bodies
HP:0011877	Increased mean platelet volume
HP:0031689	Megakaryocyte dysplasia
HP:0040185	Macrothrombocytopenia
HP:0040235	Leukocyte inclusion bodies

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000658_6	Optic nerve measurement (rim area)	9.000000e-06
GCST000696_1	End-stage renal disease (non-diabetic)	2.000000e-19
GCST000741_1	Glomerulosclerosis	5.000000e-13
GCST003098_35	Diabetic kidney disease	8.000000e-08
GCST003098_6	Diabetic kidney disease	8.000000e-08
GCST004372_2	Language performance in older adults (adjusted for episodic memory)	5.000000e-07
GCST004602_248	Mean corpuscular volume	6.000000e-14
GCST004630_40	Mean corpuscular hemoglobin	3.000000e-14
GCST006979_200	Heel bone mineral density	4.000000e-17
GCST006979_826	Heel bone mineral density	1.000000e-18
GCST007058_1	Hip circumference	6.000000e-07
GCST010083_206	Hemoglobin levels	1.000000e-12
GCST90002383_106	Hematocrit	5.000000e-12
GCST90002384_499	Hemoglobin	2.000000e-14
GCST90002385_580	High light scatter reticulocyte count	7.000000e-11
GCST90002386_494	High light scatter reticulocyte percentage of red cells	8.000000e-11
GCST90002390_320	Mean corpuscular hemoglobin	3.000000e-09
GCST90002390_321	Mean corpuscular hemoglobin	8.000000e-30
GCST90002392_137	Mean corpuscular volume	7.000000e-13
GCST90002392_138	Mean corpuscular volume	3.000000e-29
GCST90002396_90	Mean reticulocyte volume	5.000000e-10
GCST90002396_91	Mean reticulocyte volume	4.000000e-30
GCST90002397_602	Mean spheric corpuscular volume	2.000000e-19
GCST90002397_603	Mean spheric corpuscular volume	1.000000e-25
GCST90002402_646	Platelet count	6.000000e-09
GCST90002405_418	Reticulocyte count	3.000000e-10
GCST90002406_571	Reticulocyte fraction of red cells	2.000000e-10

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0007710	cognitive decline measurement
EFO:0007797	language measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0009270	heel bone mineral density
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count

MeSH disease descriptors (18)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D005921	Glomerulonephritis	C12.050.351.968.419.570.363; C12.200.777.419.570.363; C12.950.419.570.363
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D006973	Hypertension	C14.907.489
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D008575	Meniere Disease	C09.218.568.217.500
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
D051437	Renal Insufficiency	C12.050.351.968.419.780; C12.200.777.419.780; C12.950.419.780
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C563728	Cataract, Congenital Nuclear, Autosomal Recessive 1 (supp.)
C564609	Deafness, Autosomal Recessive (supp.)
C566395	Diabetes Mellitus, Insulin-Dependent, 17 (supp.)
C535860	Hemangioma, capillary infantile (supp.)
C537831	Macrothrombocytopenia progressive deafness (supp.)
C537832	Macular dystrophy, atypical vitelliform (supp.)
C537357	Methylenetetrahydrofolate reductase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2189151 (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: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.01	Kd	97.28	nM	CHEMBL5653589
7.01	ED50	97.28	nM	CHEMBL5653589
6.12	Kd	756.1	nM	CHEMBL3752910
6.12	ED50	756.1	nM	CHEMBL3752910
5.69	IC50	2050	nM	MOLIBRESIB
5.40	IC50	4000	nM	CHEMBL1328324

PubChem BioAssay actives

4 with measured affinity, of 14 total; 4 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148805: Binding affinity to human MYH9 incubated for 45 mins by Kinobead based pull down assay	kd	0.0973	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148805: Binding affinity to human MYH9 incubated for 45 mins by Kinobead based pull down assay	kd	0.7561	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178906: Inhibition of MYH9 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	2.0500	uM
3a-hydroxy-6-methyl-1-phenyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	1360374: Inhibition of human non-muscle myosin 2a	ic50	4.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, increases expression, affects cotreatment	5
Valproic Acid	increases expression, affects expression, decreases methylation	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases methylation, affects expression	2
chromium hexavalent ion	increases abundance, decreases expression	2
Benzo(a)pyrene	decreases expression	2
Cisplatin	decreases expression, decreases response to substance, increases expression, affects cotreatment	2
Dinitrochlorobenzene	affects binding, increases metabolic processing	2
Doxorubicin	affects expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression, increases reaction	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
5-chloro-2-methyl-4-isothiazolin-3-one	increases metabolic processing	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
cupric oxide	decreases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209362	Binding	Binding affinity to myosin-9 in human HCT116 cell lysates at 0.6 uM after 1 hr using coomassie blue staining by SDS-PAGE based pull down assay	An Hsp90 modulator that exhibits a unique mechanistic profile. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SZ58	HAP1 MYH9 (-) 1	Cancer cell line	Male
CVCL_SZ59	HAP1 MYH9 (-) 2	Cancer cell line	Male
CVCL_VE99	MUi010-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

300 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
NCT02242656	PHASE3	WITHDRAWN	A Phase III Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Investigational Product MP-101 in Subjects With Short Bowel Syndrome Who Have Had an Inadequate Response to Anti-Diarrheals
NCT02246816	PHASE3	WITHDRAWN	A Open Label Extension Study for Subjects That Complete Study MP-101-CL-001
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
NCT00925236	Not specified	COMPLETED	Phenotypic and Genotypic Identification and Characterization of MYH9-related Constitutional Thrombocytopenia
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