MYO9B

Summary

MYO9B (myosin IXB, HGNC:7609) is a protein-coding gene on chromosome 19p13.11, encoding Unconventional myosin-IXb (Q13459). Myosins are actin-based motor molecules with ATPase activity.

This gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). The protein has four IQ motifs located in the neck domain that bind calmodulin, which serves as a light chain. The protein complex has a single-headed structure and exhibits processive movement on actin filaments toward the minus-end. The protein also has rho-GTPase activity. Polymorphisms in this gene are associated with celiac disease and ulcerative colitis susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4650 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease type 2 (Moderate, GenCC)
• GWAS associations: 82
• Clinical variants (ClinVar): 444 total — 1 likely-pathogenic
• MANE Select transcript: NM_004145

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7609
Approved symbol	MYO9B
Name	myosin IXB
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099331
Ensembl biotype	protein_coding
OMIM	602129
Entrez	4650

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 protein_coding, 8 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000397274, ENST00000593411, ENST00000593533, ENST00000594824, ENST00000594971, ENST00000595618, ENST00000595641, ENST00000596942, ENST00000597073, ENST00000597572, ENST00000597881, ENST00000598101, ENST00000598419, ENST00000598464, ENST00000599420, ENST00000601490, ENST00000601749, ENST00000602158, ENST00000602177, ENST00000682292, ENST00000896315, ENST00000940732, ENST00000940733, ENST00000968092, ENST00000968093

RefSeq mRNA: 2 — MANE Select: NM_004145 NM_001130065, NM_004145

CCDS: CCDS46010, CCDS92551

Canonical transcript exons

ENST00000682292 — 40 exons

Exon	Start	End
ENSE00000777942	17210333	17210380
ENSE00000777949	17206248	17206376
ENSE00000777953	17202842	17202883
ENSE00000777958	17198184	17198308
ENSE00000777959	17197792	17197858
ENSE00000777960	17194556	17195473
ENSE00000777961	17192746	17193062
ENSE00000777962	17191097	17191219
ENSE00000777963	17187935	17188045
ENSE00000777970	17172759	17172963
ENSE00000777972	17172336	17172477
ENSE00000777975	17159395	17159484
ENSE00000777977	17154315	17154415
ENSE00000777978	17153967	17154066
ENSE00000777979	17152644	17152706
ENSE00000777980	17145397	17145491
ENSE00000873500	17162988	17163122
ENSE00000873501	17167943	17168064
ENSE00000873505	17207113	17207244
ENSE00000951899	17156909	17157038
ENSE00000951901	17162350	17162466
ENSE00001220494	17209586	17209709
ENSE00001528010	17210715	17210848
ENSE00001528015	17206679	17206784
ENSE00002976103	17211647	17211774
ENSE00002978171	17101660	17102557
ENSE00003461596	17185921	17186001
ENSE00003482886	17203147	17203258
ENSE00003496460	17175663	17175741
ENSE00003504787	17201926	17202024
ENSE00003515639	17183829	17183868
ENSE00003580881	17184865	17184987
ENSE00003587383	17202130	17202303
ENSE00003588868	17205263	17205336
ENSE00003592667	17200639	17200829
ENSE00003636850	17180927	17181040
ENSE00003651470	17205960	17206152
ENSE00003662447	17200293	17200426
ENSE00003917111	17211895	17213286
ENSE00003918576	17075777	17075874

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.6737 / max 1160.2352, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174454	37.3325	1814
174453	1.3099	765
174459	0.9310	520
174462	0.1003	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.62	gold quality
sural nerve	UBERON:0015488	98.34	gold quality
left testis	UBERON:0004533	98.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.07	gold quality
right testis	UBERON:0004534	98.01	gold quality
spleen	UBERON:0002106	97.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.42	gold quality
ascending aorta	UBERON:0001496	97.24	gold quality
thoracic aorta	UBERON:0001515	97.21	gold quality
descending thoracic aorta	UBERON:0002345	97.09	gold quality
cerebellar hemisphere	UBERON:0002245	97.07	gold quality
upper lobe of left lung	UBERON:0008952	97.02	gold quality
cerebellar cortex	UBERON:0002129	96.96	gold quality
monocyte	CL:0000576	96.87	gold quality
right coronary artery	UBERON:0001625	96.86	gold quality
aorta	UBERON:0000947	96.84	gold quality
stromal cell of endometrium	CL:0002255	96.69	gold quality
popliteal artery	UBERON:0002250	96.67	gold quality
tibial artery	UBERON:0007610	96.67	gold quality
spinal cord	UBERON:0002240	96.65	gold quality
right lung	UBERON:0002167	96.58	gold quality
leukocyte	CL:0000738	96.56	gold quality
mononuclear cell	CL:0000842	96.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.45	gold quality
tibial nerve	UBERON:0001323	96.21	gold quality
lower esophagus mucosa	UBERON:0035834	96.18	gold quality
lymph node	UBERON:0000029	96.02	gold quality
body of uterus	UBERON:0009853	95.99	gold quality
left coronary artery	UBERON:0001626	95.97	gold quality
ectocervix	UBERON:0012249	95.96	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	5.46
E-MTAB-7303	no	450.81
E-MTAB-5061	no	3.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting MYO9B, 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-4692	100.00	67.32	2066
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270

Literature-anchored findings (GeneRIF, showing 40)

• Myosin-IXb is a single-headed and processive motor (PMID:11801597)
• myosin IXb binds to BIG1, which regulates its Rho-GTPase activating protein activity (PMID:15644318)
• Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). (PMID:16282976)
• myosin IX uses a unique ATP hydrolysis mechanism (PMID:16338935)
• Genotyping of the three SNPs which tagged the associated haplotype was performed in a Celiac disease family dataset in a Swedish/Norwegian cohort. (PMID:16720215)
• tested the association between celiac disease and the three most associated single nucleotide polymorphisms by the transmission disequilibrium test in the Italian population (PMID:16943798)
• Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MYO9B was considerably stronger with ulcerative colitis, although weaker association with Crohn’s disease also was observed. (PMID:17087940)
• Results support a negligible influence of MYO9B polymorphisms on celiac disease predisposition. (PMID:17176439)
• The MYO9B gene rs 2305764 polymorphism is not associated to coeliac disease in coeliac children from southern Italy. The allelic frequences of the polymorphism found in these patients and in the population control were not statistically different. (PMID:17267307)
• study suggests that genetic variation in MYO9B is associated with celiac disease, systemic lupus erythematosus, and rheumatoid arthritis and that MYO9B is a general risk factor for autoimmunity (PMID:17584584)
• Our data and the results of our meta-analysis question the role of MYO9B as a causative gene for celiac disease. (PMID:17667713)
• study did not confirm the association of celiac disease with the CELIAC4 region polymorphisms described in other populations (PMID:17767555)
• demonstrate significant association of allelic variants in MYO9B with schizophrenia. To our knowledge, this is the first molecular genetic evidence for a correlation between autoimmune diseases and the risk of developing schizophrenia (PMID:17948900)
• MYO9B homozygosity might be involved in the prognosis of CD and the chance of developing RCD II and EATL. (PMID:17967566)
• Myosin IXB variants were not associated with coeliac disease in this study; however, weak evidence of association with dermatitis herpetiformis was found. (PMID:18077767)
• Minor alleles of rs962917, rs2279003, and rs2305764 polymorphisms were more frequent in diabetic patients than in controls and the haplotype carrying major alleles in rs962917*G/rs2279003*C/rs2305764*G, significantly reduced the risk of type 1 diabetes (PMID:18361936)
• No association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations (PMID:19142207)
• MYO9B variants may be involved in inflammatory bowel disease pathogenesis (PMID:19235913)
• gene polymorphism is associated with type i diabetes in Dutch but not in Brotosh population (PMID:20303373)
• These data demonstrate an association of MYO9B with ileal CD. (PMID:21515326)
• we performed genetic analysis of the MYO9B gene and the IL-2/IL-21 locus by genotyping SNPs that have been previously associated with coeliac disease or schizophrenia found no evidence for association with these two loci. (PMID:21688385)
• critical roles for Myo9b during epithelial wound healing and maintenance of tight junction integrity-key functions that may be altered in patients with Myo9b-linked inflammatory bowel disease. (PMID:22573889)
• The homozygous G/G group of theMyo9B polymorphism was associated with an increased risk for Barrett’s esophagus and esophageal adenocarcinoms (EAC) development. Also the heterozygous A/G genotype was associated with an increased risk for EAC development. (PMID:22954106)
• genetic variation MYO9B gene is associated with celiac disease as a protective or a risk factor (PMID:23368647)
• Variants in MYO9B may be involved in acute pancreatitis (PMID:24386489)
• MYO9B SNPs may influence the sub-phenotypic expression of Crohn’s disease but did not find an association between these MYO9B polymorphisms and intestinal permeability in IBD. (PMID:24966617)
• Our data suggest a link between MYO9B variants to an increased intestinal permeability in Crohn’s disease patients. (PMID:25098938)
• Results does not support the association of MYO9B with schizophrenia in Chinese population. (PMID:25710847)
• newly defined SLIT/ROBO/Myo9b/RhoA signaling pathway that restricts lung cancer progression and metastasis. (PMID:26529257)
• meta-analysis indicates that MYO9B gene polymorphisms might be not associated with coeliac disease susceptibility in Caucasians. [meta-analysis] (PMID:27219348)
• Mutating either of the two arginine fingers impaired the catalytic activity of Myo9b-RhoGAP. (PMID:27363609)
• this meta-analysis shows that MYO9B genetic polymorphism is associated with Crohn’s disease and ulcerative colitis (PMID:27435931)
• data indicate that polymorphisms in MY09B are associated with the risk of inflammatory bowel disease (PMID:27556856)
• Analysis of PTPN22, ZFAT and MYO9B polymorphisms in Turner Syndrome and risk of autoimmune disease. (PMID:28627089)
• findings demonstrated a key role of circMYO9B/miR-4316/FOXP4 axis in regulating breast cancer progression (PMID:29702064)
• Class IX Myosins: Motorized RhoGAP Signaling Molecules. (PMID:32451867)
• The RhoA regulators Myo9b and GEF-H1 are targets of cyclic nucleotide-dependent kinases in platelets. (PMID:32692911)
• TSAd Plays a Major Role in Myo9b-Mediated Suppression of Malignant Pleural Effusion by Regulating TH1/TH17 Cell Response. (PMID:33046503)
• Local Myo9b RhoGAP activity regulates cell motility. (PMID:33268376)
• Mutations in MYO9B are associated with Charcot-Marie-Tooth disease type 2 neuropathies and isolated optic atrophy. (PMID:36260368)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	MYO9B	ENSDARG00000078313
mus_musculus	Myo9b	ENSMUSG00000004677
rattus_norvegicus	Myo9b	ENSRNOG00000016256

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), MYH2 (ENSG00000125414), MYO1B (ENSG00000128641), MYO5C (ENSG00000128833), CGNL1 (ENSG00000128849), MYH8 (ENSG00000133020), MYH10 (ENSG00000133026), MYH11 (ENSG00000133392), MYO18B (ENSG00000133454), CCDC102A (ENSG00000135736), MYO1G (ENSG00000136286), MYO7A (ENSG00000137474), MYO1F (ENSG00000142347), CGN (ENSG00000143375), TMF1 (ENSG00000144747), MYH15 (ENSG00000144821), MYO10 (ENSG00000145555), CCDC102B (ENSG00000150636), MYO1E (ENSG00000157483), CCDC158 (ENSG00000163749), MYO1A (ENSG00000166866), MYO5B (ENSG00000167306), MYO7B (ENSG00000169994), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Unconventional myosin-IXb — Q13459 (reviewed: Q13459)

Alternative names: Unconventional myosin-9b

All UniProt accessions (10): Q13459, B0I1T6, M0QXP0, M0QXX1, M0QZY4, M0R0P8, M0R240, M0R2J3, M0R300, M0R332

UniProt curated annotations — full annotation on UniProt →

Function. Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions. Also acts as a GTPase activator for RHOA. Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA.

Subunit / interactions. Interacts (via IQ domains) with CALM. Interacts with RHOA. Interacts (via Rho-GAP domain) with ROBO1; this inhibits the interaction with RHOA and the stimulation of RHOA GTPase activity, and thereby increases the levels of active RHOA.

Subcellular location. Cytoplasm. Cell cortex. Perinuclear region. Cytoskeleton.

Tissue specificity. Detected in peripheral blood leukocytes (at protein level). Expressed predominantly in peripheral blood leukocytes and at lower levels, in thymus, spleen, testis, prostate, ovary, brain, small intestine and lung.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q13459-1	Long	yes
Q13459-2	Short

RefSeq proteins (2): NP_001123537, NP_004136* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR000159	RA_dom	Domain
IPR000198	RhoGAP_dom	Domain
IPR001609	Myosin_head_motor_dom-like	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR028557	RhoGAP_myosin_IXB	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036023	MYSc_Myo9	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily
IPR046987	Myo9	Family
IPR046989	RA_Myosin-IXb	Domain

Pfam: PF00063, PF00612, PF00620, PF00788

UniProt features (91 total): modified residue 26, compositionally biased region 11, helix 11, region of interest 9, sequence conflict 9, domain 7, coiled-coil region 3, mutagenesis site 3, strand 3, splice variant 2, turn 2, initiator methionine 1, chain 1, binding site 1, site 1, zinc finger region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5C5S	X-RAY DIFFRACTION	2.2
5HPY	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13459-F1	63.82	0.06

Functional residue map

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

Catalytic / active sites (1): 1735 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Ligand- & substrate-binding residues (1): 239–246

Post-translational modifications (26): 2, 716, 717, 1045, 1114, 1115, 1122, 1242, 1253, 1261, 1267, 1271, 1290, 1323, 1331, 1346, 1354, 1356, 1405, 1926 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
1739	decreases interaction with rhoa. strongly decreases stimulation of rhoa gtpase activity.
1741	decreases interaction with rhoa. decreases stimulation of rhoa gtpase activity.
1742	strongly decreases interaction with rhoa. strongly decreases stimulation of rhoa gtpase activity.

Function

Pathways and Gene Ontology

Reactome pathways

26 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-8980692	RHOA GTPase cycle
R-HSA-8985586	SLIT2:ROBO1 increases RHOA activity
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9035034	RHOF GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis
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-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-376176	Signaling by ROBO receptors
R-HSA-422475	Axon guidance
R-HSA-5663205	Infectious disease
R-HSA-9012999	RHO GTPase cycle
R-HSA-9658195	Leishmania infection
R-HSA-9664407	Parasite infection
R-HSA-9664417	Leishmania phagocytosis
R-HSA-9675108	Nervous system development
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 259 (showing top): MORF_RAGE, MORF_FLT1, REACTOME_INNATE_IMMUNE_SYSTEM, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_ROUNDABOUT_SIGNALING_PATHWAY, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOCC_RUFFLE, MORF_ESR1, GOMF_GTPASE_BINDING, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_FANCG, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY

GO Biological Process (8): Rho protein signal transduction (GO:0007266), actin filament-based movement (GO:0030048), regulation of Rho protein signal transduction (GO:0035023), Roundabout signaling pathway (GO:0035385), regulation of small GTPase mediated signal transduction (GO:0051056), lamellipodium morphogenesis (GO:0072673), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556)

GO Molecular Function (15): microfilament motor activity (GO:0000146), actin binding (GO:0003779), GTPase activator activity (GO:0005096), calmodulin binding (GO:0005516), ATP binding (GO:0005524), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), small GTPase binding (GO:0031267), ADP binding (GO:0043531), Roundabout binding (GO:0048495), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): ruffle (GO:0001726), cytoplasm (GO:0005737), cytosol (GO:0005829), actin filament (GO:0005884), cell cortex (GO:0005938), actin cytoskeleton (GO:0015629), membrane (GO:0016020), myosin complex (GO:0016459), lamellipodium (GO:0030027), perinuclear region of cytoplasm (GO:0048471), postsynaptic actin cytoskeleton (GO:0098871), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
RHO GTPase cycle	6
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signaling by ROBO receptors	1
Leishmania phagocytosis	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Innate Immune System	1
Axon guidance	1
Nervous system development	1
Disease	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
actin cytoskeleton	3
small GTPase-mediated signal transduction	2
intracellular anatomical structure	2
ATP-dependent activity	2
adenyl ribonucleotide binding	2
cell leading edge	2
plasma membrane bounded cell projection	2
actin filament-based process	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
cell surface receptor signaling pathway	1
regulation of intracellular signal transduction	1
lamellipodium organization	1
plasma membrane bounded cell projection morphogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
cytoskeletal protein binding	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
protein binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
GTPase binding	1
anion binding	1
signaling receptor binding	1
actin binding	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1

Protein interactions and networks

STRING

2714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYO9B	ARFGEF1	Q9Y6D6	857
MYO9B	RHOA	P06749	801
MYO9B	NR2F6	P10588	770
MYO9B	TOR1A	O14656	717
MYO9B	BLTP1	Q2LD37	649
MYO9B	ADAD1	Q96M93	639
MYO9B	GTF2F1	P35269	606
MYO9B	RASA1	P20936	599
MYO9B	RUSC2	Q8N2Y8	551
MYO9B	NR2F1	P10589	548
MYO9B	GRIP2	Q9C0E4	543
MYO9B	AKAP6	Q13023	538
MYO9B	SYPL1	Q16563	525
MYO9B	CALM1	P02593	513
MYO9B	CALML3	P27482	507

IntAct

61 interactions, top by confidence:

A	B	Type	Score
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
SDF4	GTPBP6	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MYO9B	NOMO1	psi-mi:“MI:0915”(physical association)	0.400
MYO9B	RCN1	psi-mi:“MI:0915”(physical association)	0.400
MYO9B	HMGN3	psi-mi:“MI:0915”(physical association)	0.400
MYO9B	H1-2	psi-mi:“MI:0915”(physical association)	0.400
MYO9B	H1-5	psi-mi:“MI:0915”(physical association)	0.400
PKN2	MYO9B	psi-mi:“MI:0915”(physical association)	0.370
FOXG1	TCERG1	psi-mi:“MI:0914”(association)	0.350
FOXL1	IFRD1	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
RIOX1	NDUFS7	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
CAMK1	PSMD12	psi-mi:“MI:0914”(association)	0.350
CALM1	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM2	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO9B	PPM1G	psi-mi:“MI:0914”(association)	0.350
NPM1	RPS3A	psi-mi:“MI:0914”(association)	0.350
VRK1	LAMTOR5	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
MCC	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
TRIM52	MEIOC	psi-mi:“MI:0914”(association)	0.350

BioGRID (136): MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS), MYO9B (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTR4, A0MQH0, A2RSQ0, A6QNS3, B2RTY4, E7EZG2, E7F3F0, E9PTA2, F4I507, O43795, O54865, P09851, P16068, P20595, P20936, P24786, P46735, P50904, P83900, P85298, Q02153, Q02440, Q05096, Q09LZ8, Q12979, Q13459, Q13507, Q16288, Q25BN1, Q49A26, Q4ZHR9, Q5R6F2, Q5SSL4, Q5ZLX4, Q63358, Q6TUI4, Q6ZUT9, Q8C170, Q8NHH1, Q91X46

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6NI28, A6QNS3, A7YY57, A8WRJ2, B2RQE8, B5DFQ4, D3ZFJ3, F1LQX4, F1LXF1, O14559, O60890, O74360, O94466, P0CAX5, P11274, P15882, P30337, P34288, P46941, P52757, P55194, P81128, P83509, P97393, Q03070, Q08DP6, Q12979, Q13017, Q13459, Q15311, Q17QN0, Q17R89, Q20498, Q52LW3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MYO9B	“down-regulates activity”	RHOA	“gtpase-activating protein”
MYO9B	“down-regulates activity”	RAC1	“gtpase-activating protein”
MYO9B	“down-regulates activity”	CDC42	“gtpase-activating protein”
MAPK1	unknown	MYO9B	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	303
Likely benign	59
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3340523	NM_004145.4(MYO9B):c.848G>T (p.Gly283Val)	Likely pathogenic

SpliceAI

6173 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17075870:GCCAG:G	donor_gain	1.0000
19:17075872:CAGG:C	donor_loss	1.0000
19:17075874:GGTG:G	donor_loss	1.0000
19:17075875:G:C	donor_loss	1.0000
19:17075875:G:GG	donor_gain	1.0000
19:17145488:GAGG:G	donor_gain	1.0000
19:17145490:GG:G	donor_gain	1.0000
19:17145491:GG:G	donor_gain	1.0000
19:17152624:T:A	acceptor_gain	1.0000
19:17152636:A:AG	acceptor_gain	1.0000
19:17152636:AAT:A	acceptor_gain	1.0000
19:17152637:A:G	acceptor_gain	1.0000
19:17152638:T:A	acceptor_gain	1.0000
19:17152638:T:G	acceptor_gain	1.0000
19:17152639:GACAG:G	acceptor_loss	1.0000
19:17152640:ACAGA:A	acceptor_loss	1.0000
19:17152641:CAG:C	acceptor_gain	1.0000
19:17152641:CAGA:C	acceptor_loss	1.0000
19:17152642:A:AG	acceptor_gain	1.0000
19:17152642:AGA:A	acceptor_gain	1.0000
19:17152643:G:GA	acceptor_gain	1.0000
19:17152643:GA:G	acceptor_gain	1.0000
19:17152643:GAG:G	acceptor_gain	1.0000
19:17152643:GAGC:G	acceptor_gain	1.0000
19:17152643:GAGCT:G	acceptor_gain	1.0000
19:17152703:AGAG:A	donor_loss	1.0000
19:17152704:GAG:G	donor_gain	1.0000
19:17152704:GAGG:G	donor_loss	1.0000
19:17152705:AGGT:A	donor_loss	1.0000
19:17152706:GGTAG:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006046 (19:17145854 A>G), RS1000016552 (19:17109514 T>C), RS1000058170 (19:17183753 C>T), RS1000086271 (19:17110701 C>A), RS1000109256 (19:17109861 T>G), RS1000117418 (19:17214210 G>A,T), RS1000144176 (19:17114553 A>G), RS1000154307 (19:17097114 G>T), RS1000155381 (19:17107261 GTGAA>G,GTGAATGAA), RS1000184329 (19:17078844 T>C), RS1000242986 (19:17151930 A>G), RS1000249030 (19:17191279 G>A,T), RS1000252596 (19:17158299 C>T), RS1000348559 (19:17157959 T>G), RS1000368590 (19:17084109 G>A)

Disease associations

OMIM: gene MIM:602129 | disease phenotypes: MIM:609753

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 2	Moderate	Autosomal recessive

Mondo (2): celiac disease, susceptibility to, 4 (MONDO:0012339), Charcot-Marie-Tooth disease type 2 (MONDO:0018993)

Orphanet (0):

HPO phenotypes

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

GWAS associations

82 associations (top):

Study	Trait	p-value
GCST000817_38	Height	3.000000e-08
GCST002390_6	Glycated hemoglobin levels	9.000000e-12
GCST003542_158	Night sleep phenotypes	9.000000e-07
GCST003814_3	Selective IgA deficiency	2.000000e-07
GCST004599_147	Mean platelet volume	3.000000e-17
GCST004602_267	Mean corpuscular volume	3.000000e-09
GCST004603_194	Platelet count	4.000000e-10
GCST004605_78	Mean corpuscular hemoglobin concentration	7.000000e-18
GCST004605_79	Mean corpuscular hemoglobin concentration	2.000000e-15
GCST004607_17	Plateletcrit	9.000000e-14
GCST004611_151	High light scatter reticulocyte count	2.000000e-11
GCST004612_173	High light scatter reticulocyte percentage of red cells	6.000000e-11
GCST004619_151	Reticulocyte fraction of red cells	6.000000e-18
GCST004619_174	Reticulocyte fraction of red cells	4.000000e-09
GCST004621_159	Red cell distribution width	8.000000e-18
GCST004621_160	Red cell distribution width	2.000000e-16
GCST004622_75	Reticulocyte count	2.000000e-13
GCST004622_76	Reticulocyte count	1.000000e-18
GCST005196_235	Coronary artery disease	7.000000e-08
GCST005908_30	Height	9.000000e-22
GCST005991_46	Platelet count	2.000000e-08
GCST005992_37	Mean corpuscular hemoglobin concentration	4.000000e-11
GCST006085_99	Prostate cancer	8.000000e-09
GCST006089_6	Prostate cancer (early onset)	3.000000e-06
GCST006804_34	Red cell distribution width	3.000000e-14
GCST007094_221	Diastolic blood pressure	5.000000e-08
GCST007099_115	Systolic blood pressure	1.000000e-06
GCST007267_155	Systolic blood pressure	4.000000e-14
GCST007930_120	Medication use (agents acting on the renin-angiotensin system)	7.000000e-13
GCST007953_4	Glycated hemoglobin levels	2.000000e-09

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004541	HbA1c measurement
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004530	triglyceride measurement
EFO:0009473	hemolysis
EFO:0004980	appendicular lean mass
EFO:0010701	mean reticulocyte volume
EFO:0007984	platelet component distribution width
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance, affects expression	3
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	decreases methylation, increases methylation, affects methylation	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
bisphenol A	decreases expression, increases expression	1
sodium arsenate	increases expression	1
arsenite	decreases reaction, affects binding	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
coumarin	affects phosphorylation	1
muconaldehyde	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
exemestane	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
ICG 001	affects expression	1
abrine	decreases expression	1
Arsenic Trioxide	decreases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Cadmium	increases abundance, increases expression	1

Cellosaurus cell lines

17 cell lines: 17 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0179	BT-474	Cancer cell line	Female
CVCL_4V65	BT474-5FU[r]	Cancer cell line	Female
CVCL_4Y08	BT-474/CMV-Luc	Cancer cell line	Female
CVCL_A2GH	LR-BT474	Cancer cell line	Female
CVCL_A4AK	BT-474 Tam2	Cancer cell line	Female
CVCL_A4CL	BT-474 Ecadherin EmGFP	Cancer cell line	Female
CVCL_AQ07	BT-474 Clone 5	Cancer cell line	Female
CVCL_AR86	BT-474 Tam1	Cancer cell line	Female
CVCL_AR96	BT-474 EEI	Cancer cell line	Female
CVCL_C9CU	BT-474-Luc2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease