MYO9A

Summary

MYO9A (myosin IXA, HGNC:7608) is a protein-coding gene on chromosome 15q23, encoding Unconventional myosin-IXa (B2RTY4). Myosins are actin-based motor molecules with ATPase activity.

This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). Unconventional myosins contain the basic domains of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with Bardet-Biedl Syndrome.

Source: NCBI Gene 4649 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myasthenic syndrome, congenital, 24, presynaptic (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 548 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 81
• MANE Select transcript: NM_006901

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7608
Approved symbol	MYO9A
Name	myosin IXA
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11061, FLJ13244, MGC71859
Ensembl gene	ENSG00000066933
Ensembl biotype	protein_coding
OMIM	604875
Entrez	4649

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 11 protein_coding, 8 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000356056, ENST00000561618, ENST00000563071, ENST00000563542, ENST00000563648, ENST00000563925, ENST00000564571, ENST00000564699, ENST00000564931, ENST00000565528, ENST00000566744, ENST00000566885, ENST00000567095, ENST00000567560, ENST00000568042, ENST00000568438, ENST00000568481, ENST00000568781, ENST00000569314, ENST00000922047, ENST00000971716, ENST00000971717

RefSeq mRNA: 1 — MANE Select: NM_006901 NM_006901

CCDS: CCDS10239

Canonical transcript exons

ENST00000356056 — 42 exons

Exon	Start	End
ENSE00001179770	71883594	71883736
ENSE00001179777	71888004	71888116
ENSE00001289837	71880335	71880558
ENSE00001308398	71878040	71878231
ENSE00001310190	71879721	71879837
ENSE00001619627	71852132	71852260
ENSE00001675393	71859735	71859796
ENSE00001688502	71830109	71830311
ENSE00001698680	71827884	71828026
ENSE00001710697	71854377	71854569
ENSE00001754888	71862500	71862611
ENSE00001944978	71822291	71827043
ENSE00002226905	71875791	71875838
ENSE00003465419	71994469	71994585
ENSE00003480033	71978171	71978292
ENSE00003484241	71938852	71938927
ENSE00003488838	71901191	71901340
ENSE00003494336	71904926	71905006
ENSE00003498053	72045724	72046634
ENSE00003503584	71893679	71893778
ENSE00003504993	71933670	71933709
ENSE00003530870	72020918	72021017
ENSE00003547553	71848845	71848968
ENSE00003554271	71903929	71904039
ENSE00003564403	71899687	71900006
ENSE00003567835	71935341	71935484
ENSE00003573640	71902941	71903063
ENSE00003578565	72027731	72027793
ENSE00003584593	72019039	72019095
ENSE00003587318	71991103	71991237
ENSE00003594937	72010350	72010447
ENSE00003598907	71967984	71968125
ENSE00003623132	71850036	71850167
ENSE00003627754	71851253	71851358
ENSE00003629672	71959901	71960096
ENSE00003645572	71897461	71899032
ENSE00003651890	71999851	71999940
ENSE00003658920	71916370	71916492
ENSE00003664579	72007826	72007952
ENSE00003670150	71951777	71951896
ENSE00003684464	72032494	72032588
ENSE00003841386	72117680	72118150

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9132 / max 164.9654, expressed in 1746 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150765	5.5121	1525
150766	3.2736	1338
150763	2.1039	1033
150761	0.5226	260
150764	0.2777	121
150762	0.1560	53
150758	0.0401	3
150759	0.0230	5
150760	0.0042	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.08	gold quality
male germ cell	CL:0000015	96.22	gold quality
sperm	CL:0000019	96.11	gold quality
secondary oocyte	CL:0000655	95.71	gold quality
sural nerve	UBERON:0015488	95.40	gold quality
olfactory bulb	UBERON:0002264	94.70	silver quality
type B pancreatic cell	CL:0000169	94.32	gold quality
tibia	UBERON:0000979	93.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.65	gold quality
renal medulla	UBERON:0000362	93.49	gold quality
dorsal root ganglion	UBERON:0000044	93.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.13	gold quality
colonic epithelium	UBERON:0000397	92.82	gold quality
cauda epididymis	UBERON:0004360	92.54	gold quality
corpus callosum	UBERON:0002336	92.48	gold quality
oocyte	CL:0000023	92.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.36	gold quality
tendon	UBERON:0000043	92.20	gold quality
middle temporal gyrus	UBERON:0002771	91.98	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.48	gold quality
trigeminal ganglion	UBERON:0001675	90.90	gold quality
nipple	UBERON:0002030	90.86	gold quality
adult organism	UBERON:0007023	90.84	gold quality
entorhinal cortex	UBERON:0002728	90.67	gold quality
caput epididymis	UBERON:0004358	90.47	gold quality
postcentral gyrus	UBERON:0002581	90.43	gold quality
cardia of stomach	UBERON:0001162	90.40	gold quality
parietal lobe	UBERON:0001872	90.09	gold quality
cerebellar vermis	UBERON:0004720	89.85	gold quality
cervix squamous epithelium	UBERON:0006922	89.83	silver quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	2241.37
E-GEOD-131882	yes	1969.08
E-GEOD-137537	yes	1276.03
E-CURD-119	yes	41.94
E-ANND-3	yes	16.41
E-GEOD-70580	no	740.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting MYO9A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4291	99.20	68.88	2969

Literature-anchored findings (GeneRIF, showing 6)

• Depletion of myosin-IXA in collectively migrating cells led to altered organization of the actin cytoskeleton and tension-dependent disruption of cell-cell adhesions, followed by an inability to form new adhesions resulting in cell scattering. (PMID:22305756)
• Vaccinia virus F11 promotes viral spread by binding to host myosin-9A and inhibit RhoA signaling. (PMID:23870313)
• MYO9A deficiency may affect the presynaptic motor axon, manifesting in congenital myasthenic syndrome. (PMID:27259756)
• analysis of actin network self-organization by a monomeric myosin IXa (PMID:27956608)
• Class IX Myosins: Motorized RhoGAP Signaling Molecules. (PMID:32451867)
• Rho-GTPase Activating Protein myosin MYO9A identified as a novel candidate gene for monogenic focal segmental glomerulosclerosis. (PMID:33412162)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	myo9ab	ENSDARG00000073843
danio_rerio	myo9aa	ENSDARG00000076729
mus_musculus	Myo9a	ENSMUSG00000039585
rattus_norvegicus	Myo9a	ENSRNOG00000011619

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), 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), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Unconventional myosin-IXa — B2RTY4 (reviewed: B2RTY4)

Alternative names: Unconventional myosin-9a

All UniProt accessions (9): B2RTY4, H3BMM1, H3BMS3, H3BP49, H3BRD5, H3BSU8, H3BTL9, H3BU05, H3BV44

UniProt curated annotations — full annotation on UniProt →

Function. Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Regulates Rho by stimulating its GTPase activity in neurons. Required for the regulation of neurite branching and motor neuron axon guidance.

Subcellular location. Membrane. Cytoplasm. Synapse. Cell projection. Growth cone.

Tissue specificity. Found to be expressed in testis and placenta and at lower levels in all the examined tissues with the exception of liver. Isoform 5: Found in leukocytes but not in brain, retina or testis.

Post-translational modifications. Phosphorylated by ALPK1 following monosodium urate monohydrate (MSU)-induced inflammation.

Disease relevance. Myasthenic syndrome, congenital, 24, presynaptic (CMS24) [MIM:618198] A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS24 inheritance is autosomal recessive. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. Lacks the ATP-binding domain which suggests that it cannot interact with actin.

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

Isoforms (5)

UniProt ID	Names	Canonical?
B2RTY4-1	1	yes
B2RTY4-2	2
B2RTY4-3	3
B2RTY4-4	4
B2RTY4-5	5

RefSeq proteins (1): NP_008832* (*=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
IPR028558	RA_Myosin-IXa	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
IPR046990	RhoGAP_myosin_IX	Domain

Pfam: PF00063, PF00130, PF00612, PF00620, PF00788

UniProt features (77 total): sequence variant 20, sequence conflict 12, region of interest 9, modified residue 9, domain 8, compositionally biased region 5, splice variant 5, coiled-coil region 3, zinc finger region 2, chain 1, transmembrane region 1, binding site 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B2RTY4-F1	58.07	0.04

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): 2098 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

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

Post-translational modifications (9): 755, 1242, 1258, 1299, 1317, 1364, 1948, 2294, 2464

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013424	RHOV GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 355 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GCM_MAP4K4, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GCM_GSPT1, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEUROGENESIS, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS

GO Biological Process (9): visual perception (GO:0007601), cell junction assembly (GO:0034329), intracellular signal transduction (GO:0035556), establishment of epithelial cell apical/basal polarity (GO:0045198), regulation of small GTPase mediated signal transduction (GO:0051056), regulation of neuron projection arborization (GO:0150011), signal transduction (GO:0007165), cell junction organization (GO:0034330), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (10): microfilament motor activity (GO:0000146), GTPase activator activity (GO:0005096), ATP binding (GO:0005524), zinc ion binding (GO:0008270), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), actin binding (GO:0003779), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): cytosol (GO:0005829), actin filament (GO:0005884), membrane (GO:0016020), unconventional myosin complex (GO:0016461), axonal growth cone (GO:0044295), synapse (GO:0045202), cytoplasm (GO:0005737), myosin complex (GO:0016459), growth cone (GO:0030426), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular anatomical structure	2
GTPase activity	2
actin cytoskeleton	2
sensory perception of light stimulus	1
cellular component assembly	1
cell junction organization	1
signal transduction	1
polarized epithelial cell differentiation	1
establishment of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
establishment of epithelial cell polarity	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
regulation of cell morphogenesis	1
regulation of cell projection organization	1
neuron projection arborization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular component organization	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
enzyme activator activity	1
GTPase regulator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
actin binding	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
cytoskeletal protein binding	1
binding	1

Protein interactions and networks

STRING

2212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYO9A	BBS4	Q96RK4	580
MYO9A	ALG14	Q96F25	559
MYO9A	LONRF2	Q1L5Z9	496
MYO9A	COLQ	Q9Y215	496
MYO9A	CALML6	Q8TD86	490
MYO9A	CALML4	Q96GE6	490
MYO9A	CALML5	Q9NZT1	490
MYO9A	CALML3	P27482	489
MYO9A	CALM1	P02593	486
MYO9A	RAPSN	Q13702	483
MYO9A	HABP4	Q5JVS0	453
MYO9A	LRP2BP	Q9P2M1	451
MYO9A	SUPT16H	Q9Y5B9	445
MYO9A	SYNCRIP	O60506	438
MYO9A	CHRND	Q07001	436

IntAct

92 interactions, top by confidence:

A	B	Type	Score
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
TBC1D15	MYO9A	psi-mi:“MI:0914”(association)	0.530
UNC45A	MYO9A	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MYO9A	KTN1	psi-mi:“MI:0915”(physical association)	0.400
MYO9A	MTNR1A	psi-mi:“MI:0915”(physical association)	0.370
MYO9A	CDC42	psi-mi:“MI:0915”(physical association)	0.370
ERBB2	MYO9A	psi-mi:“MI:0915”(physical association)	0.370
Naa10	MYO9A	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.350
MYO9A	ATP5PD	psi-mi:“MI:0914”(association)	0.350
	MYO9A	psi-mi:“MI:0914”(association)	0.350
RAF1	MYO9A	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
KRT2	IFT56	psi-mi:“MI:0914”(association)	0.350
CDC16	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (130): MYO9A (Affinity Capture-RNA), MYO9A (Affinity Capture-RNA), MYO9A (Affinity Capture-MS), MYO9A (Affinity Capture-MS), MYO9A (Proximity Label-MS), MYO9A (Proximity Label-MS), MYO9A (Affinity Capture-MS), MYO9A (Affinity Capture-MS), MYO9A (Affinity Capture-MS), MYO9A (Affinity Capture-MS), MYO9A (Affinity Capture-MS), MYO9A (Affinity Capture-MS), MYO9A (Affinity Capture-MS), MYO9A (Affinity Capture-MS), MYO9A (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, A4IF90, A4II46, A6NI28, A6QNS3, A6X8Z5, A7KAX9, A7YY57, B2RQE8, B2RTY4, B5DFQ4, D3ZZN9, E7EZG2, E7F3F0, F1LXF1, O14014, O14559, O60890, O94466, P0CAX5, P11274, P15882, P30337, P34288, P38339, P39960, P46941, P52757, P81128, P97393, P98171, Q03070, Q08DP6, Q12979, Q13017, Q17QN0, Q20498, Q2M1Z3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MYO9A	“down-regulates activity”	RHOA	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
Activation of BAD and translocation to mitochondria	7	95.2×	6e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	84.0×	9e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	84.0×	9e-11
Activation of BH3-only proteins	7	62.1×	9e-10
RHO GTPases activate PKNs	7	39.6×	3e-08
Intrinsic Pathway for Apoptosis	7	36.6×	4e-08
FOXO-mediated transcription	5	30.0×	1e-05
SARS-CoV-1-host interactions	7	22.0×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	22.1×	9e-04
intracellular protein localization	8	10.1×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	354
Likely benign	63
Benign	73

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1458323	NC_000015.9:g.(?72103084)(74244178_?)del	Pathogenic
686724	GRCh37/hg19 15q23(chr15:72194247-72249034)x1	Pathogenic
1676435	NM_006901.4(MYO9A):c.3001-2A>G	Likely pathogenic
4291715	NM_006901.4(MYO9A):c.1699C>T (p.Gln567Ter)	Likely pathogenic

SpliceAI

7266 predictions. Top by Δscore:

Variant	Effect	Δscore
15:71827044:C:CC	acceptor_gain	1.0000
15:71827879:CTTA:C	donor_loss	1.0000
15:71827880:TTACC:T	donor_loss	1.0000
15:71827881:TA:T	donor_loss	1.0000
15:71827882:A:AC	donor_gain	1.0000
15:71827882:A:AG	donor_loss	1.0000
15:71827882:AC:A	donor_gain	1.0000
15:71827883:C:CA	donor_gain	1.0000
15:71827883:CC:C	donor_gain	1.0000
15:71827883:CCT:C	donor_gain	1.0000
15:71827883:CCTG:C	donor_gain	1.0000
15:71827883:CCTGA:C	donor_gain	1.0000
15:71828022:CCTCC:C	acceptor_gain	1.0000
15:71828023:CTCC:C	acceptor_gain	1.0000
15:71828023:CTCCC:C	acceptor_gain	1.0000
15:71828024:TCC:T	acceptor_gain	1.0000
15:71828024:TCCC:T	acceptor_gain	1.0000
15:71828025:CC:C	acceptor_gain	1.0000
15:71828025:CCC:C	acceptor_gain	1.0000
15:71828026:CC:C	acceptor_gain	1.0000
15:71828027:C:CC	acceptor_gain	1.0000
15:71828027:C:T	acceptor_gain	1.0000
15:71828028:T:A	acceptor_loss	1.0000
15:71828035:C:CT	acceptor_gain	1.0000
15:71830104:CTCA:C	donor_gain	1.0000
15:71830106:CACT:C	donor_loss	1.0000
15:71830107:A:AC	donor_gain	1.0000
15:71830107:ACTT:A	donor_gain	1.0000
15:71830108:C:CA	donor_gain	1.0000
15:71830108:CT:C	donor_gain	1.0000

AlphaMissense

16873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:71854397:A:G	L2109P	1.000
15:71862506:A:G	C2029R	1.000
15:71862554:A:G	C2013R	1.000
15:72010398:A:G	L402P	1.000
15:72045797:A:G	L256P	1.000
15:72045820:G:C	S248R	1.000
15:72045820:G:T	S248R	1.000
15:72045822:T:G	S248R	1.000
15:72046067:A:G	L166P	1.000
15:72046250:A:G	F105S	1.000
15:72046299:A:G	W89R	1.000
15:72046299:A:T	W89R	1.000
15:72046344:A:G	W74R	1.000
15:72046344:A:T	W74R	1.000
15:71851259:A:G	L2192P	0.999
15:71851271:A:G	L2188P	0.999
15:71852194:A:G	L2138P	0.999
15:71852202:T:A	K2135N	0.999
15:71852202:T:G	K2135N	0.999
15:71852203:T:A	K2135I	0.999
15:71854478:A:G	L2082P	0.999
15:71859792:G:C	C2032W	0.999
15:71859794:A:G	C2032R	0.999
15:71862504:G:C	C2029W	0.999
15:71862530:A:G	W2021R	0.999
15:71862530:A:T	W2021R	0.999
15:71862543:A:C	C2016W	0.999
15:71862544:C:T	C2016Y	0.999
15:71862545:A:G	C2016R	0.999
15:71862552:A:C	C2013W	0.999

dbSNP variants (sampled 300 via entrez): RS1000009859 (15:72110473 T>C), RS1000016133 (15:71977071 G>A), RS1000033502 (15:72075856 C>A,G), RS1000037268 (15:71900171 A>G,T), RS1000063104 (15:72111503 TAATA>T), RS1000065849 (15:72117631 G>A,C,T), RS1000071572 (15:72003877 C>T), RS1000098661 (15:71937343 A>G), RS1000107248 (15:71980530 T>A,G), RS1000107276 (15:71936330 G>A), RS1000132173 (15:72091598 C>A,G,T), RS1000139823 (15:72069198 C>G,T), RS1000147947 (15:72024186 A>G), RS1000151224 (15:71937113 T>C), RS1000151588 (15:71980574 T>G)

Disease associations

OMIM: gene MIM:604875 | disease phenotypes: MIM:618198, MIM:272800, MIM:211400

GenCC curated gene-disease

Disease	Classification	Inheritance
myasthenic syndrome, congenital, 24, presynaptic	Strong	Autosomal recessive
presynaptic congenital myasthenic syndrome	Supportive	Autosomal dominant
arthrogryposis syndrome	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
arthrogryposis syndrome	Limited	AR

Mondo (8): myasthenic syndrome, congenital, 24, presynaptic (MONDO:0032597), focal segmental glomerulosclerosis (MONDO:0100313), Tay-Sachs disease (MONDO:0010100), congenital portosystemic shunt (MONDO:0018811), presynaptic congenital myasthenic syndrome (MONDO:0700466), bronchiectasis (MONDO:0004822), arthrogryposis syndrome (MONDO:0015225), (MONDO:0020345)

Orphanet (3): Tay-Sachs disease (Orphanet:845), Congenital portosystemic shunt (Orphanet:480531), Presynaptic congenital myasthenic syndromes (Orphanet:98914)

HPO phenotypes

81 total (30 of 81 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000308	Microretrognathia
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000508	Ptosis
HP:0000565	Esotropia
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000651	Diplopia
HP:0000657	Oculomotor apraxia
HP:0000750	Delayed speech and language development
HP:0000768	Pectus carinatum
HP:0000961	Cyanosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001283	Bulbar palsy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001374	Congenital hip dislocation
HP:0001382	Joint hypermobility
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000817_69	Height	3.000000e-08
GCST001823_21	Metabolite levels (HVA/MHPG ratio)	2.000000e-06
GCST004371_1	Rate of cognitive decline in mild cognitive impairment (time interaction)	1.000000e-15
GCST004601_127	Red blood cell count	5.000000e-10
GCST006436_15	Triglyceride levels	3.000000e-09
GCST006976_99	Macular thickness	1.000000e-08
GCST007733_16	Serum uric acid levels	4.000000e-08
GCST008971_98	Urate levels	4.000000e-09
GCST008972_240	Urate levels	3.000000e-11
GCST010083_289	Hemoglobin levels	1.000000e-14
GCST010244_97	Triglyceride levels	4.000000e-09
GCST010396_303	Gut microbiota (bacterial taxa, hurdle binary method)	5.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005131	HVA measurement
EFO:0005133	MHPG measurement
EFO:0007710	cognitive decline measurement
EFO:0008336	disease progression measurement
EFO:0004305	erythrocyte count
EFO:0004530	triglyceride measurement
EFO:0004761	uric acid measurement
EFO:0004531	urate measurement
EFO:0004509	hemoglobin measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001987	Bronchiectasis	C08.127.384
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
D013661	Tay-Sachs Disease	C10.228.140.163.100.435.825.300.300.500; C16.320.565.189.435.825.300.300.500; C16.320.565.398.641.803.350.300.850; C16.320.565.595.554.825.300.300.840; C18.452.132.100.435.825.300.300.500; C18.452.584.563.641.803.350.300.850; C18.452.648.189.435.825.300.300.500; C18.452.648.398.641.803.350.300.850; C18.452.648.595.554.825.300.300.840

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Coal	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT02030015	PHASE4	TERMINATED	Synergistic Enteral Regimen for Treatment of the Gangliosidoses
NCT00749866	PHASE4	COMPLETED	Long Term Nebulised Gentamicin in Patients With Bronchiectasis
NCT00816309	PHASE4	COMPLETED	Is Regular Chest Physiotherapy an Effective Treatment in Severe, Non Cystic Fibrosis Bronchiectasis?
NCT00868075	PHASE4	COMPLETED	Pulmonary Rehabilitation in Non Cystic Fibrosis Bronchiectasis
NCT01299181	PHASE4	COMPLETED	A Trial of Atorvastatin as an Anti-Inflammatory Agent in Non-Cystic Fibrosis Bronchiectasis
NCT01299194	PHASE4	COMPLETED	Atorvastatin in Bronchiectasis in Patients With Pseudomonas Aeruginosa
NCT01677403	PHASE4	UNKNOWN	A Study to Access Safety and Efficacy of Nebulized Tobramycin in Patients With Bronchiectasis
NCT01684683	PHASE4	COMPLETED	The Effect of Theophylline in the Treatment of Bronchiectasis
NCT01769898	PHASE4	COMPLETED	The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis
NCT02047773	PHASE4	COMPLETED	Bacterial Load Guided Therapy for Severe Bronchiectasis Exacerbations
NCT02107274	PHASE4	COMPLETED	Efficacy of Azithromycin in Treatment of Bronchiectasis
NCT02507843	PHASE4	UNKNOWN	Vitamin D as an Adjunctive Treatment in Patients With Non-Cystic Fibrosis Bronchiectasis
NCT02509091	PHASE4	UNKNOWN	Therapy of Bronchoalveolar Lavage and Local Amikacin Injection in Patients With Acute Exacerbation of Bronchiectasis
NCT02546297	PHASE4	UNKNOWN	Comparisons of Inhaled LAMA or LAMA+LABA or ICS+LABA for COPD With Bronchiectasis
NCT02782312	PHASE4	COMPLETED	Salmeterol-Fluticasone Combined Inhaled Therapy for Non-cystic Fibrosis Bronchiectasis
NCT03147443	PHASE4	UNKNOWN	Evaluating the Effects of Traditional Chinese Medicine by N-of-1 Trials
NCT03262142	PHASE4	TERMINATED	Targeted AntiBiotics for Chronic Pulmonary Diseases
NCT03737617	PHASE4	WITHDRAWN	Immunoglobulin Replacement Therapy for Immunoglobulin G Subclass 2 Deficient Patients With Bronchiectasis
NCT04601792	PHASE4	UNKNOWN	A Series of N-of-1 Trials of Traditional Chinese Medicine Based on Bayesian Method
NCT04765033	PHASE4	COMPLETED	Trial on The Efficacy of Hypertonic Saline on Non-CF CSLD.
NCT06035055	PHASE4	UNKNOWN	Ceftolozane/Tazobactam Continuous Infusion for Infective Exacerbations of Cystic Fibrosis and Bronchiectasis
NCT06242795	PHASE4	RECRUITING	Hypertonic Saline in NCFB
NCT06551337	PHASE4	RECRUITING	Vitamin D Replacement in Bronchiectasis
NCT07114120	PHASE4	RECRUITING	Clinical Study on the Treatment of Stable Bronchiectasis With Bailing Capsules Combined With Guben Kechuan Granules
NCT07283497	PHASE4	RECRUITING	Itraconazole Therapy In Bronchiectasis With Airway Mold
NCT07608328	PHASE4	NOT_YET_RECRUITING	Azithromycin to Modify Bronchiectasis Exacerbation Risk
NCT01164098	PHASE3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT02683889	PHASE3	COMPLETED	Use of Acthar in Patients With FSGS That Will be Undergoing Renal Transplantation
NCT03298698	PHASE3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT03493685	PHASE3	COMPLETED	Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT05183646	PHASE3	RECRUITING	A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
NCT07220083	PHASE3	RECRUITING	A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
NCT04221451	PHASE3	TERMINATED	A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2
NCT00105183	PHASE3	COMPLETED	EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection
NCT00277537	PHASE3	COMPLETED	Safety and Efficacy of Bronchitol in Bronchiectasis