MYL9

Summary

MYL9 (myosin light chain 9, HGNC:15754) is a protein-coding gene on chromosome 20q11.23, encoding Myosin regulatory light polypeptide 9 (P24844). Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation.

Myosin, a structural component of muscle, consists of two heavy chains and four light chains. The protein encoded by this gene is a myosin light chain that may regulate muscle contraction by modulating the ATPase activity of myosin heads. The encoded protein binds calcium and is activated by myosin light chain kinase. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10398 — RefSeq curated summary.

At a glance

• Gene–disease (curated): megacystis-microcolon-intestinal hypoperistalsis syndrome 4 (Strong, GenCC)
• Clinical variants (ClinVar): 1 total
• Phenotypes (HPO): 11
• MANE Select transcript: NM_006097

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15754
Approved symbol	MYL9
Name	myosin light chain 9
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	MYRL2, MLC2, LC20, MRLC1
Ensembl gene	ENSG00000101335
Ensembl biotype	protein_coding
OMIM	609905
Entrez	10398

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000279022, ENST00000346786, ENST00000866572, ENST00000866573, ENST00000866574, ENST00000866575, ENST00000866576, ENST00000866577, ENST00000866578, ENST00000866579, ENST00000866580, ENST00000866581, ENST00000866582, ENST00000866583, ENST00000946382

RefSeq mRNA: 2 — MANE Select: NM_006097 NM_006097, NM_181526

CCDS: CCDS13276, CCDS13277

Canonical transcript exons

ENST00000279022 — 4 exons

Exon	Start	End
ENSE00001277524	36544859	36545068
ENSE00001746408	36548032	36548193
ENSE00001928726	36541519	36541561
ENSE00003715347	36549077	36551447

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 529.0153 / max 14260.2565, expressed in 1507 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184409	404.3680	1463
184408	122.0573	1478
184410	2.0624	670
184411	0.5275	277

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	99.97	gold quality
tibial artery	UBERON:0007610	99.97	gold quality
right coronary artery	UBERON:0001625	99.96	gold quality
aorta	UBERON:0000947	99.95	gold quality
lower esophagus	UBERON:0013473	99.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.95	gold quality
ascending aorta	UBERON:0001496	99.94	gold quality
thoracic aorta	UBERON:0001515	99.94	gold quality
descending thoracic aorta	UBERON:0002345	99.94	gold quality
left coronary artery	UBERON:0001626	99.93	gold quality
saphenous vein	UBERON:0007318	99.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.93	gold quality
coronary artery	UBERON:0001621	99.92	gold quality
blood vessel layer	UBERON:0004797	99.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.90	gold quality
apex of heart	UBERON:0002098	99.88	gold quality
mucosa of stomach	UBERON:0001199	99.86	gold quality
right atrium auricular region	UBERON:0006631	99.86	gold quality
body of uterus	UBERON:0009853	99.85	gold quality
left uterine tube	UBERON:0001303	99.81	gold quality
cauda epididymis	UBERON:0004360	99.81	gold quality
myometrium	UBERON:0001296	99.72	gold quality
colonic epithelium	UBERON:0000397	99.70	gold quality
right adrenal gland cortex	UBERON:0035827	99.70	gold quality
urethra	UBERON:0000057	99.69	gold quality
right adrenal gland	UBERON:0001233	99.69	gold quality
left adrenal gland cortex	UBERON:0035825	99.67	gold quality
left adrenal gland	UBERON:0001234	99.66	gold quality
lower esophagus mucosa	UBERON:0035834	99.66	gold quality
endocervix	UBERON:0000458	99.64	gold quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 42.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	12840.73
E-CURD-126	yes	10057.37
E-MTAB-10885	yes	9783.00
E-MTAB-8410	yes	9153.88
E-HCAD-1	yes	7118.46
E-MTAB-9906	yes	6833.65
E-HCAD-11	yes	6705.46
E-GEOD-124263	yes	6497.06
E-MTAB-8322	yes	6477.19
E-MTAB-10287	yes	6174.27
E-HCAD-15	yes	5932.14
E-GEOD-134144	yes	5031.50
E-CURD-46	yes	4424.38
E-MTAB-9841	yes	3869.27
E-MTAB-8142	yes	3536.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, JUN, JUNB, MAL, RUNX1, SRF

miRNA regulators (miRDB)

23 targeting MYL9, 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-4455	100.00	65.48	1587
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-10396B-5P	94.99	63.57	358
HSA-MIR-1908-5P	94.99	63.41	352
HSA-MIR-663A	94.99	63.54	378

Literature-anchored findings (GeneRIF, showing 26)

• The FHC-mediated structural perturbations in RLC that affect Ca(2+) binding properties of mutated myocardium are responsible for triggering the abnormal function of the heart that in turn might initiate a hypertrophic process and lead to heart failure. (PMID:16076902)
• Smooth muscle type isoform, MLC-2C, is the inducible isoform, and might play a crucial role in monocyte/macrophage cell lineage. (PMID:18480596)
• use of a shRNA to decrease MYL9 expression showed that MYL9 was involved in proplatelet formation (PMID:19724058)
• Endogenous Nogo-B, which may exert its effects through ARPC 2/3 and MYL-9, is necessary for the migration and contraction of airway smooth muscle cells. (PMID:21251247)
• surface CD3 expression proceeds through both MYL9-dependent and MYL9-independent pathways (i.e. the protein kinase C- dependent pathway) in Jurkat cells. (PMID:23538510)
• Overexpression of MRTF-A significantly promoted the migration of MCF-7 cells through its transactivation effects on MYL9 and CYR61 genes (PMID:24084383)
• Overexpression of SMYD3 promotes MRTF-A-mediated upregulation of MYL9 and migration of MCF-7 breast cancer cells (PMID:24189459)
• the decreased expression of MYL9 may play an important role in tumor progression of prostate cancer (PMID:24338276)
• These findings suggested that low MYLK and MYL9 expressions might be associated with the development of NSCLC. (PMID:25179839)
• At the cleavage furrow Arv1 recruits myosin heavy chain 9 (MYH9) and myosin light chain 9 (MYL9) by interacting with IQ-motif-containing GTPase-activating protein (IQGAP1). (PMID:27104745)
• MYL9 expression might be a promising prognostic marker and therapeutic target in ESCC (PMID:28388691)
• Despite the absence of human or animal phenotype related to MYL9, a cause-effect relationship between MYL9 and the Megacystis-microcolon-intestinal hypoperistalsis syndrome seems biologically plausible (PMID:29453416)
• The association of high MYL9 expression with poor prognosis in newly diagnosed glioblastoma (GBM) patients and increased expression in recurrent GBM is indicative of its role in conferring tumour aggressiveness. (PMID:31270134)
• Myosin Light Chain 9/12 Regulates the Pathogenesis of Inflammatory Bowel Disease. (PMID:33584659)
• CD4+ T cells in inflammatory diseases: pathogenic T-helper cells and the CD69-Myl9 system. (PMID:34427648)
• High Expression of MYL9 Indicates Poor Clinical Prognosis of Epithelial Ovarian Cancer. (PMID:34551701)
• The landscape of prognostic and immunological role of myosin light chain 9 (MYL9) in human tumors. (PMID:34729929)
• Clinicopathological significance of MYL9 expression in pancreatic ductal adenocarcinoma. (PMID:34821071)
• Research progress in myosin light chain 9 in malignant tumors.", trans “9. (PMID:34911847)
• Myosin light chain 9 promotes the proliferation, invasion, migration and angiogenesis of colorectal cancer cells by binding to Yes-associated protein 1 and regulating Hippo signaling. (PMID:34974798)
• Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity. (PMID:35895716)
• Increased Myosin light chain 9 expression during Kawasaki disease vasculitis. (PMID:36685558)
• LAMB3 Promotes Myofibrogenesis and Cytoskeletal Reorganization in Endometrial Stromal Cells via the RhoA/ROCK1/MYL9 Pathway. (PMID:37801199)
• MYL9 expressed in cancer-associated fibroblasts regulate the immune microenvironment of colorectal cancer and promotes tumor progression in an autocrine manner. (PMID:37926835)
• MYL9 promotes squamous cervical cancer migration and invasion by enhancing aerobic glycolysis. (PMID:37950670)
• The interplay between alterations in esophageal microbiota associated with Th17 immune response and impaired LC20 phosphorylation in achalasia. (PMID:38472375)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	myl9b	ENSDARG00000008030
danio_rerio	myl9a	ENSDARG00000038123
mus_musculus	Myl9	ENSMUSG00000067818
rattus_norvegicus	Myl9	ENSRNOG00000020246
drosophila_melanogaster	sqh	FBGN0003514
caenorhabditis_elegans		WBGENE00003372

Paralogs (7): MYL12A (ENSG00000101608), MYL10 (ENSG00000106436), MYL7 (ENSG00000106631), MYL2 (ENSG00000111245), MYL12B (ENSG00000118680), MYL11 (ENSG00000180209), MYL5 (ENSG00000215375)

Protein

Protein identifiers

Myosin regulatory light polypeptide 9 — P24844 (reviewed: P24844)

Alternative names: 20 kDa myosin light chain, MLC-2C, Myosin RLC, Myosin regulatory light chain 2, smooth muscle isoform, Myosin regulatory light chain 9, Myosin regulatory light chain MRLC1

All UniProt accessions (2): P24844, A0A384NY64

UniProt curated annotations — full annotation on UniProt →

Function. Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation. Implicated in cytokinesis, receptor capping, and cell locomotion. In myoblasts, may regulate PIEZO1-dependent cortical actomyosin assembly involved in myotube formation.

Subunit / interactions. Myosin is a hexamer of 2 heavy chains and 4 light chains: interacts with myosin heavy chain MYO19. Interacts with LUZP1; the interaction results in inhibition of phosphorylation of MYL9 by DAPK3.

Subcellular location. Cytoplasm. Cytoskeleton. Cell cortex.

Tissue specificity. Smooth muscle tissues and in some, but not all, nonmuscle cells.

Post-translational modifications. Phosphorylation increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity. It is required to generate the driving force in the migration of the cells but not necessary for localization of myosin-2 at the leading edge. Phosphorylation is required for myotube formation. Phosphorylated by DAPK3; DAPK3-mediated phosphorylation is inhibited by LUZP1.

Disease relevance. Megacystis-microcolon-intestinal hypoperistalsis syndrome 4 (MMIHS4) [MIM:619365] A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS4 inheritance is autosomal recessive. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. This chain binds calcium.

Isoforms (2)

UniProt ID	Names	Canonical?
P24844-1	1	yes
P24844-2	2

RefSeq proteins (2): NP_006088, NP_852667 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR050403	Myosin_RLC	Family

Pfam: PF13499

UniProt features (21 total): sequence conflict 6, binding site 4, modified residue 3, domain 3, initiator methionine 1, chain 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24844-F1	84.10	0.63

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 (4): 53; 42; 44; 46

Post-translational modifications (3): 2, 19, 20

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse
R-HSA-445355	Smooth Muscle Contraction
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-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-212436	Generic Transcription Pathway
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-373755	Semaphorin interactions
R-HSA-397014	Muscle contraction
R-HSA-400685	Sema4D in semaphorin signaling
R-HSA-422475	Axon guidance
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9675108	Nervous system development
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 298 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, WWTAAGGC_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_PLATELET_ACTIVATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, KEGG_TIGHT_JUNCTION, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, SRF_Q5_01, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_WOUND_HEALING, GOBP_CELL_CELL_ADHESION, BROWNE_HCMV_INFECTION_48HR_DN, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP

GO Biological Process (4): regulation of muscle contraction (GO:0006937), myofibril assembly (GO:0030239), stress fiber assembly (GO:0043149), platelet aggregation (GO:0070527)

GO Molecular Function (6): structural constituent of cytoskeleton (GO:0005200), calcium ion binding (GO:0005509), structural constituent of muscle (GO:0008307), myosin heavy chain binding (GO:0032036), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): stress fiber (GO:0001725), cytoplasm (GO:0005737), cytosol (GO:0005829), muscle myosin complex (GO:0005859), cell cortex (GO:0005938), myosin II complex (GO:0016460), myofibril (GO:0030016), Z disc (GO:0030018), cytoskeleton (GO:0005856), myosin complex (GO:0016459)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
RHO GTPase Effectors	4
Axon guidance	2
EPH-Ephrin signaling	1
Sema4D in semaphorin signaling	1
Muscle contraction	1
Transcriptional regulation by RUNX1	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
RNA Polymerase II Transcription	1
Semaphorin interactions	1
Nervous system development	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
actomyosin structure organization	2
structural molecule activity	2
cytoplasm	2
contractile muscle fiber	2
muscle contraction	1
regulation of muscle system process	1
cellular component assembly involved in morphogenesis	1
striated muscle cell development	1
supramolecular fiber organization	1
membraneless organelle assembly	1
contractile actin filament bundle assembly	1
platelet activation	1
homotypic cell-cell adhesion	1
cytoskeleton	1
cytoskeleton organization	1
metal ion binding	1
myosin binding	1
binding	1
cation binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular anatomical structure	1
myosin II complex	1
cell periphery	1
myosin complex	1
I band	1
intracellular membraneless organelle	1
actin cytoskeleton	1
protein-containing complex	1

Protein interactions and networks

STRING

3138 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYL9	PPP1R12C	Q9BZL4	884
MYL9	MYLK2	Q9H1R3	873
MYL9	PPP1R12A	O14974	817
MYL9	MYLK	Q15746	785
MYL9	TAGLN	Q01995	780
MYL9	MYOD1	P15172	774
MYL9	CDC42BPA	Q5VT25	758
MYL9	PPP1CB	P37140	726
MYL9	MYH10	P35580	720
MYL9	MYBPC3	Q14896	713
MYL9	MYH11	P35749	708
MYL9	MYBPC2	Q14324	682
MYL9	RHOA	P06749	631
MYL9	LMOD1	P29536	619
MYL9	ACTA2	P03996	615

IntAct

55 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DISC1	Ccdc141	psi-mi:“MI:0914”(association)	0.630
S100A4	OIP5	psi-mi:“MI:0914”(association)	0.530
ERBB2	HAX1	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
MYL9	Ccdc141	psi-mi:“MI:0915”(physical association)	0.460
Ccdc141	MYL9	psi-mi:“MI:0403”(colocalization)	0.460
PRKAA1	MYL9	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MYL9	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
MYL9	CCDC141	psi-mi:“MI:0915”(physical association)	0.400
MYL9	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
FOXD3	MYL12B	psi-mi:“MI:0914”(association)	0.350
FOXP1	MYL12B	psi-mi:“MI:0914”(association)	0.350
OCRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
AKT3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): MYL9 (Two-hybrid), EIF2S2 (Co-fractionation), EIF3I (Co-fractionation), PIP4K2B (Co-fractionation), PIP4K2C (Co-fractionation), MYL9 (Affinity Capture-MS), MYL9 (Affinity Capture-MS), MYL9 (Affinity Capture-MS), MYL9 (Affinity Capture-MS), MYL9 (Affinity Capture-MS), MYL9 (Affinity Capture-MS), MYL9 (Reconstituted Complex), MYL9 (Affinity Capture-MS), MYL9 (Affinity Capture-MS), MYL9 (Affinity Capture-MS)

ESM2 similar proteins: A0A125YHX7, A0A125YZN2, A4IF97, J9W034, O14950, O23184, O74435, O82659, P02612, P08733, P13832, P15845, P18666, P19105, P24032, P24844, P29269, P40423, P41208, P41209, P41210, P41691, P48593, P53441, Q09510, Q0IQB6, Q0IUU4, Q12798, Q24956, Q27177, Q27178, Q27179, Q2TBN3, Q32LE3, Q338P8, Q39584, Q3SEK0, Q3SEK2, Q3THE2, Q40642

Diamond homologs: A2WN93, A2WNH1, A2Y609, A3E3H0, A3E4D8, A3E4F9, A4IF97, A4UHC0, A8CEP3, A8I1Q0, B7SNI3, F1SSF9, O14950, O93409, O94739, P02597, P02598, P02608, P02609, P02610, P02611, P02612, P02613, P04112, P04113, P04353, P04464, P04466, P05419, P05944, P05963, P07461, P08051, P08052, P08733, P0DH95, P0DH96, P10916, P11120, P13543

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
PRKCA	down-regulates	MYL9	phosphorylation
CDC42BPA	up-regulates	MYL9	phosphorylation
DAPK3	up-regulates	MYL9	phosphorylation
MYLK	up-regulates	MYL9	phosphorylation
ROCK2	“up-regulates activity”	MYL9	phosphorylation
PTK2	“up-regulates activity”	MYL9	phosphorylation
ROCK1	up-regulates	MYL9	phosphorylation
CIT	“up-regulates activity”	MYL9	phosphorylation
ROCK1	“up-regulates activity”	MYL9	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
Sema4D induced cell migration and growth-cone collapse	5	86.5×	7e-07
EPH-Ephrin signaling	5	25.1×	6e-05
Muscle contraction	5	11.7×	2e-03
Axon guidance	6	8.2×	2e-03
Nervous system development	6	7.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
in utero embryonic development	7	13.3×	5e-04
negative regulation of apoptotic process	7	6.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

475 predictions. Top by Δscore:

Variant	Effect	Δscore
20:36545038:G:GT	donor_gain	1.0000
20:36545064:GCTGG:G	donor_gain	1.0000
20:36545065:C:G	donor_gain	1.0000
20:36545067:GG:G	donor_gain	1.0000
20:36545068:GG:G	donor_gain	1.0000
20:36545069:G:C	donor_loss	1.0000
20:36545069:G:GG	donor_gain	1.0000
20:36545070:T:G	donor_loss	1.0000
20:36548184:G:GT	donor_gain	1.0000
20:36549068:T:TA	acceptor_gain	1.0000
20:36549072:CGCAG:C	acceptor_loss	1.0000
20:36549074:CAGGT:C	acceptor_loss	1.0000
20:36549075:A:AG	acceptor_gain	1.0000
20:36549076:G:GA	acceptor_gain	1.0000
20:36549076:GGT:G	acceptor_gain	1.0000
20:36541557:ACCAG:A	donor_loss	0.9900
20:36541558:CCAG:C	donor_loss	0.9900
20:36541559:CAG:C	donor_loss	0.9900
20:36541560:AGGTG:A	donor_loss	0.9900
20:36541561:GGTGG:G	donor_loss	0.9900
20:36541562:G:C	donor_loss	0.9900
20:36541563:T:G	donor_loss	0.9900
20:36544854:T:A	acceptor_gain	0.9900
20:36544855:GCAG:G	acceptor_loss	0.9900
20:36544856:CAG:C	acceptor_loss	0.9900
20:36544857:A:AG	acceptor_gain	0.9900
20:36544857:A:C	acceptor_loss	0.9900
20:36544857:AG:A	acceptor_gain	0.9900
20:36544857:AGG:A	acceptor_gain	0.9900
20:36544858:G:GG	acceptor_gain	0.9900

AlphaMissense

1178 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:36544989:G:C	K35N	1.000
20:36544989:G:T	K35N	1.000
20:36544993:G:C	A37P	1.000
20:36544996:T:C	F38L	1.000
20:36544997:T:C	F38S	1.000
20:36544998:C:A	F38L	1.000
20:36544998:C:G	F38L	1.000
20:36545009:A:T	D42V	1.000
20:36545030:T:A	I49N	1.000
20:36545045:T:C	L54P	1.000
20:36545057:T:C	L58P	1.000
20:36548094:T:C	F83L	1.000
20:36548095:T:C	F83S	1.000
20:36548096:C:A	F83L	1.000
20:36548096:C:G	F83L	1.000
20:36548104:T:C	F86S	1.000
20:36548107:T:A	L87H	1.000
20:36548107:T:C	L87P	1.000
20:36549098:T:C	L123P	1.000
20:36549110:T:C	L127P	1.000
20:36544951:T:C	F23L	0.999
20:36544952:T:G	F23C	0.999
20:36544953:C:A	F23L	0.999
20:36544953:C:G	F23L	0.999
20:36544960:T:A	F26I	0.999
20:36544960:T:C	F26L	0.999
20:36544961:T:C	F26S	0.999
20:36544961:T:G	F26C	0.999
20:36544962:T:A	F26L	0.999
20:36544962:T:G	F26L	0.999

dbSNP variants (sampled 300 via entrez): RS1000426094 (20:36539850 A>C), RS1000528856 (20:36540068 T>C), RS1000643676 (20:36539720 T>C,G), RS1000828662 (20:36551083 A>G), RS1001111160 (20:36545569 G>T), RS1001579781 (20:36550219 T>C), RS1001630446 (20:36549885 C>T), RS1001743750 (20:36544592 G>C), RS1002161275 (20:36540423 C>T), RS1002453046 (20:36550760 G>C), RS1002539911 (20:36542547 C>A,T), RS1003314377 (20:36548518 G>A,C), RS1003537016 (20:36543704 G>A), RS1003889389 (20:36544424 AC>A), RS1003949292 (20:36550367 G>A,C)

Disease associations

OMIM: gene MIM:609905 | disease phenotypes: MIM:155310

GenCC curated gene-disease

Disease	Classification	Inheritance
megacystis-microcolon-intestinal hypoperistalsis syndrome 4	Strong	Autosomal recessive

Mondo (2): visceral myopathy 1 (MONDO:0020754), megacystis-microcolon-intestinal hypoperistalsis syndrome 4 (MONDO:0030296)

Orphanet (1): Familial visceral myopathy (Orphanet:2604)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000021	Megacystis
HP:0000787	Nephrolithiasis
HP:0001562	Oligohydramnios
HP:0002205	Recurrent respiratory infections
HP:0003270	Abdominal distention
HP:0010945	Fetal pyelectasis
HP:0011499	Mydriasis
HP:0012762	Cerebral white matter atrophy
HP:0100771	Hypoperistalsis

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
ML 7	decreases reaction, increases phosphorylation, decreases activity, decreases phosphorylation, decreases expression	7
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	4
bisphenol A	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	3
Y 27632	decreases reaction, increases phosphorylation	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Carbamazepine	affects expression, decreases activity, decreases phosphorylation	2
Lipopolysaccharides	increases phosphorylation, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	decreases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
Allura Red AC Dye	increases phosphorylation, increases reaction	1
lead acetate	increases expression	1
methylselenic acid	increases expression	1
decabromobiphenyl ether	decreases expression	1
quercitrin	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
trimellitic anhydride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1CF	Abcam A-431 MYL9 KO	Cancer cell line	Female
CVCL_B1Y1	Abcam HeLa MYL9 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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