MYOCD

Summary

MYOCD (myocardin, HGNC:16067) is a protein-coding gene on chromosome 17p12, encoding Myocardin (Q8IZQ8). Smooth muscle cells (SM) and cardiac muscle cells-specific transcriptional factor which uses the canonical single or multiple CArG boxes DNA sequence.

This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 93649 — RefSeq curated summary.

At a glance

• Gene–disease (curated): megabladder, congenital (Strong, GenCC)
• GWAS associations: 38
• Clinical variants (ClinVar): 157 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_001146312

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16067
Approved symbol	MYOCD
Name	myocardin
Location	17p12
Locus type	gene with protein product
Status	Approved
Aliases	MYCD
Ensembl gene	ENSG00000141052
Ensembl biotype	protein_coding
OMIM	606127
Entrez	93649

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000343344, ENST00000395988, ENST00000425538, ENST00000443061, ENST00000579237, ENST00000860865, ENST00000860866, ENST00000968132

RefSeq mRNA: 3 — MANE Select: NM_001146312 NM_001146312, NM_001378306, NM_153604

CCDS: CCDS11163, CCDS54091

Canonical transcript exons

ENST00000425538 — 14 exons

Exon	Start	End
ENSE00001689732	12763073	12768949
ENSE00001904591	12665890	12666243
ENSE00002765655	12705128	12705193
ENSE00002807997	12758085	12758213
ENSE00002865178	12760650	12760707
ENSE00002877323	12717346	12717421
ENSE00003539252	12722847	12723008
ENSE00003548909	12715519	12715574
ENSE00003705115	12756414	12756557
ENSE00003706851	12745919	12746072
ENSE00003707295	12744183	12744436
ENSE00003709048	12739203	12739328
ENSE00003710076	12752414	12753346
ENSE00003710479	12736161	12736336

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 98.90.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8972 / max 158.6406, expressed in 469 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159616	1.4366	347
159617	0.9834	294
159618	0.2602	129
159619	0.2169	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	98.90	gold quality
saphenous vein	UBERON:0007318	98.61	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.44	gold quality
myocardium	UBERON:0002349	94.70	gold quality
heart right ventricle	UBERON:0002080	93.93	gold quality
nipple	UBERON:0002030	91.75	gold quality
urethra	UBERON:0000057	89.60	gold quality
right coronary artery	UBERON:0001625	89.52	gold quality
superficial temporal artery	UBERON:0001614	89.46	gold quality
ascending aorta	UBERON:0001496	89.14	gold quality
thoracic aorta	UBERON:0001515	89.04	gold quality
aorta	UBERON:0000947	88.68	gold quality
smooth muscle tissue	UBERON:0001135	88.50	gold quality
urinary bladder	UBERON:0001255	88.34	gold quality
popliteal artery	UBERON:0002250	88.34	gold quality
seminal vesicle	UBERON:0000998	88.31	gold quality
tibial artery	UBERON:0007610	88.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.57	gold quality
lower esophagus	UBERON:0013473	87.54	gold quality
myometrium	UBERON:0001296	87.10	gold quality
caput epididymis	UBERON:0004358	86.93	gold quality
colonic epithelium	UBERON:0000397	86.66	gold quality
left ventricle myocardium	UBERON:0006566	86.65	silver quality
coronary artery	UBERON:0001621	86.48	gold quality
descending thoracic aorta	UBERON:0002345	85.94	gold quality
left coronary artery	UBERON:0001626	85.88	gold quality
corpus epididymis	UBERON:0004359	85.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.55	gold quality
vena cava	UBERON:0004087	83.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	7.98
E-ANND-3	yes	5.61

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
ACTA2	Unknown
ACTG2	Activation
BMP10
CNN1	Activation
ITGA8
MYLK	Activation
MYOCD
SGCA	Activation
TAGLN	Activation

Upstream regulators (CollecTRI, top): ARNT, ELK1, FOS, FOXC1, FOXO3, GATA4, GATA6, HESX1, HEY2, HNF4A, IRF6, IRF9, KLF15, KLF4, KLF5, MECP2, MEF2A, MEF2C, MSC, MYOCD, MYOD1, NFATC3, NFKB, NKX2-5, NR1I2, RELA, SIRT1, SMAD2, SMAD3, SMARCA1, SOX9, TEAD1, TGFB1, TSHZ3

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-12133	99.92	71.82	2006

Literature-anchored findings (GeneRIF, showing 40)

• Myocardin is a critical serum response factor cofactor regulating smooth muscle cell differentiation; forced expression of myocardin activated expression of SM22 alpha, smooth muscle alpha-actin, and calponin-h1 genes in mouse ES cells (PMID:12640126)
• HERP1 and myocardin expression was localized to smooth muscle cells in the neointima in human coronary atherosclerotic lesions. (PMID:16151017)
• myocardin-MYOCD overexpression in small cerebral arteries appears to initiate independently of amyloid beta-peptide a pathogenic pathway mediating arterial hypercontractility (PMID:17215356)
• Myocardin is frequently repressed during malignant transformation, contributing to a differentiation defect (PMID:17292825)
• the SRC3-myocardin interaction is a site of convergence for nuclear hormone receptor-mediated and VSMC-specific gene regulation (PMID:17360478)
• Data show that fibroblasts from human postmyocardial infarction scars acquire properties of cardiomyocytes after transduction with a recombinant myocardin gene. (PMID:17579192)
• Forced expression of the myocardin (MyoC) gene in human ventricular scar fibroblasts leads to MyoC-dependent activation of genes that encode connexins, strongly enforcing intercellular electrical coupling. (PMID:17938287)
• data suggest that functional natural myocardin promoter variation might be a genetic factor contributing to inter-individual differences in the development of cardiac hypertrophy (PMID:18028454)
• Myocd is sufficient for the establishment of a SMC-like contractile phenotype. (PMID:18451334)
• Foxo3a could negatively regulate myocardin expression levels through up-regulating catalase and the consequent reduction of ROS levels (PMID:18772130)
• A rare human sequence variant reveals myocardin autoinhibition (PMID:18852265)
• We suggest that SRF and MYOCD function as a transcriptional switch, controlling Abeta cerebrovascular clearance and progression of AD. (PMID:19098903)
• Results show that human retroperitoneal LMS differentiation is dependent on MYOCD amplification/overexpression, suggesting that in these well-differentiated LMS, differentiation could be a consequence of an acquired genomic alteration. (PMID:19276386)
• analysis of a novel mode of modulation of SM gene transcription by ERK1/2 through a direct phosphorylation of myocardin (PMID:19776005)
• MYOCD can discriminate among several juxtaposed CArG elements, presumably through its novel partnership with NKX3.1, to optimally transactivate the human ACTG2 promoter (PMID:19797053)
• Results reveal the first ion channel subunit as a direct target of SRF-MYOCD transactivation, providing further insight into the role of MYOCD as a master regulator of the SMC contractile phenotype. (PMID:19801679)
• Myocardin was identified as a novel gene upregulated in human cervical ripening. (PMID:19883264)
• the evaluation of myocardin expression is useful in distinguishing uterine smooth muscle tumors from endometrial stromal sarcomas (PMID:19952936)
• Results indicate that the downregulation of myocardin expression facilitates cell cycle progression via the reduction of p21 expression in human leimyosarcomas (PMID:20068148)
• These results are the first to show relative expression and activities of the major myocardin isoforms across disparate spec (PMID:20385216)
• These findings suggest a role of microRNA-1 in the negative feedback loop in the regulation of smooth muscle contractility induced by myocardin. (PMID:20458751)
• A positive association was observed between response to methadone and two variants in the genes MYOCD and GRM6. (PMID:20560679)
• Epigenetic inactivation of Myocardin is a frequent and tumor-specific event in nasopharyngeal carcinoma. (PMID:20848417)
• Induction of microRNA-1 by myocardin in smooth muscle cells inhibits cell proliferation. (PMID:21051663)
• Vascular smooth muscle proteasomal degradation of myocardin is required for its transcriptional activity. (PMID:21506120)
• Transforming growth factor-beta1-induced transcript 1 protein, a novel marker for smooth muscle contractile phenotype, is regulated by serum response factor/myocardin protein. (PMID:21984848)
• Nuclear uPAR associates with myocardin, which is then recruited from the promoters of serum response factor target genes and undergoes proteasomal degradation. (PMID:22075245)
• Hypertension negates the activity of myocardin in vascular smooth muscle cells. (PMID:22843699)
• Myocardin increases the development and maturation of smooth muscle cell-like cells from human embryonic stem cells despite not activating the full repertoire of smooth muscle cell genes. (PMID:22937150)
• The dynamic expression of Sox9 and the interaction between TSHZ3, SOX9 and MYOCD provide a mechanism that regulates the pace the myogenic program in the ureter. (PMID:23671695)
• ChIP analysis established that PDGF-BB-induced repression of Myocd gene expression is most likely regulated by enhanced binding of Klf4 and Klf5 to a lesser extent, to the PRR of PrmM (PMID:24060351)
• the first evidence demonstrating that TEAD1 is a novel general repressor of smooth muscle-specific gene expression through interfering with myocardin binding to SRF. (PMID:24344135)
• Myocardin meditates apoptosis in breast cancer through affecting maspin re-expression and epigenetic modification. (PMID:24607789)
• Early cardiac marker gene myocardin levels in peripheral blood mononuclear cells reflect severity in stable coronary artery disease. (PMID:24681789)
• it is probably that miR135b promotes proliferation, invasion and migration of osteosarcoma cells by degrading myocardin (PMID:25190111)
• TNFalpha differentially regulates myocardin expression and activity (PMID:25384061)
• Propose myocardin as a guardian of the contractile, noninflammatory VSMC phenotype, with loss of myocardin representing a critical permissive step in the process of phenotypic transition and inflammatory activation, at the onset of vascular disease. (PMID:25614278)
• TMEM16A and myocardin form a positive feedback loop that is disrupted by KLF5 during Ang II-induced vascular remodeling. (PMID:26077572)
• STAT3 protein regulates vascular smooth muscle cell phenotypic switch by interaction with myocardin and SRF. (PMID:26100622)
• inhibition of GSK-3beta reduces myocardin transcriptional activity, suggesting a role for GSK-3beta in myocardin transcriptional activity and smooth muscle differentiation (PMID:26129946)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Myocd	ENSMUSG00000020542
rattus_norvegicus	Myocd	ENSRNOG00000003669
drosophila_melanogaster	Mrtf	FBGN0052296
caenorhabditis_elegans		WBGENE00004145

Paralogs (2): MRTFB (ENSG00000186260), MRTFA (ENSG00000196588)

Protein

Protein identifiers

Myocardin — Q8IZQ8 (reviewed: Q8IZQ8)

All UniProt accessions (3): Q8IZQ8, J3KSX3, Q6N065

UniProt curated annotations — full annotation on UniProt →

Function. Smooth muscle cells (SM) and cardiac muscle cells-specific transcriptional factor which uses the canonical single or multiple CArG boxes DNA sequence. Acts as a cofactor of serum response factor (SRF) with the potential to modulate SRF-target genes. Plays a crucial role in cardiogenesis, urinary bladder development, and differentiation of the smooth muscle cell lineage (myogenesis). Positively regulates the transcription of genes involved in vascular smooth muscle contraction.

Subunit / interactions. Homodimer. Interacts with SRF, its association does not depend on specific DNA sequences for ternary complex formation. Interacts with MLLT7/FOXO4. Interacts (via C-terminal) with EP300 (via the CREB-binding domain). Interacts with HDAC4 and HDAC5. Interacts with MEF2C. Interacts (via C-terminus) with STUB1/CHIP. Interacts with PURB.

Subcellular location. Nucleus.

Tissue specificity. Expressed in the heart, aorta and bladder. Expressed in smooth muscle cell-containing tissues: stomach, small intestine, colon, lung, placenta and uterus. Very faint expression in prostate and skeletal muscle.

Post-translational modifications. Ubiquitinated; by STUB1/CHIP at the C-terminus, leading to its degradation by the proteasome. Phosphorylation by GSK3B is required for STUB1/CHIP-mediated ubiquitination. Phosphorylation negatively regulates the intrinsic myocardin transcriptional activity. Phosphorylated; by GSK3B.

Disease relevance. Megabladder, congenital (MGBL) [MIM:618719] An autosomal dominant congenital anomaly characterized by a massively dilated urinary bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, and incomplete penetrance. Affected males frequently die in utero. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal region contains a general transcription activation domain. The N-terminal region, comprising a basic and a Gln-rich domain, confers transcriptional potency and specificity by mediating association with the MADS box of SRF. The basic domain may be required for nuclear localization. The SAP domain is important for transactivation and ternary complex formation.

Induction. Up-regulated during end-stage heart failure caused by dilated cardiomyopathy.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IZQ8-1	1, Myocardin-A	yes
Q8IZQ8-2	2, Myocardin-C
Q8IZQ8-3	3, Myocardin-B

RefSeq proteins (3): NP_001139784, NP_001365235, NP_705832 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003034	SAP_dom	Domain
IPR004018	RPEL_repeat	Repeat
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR043451	Myocardin-like	Family

Pfam: PF02037, PF02755

UniProt features (37 total): modified residue 12, region of interest 6, compositionally biased region 6, splice variant 4, repeat 3, sequence variant 2, chain 1, coiled-coil region 1, short sequence motif 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZQ8-F1	56.16	0.20

Functional residue map

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

Post-translational modifications (12): 451, 455, 459, 463, 626, 630, 634, 638, 815, 862, 869, 896

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9733709	Cardiogenesis
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 330 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, chr17p12, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_GROWTH, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP

GO Biological Process (45): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cell growth by extracellular stimulus (GO:0001560), vasculogenesis (GO:0001570), response to hypoxia (GO:0001666), cardiac ventricle development (GO:0003231), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), cardiac muscle cell apoptotic process (GO:0010659), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), negative regulation of myotube differentiation (GO:0010832), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), cardiocyte differentiation (GO:0035051), regulation of myoblast differentiation (GO:0045661), transcription initiation-coupled chromatin remodeling (GO:0045815), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of smooth muscle contraction (GO:0045987), lung alveolus development (GO:0048286), digestive tract development (GO:0048565), smooth muscle cell differentiation (GO:0051145), regulation of smooth muscle cell differentiation (GO:0051150), positive regulation of smooth muscle cell differentiation (GO:0051152), cardiac muscle cell differentiation (GO:0055007), ventricular cardiac muscle cell differentiation (GO:0055012), uterus development (GO:0060065), urinary bladder development (GO:0060157), negative regulation of cell adhesion molecule production (GO:0060354), cardiac muscle cell myoblast differentiation (GO:0060379), cardiac vascular smooth muscle cell differentiation (GO:0060947), ductus arteriosus closure (GO:0097070), negative regulation of amyloid-beta clearance (GO:1900222), regulation of phenotypic switching (GO:1900239), positive regulation of miRNA transcription (GO:1902895), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706), negative regulation of vascular associated smooth muscle cell migration (GO:1904753), negative regulation of platelet-derived growth factor receptor-beta signaling pathway (GO:2000587), positive regulation of cardiac muscle cell differentiation (GO:2000727), negative regulation of skeletal muscle cell differentiation (GO:2001015), chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (7): transcription coactivator activity (GO:0003713), histone acetyltransferase binding (GO:0035035), histone deacetylase binding (GO:0042826), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), R-SMAD binding (GO:0070412), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
cell differentiation	2
cell population proliferation	2
regulation of cell population proliferation	2
positive regulation of DNA-templated transcription	2
enzyme binding	2
negative regulation of DNA-templated transcription	1
regulation of cell growth	1
cellular response to stimulus	1
blood vessel morphogenesis	1
response to stress	1
response to decreased oxygen levels	1
cardiac chamber development	1
positive regulation of cellular process	1
negative regulation of cellular process	1
striated muscle cell apoptotic process	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
regulation of myotube differentiation	1
myotube differentiation	1
negative regulation of striated muscle cell differentiation	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
heart development	1
myoblast differentiation	1
regulation of cell differentiation	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
smooth muscle contraction	1
regulation of smooth muscle contraction	1
positive regulation of muscle contraction	1
lung development	1
anatomical structure development	1

Protein interactions and networks

STRING

2884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYOCD	SRF	P11831	999
MYOCD	TAGLN	Q01995	876
MYOCD	NKX2-5	P52952	831
MYOCD	KLF4	P78338	824
MYOCD	HAND2	P61296	820
MYOCD	MEF2C	Q06413	809
MYOCD	GATA4	P43694	808
MYOCD	PHACTR1	Q9C0D0	802
MYOCD	TBX5	Q99593	798
MYOCD	CNN1	P51911	794
MYOCD	MYH11	P35749	779
MYOCD	EP300	Q09472	772
MYOCD	FOXO4	P98177	768
MYOCD	MRTFA	Q969V6	766
MYOCD	HDAC4	P56524	721

IntAct

14 interactions, top by confidence:

A	B	Type	Score
GOPC	MYOCD	psi-mi:“MI:0915”(physical association)	0.670
MYOCD	GOPC	psi-mi:“MI:0915”(physical association)	0.670
SRF	MYOCD	psi-mi:“MI:0915”(physical association)	0.520
MYOCD	SRF	psi-mi:“MI:0915”(physical association)	0.520
	MYOCD	psi-mi:“MI:0915”(physical association)	0.370
CCL1	MYOCD	psi-mi:“MI:0915”(physical association)	0.370
IL20	MYOCD	psi-mi:“MI:0915”(physical association)	0.370
ARRB2		psi-mi:“MI:0914”(association)	0.350

BioGRID (31): MYOCD (Two-hybrid), MYOCD (Reconstituted Complex), MYOCD (Reconstituted Complex), NCOA3 (Phenotypic Suppression), SRF (Affinity Capture-Western), MKL1 (Reconstituted Complex), MYOCD (Proximity Label-MS), MYOCD (Positive Genetic), HNRNPUL1 (Cross-Linking-MS (XL-MS)), MYOCD (Affinity Capture-Western), MYOCD (Affinity Capture-Western), SMARCA4 (Affinity Capture-Western), SRF (Affinity Capture-Western), SMARCA4 (Reconstituted Complex), MYOCD (Affinity Capture-Western)

ESM2 similar proteins: A0A0R4IYX6, A0A1L8H0H2, A5X7A0, A7XYJ6, E1BE02, F6NSX9, F8VPJ6, O35914, O57415, P37275, P59598, P59759, Q03172, Q13029, Q2KHR2, Q3UH06, Q5EXX3, Q5R7F2, Q5ZIE8, Q5ZLR2, Q62947, Q63755, Q64318, Q6NRM0, Q6ZPY7, Q76L83, Q7LBC6, Q7YR76, Q80VX4, Q86V15, Q8BHZ4, Q8BLG0, Q8BRH4, Q8BX22, Q8BZ32, Q8C0C0, Q8IZQ8, Q8NEZ4, Q8R5I7, Q8VIM5

Diamond homologs: A7E346, Q0ZCJ7, Q6ZN01, Q7YR76, Q8IZQ8, Q8R5I7, Q8VIM5, P59759, Q8AYC1, Q8AYC2, Q8K4J6, Q969V6, Q9ULH7

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
KLF4	down-regulates	MYOCD
MYOCD	down-regulates	KLF4
MYOCD	up-regulates	SRF	binding
TGFB1	“up-regulates quantity by expression”	MYOCD	“transcriptional regulation”
GSK3B	“down-regulates activity”	MYOCD	phosphorylation
MYOCD	“up-regulates quantity by expression”	ACTG2	“transcriptional regulation”
PRKCA	“down-regulates activity”	MYOCD	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	99
Likely benign	9
Benign	31

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
689480	NM_001146312.3(MYOCD):c.343C>T (p.Arg115Ter)	Pathogenic
689481	NM_001146312.3(MYOCD):c.1053_1054del (p.Asn351fs)	Pathogenic
1328432	NM_001146312.3(MYOCD):c.971+3_971+6del	Likely pathogenic
3377179	NM_001146312.3(MYOCD):c.232del (p.Val78fs)	Likely pathogenic
3382937	NM_001146312.3(MYOCD):c.55+2T>C	Likely pathogenic

SpliceAI

2084 predictions. Top by Δscore:

Variant	Effect	Δscore
17:12715517:A:AG	acceptor_gain	1.0000
17:12715518:G:GG	acceptor_gain	1.0000
17:12715571:CAAG:C	donor_loss	1.0000
17:12715572:AAGG:A	donor_loss	1.0000
17:12715575:GT:G	donor_loss	1.0000
17:12715576:T:A	donor_loss	1.0000
17:12722845:A:AG	acceptor_gain	1.0000
17:12722846:G:GG	acceptor_gain	1.0000
17:12723004:AAAAG:A	donor_loss	1.0000
17:12723005:AAAG:A	donor_loss	1.0000
17:12723007:AGG:A	donor_loss	1.0000
17:12723008:GG:G	donor_loss	1.0000
17:12723009:G:C	donor_loss	1.0000
17:12744181:A:AG	acceptor_gain	1.0000
17:12744182:G:GA	acceptor_gain	1.0000
17:12744182:G:GG	acceptor_gain	1.0000
17:12744182:GTCC:G	acceptor_gain	1.0000
17:12744182:GTCCA:G	acceptor_gain	1.0000
17:12744431:GCT:G	donor_gain	1.0000
17:12744432:CTTAA:C	donor_gain	1.0000
17:12744433:TTAA:T	donor_gain	1.0000
17:12744434:TAA:T	donor_gain	1.0000
17:12744435:AA:A	donor_gain	1.0000
17:12744436:AG:A	donor_loss	1.0000
17:12744437:G:GG	donor_gain	1.0000
17:12744438:T:A	donor_loss	1.0000
17:12752409:TTTA:T	acceptor_loss	1.0000
17:12752410:TTA:T	acceptor_loss	1.0000
17:12752411:TA:T	acceptor_loss	1.0000
17:12752413:G:GT	acceptor_loss	1.0000

AlphaMissense

6497 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:12744253:T:C	L263P	1.000
17:12744255:A:G	K264E	1.000
17:12744257:A:C	K264N	1.000
17:12744257:A:T	K264N	1.000
17:12744258:T:C	Y265H	1.000
17:12744258:T:G	Y265D	1.000
17:12744259:A:C	Y265S	1.000
17:12744259:A:G	Y265C	1.000
17:12744261:C:A	H266N	1.000
17:12744261:C:G	H266D	1.000
17:12744262:A:G	H266R	1.000
17:12744263:C:A	H266Q	1.000
17:12744263:C:G	H266Q	1.000
17:12744267:T:C	Y268H	1.000
17:12744267:T:G	Y268D	1.000
17:12744268:A:C	Y268S	1.000
17:12744268:A:G	Y268C	1.000
17:12744334:T:C	L290P	1.000
17:12744355:T:C	L297P	1.000
17:12744361:T:C	L299P	1.000
17:12752424:T:C	L379S	1.000
17:12752427:G:C	R380T	1.000
17:12752428:A:C	R380S	1.000
17:12752428:A:T	R380S	1.000
17:12752436:T:A	L383H	1.000
17:12752436:T:C	L383P	1.000
17:12752469:A:T	K394I	1.000
17:12752470:A:C	K394N	1.000
17:12752470:A:T	K394N	1.000
17:12752478:T:A	L397H	1.000

dbSNP variants (sampled 300 via entrez): RS1000008196 (17:12738028 T>C), RS1000026502 (17:12765611 C>T), RS1000036193 (17:12694909 G>A,T), RS1000105005 (17:12727395 C>T), RS1000139050 (17:12718860 G>A), RS1000140795 (17:12760129 A>G), RS1000151305 (17:12685459 A>C), RS1000154957 (17:12680432 G>A), RS1000162592 (17:12714159 C>A,T), RS1000178047 (17:12756644 C>A,G,T), RS1000192684 (17:12676494 T>C), RS1000226885 (17:12673485 T>A), RS1000237822 (17:12679870 A>G), RS1000252253 (17:12759964 G>C), RS1000262792 (17:12759792 C>A)

Disease associations

OMIM: gene MIM:606127 | disease phenotypes: MIM:618719, MIM:100100

GenCC curated gene-disease

Disease	Classification	Inheritance
megabladder, congenital	Strong	Autosomal dominant

Mondo (3): megabladder, congenital (MONDO:0032879), intellectual disability (MONDO:0001071), prune belly syndrome (MONDO:0007032)

Orphanet (2): Prune belly syndrome (Orphanet:2970), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0003774	Stage 5 chronic kidney disease
HP:0004719	Hyperechogenic kidneys
HP:0010956	Fetal megacystis
HP:0011664	Left ventricular noncompaction cardiomyopathy
HP:0100611	Multiple glomerular cysts

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST001555_4	Testosterone levels	4.000000e-06
GCST003825_1	Systolic blood pressure change trajectory	4.000000e-06
GCST003825_3	Systolic blood pressure change trajectory	1.000000e-06
GCST006061_53	Atrial fibrillation	7.000000e-09
GCST006414_34	Atrial fibrillation	1.000000e-11
GCST007045_44	PR interval	1.000000e-11
GCST007226_15	PR interval	9.000000e-09
GCST008422_10	QRS duration	2.000000e-09
GCST009391_1022	Metabolite levels	9.000000e-06
GCST010321_154	PR interval	2.000000e-54
GCST010396_223	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06
GCST010796_5055	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-20
GCST010796_5056	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_5057	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-10
GCST010796_5058	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-11
GCST010796_5059	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-12
GCST010796_5060	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-14
GCST010796_5061	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-15
GCST010796_5062	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-16
GCST010796_5063	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-17
GCST010796_5064	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-19
GCST010796_5065	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-19
GCST010796_5066	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-18
GCST010796_5067	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-19
GCST010796_5068	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-17
GCST010796_5069	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-16
GCST010796_5070	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-15
GCST010796_5071	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-14
GCST010796_5072	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-13
GCST010796_5073	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004908	testosterone measurement
EFO:0006944	systolic blood pressure change measurement
EFO:0004462	PR interval
EFO:0010360	lysophosphatidylcholine 18:1 measurement
EFO:0007874	gut microbiome measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D011535	Prune Belly Syndrome	C16.131.077.745

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1714984	MYOCD		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	5
bisphenol A	decreases expression, decreases methylation	2
trichostatin A	increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
TAK-243	increases sumoylation	1
geldanamycin	increases expression	1
N(4)-hydroxycytidine	decreases expression	1
terbufos	increases methylation	1
trimellitic anhydride	decreases expression	1
sulforaphane	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
SB 203580	decreases reaction, increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Bleomycin	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders