MYOD1

Summary

MYOD1 (myogenic differentiation 1, HGNC:7611) is a protein-coding gene on chromosome 11p15.1, encoding Myoblast determination protein 1 (P15172). Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation.

This gene encodes a nuclear protein that belongs to the basic helix-loop-helix family of transcription factors and the myogenic factors subfamily. It regulates muscle cell differentiation by inducing cell cycle arrest, a prerequisite for myogenic initiation. The protein is also involved in muscle regeneration. It activates its own transcription which may stabilize commitment to myogenesis.

Source: NCBI Gene 4654 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 81 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 60
• Transcription factor: yes — 165 downstream targets (CollecTRI)
• MANE Select transcript: NM_002478

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7611
Approved symbol	MYOD1
Name	myogenic differentiation 1
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	PUM, MYOD, bHLHc1
Ensembl gene	ENSG00000129152
Ensembl biotype	protein_coding
OMIM	159970
Entrez	4654

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000250003

RefSeq mRNA: 1 — MANE Select: NM_002478 NM_002478

CCDS: CCDS7826

Canonical transcript exons

ENST00000250003 — 3 exons

Exon	Start	End
ENSE00000886528	17720902	17720980
ENSE00001128854	17721255	17722136
ENSE00001236272	17719571	17720412

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 91.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0374 / max 199.8132, expressed in 107 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113285	0.6912	83
113288	0.2688	71
113287	0.0447	27
113286	0.0327	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
triceps brachii	UBERON:0001509	91.98	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.44	silver quality
gluteal muscle	UBERON:0002000	90.93	silver quality
vastus lateralis	UBERON:0001379	90.84	silver quality
quadriceps femoris	UBERON:0001377	90.06	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.94	gold quality
biceps brachii	UBERON:0001507	88.99	silver quality
hindlimb stylopod muscle	UBERON:0004252	88.52	gold quality
skeletal muscle tissue	UBERON:0001134	87.52	gold quality
diaphragm	UBERON:0001103	87.45	gold quality
gastrocnemius	UBERON:0001388	87.43	gold quality
muscle organ	UBERON:0001630	86.60	gold quality
skeletal muscle organ	UBERON:0014892	86.60	gold quality
muscle of leg	UBERON:0001383	85.65	gold quality
muscle tissue	UBERON:0002385	81.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.56	gold quality
deltoid	UBERON:0001476	81.13	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.69	gold quality
pons	UBERON:0000988	75.70	gold quality
tibialis anterior	UBERON:0001385	75.35	silver quality
lateral nuclear group of thalamus	UBERON:0002736	75.18	gold quality
upper arm skin	UBERON:0004263	75.01	gold quality
superficial temporal artery	UBERON:0001614	74.68	gold quality
superior surface of tongue	UBERON:0007371	74.55	gold quality
nasal cavity epithelium	UBERON:0005384	74.49	gold quality
vena cava	UBERON:0004087	74.47	gold quality
saphenous vein	UBERON:0007318	74.24	gold quality
gingival epithelium	UBERON:0001949	74.13	gold quality
hair follicle	UBERON:0002073	74.13	gold quality
cardia of stomach	UBERON:0001162	74.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

165 targets.

Target	Regulation
ABCB1
ACACB	Unknown
ACHE
ACSL5	Activation
ACTA2
ACTB
ACTC1	Unknown
ADAM2
ADRA1D
AGT
AKT1
AKT2
ANK1	Activation
ANKRD2
ARNT	Activation
ATP9A
ATP9B
BARX2
BCL2
BCL2L1
BPIFA4P
BRCA1	Unknown
BRCA2	Repression
CAND2
CAT
CCNB1
CCND1
CCND3	Activation
CCNE1	Activation
CDH15

JASPAR motifs

Motif	Name	Family
MA0499.2	MYOD1	MyoD/ASC-related factors
MA0499.3	MYOD1	MyoD/ASC-related factors

JASPAR matrix evidence (PMIDs): PMID:20412780

Upstream regulators (CollecTRI, top): ANGPT1, AP1, BARX2, BHLHE40, BHLHE41, BMAL1, CAPN3, CLOCK, CREB1, CTNNB1, DDIT3, DIO2, E2F1, EID2B, ESR1, FGF8, FOS, FOXC2, FOXO1, FOXO3, HES1, HOXA11, ID2, JUN, MEF2A, MKX, MSX1, MSX2, MYC, MYF5, MYF6, MYOD1, MYOG, NCOR1, NFIA, NOTCH1, NR2F2, PAX3, PAX7, PITX2

miRNA regulators (miRDB)

24 targeting MYOD1, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-4790-5P	96.67	67.45	167
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-324-5P	95.68	65.20	560
HSA-MIR-6769A-3P	94.91	61.36	412
HSA-MIR-3178	89.40	60.05	100
HSA-MIR-10394-3P	85.92	60.60	39

Literature-anchored findings (GeneRIF, showing 40)

• The myogenic basic helix-loop-helix family of transcription factors, MyoD, Myf5, myogenin, and MRF4, can each activate the muscle differentiation program. (PMID:12105204)
• MYOD1 hypermethylation plays an important role in colorectal cancer and may be a novel prognostic factor. (PMID:14767572)
• MyoD modulates the rate of Id1 degradation and suggest a dynamic interplay of these factors (PMID:15163661)
• Hypermethylation of MYOD1 is statistically significantly associated with poor disease outcome in cervical cancer. (PMID:15251938)
• degradation is modulated by E12 and E47 (PMID:16007194)
• This review highlights studies of molecular mechanisms by which the muscle-specific myogenic basic helix-loop-helix protein MyoD interacts with other regulatory factors to coordinate gene expression in a controlled and ordered manner. (PMID:16099183)
• The expression of MyoD1 was more sensitive but less specific in patients with rhabdomyosarcoma. (PMID:16435141)
• Myogenin and myogenic differentiation factor D (MyoD) mRNAs increased (P < 0.05) in young and old, whereas myogenic factor (myf)-5 mRNA increased in young only (P < 0.05). Myf-6 protein increased (P < 0.05) in both young and old. (PMID:16614355)
• The results establish that cdk9/cyclin T2a-mediated coactivation of MyoD depends on serine 37 phosphorylation. (PMID:16841087)
• MyoD below a threshold level and its displacement from the mitotic chromatin could present another window in the cell cycle for resetting the myogenic transcriptional program and to maintain the myogenic determination of the proliferating cells. (PMID:17014844)
• MYOD1 is a positive diagnostic for biliary tract rhabdomyosarcoma. (PMID:17378682)
• Expression of both the endogenous MyoD gene and a reporter gene driven by MyoD regulatory elements is similar in wild-type and homozygous null Gig1(nlacZ) transgenic MyoD1 mouse embryos. (PMID:17693064)
• identified a negative regulatory element in the alpha-SG distal promoter including two conserved E-boxes (E1 and E2), which interact with MyoD (PMID:18078839)
• a nonconventional interaction between HP1 and a tissue-specific transcription factor, MyoD. In addition, they strongly suggest that HP1 isoforms play important roles during muscle terminal differentiation in an isoform-dependent manner. (PMID:18599480)
• NFAT and MyoD cooperation regulates myogenin expression and myogenesis (PMID:18676376)
• multiple inhibitory mechanisms can be suppressed and myogenic differentiation can be induced in the RD rhabdomyosarcomas by increasing the abundance of MyoD:E-protein heterodimers (PMID:19299559)
• The methylation of MYOD1 in the normal colonic mucosa was significantly correlated with K-ras mutation in neoplastic tissue arising from the mucosa. (PMID:19733896)
• calpain 3 participates in the establishment of the pool of reserve cells by decreasing the transcriptional activity of the key myogenic regulator MyoD via proteolysis independently of the ubiquitin-proteasome degradation pathway. (PMID:20139084)
• Transgenic Pax7 and MyoD are not essential for myogenic differentiation and participation of bone marrow-derived myogenic progenitors in muscle regeneration. (PMID:20333749)
• MyoD and c-myb are involved in regulation of basal and estrogen-induced transcription activity of the BRCA1 gene (PMID:20364308)
• Mef2d, Six4, and p38alpha MAPK function coordinately as regulators of a master regulator to mediate expression of MyoD target genes. (PMID:20716948)
• Knockdown of MyoD and PEA3 attenuated MDR1 expression and increased the sensitivity of multidrug resistant cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. (PMID:20980337)
• MyoD can play an active role in Alveolar rhabdomyosarcoma (ARMS)by augmenting Pax7-FKHR function. (PMID:21321994)
• Increases in MYOD indicate that 1 week of conventional resistance exercise may increase myogenic activity, including satellite cell proliferation and differentiation, respectively, in younger men. (PMID:21326383)
• The myofibroblasts demonstrate the capacity for de-differentiation and proliferation by modulation of endogenous levels of MyoD. (PMID:21440539)
• Data demonstrate radical acceleration of iPSC creation with a fusion gene between Oct4 and the powerful transactivation domain (TAD) of MyoD. (PMID:21732495)
• BAF60c-MyoD complex directs recruitment of SWI/SNF to muscle loci in response to differentiation cues. (PMID:22068056)
• Using MYOD1, study shows that an nucleosome-depleted region at the minimal enhancer region allows reprogramming to be initiated, which occurs in response to signals such as the forced expression of Myod1 in fibroblasts. (PMID:22153073)
• the involvement of HUWE1 in the ubiquitination and proteasomal degradation of MyoD was described. (PMID:22277673)
• Promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer. (PMID:22591756)
• results suggest that MyoD and TIP120B potentiate each other at gene expression and post-translation levels, respectively, which may promote myogenesis cooperatively (PMID:22613845)
• Human squamous cell carcinomas and malignant melanomas contain significantly more Myo/Nog cells than basal cell carcinomas. (PMID:22621191)
• MYOD1-transduced amnion-derived cells are capable of the dystrophin expression necessary for myogenic differentiation. (PMID:22727434)
• SREBP-1 regulate muscle protein synthesis through the downregulation of the expression of MYOD1, MYOG and MEF2C factors. (PMID:23226416)
• Using both primary human muscle cells and RD rhabdomyosarcoma cells, the study shows that MyoD binds in a similar genome-wide pattern in both tumor and normal cells but binds poorly at a subset of myogenic genes that fail to activate in the tumor cells. (PMID:23230269)
• CRABP2 promotes myoblast differentiation and is modulated by the transcription factors MyoD and Sp1 in C2C12 cells. (PMID:23383201)
• Direct reprogramming of fibroblasts to myocytes via bacterial injection of MyoD protein. (PMID:23438194)
• Although expression of MyoD in a proliferating tumor is insufficient to prevent tumor progression, its expression in the cerebellum hinders medulloblastoma genesis. (PMID:24092238)
• MYOD1 homozygous mutations are frequent, recurrent and pathognomonic events in adult-type spindle cell Rhabdomyosarcoma (PMID:24272621)
• analysis of a mutation in MYOD1 that may have a role in progression of embryonal rhabdomyosarcoma and may be associated with mutations altering PI3K-AKT pathway components (PMID:24793135)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	myod1	ENSDARG00000030110
mus_musculus	Myod1	ENSMUSG00000009471
rattus_norvegicus	Myod1	ENSRNOG00000011306
drosophila_melanogaster	nau	FBGN0002922
caenorhabditis_elegans		WBGENE00001948

Paralogs (3): MYF6 (ENSG00000111046), MYF5 (ENSG00000111049), MYOG (ENSG00000122180)

Protein

Protein identifiers

Myoblast determination protein 1 — P15172 (reviewed: P15172)

Alternative names: Class C basic helix-loop-helix protein 1, Myogenic factor 3

All UniProt accessions (1): P15172

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with MYF5 and MYOG, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Interacts with and is inhibited by the twist protein. This interaction probably involves the basic domains of both proteins.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Seems to form active heterodimers with ITF-2. Interacts with SUV39H1. Interacts with DDX5. Interacts with CHD2. Interacts with TSC22D3. Interacts with SETD3. Interacts with P-TEFB complex; promotes the transcriptional activity of MYOD1 through its CDK9-mediated phosphorylation. Interacts with CSRP3. Interacts with NUPR1.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated by CDK9. This phosphorylation promotes its function in muscle differentiation. Acetylated by a complex containing EP300 and PCAF. The acetylation is essential to activate target genes. Conversely, its deacetylation by SIRT1 inhibits its function. Ubiquitinated on the N-terminus; which is required for proteasomal degradation. Methylation at Lys-104 by EHMT2/G9a inhibits myogenic activity.

Disease relevance. Congenital myopathy 17 (CMYO17) [MIM:618975] An autosomal recessive muscular disorder characterized by hypotonia and respiratory insufficiency apparent soon after birth, high diaphragmatic dome on imaging, poor overall growth, pectus excavatum, dysmorphic facies, and renal anomalies in some affected individuals. Additional variable features include delayed motor development, mildly decreased endurance, distal arthrogryposis, and lung hypoplasia resulting in early death. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_002469* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002546	MyoD_N	Domain
IPR011598	bHLH_dom	Domain
IPR022032	Myf5	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR039704	Myogenic_factor	Family

Pfam: PF00010, PF01586, PF12232

UniProt features (15 total): sequence variant 4, sequence conflict 3, region of interest 2, compositionally biased region 2, chain 1, domain 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15172-F1	62.04	0.22

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 (2): 104, 1

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-525793	Myogenesis
R-HSA-9839394	TGFBR3 expression
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9839373	Signaling by TGFBR3

MSigDB gene sets: 374 (showing top): GOBP_REGULATION_OF_SKELETAL_MUSCLE_TISSUE_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_SKELETAL_MUSCLE_ADAPTATION, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, NIKOLSKY_OVERCONNECTED_IN_BREAST_CANCER, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (39): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), muscle organ development (GO:0007517), myoblast fate determination (GO:0007518), skeletal muscle tissue development (GO:0007519), myoblast fusion (GO:0007520), cellular response to starvation (GO:0009267), myotube cell development (GO:0014904), myotube differentiation involved in skeletal muscle regeneration (GO:0014908), skeletal muscle cell differentiation (GO:0035914), muscle cell fate commitment (GO:0042693), positive regulation of skeletal muscle tissue regeneration (GO:0043415), regulation of RNA splicing (GO:0043484), skeletal muscle fiber adaptation (GO:0043503), positive regulation of myoblast differentiation (GO:0045663), positive regulation of transcription by RNA polymerase II (GO:0045944), skeletal muscle fiber development (GO:0048741), positive regulation of skeletal muscle fiber development (GO:0048743), positive regulation of muscle cell differentiation (GO:0051149), cellular response to tumor necrosis factor (GO:0071356), cellular response to glucocorticoid stimulus (GO:0071385), cellular response to estradiol stimulus (GO:0071392), cellular response to oxygen levels (GO:0071453), positive regulation of myoblast fusion (GO:1901741), positive regulation of snRNA transcription by RNA polymerase II (GO:1905382), negative regulation of myoblast proliferation (GO:2000818), regulation of DNA-templated transcription (GO:0006355), protein phosphorylation (GO:0006468), tissue development (GO:0009888), regulation of gene expression (GO:0010468), myotube differentiation (GO:0014902), cell differentiation (GO:0030154), muscle cell differentiation (GO:0042692), skeletal muscle tissue regeneration (GO:0043403), myoblast differentiation (GO:0045445), positive regulation of DNA-templated transcription (GO:0045893), animal organ development (GO:0048513), striated muscle cell differentiation (GO:0051146)

GO Molecular Function (22): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity (GO:0001216), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), nuclear receptor binding (GO:0016922), chromatin DNA binding (GO:0031490), ubiquitin protein ligase binding (GO:0031625), protein homodimerization activity (GO:0042803), bHLH transcription factor binding (GO:0043425), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), promoter-specific chromatin binding (GO:1990841), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), enzyme binding (GO:0019899), sequence-specific DNA binding (GO:0043565), protein dimerization activity (GO:0046983)

GO Cellular Component (7): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), myofibril (GO:0030016), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Developmental Biology	1
Signaling by TGFBR3	1
CHD chromatin remodelers	1
Signal Transduction	1
Signaling by TGFB family members	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription cis-regulatory region binding	4
myotube differentiation	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
skeletal muscle tissue regeneration	2
skeletal muscle tissue development	2
muscle cell differentiation	2
positive regulation of cell differentiation	2
regulation of transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
chromatin	2
DNA-binding transcription factor activity	2
binding	2
chromatin binding	2
DNA-binding transcription factor binding	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
DNA-templated transcription	1
animal organ development	1
muscle structure development	1
cell fate determination	1
myoblast fate commitment	1
striated muscle tissue development	1
skeletal muscle organ development	1
syncytium formation by cell-cell fusion	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
striated muscle cell development	1
cell differentiation	1
cell fate commitment	1
regulation of skeletal muscle tissue regeneration	1
positive regulation of developmental growth	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
skeletal muscle adaptation	1
cellular response to stimulus	1

Protein interactions and networks

STRING

3338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYOD1	SMARCD3	Q6STE5	986
MYOD1	MRLN	P0DMT0	958
MYOD1	PAX3	P23760	947
MYOD1	EP300	Q09472	947
MYOD1	TCF3	P15883	939
MYOD1	MEF2A	Q02078	937
MYOD1	TCF4	P15884	910
MYOD1	SMAD3	P84022	904
MYOD1	PAX7	P23759	900
MYOD1	SMARCA4	P51532	888
MYOD1	DDX17	Q92841	887
MYOD1	FBXO32	Q969P5	858
MYOD1	MDFI	Q99750	853
MYOD1	KAT2B	Q92831	851
MYOD1	MEF2C	Q06413	847

IntAct

35 interactions, top by confidence:

A	B	Type	Score
MYOD1	AP1M1	psi-mi:“MI:0915”(physical association)	0.560
MYOD1	IGFN1	psi-mi:“MI:0915”(physical association)	0.560
MYOD1	EXOC3L1	psi-mi:“MI:0915”(physical association)	0.560
TCF21	MYOD1	psi-mi:“MI:0915”(physical association)	0.560
MYOD1	LMO4	psi-mi:“MI:0915”(physical association)	0.560
MYOD1	FIGLA	psi-mi:“MI:0915”(physical association)	0.560
SRF	MYOD1	psi-mi:“MI:0407”(direct interaction)	0.530
MYOD1	SRF	psi-mi:“MI:0915”(physical association)	0.530
TCF3	MYOD1	psi-mi:“MI:0915”(physical association)	0.520
SIRT2	MYOD1	psi-mi:“MI:0914”(association)	0.460
MYOD1	SIRT2	psi-mi:“MI:0914”(association)	0.460
CSRP3	MYOD1	psi-mi:“MI:0407”(direct interaction)	0.440
MYOD1	TCF4	psi-mi:“MI:0914”(association)	0.420
CCL1	MYOD1	psi-mi:“MI:0915”(physical association)	0.370
MYOD1	KPNA3	psi-mi:“MI:0915”(physical association)	0.370
POLR2G	MYOD1	psi-mi:“MI:0915”(physical association)	0.370
MYOD1	PSME2	psi-mi:“MI:0915”(physical association)	0.370
MYOD1	C2orf88	psi-mi:“MI:0915”(physical association)	0.370
MYOD1	SMAD7	psi-mi:“MI:0915”(physical association)	0.370
MYOD1	SMAD4	psi-mi:“MI:0915”(physical association)	0.370
MYOD1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
AP1M1	MYOD1	psi-mi:“MI:0915”(physical association)	0.000
IGFN1	MYOD1	psi-mi:“MI:0915”(physical association)	0.000
EXOC3L1	MYOD1	psi-mi:“MI:0915”(physical association)	0.000
TCF21	MYOD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (251): MYOD1 (Biochemical Activity), MYOD1 (Affinity Capture-Western), HUWE1 (Affinity Capture-Western), MYOD1 (Biochemical Activity), ID2 (Two-hybrid), FBXO32 (Two-hybrid), FBXO32 (Affinity Capture-Western), MYOD1 (Biochemical Activity), KAT2B (Affinity Capture-Western), MYOD1 (Affinity Capture-Western), MYOD1 (Two-hybrid), MYOD1 (Affinity Capture-Western), STAT3 (Affinity Capture-Western), MYOD1 (Reconstituted Complex), MYOD1 (Reconstituted Complex)

ESM2 similar proteins: A2WSZ6, A2WZI4, A2XX39, A2YXQ7, A2ZMR9, A2ZVY5, A3BYC1, B1B534, B8AWM1, B8AX53, B8BF91, B8BGV5, P15172, Q0E342, Q0E3C3, Q0J3Y7, Q0JEE2, Q10EC6, Q10ED2, Q2QM59, Q2QW44, Q5IS79, Q5JLR7, Q5NBM8, Q5VM82, Q5W6D6, Q652B0, Q688U3, Q6AWX7, Q6EPZ0, Q6ER21, Q6IEN1, Q6L5G1, Q6S3I3, Q6Z528, Q6Z869, Q6ZBS8, Q70UV1, Q7EXZ2, Q7RTV3

Diamond homologs: B6VQA1, M0QWB7, O13125, O13126, O35885, O42202, O57598, O96004, P09774, P09775, P10083, P10084, P10085, P13349, P15172, P15375, P17667, P19335, P19359, P19360, P22816, P23409, P24699, P29331, P34061, P34555, P46581, P48987, P49811, P50553, P57100, P57101, P57102, P59101, P61295, P61296, P70447, P70562, P70595, P70660

SIGNOR signaling

109 interactions.

A	Effect	B	Mechanism
SIRT2	down-regulates	MYOD1	deacetylation
HDAC1	down-regulates	MYOD1	binding
CDK1	down-regulates	MYOD1	phosphorylation
PBX1	“up-regulates activity”	MYOD1	binding
MSX1	“down-regulates quantity by repression”	MYOD1	“transcriptional regulation”
MAPK14	“up-regulates activity”	MYOD1
MYOD1	“up-regulates quantity by expression”	MYOG	“transcriptional regulation”
MYOD1	up-regulates	SMARCD3	binding
“RNA helicases DDX5/DDX17”	up-regulates	MYOD1	binding
MYOD1	“form complex”	“MYOD1/SWI/SNF complex”	binding
MYOD1	up-regulates	SMARCA4	binding
CTNNB1	“up-regulates activity”	MYOD1	binding
WWTR1	up-regulates	MYOD1	binding
PITX2	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
CDK2	down-regulates	MYOD1	phosphorylation
CDK4	down-regulates	MYOD1	binding
CREB1	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
RB1	up-regulates	MYOD1	binding
SHH	up-regulates	MYOD1
FOXO3	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
PAX3	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
PAX7	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
FBXO32	“down-regulates quantity by destabilization”	MYOD1	ubiquitination
WNT6	up-regulates	MYOD1
WNT7B	up-regulates	MYOD1
FGF8	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
TCF3	“up-regulates activity”	MYOD1	binding
CyclinE/CDK2	down-regulates	MYOD1	phosphorylation

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	56
Likely benign	14
Benign	5

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
631486	NM_002478.5(MYOD1):c.557dup (p.Arg188fs)	Pathogenic
816937	NM_002478.5(MYOD1):c.188C>A (p.Ser63Ter)	Pathogenic
976484	NM_002478.5(MYOD1):c.697G>T (p.Glu233Ter)	Pathogenic
3341452	NM_002478.5(MYOD1):c.468T>A (p.Tyr156Ter)	Likely pathogenic
3764541	NM_002478.5(MYOD1):c.352G>T (p.Glu118Ter)	Likely pathogenic

SpliceAI

229 predictions. Top by Δscore:

Variant	Effect	Δscore
11:17720408:GCATG:G	donor_gain	1.0000
11:17720410:ATGG:A	donor_loss	1.0000
11:17720413:G:GG	donor_gain	1.0000
11:17720413:GTAAG:G	donor_loss	1.0000
11:17720414:T:G	donor_loss	1.0000
11:17720893:T:A	acceptor_gain	1.0000
11:17720897:T:TA	acceptor_gain	1.0000
11:17720897:TGCA:T	acceptor_loss	1.0000
11:17720898:GCAG:G	acceptor_loss	1.0000
11:17720899:CAGAT:C	acceptor_loss	1.0000
11:17720900:A:AC	acceptor_loss	1.0000
11:17720900:A:AG	acceptor_gain	1.0000
11:17720900:AGAT:A	acceptor_gain	1.0000
11:17720900:AGATG:A	acceptor_gain	1.0000
11:17720901:G:GT	acceptor_gain	1.0000
11:17720901:GA:G	acceptor_gain	1.0000
11:17720901:GAT:G	acceptor_gain	1.0000
11:17720901:GATG:G	acceptor_gain	1.0000
11:17720901:GATGG:G	acceptor_gain	1.0000
11:17720978:GCG:G	donor_gain	1.0000
11:17720981:G:GG	donor_gain	1.0000
11:17721253:A:AG	acceptor_gain	1.0000
11:17721254:G:GG	acceptor_gain	1.0000
11:17721254:GA:G	acceptor_gain	1.0000
11:17720439:G:GT	donor_gain	0.9900
11:17720979:CGGTG:C	donor_loss	0.9900
11:17720981:G:GC	donor_loss	0.9900
11:17720982:T:G	donor_loss	0.9900
11:17721250:C:CA	acceptor_gain	0.9900
11:17721254:GAA:G	acceptor_gain	0.9900

AlphaMissense

2079 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:17720059:T:C	C93R	1.000
11:17720068:T:A	W96R	1.000
11:17720068:T:C	W96R	1.000
11:17720070:G:C	W96C	1.000
11:17720070:G:T	W96C	1.000
11:17720074:T:C	C98R	1.000
11:17720075:G:A	C98Y	1.000
11:17720076:C:G	C98W	1.000
11:17720083:T:C	C101R	1.000
11:17720084:G:A	C101Y	1.000
11:17720113:C:A	R111S	1.000
11:17720123:C:A	A114D	1.000
11:17720131:C:A	R117S	1.000
11:17720131:C:T	R117C	1.000
11:17720134:G:A	E118K	1.000
11:17720135:A:T	E118V	1.000
11:17720136:G:C	E118D	1.000
11:17720136:G:T	E118D	1.000
11:17720143:C:A	R121S	1.000
11:17720147:T:A	L122Q	1.000
11:17720147:T:C	L122P	1.000
11:17720160:T:A	N126K	1.000
11:17720160:T:G	N126K	1.000
11:17720164:G:C	A128P	1.000
11:17720167:T:A	F129I	1.000
11:17720167:T:C	F129L	1.000
11:17720168:T:C	F129S	1.000
11:17720168:T:G	F129C	1.000
11:17720169:T:A	F129L	1.000
11:17720169:T:G	F129L	1.000

dbSNP variants (sampled 300 via entrez): RS1000948922 (11:17721858 G>C,T), RS1001100220 (11:17721836 C>T), RS1001125149 (11:17722063 C>A,T), RS1001390390 (11:17718153 G>A,C), RS1001463904 (11:17718463 A>T), RS1001841674 (11:17720060 G>C), RS1003106291 (11:17719625 C>A), RS1003252605 (11:17718898 G>A), RS1004247812 (11:17720725 C>T), RS1004377318 (11:17720141 G>A,C,T), RS1004798577 (11:17719491 C>T), RS1004977598 (11:17718919 A>G), RS1005223755 (11:17719271 C>T), RS1005637567 (11:17721074 C>T), RS1005803509 (11:17718166 T>A,G)

Disease associations

OMIM: gene MIM:159970 | disease phenotypes: MIM:618975, MIM:160150, MIM:614408, MIM:617468

GenCC curated gene-disease

Disease	Classification	Inheritance
myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies	Strong	Autosomal recessive
fetal akinesia deformation sequence 1	Supportive	Autosomal recessive

Mondo (4): myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies (MONDO:0033548), autosomal dominant centronuclear myopathy (MONDO:0008048), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101)

Orphanet (2): Arthrogryposis multiplex congenita (Orphanet:1037), Autosomal dominant centronuclear myopathy (Orphanet:169189)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000074	Ureteropelvic junction obstruction
HP:0000089	Renal hypoplasia
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000331	Short chin
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000476	Cystic hygroma
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000565	Esotropia
HP:0000689	Dental malocclusion
HP:0000767	Pectus excavatum
HP:0000774	Narrow chest
HP:0001059	Pterygium
HP:0001182	Tapered finger
HP:0001188	Hand clenching

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003542_112	Night sleep phenotypes	2.000000e-06
GCST005951_67	Body mass index	6.000000e-09
GCST005951_68	Body mass index	3.000000e-09
GCST009391_1993	Metabolite levels	1.000000e-06
GCST012335_17	Hodgkin’s lymphoma	4.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010542	ureidopropionic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases expression	2
naringenin	affects cotreatment, increases expression	1
bakuchiol	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
boric acid	affects expression, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carmustine	decreases expression	1
Catechin	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	affects cotreatment, increases expression	1
Dihydrotestosterone	increases expression	1
Tamoxifen	decreases expression	1
Isotretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Raloxifene Hydrochloride	decreases expression	1

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0BR	NCC-ssRMS2-C1	Cancer cell line	Male
CVCL_A0XB	SRH	Cancer cell line	Female
CVCL_A4I8	SEES3-1V human MYOD1, clone1	Embryonic stem cell	Male
CVCL_A4I9	SEES3-1V human MYOD1, clone2	Embryonic stem cell	Male
CVCL_A4J0	SEES3-1V human MYOD1, clone3	Embryonic stem cell	Male
CVCL_B8L3	Abcam HCT 116 MYOD1 KO	Cancer cell line	Male
CVCL_B8ZA	Abcam MCF-7 MYOD1 KO	Cancer cell line	Female
CVCL_B9NA	Abcam A-549 MYOD1 KO	Cancer cell line	Male
CVCL_ZE13	NCC-ssRMS1-C1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05393375	Not specified	COMPLETED	Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation
NCT05673265	Not specified	UNKNOWN	Pediatric and Adult Registry for Patients With ARThrogryposis
NCT06130592	Not specified	UNKNOWN	Technical Feasibility Study of Ultrasound Muscle Imaging in Antenatal Ultrasound
NCT07360574	Not specified	NOT_YET_RECRUITING	Piezo2-related Arthrogryposis & physiopathOLOgy 3