MYOD1
protein-codingmyogenic differentiation 1, the group of Basic helix-loop-helix proteins|Myogenic regulatory family
Gene summary
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. [provided by RefSeq, Jul 2008]
- MYF3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0033548
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0033548
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0100101
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0033548
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Pulmonary; Renal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MYOD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002478.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 2 | 12 | |||
| missense | 57 | 5 | 1 | 63 | ||
| nonsense | 2 | 2 | 4 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 2 | 57 | 15 | 3 | 80 |
Highest pathogenic variant AF is 0.000030817064
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002469.2 | 3 | MANE Select | |
| Ensembl | ENSP00000250003.3 | 3 | MANE Select | |
| Ensembl | ENSP00000802516.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| myod1 | Danio rerio | Structure: fast muscle cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miRs in Muscle Cell Differentiation
- Cell Differentiation - Index expanded
- Cell Differentiation - Index
- ID signaling pathway
- Developmental Biology
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- regulation of transcription by RNA polymerase II
- protein phosphorylation
- muscle organ development
- myoblast fate determination
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- chromatin binding
Cellular Component
- nuclear chromatin
- nucleus
- nucleoplasm
- transcription factor complex
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250003
- Coding exons
- 3
- Length
- 2564
- Individuals with no LoFs
- 125369
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125374
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.394 | 201 | 186 | 1.08 | 0.00000876 | 2032 |
| Missense (PolyPhen) | 70 | 72.04 | 0.97168 | 852 | ||
| Synonymous | -0.421 | 90 | 85.1 | 1.06 | 0.00000426 | 684 |
| Loss of Function | 1.51 | 2 | 5.99 | 0.334 | 2.53e-7 | 83 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000037 | 0.000035 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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 (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.820
Intolerance Scores
- LoFtool
- 0.264
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |