MDFI
protein-codingMyoD family inhibitor
Gene summary
This protein is a transcription factor that negatively regulates other myogenic family proteins. Studies of the mouse homolog, I-mf, show that it interferes with myogenic factor function by masking nuclear localization signals and preventing DNA binding. Knockout mouse studies show defects in the formation of vertebrae and ribs that also involve cartilage formation in these structures. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MDFI variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005586.4. 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 | 1 | 1 | ||||
| missense | 37 | 1 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 38 | 1 | 1 | 40 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005577.1 | 4 | MANE Select | |
| Ensembl | ENSP00000230321.6 | 4 | MANE Select | |
| RefSeq | NP_001287733.1 | 4 | Standard | |
| RefSeq | NP_001287734.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- dorsal/ventral axis specification
- negative regulation of Wnt signaling pathway
- cytoplasmic sequestering of transcription factor
- negative regulation of DNA binding
Molecular Function
- protein binding
- transcription factor binding
- identical protein binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000230321
- Coding exons
- 4
- Length
- 17365
- Individuals with no LoFs
- 125701
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125716
- p
- 0.0000597
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.124 | 134 | 138 | 0.970 | 0.00000794 | 1570 |
| Missense (PolyPhen) | 42 | 53.174 | 0.78987 | 660 | ||
| Synonymous | -1.02 | 74 | 63.7 | 1.16 | 0.00000457 | 500 |
| Loss of Function | 2.08 | 2 | 8.58 | 0.233 | 3.70e-7 | 104 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00044 | 0.00042 | rare |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits the transactivation activity of the Myod family of myogenic factors and represses myogenesis. Acts by associating with Myod family members and retaining them in the cytoplasm by masking their nuclear localization signals. Can also interfere with the DNA-binding activity of Myod family members. Plays an important role in trophoblast and chondrogenic differentiation. Regulates the transcriptional activity of TCF7L1/TCF3 by interacting directly with TCF7L1/TCF3 and preventing it from binding DNA. Binds to the axin complex, resulting in an increase in the level of free beta-catenin. Affects axin regulation of the WNT and JNK signaling pathways (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.185
Intolerance Scores
- LoFtool
- 0.275
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.940
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |