MDFIC
protein-codingMyoD family inhibitor domain containing
Gene summary
This gene product is a member of a family of proteins characterized by a specific cysteine-rich C-terminal domain, which is involved in transcriptional regulation of viral genome expression. Alternative translation initiation from an upstream non-AUG (GUG), and an in-frame, downstream AUG codon, results in the production of two isoforms, p40 and p32, respectively, which have different subcellular localization; p32 is mainly found in the cytoplasm, whereas p40 is targeted to the nucleolus. Both isoforms have transcriptional regulatory activity that is attributable to the cysteine-rich C-terminal domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~97.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0031043
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0031043
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0031043
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular
Intervention: Cardiovascular
Rationale: Individuals have been described as having lymphatic and other cardiovascular anomalies, and awareness may enable early diagnosis and medical and/or surgical management related to the malformations
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MDFIC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001166345.3. 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 | 3 | 3 | ||||
| missense | 42 | 6 | 48 | |||
| nonsense | 1 | 2 | 3 | |||
| start loss | 2 | 2 | ||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 1 | 4 | 5 | |||
| Total | 2 | 5 | 48 | 9 | 0 | 64 |
Highest pathogenic variant AF is 0.00016171104
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001159817.1 | 4 | MANE Select | |
| Ensembl | ENSP00000377126.1 | 4 | MANE Select | |
| RefSeq | NP_001159818.3 | 3 | Standard | |
| RefSeq | NP_951038.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of nuclear beta catenin signaling and target gene transcription
Biological Process
- activation of JUN kinase activity
- viral process
- regulation of Wnt signaling pathway
- negative regulation of protein import into nucleus
- negative regulation of transcription, DNA-templated
Molecular Function
- protein binding
- transcription factor binding
- cyclin binding
- Tat protein binding
Cellular Component
- nucleus
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000257724
- Coding exons
- 5
- Length
- 97048
- Individuals with no LoFs
- 125645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 57
- Defined
- 125702
- p
- 0.000227
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.289 | 167 | 157 | 1.06 | 0.00000756 | 2254 |
| Missense (PolyPhen) | 76 | 68.634 | 1.1073 | 890 | ||
| Synonymous | -0.102 | 60 | 59.0 | 1.02 | 0.00000313 | 721 |
| Loss of Function | 1.88 | 4 | 10.6 | 0.377 | 4.46e-7 | 158 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a transcriptional activator or repressor. Inhibits the transcriptional activation of Zic family proteins ZIC1, ZIC2 and ZIC3. Retains nuclear Zic proteins ZIC1, ZIC2 and ZIC3 in the cytoplasm. Modulates the expression from both cellular and viral promoters. Down-regulates Tat-dependent transcription of the human immunodeficiency virus type 1 (HIV-1) LTR by interacting with HIV-1 Tat and Rev and impairing their nuclear import, probably by rendering the NLS domains inaccessible to importin- beta. Also stimulates activation of human T-cell leukemia virus type I (HTLV-I) LTR. 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. {ECO:0000269|PubMed:10671520, ECO:0000269|PubMed:12192039, ECO:0000269|PubMed:12944466, ECO:0000269|PubMed:16260749, ECO:0000269|Ref.6}.;
Recessive Scores
- pRec
- 0.185
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.798
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |