TFEC
protein-codingtranscription factor EC, the group of Basic helix-loop-helix proteins
Gene summary
This gene encodes a member of the micropthalmia (MiT) family of basic helix-loop-helix leucine zipper transcription factors. MiT transcription factors regulate the expression of target genes by binding to E-box recognition sequences as homo- or heterodimers, and play roles in multiple cellular processes including survival, growth and differentiation. The encoded protein is a transcriptional activator of the nonmuscle myosin II heavy chain-A gene, and may also co-regulate target genes in osteoclasts as a heterodimer with micropthalmia-associated transcription factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~224.7 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 TFEC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012252.4. 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 | 3 | 3 | ||||
| missense | 44 | 1 | 1 | 46 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 45 | 1 | 4 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036384.1 | 7 | MANE Select | |
| Ensembl | ENSP00000265440.7 | 7 | MANE Select | |
| RefSeq | NP_001018068.1 | 6 | Standard | |
| RefSeq | NP_001231512.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tfec | Danio rerio | Structure: nucleate erythrocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- C-MYB transcription factor network
Biological Process
- cellular response to heat
- positive regulation of transcription by RNA polymerase II
- negative regulation of nucleic acid-templated transcription
Molecular Function
- 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
- DNA-binding transcription factor activity
- transcription coactivator activity
Cellular Component
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265440
- Coding exons
- 7
- Length
- 224749
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 65
- Defined
- 125741
- p
- 0.000262
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0922 | 182 | 179 | 1.02 | 0.00000861 | 2263 |
| Missense (PolyPhen) | 48 | 54.799 | 0.87593 | 739 | ||
| Synonymous | -0.979 | 73 | 63.1 | 1.16 | 0.00000306 | 659 |
| Loss of Function | 1.12 | 14 | 19.3 | 0.726 | 0.00000112 | 212 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0017 | 0.0017 | notable |
| Latino/Admixed American | 0.00053 | 0.00052 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00039 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.00085 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional regulator that acts as a repressor or an activator. Acts as a transcriptional repressor on minimal promoter containing element F (that includes an E-box sequence). Binds to element F in an E-box sequence-specific manner. Acts as a transcriptional transactivator on the proximal promoter region of the tartrate-resistant acid phosphatase (TRAP) E-box containing promoter (By similarity). Collaborates with MITF in target gene activation (By similarity). Acts as a transcriptional repressor on minimal promoter containing mu E3 enhancer sequence (By similarity). Binds to mu E3 DNA sequence of the immunoglobulin heavy-chain gene enhancer (By similarity). Binds DNA in a homo- or heterodimeric form. {ECO:0000250, ECO:0000269|PubMed:11467950, ECO:0000269|PubMed:9256061}.;
Recessive Scores
- pRec
- 0.183
Intolerance Scores
- LoFtool
- 0.410
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.26
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.657
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |