TCF7
protein-codingtranscription factor 7, the group of TCF/LEF transcription factor family|Wnt enhanceosome complex
Gene summary
This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling. [provided by RefSeq, Oct 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.2 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 TCF7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003202.5. 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 | 1 | 2 | 3 | |||
| missense | 63 | 1 | 64 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 67 | 3 | 0 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003193.2 | 10 | MANE Select | |
| Ensembl | ENSP00000340347.5 | 10 | MANE Select | |
| RefSeq | NP_001128323.2 | 8 | Standard | |
| RefSeq | NP_001333354.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tcf7 | Danio rerio | Structure: pectoral fin Quality: undulate abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gastric cancer - Homo sapiens (human)
- Adherens junction - Homo sapiens (human)
- Cushing,s syndrome - Homo sapiens (human)
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)
- Acute myeloid leukemia - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- regulation of transcription, DNA-templated
- regulation of transcription by RNA polymerase II
- immune response
- neural tube development
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- nuclear euchromatin
- nuclear body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000342854
- Coding exons
- 10
- Length
- 37155
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125747
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.506 | 173 | 193 | 0.898 | 0.0000109 | 2456 |
| Missense (PolyPhen) | 68 | 101.23 | 0.67176 | 1074 | ||
| Synonymous | -1.77 | 104 | 83.5 | 1.25 | 0.00000546 | 767 |
| Loss of Function | 2.47 | 7 | 18.5 | 0.379 | 8.83e-7 | 229 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000058 | 0.000054 | rare |
| Finnish | 0.00075 | 0.00074 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000068 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator involved in T-cell lymphocyte differentiation. Necessary for the survival of CD4(+) CD8(+) immature thymocytes. Isoforms lacking the N-terminal CTNNB1 binding domain cannot fulfill this role. Binds to the T- lymphocyte-specific enhancer element (5'-WWCAAAG-3') found in the promoter of the CD3E gene. May also act as feedback transcriptional repressor of CTNNB1 and TCF7L2 target genes. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7 and CTNNB1.;
Intolerance Scores
- LoFtool
- 0.0491
- RVIS EVS
- 0.11
- RVIS percentile EVS
- 62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.860
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |