TFCP2L1
protein-codingtranscription factor CP2 like 1
Gene summary
Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~68.6 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 TFCP2L1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014553.3. 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 | 2 | 2 | ||||
| missense | 49 | 1 | 50 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 1 | 52 | 0 | 3 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055368.1 | 15 | MANE Select | |
| Ensembl | ENSP00000263707.5 | 15 | MANE Select | |
| Ensembl | ENSP00000549636.1 | 14 | Standard | |
| Ensembl | ENSP00000549636.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- cell morphogenesis
- epithelial cell maturation
- regulation of transcription by RNA polymerase II
- steroid biosynthetic process
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- transcription corepressor activity
- sequence-specific DNA binding
Cellular Component
- fibrillar center
- nucleus
- mitochondrion
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263707
- Coding exons
- 15
- Length
- 68621
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125743
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.63 | 213 | 291 | 0.731 | 0.0000181 | 3130 |
| Missense (PolyPhen) | 66 | 121.4 | 0.54368 | 1273 | ||
| Synonymous | 0.418 | 119 | 125 | 0.952 | 0.00000836 | 904 |
| Loss of Function | 5.18 | 1 | 33.2 | 0.0302 | 0.00000191 | 333 |
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) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that facilitates establishment and maintenance of pluripotency in embryonic stem cells (ESCs) (PubMed:25215486, PubMed:26906118). With KLF2, acts as the major effector of self-renewal that mediates induction of pluripotency downstream of LIF/STAT3 and Wnt/beta-catenin signaling (By similarity). Required for normal duct development in the salivary gland and kidney (By similarity). Coordinates the development of the kidney collecting ducts intercalated (IC) and principal (PC) cells, which regulate acid-base and salt-water homeostasis, respectively (By similarity). Regulates the expression of IC genes including subunits B1 and D2 of the V-ATPase complex, OXGR1, CA12, SLC4A1, AQP6 and IC-specific transcription factor FOXI1 (By similarity). Regulates also the expression of JAG1 and subsequent notch signaling in the collecting duct (By similarity). JAG1 initiates notch signaling in PCs but inhibits notch signaling in ICs (By similarity). Acts as a transcriptional suppressor that may suppress UBP1-mediated transcriptional activation (By similarity). Modulates the placental expression of CYP11A1 (PubMed:10644752). {ECO:0000250|UniProtKB:Q3UNW5, ECO:0000269|PubMed:10644752, ECO:0000269|PubMed:25215486, ECO:0000269|PubMed:26906118}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.0581
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.575
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |