CXXC1
protein-codingCXXC finger protein 1, the group of PHD finger proteins|Zinc fingers CXXC-type
Gene summary
This gene encodes a protein that functions as a transcriptional activator that binds specifically to non-methylated CpG motifs through its CXXC domain. The protein is a component of the SETD1 complex, regulates gene expression and is essential for vertebrate development. [provided by RefSeq, Sep 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.5 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 CXXC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014593.4. 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 | 4 | 7 | |||
| missense | 73 | 73 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 81 | 3 | 4 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055408.2 | 15 | MANE Select | |
| Ensembl | ENSP00000285106.6 | 15 | MANE Select | |
| RefSeq | NP_001095124.1 | 15 | Standard | |
| Ensembl | ENSP00000390475.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cxxc1b | Danio rerio | Structure: blood vasculature Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- XBP1(S) activates chaperone genes
Biological Process
- regulation of transcription, DNA-templated
- regulation of transcription by RNA polymerase II
- IRE1-mediated unfolded protein response
- positive regulation of transcription, DNA-templated
- histone H3-K4 methylation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- proximal promoter sequence-specific DNA binding
- protein binding
- zinc ion binding
- histone methyltransferase activity (H3-K4 specific)
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- nuclear matrix
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000412036
- Coding exons
- 15
- Length
- 5962
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.15 | 256 | 442 | 0.579 | 0.0000325 | 4289 |
| Missense (PolyPhen) | 73 | 217 | 0.3364 | 2161 | ||
| Synonymous | -1.14 | 182 | 163 | 1.11 | 0.0000102 | 1274 |
| Loss of Function | 4.67 | 7 | 38.1 | 0.183 | 0.00000201 | 433 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG. {ECO:0000269|PubMed:21407193}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.286
- RVIS EVS
- -0.93
- RVIS percentile EVS
- 9.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |