CXXC5
protein-codingCXXC finger protein 5, the group of Zinc fingers CXXC-type
Gene summary
The protein encoded by this gene is a retinoid-inducible nuclear protein containing a CXXC-type zinc finger motif. The encoded protein is involved in myelopoiesis, is required for DNA damage-induced p53 activation, regulates the differentiation of C2C12 myoblasts into myocytes, and negatively regulates cutaneous wound healing. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.6 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 CXXC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016463.9. 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 | 1 | ||||
| missense | 42 | 4 | 46 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 42 | 5 | 0 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057547.5 | 2 | MANE Select | |
| Ensembl | ENSP00000302543.3 | 2 | MANE Select | |
| RefSeq | NP_001304128.1 | 2 | Standard | |
| RefSeq | NP_001304129.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cxxc5a | Danio rerio | Structure: caudal vein plexus Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Signaling by Nuclear Receptors
- Estrogen-dependent gene expression
- ESR-mediated signaling
Biological Process
- negative regulation of transcription by RNA polymerase II
- positive regulation of I-kappaB kinase/NF-kappaB signaling
Molecular Function
- protein binding
- transcription factor binding
- zinc ion binding
- sequence-specific DNA binding
Cellular Component
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302517
- Coding exons
- 2
- Length
- 36584
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.58 | 157 | 223 | 0.703 | 0.0000155 | 2102 |
| Missense (PolyPhen) | 34 | 73.653 | 0.46162 | 678 | ||
| Synonymous | 0.607 | 90 | 97.6 | 0.922 | 0.00000773 | 682 |
| Loss of Function | 2.47 | 0 | 7.13 | 0.00 | 3.70e-7 | 85 |
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 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May indirectly participate in activation of the NF- kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells (By similarity). Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis. Transcription factor. Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ (PubMed:23303788). {ECO:0000250, ECO:0000269|PubMed:19182210, ECO:0000269|PubMed:19557330, ECO:0000269|PubMed:23303788}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.927
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |