CDK5RAP3
protein-codingCDK5 regulatory subunit associated protein 3
Gene summary
This gene encodes a protein that has been reported to function in signaling pathways governing transcriptional regulation and cell cycle progression. It may play a role in tumorigenesis and metastasis. A pseudogene of this gene is located on the long arm of chromosome 20. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, May 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.0 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 CDK5RAP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_176096.3. 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 | 1 | 3 | |||
| missense | 80 | 2 | 82 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 90 | 3 | 0 | 93 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_788276.1 | 14 | MANE Select | |
| Ensembl | ENSP00000344683.4 | 14 | MANE Select | |
| RefSeq | NP_001265126.1 | 14 | Standard | |
| RefSeq | NP_001265127.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cdk5rap3 | Danio rerio | Structure: blastoderm cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in leukocytes - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
Biological Process
- regulation of cyclin-dependent protein serine/threonine kinase activity
- negative regulation of protein phosphorylation
- mitotic G2 DNA damage checkpoint
- regulation of mitotic cell cycle
- brain development
Molecular Function
- protein binding
- protein kinase binding
- cyclin binding
- ubiquitin-like protein ligase binding
- mitogen-activated protein kinase binding
Cellular Component
- nucleus
- nucleolus
- cytoplasm
- centrosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338399
- Coding exons
- 14
- Length
- 13965
- Individuals with no LoFs
- 124720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 93
- Defined
- 124813
- p
- 0.000373
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.484 | 258 | 281 | 0.919 | 0.0000155 | 3262 |
| Missense (PolyPhen) | 79 | 92.162 | 0.85718 | 1169 | ||
| Synonymous | -0.453 | 124 | 118 | 1.05 | 0.00000686 | 989 |
| Loss of Function | 1.18 | 26 | 33.4 | 0.779 | 0.00000178 | 353 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.00032 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00051 | 0.00051 | rare |
| South Asian | 0.00052 | 0.00052 | rare |
| Other | 0.00083 | 0.00082 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable tumor suppressor initially identified as a CDK5R1 interactor controlling cell proliferation (PubMed:12054757, PubMed:12737517). Negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation (PubMed:17785205, PubMed:20228063). Also regulates mitotic G2/M transition checkpoint and mitotic G2 DNA damage checkpoint (PubMed:15790566, PubMed:19223857). Through its interaction with CDKN2A/ARF and MDM2 may induce MDM2-dependent p53/TP53 ubiquitination, stabilization and activation in the nucleus, thereby promoting G1 cell cycle arrest and inhibition of cell proliferation (PubMed:16173922). May play a role in the unfolded protein response, mediating the ufmylation of multiple proteins in response to endoplasmic reticulum stress (PubMed:23152784). May also play a role in the rupture of the nuclear envelope during apoptosis (PubMed:23478299). May regulate MAPK14 activity by regulating its dephosphorylation by PPM1D/WIP1 (PubMed:21283629). {ECO:0000269|PubMed:12054757, ECO:0000269|PubMed:12737517, ECO:0000269|PubMed:15790566, ECO:0000269|PubMed:16173922, ECO:0000269|PubMed:17785205, ECO:0000269|PubMed:19223857, ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:21283629, ECO:0000269|PubMed:23152784, ECO:0000269|PubMed:23478299}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.821
- RVIS EVS
- 0.62
- RVIS percentile EVS
- 83.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.941
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |