CRK
protein-codingCRK proto-oncogene, adaptor protein, the group of SH2 domain containing
Gene summary
This gene encodes a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. The product of this gene has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~42.5 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 CRK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016823.4. 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 | 2 | 3 | 5 | |||
| missense | 32 | 32 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 33 | 2 | 3 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_058431.2 | 3 | MANE Select | |
| Ensembl | ENSP00000300574.2 | 3 | MANE Select | |
| RefSeq | NP_005197.3 | 3 | Standard | |
| Ensembl | ENSP00000381942.5 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| crk | Danio rerio | Structure: fast muscle cell Quality: mononucleate abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chronic myeloid leukemia - Homo sapiens (human)
- Focal adhesion - Homo sapiens (human)
- Fc gamma R-mediated phagocytosis - Homo sapiens (human)
- Renal cell carcinoma - Homo sapiens (human)
- Neurotrophin signaling pathway - Homo sapiens (human)
Biological Process
- activation of MAPKK activity
- neuron migration
- response to yeast
- regulation of transcription by RNA polymerase II
- lipid metabolic process
Molecular Function
- phosphotyrosine residue binding
- SH3/SH2 adaptor activity
- insulin-like growth factor receptor binding
- protein binding
- cytoskeletal protein binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- plasma membrane
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000300574
- Coding exons
- 3
- Length
- 42474
- Individuals with no LoFs
- 124329
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124330
- p
- 0.00000402
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.37 | 91 | 181 | 0.504 | 0.00000962 | 1961 |
| Missense (PolyPhen) | 18 | 57.693 | 0.312 | 658 | ||
| Synonymous | 0.105 | 77 | 78.2 | 0.985 | 0.00000463 | 608 |
| Loss of Function | 3.27 | 1 | 14.4 | 0.0694 | 9.63e-7 | 138 |
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) | 0.0000089 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Isoform Crk-II: Regulates cell adhesion, spreading and migration. Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling. {ECO:0000269|PubMed:11870224, ECO:0000269|PubMed:1630456, ECO:0000269|PubMed:17515907, ECO:0000269|PubMed:19004829}.;
Recessive Scores
- pRec
- 0.533
Intolerance Scores
- LoFtool
- 0.0539
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |