CBLC
protein-codingCbl proto-oncogene C, the group of Ring finger proteins
Gene summary
This gene encodes a member of the Cbl family of E3 ubiquitin ligases. Cbl proteins play important roles in cell signaling through the ubiquitination and subsequent downregulation of tyrosine kinases. Expression of this gene may be restricted to epithelial cells, and alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.8 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 CBLC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012116.4. 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 | 1 | 1 | ||||
| missense | 66 | 6 | 72 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 70 | 7 | 0 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036248.3 | 10 | MANE Select | |
| Ensembl | ENSP00000494162.1 | 10 | MANE Select | |
| RefSeq | NP_001124324.1 | 9 | Standard | |
| Ensembl | ENSP00000340250.4 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Angiopoietin Like Protein 8 Regulatory Pathway
- EGF-EGFR Signaling Pathway
- Insulin Signaling
Biological Process
- ubiquitin-dependent protein catabolic process
- signal transduction
- cell surface receptor signaling pathway
- negative regulation of epidermal growth factor-activated receptor activity
- protein ubiquitination
Molecular Function
- phosphotyrosine residue binding
- epidermal growth factor receptor binding
- calcium ion binding
- zinc ion binding
- SH3 domain binding
Cellular Component
- plasma membrane
- membrane raft
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000270279
- Coding exons
- 10
- Length
- 22766
- Individuals with no LoFs
- 118822
- Homozygous LoFs
- 380
- Heterozygous LoFs
- 6545
- Defined
- 125747
- p
- 0.0279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.374 | 254 | 271 | 0.936 | 0.0000152 | 3021 |
| Missense (PolyPhen) | 115 | 112.95 | 1.0182 | 1228 | ||
| Synonymous | -0.367 | 123 | 118 | 1.04 | 0.00000705 | 977 |
| Loss of Function | 1.02 | 19 | 24.4 | 0.778 | 0.00000117 | 259 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.21 | 0.19 | notable |
| Latino/Admixed American | 0.011 | 0.011 | notable |
| Ashkenazi Jewish | 0.024 | 0.023 | notable |
| East Asian | 0.086 | 0.081 | notable |
| Finnish | 0.034 | 0.032 | notable |
| European (Non-Finnish) | 0.0029 | 0.0027 | notable |
| South Asian | 0.038 | 0.035 | notable |
| Other | 0.016 | 0.015 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Functionally coupled with the E2 ubiquitin-protein ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-419'. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival. {ECO:0000269|PubMed:10362357, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:18753381, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173}.;
Recessive Scores
- pRec
- 0.372
Intolerance Scores
- LoFtool
- 0.173
- RVIS EVS
- 1
- RVIS percentile EVS
- 90.65
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.551
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |