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Gene Gene information from NCBI Gene database.
Entrez ID 867
Gene name Cbl proto-oncogene
Gene symbol CBL
Synonyms (NCBI Gene)
C-CBLCBL2FRA11BNSLLRNF55
Chromosome 11
Chromosome location 11q23.3
Summary This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin con
SNPs SNP information provided by dbSNP.
26 Show/Hide all (26)
SNP ID Visualize variation Clinical significance Consequence
rs143264567 A>C,G Conflicting-interpretations-of-pathogenicity Coding sequence variant, missense variant
rs143840974 G>A,C Likely-benign, conflicting-interpretations-of-pathogenicity, benign, benign-likely-benign Coding sequence variant, synonymous variant
rs150811339 G>A Conflicting-interpretations-of-pathogenicity Missense variant, coding sequence variant
rs199788586 A>T Uncertain-significance, conflicting-interpretations-of-pathogenicity Coding sequence variant, missense variant
rs267606704 A>C,G Pathogenic Coding sequence variant, missense variant
miRNA miRNA information provided by mirtarbase database.
1407 Show/Hide all (1407)
miRTarBase ID miRNA Experiments Reference
MIRT051757 hsa-let-7c-5p CLASH 23622248
MIRT050866 hsa-miR-17-5p CLASH 23622248
MIRT054868 hsa-miR-150-5p Luciferase reporter assayMicroarrayqRT-PCR 23604034
MIRT437868 hsa-miR-98-5p MicroarrayqRT-PCRWestern blot 23434382
MIRT437868 hsa-miR-98-5p MicroarrayqRT-PCRWestern blot 23434382
Gene ontology (GO) Gene Ontology (GO) annotations describing the biological processes, molecular functions, and cellular components associated with a gene.
81 Show/Hide all (81)
GO ID Ontology Definition Evidence Reference
GO:0000209 Process Protein polyubiquitination IEA
GO:0001784 Function Phosphotyrosine residue binding IEA
GO:0004842 Function Ubiquitin-protein transferase activity IEA
GO:0004842 Function Ubiquitin-protein transferase activity TAS 15465819
GO:0005509 Function Calcium ion binding IEA
Other IDs Other IDs provides unique identifiers for this gene in OMIM, HGNC, and Ensembl databases.
MIM HGNC e!Ensembl
165360 1541 ENSG00000110395
Protein Protein information from UniProt database.
UniProt ID Unique identifier for the protein in the UniProt database. Click to view detailed protein information.
P22681
Protein name E3 ubiquitin-protein ligase CBL (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene) (Proto-oncogene c-Cbl) (RING finger protein 55) (RING-type E3 ubiquitin transferase CBL) (Signal transduction protein CBL)
Protein function E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, PubMed:14739300, PubMed:15190072, PubMed:17509076,
PDB 1B47 , 1FBV , 1YVH , 2CBL , 2JUJ , 2K4D , 2OO9 , 2Y1M , 2Y1N , 3BUM , 3BUN , 3BUO , 3BUW , 3BUX , 3OB1 , 3OB2 , 3PLF , 4A49 , 4A4B , 4A4C , 4GPL , 5HKW , 5HKX , 5HKY , 5HKZ , 5HL0 , 5J3X , 5O76 , 6O02 , 6O03 , 6XAR , 7SIY
Family and domains

Pfam

Accession ID Position in sequence Description Type
PF00627 UBA 856 → 892 UBA/TS-N domain Domain
PF02262 Cbl_N 51 → 175 CBL proto-oncogene N-terminal domain 1 Domain
PF02761 Cbl_N2 179 → 262 CBL proto-oncogene N-terminus, EF hand-like domain Domain
PF02762 Cbl_N3 264 → 349 CBL proto-oncogene N-terminus, SH2-like domain Domain
PF14447 Prok-RING_4 381 → 434 Family
Sequence
MAGNVKKSSGAGGGSGSGGSGSGGLIGLMKDAFQPHHHHHHHLSPHPPGTVDKKMVEKCW
KLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRYEGKMETLGENEYFRVFME
NLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQ
GDTFR
ITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFE
FDIFTRLFQPWSSLLRNWNSLA
VTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRL
GQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRNQNPDL
TGLCEPTPQDH
IKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCR
CEIKGTEPIVVDPF
DPRGSGSLLRQGAEGAPSPNYDDDDDERADDTLFMMKELAGAKVER
PPSPFSMAPQASLPPVPPRLDLLPQRVCVPSSASALGTASKAASGSLHKDKPLPVPPTLR
DLPPPPPPDRPYSVGAESRPQRRPLPCTPGDCPSRDKLPPVPSSRLGDSWLPRPIPKVPV
SAPSSSDPWTGRELTNRHSLPFSLPSQMEPRPDVPRLGSTFSLDTSMSMNSSPLVGPECD
HPKIKPSSSANAIYSLAARPLPVPKLPPGEQCEGEEDTEYMTPSSRPLRPLDTSQSSRAC
DCDQQIDSCTYEAMYNIQSQAPSITESSTFGEGNLAAAHANTGPEESENEDDGYDVPKPP
VPAVLARRTLSDISNASSSFGWLSLDGDPTTNVTEGSQVPERPPKPFPRRINSERKAGSC
QQGSGPAASAATASPQLSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFVSISS
PAHVAT
Sequence length 906
Interactions View interactions
Pathways Pathway information has different metabolic/signaling pathways associated with genes.
KEGG Pathway Reactome Pathway
ErbB signaling pathway Interleukin-6 signaling
Ubiquitin mediated proteolysis Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
Endocytosis Spry regulation of FGF signaling
Insulin signaling pathway Regulation of KIT signaling
Bacterial invasion of epithelial cells EGFR downregulation
Pathways in cancer TGF-beta receptor signaling activates SMADs
Proteoglycans in cancer Constitutive Signaling by EGFRvIII
Chronic myeloid leukemia Negative regulation of FGFR1 signaling
  Negative regulation of FGFR2 signaling
  Negative regulation of FGFR3 signaling
  Negative regulation of FGFR4 signaling
  Negative regulation of MET activity
  PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1
  Cargo recognition for clathrin-mediated endocytosis
  Clathrin-mediated endocytosis
  InlB-mediated entry of Listeria monocytogenes into host cell
  Regulation of signaling by CBL
Associated diseases Disease associations from ClinVar (causal & non-causal) and other databases (OMIM, Orphanet, GWAS, etc.).
52
Evidence Score: ★☆☆☆☆  Gene-disease association found in Text Mining only ★★☆☆☆  Found in Text Mining and Unknown/Other Associations ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants) ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Show/Hide Causal Diseases (16)
Phenotype Name Clinical Significance dbSNP ID RCV Accession Evidence Score
Acute myeloid leukemia Likely pathogenic; Pathogenic rs397517076, rs1592400784 RCV005889981
RCV005906931
★★★★★
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cardiovascular phenotype Likely pathogenic; Pathogenic rs727504426, rs397517076, rs2496939296, rs267606706 RCV005791822
RCV005532590
RCV002453119
RCV005791808
★★★★★
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CBL-related disorder Likely pathogenic; Pathogenic rs2135301614, rs727504426, rs397517076, rs267606706, rs267606704, rs267606707, rs2496939189, rs397507489, rs1555230070, rs387906666, rs397517077, rs1592400784 RCV002274444
RCV001808423
RCV001249230
RCV001814073
RCV003314050
View all (10 more)
★★★★★
★★★★★
ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Fragile site 11b Pathogenic rs397517076 RCV001249230
★★★★★
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Glioma susceptibility 1 Pathogenic rs397517076 RCV005888561
★★★★★
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Unknown / Other Associations ClinVar entries with uncertain/conflicting evidence, and associations from other databases (OMIM, Orphanet, GWAS, etc.) where the gene is not established as causal.
Show/Hide Unknown Diseases (36)
Phenotype Name Clinical Significance Source Reference Evidence Score
Acute myeloid leukemia with NPM1 somatic mutations Uncertain significance ClinVar —
★★★★★
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
B lymphoblastic leukemia lymphoma with hyperdiploidy Uncertain significance ClinVar —
★★★★★
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Central nervous system germ cell tumor Conflicting classifications of pathogenicity ClinVar —
★★★★★
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Cervical cancer Benign ClinVar —
★★★★★
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney Benign ClinVar —
★★★★★
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Associations from Text Mining Disease associations identified through text mining
Show/Hide Text Mining Associations (194)
Disease Name Disease (Merged) Source PMID Relationship Type Evidence Score
Abdominal Cryptorchidism Cryptorchidism CTD_human_DG 20694012
★★★★★
★☆☆☆☆
Found in Text Mining only
Abetalipoproteinemia Abetalipoproteinemia BEFREE 11857085
★★★★★
★☆☆☆☆
Found in Text Mining only
Acquired cubitus valgus Cubitus valgus HPO_DG
★★★★★
★☆☆☆☆
Found in Text Mining only
Acute leukemia Leukemia BEFREE 19276253, 2013228, 26104663
★★★★★
★☆☆☆☆
Found in Text Mining only
Acute lymphocytic leukemia Lymphocytic Leukemia BEFREE 19276253, 22591685
★★★★★
★☆☆☆☆
Found in Text Mining only
Acute monocytic leukemia Monocytic Leukemia BEFREE 20674974, 29417354
★★★★★
★☆☆☆☆
Found in Text Mining only
Adult Acute Lymphocytic Leukemia Lymphocytic Leukemia BEFREE 19276253, 22591685
★★★★★
★☆☆☆☆
Found in Text Mining only
Aggressive systemic mastocytosis Systemic Mastocytosis Orphanet
★★★★★
★☆☆☆☆
Found in Text Mining only
Anemia Refractory Refractory anemia Pubtator 20678218 Associate
★★★★★
★☆☆☆☆
Found in Text Mining only
ANOPHTHALMIA AND PULMONARY HYPOPLASIA Syndromic microphthalmia BEFREE 25348515
★★★★★
★☆☆☆☆
Found in Text Mining only