CBLC

Cbl proto-oncogene C, the group of Ring finger proteins

Basic information

Region (hg38): 19:44777868-44800652

Links

ENSG00000142273 ∙ NCBI:23624 ∙ OMIM:608453 ∙ HGNC:15961 ∙ Uniprot:Q9ULV8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CBLC gene.

• Inborn genetic diseases (12 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CBLC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			10	2		12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	10	3	0

Variants in CBLC

This is a list of pathogenic ClinVar variants found in the CBLC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-44778046-G-A		not specified	Likely benign (Jan 10, 2023)
19-44778053-C-G		not specified	Uncertain significance (Jun 09, 2022)
19-44778140-C-T		not specified	Uncertain significance (Dec 13, 2023)
19-44778157-T-C		not specified	Uncertain significance (Oct 29, 2021)
19-44778294-C-G			Likely benign (Jul 21, 2018)
19-44780907-G-A		not specified	Uncertain significance (Nov 07, 2022)
19-44780915-G-T		not specified	Uncertain significance (Jan 23, 2024)
19-44780946-A-T		not specified	Uncertain significance (Mar 07, 2024)
19-44780978-A-G		not specified	Uncertain significance (Jan 20, 2023)
19-44780991-A-G		not specified	Uncertain significance (Jun 28, 2023)
19-44780993-A-G		not specified	Likely benign (Jan 05, 2022)
19-44781024-C-A		not specified	Uncertain significance (Dec 27, 2022)
19-44781050-C-G		not specified	Uncertain significance (Jan 24, 2024)
19-44781296-C-T		not specified	Uncertain significance (Aug 19, 2021)
19-44784397-G-A		not specified	Uncertain significance (Dec 01, 2022)
19-44790075-G-A		not specified	Likely benign (Dec 22, 2023)
19-44792389-C-G		not specified	Uncertain significance (Jan 03, 2024)
19-44792471-C-T		not specified	Uncertain significance (Nov 15, 2021)
19-44794216-G-T		not specified	Uncertain significance (Jan 07, 2022)
19-44800398-C-G		not specified	Uncertain significance (Dec 27, 2023)
19-44800412-C-T		not specified	Uncertain significance (Sep 17, 2021)
19-44800432-G-A		not specified	Uncertain significance (Nov 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CBLC	protein_coding	protein_coding	ENST00000270279	10	22766

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.24e-11	0.332	118822	380	6545	125747	0.0279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.374	254	271	0.936	0.0000152	3021
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.218	0.197
Ashkenazi Jewish	0.0244	0.0232
East Asian	0.0857	0.0811
Finnish	0.0343	0.0323
European (Non-Finnish)	0.00288	0.00273
Middle Eastern	0.0857	0.0811
South Asian	0.0384	0.0354
Other	0.0162	0.0153

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Endocytosis - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Angiopoietin Like Protein 8 Regulatory Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;ErbB Signaling Pathway;GPCR Adenosine A2A receptor;GPCR signaling-G alpha s PKA and ERK;EGFR1 (Consensus)

Recessive Scores

• pRec: 0.372

Intolerance Scores

• loftool: 0.173
• rvis_EVS: 1
• rvis_percentile_EVS: 90.65

Haploinsufficiency Scores

• pHI: 0.0784
• hipred: N
• hipred_score: 0.340
• ghis: 0.481

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.551

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cblc
• Phenotype: normal phenotype

Gene ontology

• 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;negative regulation of epidermal growth factor receptor signaling pathway;negative regulation of MAP kinase activity
• Cellular component: plasma membrane;membrane raft
• Molecular function: phosphotyrosine residue binding;epidermal growth factor receptor binding;calcium ion binding;zinc ion binding;SH3 domain binding;receptor tyrosine kinase binding;ubiquitin protein ligase activity