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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CBLC
Cbl proto-oncogene C
Chromosome 19 · 19q13.32
NCBI Gene: 23624Ensembl: ENSG00000142273.14HGNC: HGNC:15961UniProt: Q9ULV8
51PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ubiquitin-dependent protein catabolic processphosphotyrosine residue bindingepidermal growth factor receptor bindingnegative regulation of epidermal growth factor receptor signaling pathwayneurodegenerative diseasecutaneous melanomanon-small cell lung carcinomalung adenocarcinoma
✦AI Summary

CBLC (Cbl proto-oncogene C) functions as an E3 ubiquitin-protein ligase that transfers ubiquitin from E2 enzymes to target proteins for proteasomal degradation. It negatively regulates epidermal growth factor receptor (EGFR) signaling by ubiquitinating activated EGFR and inhibiting MAPK1 activation [UniProt Function]. CBLC also promotes ubiquitination of phosphorylated SRC and modulates RET signaling in collaboration with CD2AP, regulating the rate of RET degradation after ligand activation [UniProt Function]. However, the provided PubMed abstracts do not discuss CBLC proto-oncogene C function. Instead, they extensively address MMACHC (also designated CblC in biochemical literature), a distinct protein involved in vitamin B12 metabolism 1. MMACHC processes dietary cobalamin by removing the upper-axial ligand to generate cob(II)alamin, an essential precursor for two B12-dependent enzymes: cytosolic methionine synthase and mitochondrial methylmalonyl-CoA mutase 1. Mutations in MMACHC cause cblC disease, the most common inborn error of intracellular cobalamin metabolism, characterized by combined homocysteinuria and methylmalonic aciduria 2. Early-onset patients present severe multisystem disease with neurological, ocular, and hematological manifestations, while late-onset patients show milder progressive neurological symptoms 2. Treatment with parenteral hydroxocobalamin significantly improves survival 3. The abstracts provide no information supporting CBLC proto-oncogene C's clinical relevance or disease associations.

Sources cited
1
MMACHC (CblC) processes dietary cobalamin by removing the upper-axial ligand to generate cob(II)alamin, a precursor for methionine synthase and methylmalonyl-CoA mutase
PMID: 35337623
2
Cbl-C defect causes accumulation of methylmalonic acid and homocysteine, decreased methionine synthesis, with heterogeneous clinical presentations ranging from early-onset multisystem disease to late-onset neurological symptoms
PMID: 20632110
3
Parenteral hydroxocobalamin treatment in suspected remethylation disorders significantly improves survival and reduces severe complications
PMID: 27905001
4
Late-onset cblC disease presents with neuropathy/myelopathy, encephalopathy, psychiatric symptoms, thrombotic microangiopathy, and other complications; treatment typically leads to improvement or recovery
PMID: 38245797
5
CblC receives vitamin B12 as it enters the cytoplasm and converts varied B12 derivatives to cob(II)alamin intermediate for cofactor delivery to client enzymes
PMID: 35589192
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.39Weak
cutaneous melanomaOpen Targets
0.22Weak
non-small cell lung carcinomaOpen Targets
0.19Weak
lung adenocarcinomaOpen Targets
0.19Weak
squamous cell lung carcinomaOpen Targets
0.19Weak
acute myeloid leukemiaOpen Targets
0.19Weak
melanomaOpen Targets
0.19Weak
breast carcinomaOpen Targets
0.19Weak
gastrointestinal stromal tumorOpen Targets
0.19Weak
Merkel cell skin cancerOpen Targets
0.19Weak
bile duct carcinomaOpen Targets
0.18Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.18Weak
cervical squamous cell carcinomaOpen Targets
0.18Weak
clear cell renal carcinomaOpen Targets
0.18Weak
colon adenocarcinomaOpen Targets
0.18Weak
colorectal adenocarcinomaOpen Targets
0.18Weak
Hepatobiliary NeoplasmOpen Targets
0.18Weak
hepatocellular carcinomaOpen Targets
0.18Weak
multiple myelomaOpen Targets
0.18Weak
Placental ChoriocarcinomaOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SRCProtein interaction100%CRKProtein interaction100%SH3KBP1Protein interaction100%EGFRProtein interaction91%FYNProtein interaction91%SH3GL1Protein interaction91%
Tissue Expression6 tissues
Liver
100%
Brain
4%
Lung
3%
Ovary
0%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
CBLCSRCCRKSH3KBP1EGFRFYNSH3GL1
PROTEIN STRUCTURE
Preparing viewer…
PDB3VRP · 1.52 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.06LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.82 [0.65–1.06]
RankingsWhere CBLC stands among ~20K protein-coding genes
  • #8,654of 20,598
    Most Researched51
  • #10,626of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedCBLC
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Late-onset methylmalonic acidemia and homocysteinemia (cblC disease): systematic review.
PMID: 38245797
Orphanet J Rare Dis · 2024
1.00
2
Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency.
PMID: 27905001
J Inherit Metab Dis · 2017
0.90
3
Cobalamin C defect: natural history, pathophysiology, and treatment.
PMID: 20632110
J Inherit Metab Dis · 2011
0.80
4
Molecular genetic characterization of cblC defects in 126 pedigrees and prenatal genetic diagnosis of pedigrees with combined methylmalonic aciduria and homocystinuria.
PMID: 30157807
BMC Med Genet · 2018
0.70
5
Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7-year study in eastern coastal areas of China.
PMID: 36787440
Mol Genet Genomic Med · 2023
0.60