CBLB
Cbl proto-oncogene B, the group of Ring finger proteins
Basic information
Region (hg38): 3:105655461-105869552
Links
Phenotypes
GenCC
Source:
- autoimmune disease, multisystem, infantile-onset, 3 (Strong), mode of inheritance: AR
- autoimmune disease, multisystem, infantile-onset, 3 (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Autoimmune disease, multisystem, infantile-onset, 3 | AR | Allergy/Immunology/Infectious | The condition may manifest with a variety of autoimmune manifestations, and medical management (eg, with IVIG or corticosteroids) has been described in some individuals | Allergy/Immunology/Infectious | 36006710 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CBLB 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 | 11 | 16 | ||||
| missense | 42 | 46 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 42 | 6 | 14 |
Variants in CBLB
This is a list of pathogenic ClinVar variants found in the CBLB region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-105659038-C-T | not specified | not provided (Sep 19, 2013) | ||
| 3-105659118-G-C | not specified | Uncertain significance (Jan 17, 2023) | ||
| 3-105659193-C-T | not specified | Uncertain significance (Aug 08, 2022) | ||
| 3-105659203-G-C | not specified | Uncertain significance (Jan 05, 2022) | ||
| 3-105659217-G-C | not specified | not provided (Sep 19, 2013) | ||
| 3-105670240-T-C | CBLB-related disorder | Benign (Oct 28, 2019) | ||
| 3-105670257-A-G | not specified | Uncertain significance (Dec 05, 2022) | ||
| 3-105670257-A-T | not specified | Uncertain significance (May 23, 2023) | ||
| 3-105670275-T-C | not specified • CBLB-related disorder | Benign (Jan 28, 2020) | ||
| 3-105670302-T-C | not specified | Uncertain significance (Jan 19, 2024) | ||
| 3-105670309-A-G | CBLB-related disorder | Benign (Nov 06, 2019) | ||
| 3-105670346-A-G | not specified | Uncertain significance (Dec 11, 2023) | ||
| 3-105678451-T-C | not specified | Uncertain significance (May 28, 2024) | ||
| 3-105678460-G-A | not specified | Uncertain significance (Dec 27, 2023) | ||
| 3-105678469-C-T | not specified | Uncertain significance (Mar 06, 2023) | ||
| 3-105681576-T-C | CBLB-related disorder | Benign (Oct 28, 2019) | ||
| 3-105681597-A-C | not specified | Uncertain significance (Jul 19, 2022) | ||
| 3-105685324-C-G | not specified | Uncertain significance (Oct 03, 2022) | ||
| 3-105685345-A-G | not specified | Uncertain significance (Oct 04, 2022) | ||
| 3-105685347-T-C | not specified | Uncertain significance (Jul 05, 2023) | ||
| 3-105685369-A-C | not specified | Uncertain significance (May 06, 2024) | ||
| 3-105685406-A-T | not specified | Uncertain significance (Mar 04, 2024) | ||
| 3-105685411-C-T | not specified | Uncertain significance (Dec 27, 2023) | ||
| 3-105685414-C-G | not specified | Uncertain significance (May 08, 2023) | ||
| 3-105685454-C-T | CBLB-related disorder | Benign/Likely benign (Mar 01, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CBLB | protein_coding | protein_coding | ENST00000264122 | 18 | 214092 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00175 | 125736 | 0 | 12 | 125748 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.29 | 460 | 545 | 0.844 | 0.0000298 | 6406 |
| Missense in Polyphen | 151 | 222.53 | 0.67856 | 2608 | ||
| Synonymous | -0.525 | 199 | 190 | 1.05 | 0.0000100 | 1942 |
| Loss of Function | 5.59 | 7 | 49.4 | 0.142 | 0.00000287 | 580 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000119 | 0.000119 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000797 | 0.0000703 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000166 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B- cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T- cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694}.;
- Pathway
- T cell receptor signaling pathway - Homo sapiens (human);Endocytosis - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Measles - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Angiopoietin Like Protein 8 Regulatory Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;T-Cell antigen Receptor (TCR) Signaling Pathway;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;GPCR Adenosine A2A receptor;Signaling by the B Cell Receptor (BCR);TCR;Immune System;Adaptive Immune System;KitReceptor;Antigen processing: Ubiquitination & Proteasome degradation;BCR;Class I MHC mediated antigen processing & presentation;GPCR signaling-G alpha s PKA and ERK;EGFR1;IL-7;CD40/CD40L signaling;Fc-epsilon receptor I signaling in mast cells;Internalization of ErbB1;Calcineurin-regulated NFAT-dependent transcription in lymphocytes
(Consensus)
Recessive Scores
- pRec
- 0.382
Intolerance Scores
- loftool
- 0.104
- rvis_EVS
- -0.84
- rvis_percentile_EVS
- 11.4
Haploinsufficiency Scores
- pHI
- 0.485
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.534
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.859
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cblb
- Phenotype
- immune system phenotype; liver/biliary system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype;
Gene ontology
- Biological process
- NLS-bearing protein import into nucleus;signal transduction;cell surface receptor signaling pathway;negative regulation of epidermal growth factor-activated receptor activity;protein ubiquitination;regulation of platelet-derived growth factor receptor-alpha signaling pathway
- Cellular component
- nucleoplasm;cytosol;plasma membrane;membrane raft
- Molecular function
- phosphotyrosine residue binding;calcium ion binding;protein binding;zinc ion binding;SH3 domain binding;receptor tyrosine kinase binding;ubiquitin protein ligase activity