KEAP1
Basic information
Region (hg38): 19:10486125-10503558
Links
Phenotypes
GenCC
Source:
- goiter, multinodular 1, with or without Sertoli-Leydig cell tumors (Supportive), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (47 variants)
- not_provided (11 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KEAP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000203500.2. Only rare variants are included in the table.
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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 7 | |||||
missense | 49 | 52 | ||||
nonsense | 2 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
splice donor/acceptor (+/-2bp) | 4 | |||||
Total | 0 | 0 | 55 | 10 | 0 |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
KEAP1 | protein_coding | protein_coding | ENST00000171111 | 5 | 17622 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.000388 | 0.999 | 125727 | 0 | 21 | 125748 | 0.0000835 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 3.80 | 206 | 427 | 0.483 | 0.0000300 | 4071 |
Missense in Polyphen | 45 | 165.03 | 0.27268 | 1571 | ||
Synonymous | 0.733 | 176 | 189 | 0.932 | 0.0000148 | 1246 |
Loss of Function | 3.10 | 11 | 29.1 | 0.379 | 0.00000195 | 244 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000122 | 0.000122 |
Ashkenazi Jewish | 0.000307 | 0.000298 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.0000819 | 0.0000791 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.000174 | 0.000163 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome. {ECO:0000269|PubMed:14585973, ECO:0000269|PubMed:15379550, ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:17046835}.;
- Pathway
- Ubiquitin mediated proteolysis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Quercetin and Nf-kB- AP-1 Induced Cell Apoptosis;Nuclear Receptors Meta-Pathway;NRF2 pathway;Transcriptional activation by NRF2;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;mRNA, protein, and metabolite inducation pathway by cyclosporin A;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;oxidative stress induced gene expression via nrf2;Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation;Ub-specific processing proteases;Deubiquitination
(Consensus)
Recessive Scores
- pRec
- 0.209
Intolerance Scores
- loftool
- 0.303
- rvis_EVS
- -1.13
- rvis_percentile_EVS
- 6.43
Haploinsufficiency Scores
- pHI
- 0.238
- hipred
- Y
- hipred_score
- 0.765
- ghis
- 0.618
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.942
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Keap1
- Phenotype
- digestive/alimentary phenotype; respiratory system phenotype; 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); homeostasis/metabolism phenotype; growth/size/body region 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);
Gene ontology
- Biological process
- in utero embryonic development;proteasomal ubiquitin-independent protein catabolic process;viral process;protein ubiquitination;protein deubiquitination;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;cytoplasmic sequestering of transcription factor;negative regulation of DNA-binding transcription factor activity;post-translational protein modification;regulation of epidermal cell differentiation;cellular response to interleukin-4
- Cellular component
- nucleoplasm;cytoplasm;endoplasmic reticulum;microtubule organizing center;cytosol;actin filament;midbody;Cul3-RING ubiquitin ligase complex
- Molecular function
- protein binding;transcription factor binding;protein homodimerization activity;disordered domain specific binding