KEAP1

kelch like ECH associated protein 1, the group of BTB domain containing|Kelch like

Basic information

Region (hg38): 19:10486124-10503558

Links

ENSG00000079999 ∙ NCBI:9817 ∙ OMIM:606016 ∙ HGNC:23177 ∙ Uniprot:Q14145 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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 ClinVar and linked to the KEAP1 gene.

• not provided (15 variants)
• Inborn genetic diseases (15 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.

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				7		7
missense			15	2		17
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	15	10	1

Variants in KEAP1

This is a list of pathogenic ClinVar variants found in the KEAP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-10486666-TCTG-T			Likely benign (Dec 31, 2019)
19-10486747-C-T		not specified	Uncertain significance (Oct 06, 2021)
19-10486819-C-A			not provided (-)
19-10486820-T-G			not provided (-)
19-10489190-A-T			not provided (-)
19-10489191-C-A			not provided (-)
19-10489261-C-G		not specified	Uncertain significance (Nov 18, 2022)
19-10489313-G-A			Likely benign (Dec 31, 2019)
19-10489655-G-A			Likely benign (Apr 02, 2018)
19-10489684-T-C		not specified	Uncertain significance (Aug 13, 2021)
19-10489686-C-T		not specified	Uncertain significance (Dec 28, 2023)
19-10489724-A-C		not specified	Uncertain significance (Jul 09, 2021)
19-10489756-C-T		not specified	Uncertain significance (Aug 04, 2023)
19-10489863-C-T			Benign (Dec 31, 2019)
19-10491583-A-G		not specified	Uncertain significance (Jun 23, 2023)
19-10491584-C-T		not specified	Uncertain significance (Mar 01, 2023)
19-10491677-T-TG		Lung cancer	Pathogenic (Jun 15, 2021)
19-10491680-G-T		not specified	Uncertain significance (Jan 04, 2022)
19-10491691-G-A			Likely benign (Dec 09, 2017)
19-10491750-G-A			Likely benign (Mar 01, 2023)
19-10491786-C-T			Likely benign (Jun 23, 2018)
19-10491791-C-T		not specified	Uncertain significance (Jan 06, 2023)
19-10491796-A-G			Likely benign (Aug 16, 2018)
19-10491910-G-A		not specified	Uncertain significance (Mar 20, 2023)
19-10492088-G-A		not specified	Uncertain significance (-)

GnomAD

Source: gnomAD

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: dbNSFP

• 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