KLHL2

kelch like family member 2, the group of BTB domain containing|Kelch like

Basic information

Region (hg38): 4:165207561-165323156

Links

ENSG00000109466 ∙ NCBI:11275 ∙ OMIM:605774 ∙ HGNC:6353 ∙ Uniprot:O95198 ∙ 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 KLHL2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL2 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				1		1
missense			14	1		15
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	14	3	0

Variants in KLHL2

This is a list of pathogenic ClinVar variants found in the KLHL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-165219947-G-T		not specified	Uncertain significance (Apr 07, 2022)
4-165219985-C-T			Likely benign (Sep 01, 2022)
4-165228832-A-C		not specified	Uncertain significance (Sep 29, 2023)
4-165238819-G-A		not specified	Uncertain significance (May 30, 2024)
4-165238877-A-T		not specified	Uncertain significance (Oct 30, 2023)
4-165263300-G-A		not specified	Uncertain significance (Jan 25, 2023)
4-165297684-C-T		not specified	Uncertain significance (Mar 07, 2024)
4-165299516-G-A		not specified	Uncertain significance (May 28, 2023)
4-165299538-G-A		not specified	Uncertain significance (Sep 20, 2023)
4-165299619-T-A		not specified	Uncertain significance (Jun 26, 2023)
4-165299626-C-G			Likely benign (Mar 01, 2023)
4-165305644-A-G		not specified	Uncertain significance (Jun 07, 2024)
4-165305681-G-A		not specified	Uncertain significance (Feb 06, 2023)
4-165310621-G-A		not specified	Uncertain significance (Sep 04, 2024)
4-165310649-A-G		not specified	Uncertain significance (Dec 06, 2023)
4-165311490-A-G		not specified	Uncertain significance (Oct 25, 2023)
4-165313309-G-C		not specified	Uncertain significance (Dec 14, 2021)
4-165314072-T-A		not specified	Uncertain significance (Sep 22, 2022)
4-165314106-G-A		not specified	Uncertain significance (Dec 01, 2022)
4-165314121-G-A		not specified	Likely benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL2	protein_coding	protein_coding	ENST00000514860	15	115539

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000145	125743	0	4	125747	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.89	134	334	0.401	0.0000175	3909
Missense in Polyphen		17	111.09	0.15302		1314
Synonymous	0.765	105	115	0.909	0.00000606	1106
Loss of Function	5.09	2	34.0	0.0588	0.00000171	417

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000141	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation (By similarity). Responsible for degradative ubiquitination of the WNK kinases WNK1, WNK3 and WNK4. Plays a role in the reorganization of the actin cytoskeleton. Promotes growth of cell projections in oligodendrocyte precursors. {ECO:0000250, ECO:0000269|PubMed:15715669, ECO:0000269|PubMed:23838290}.
• Pathway: 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 (Consensus)

Recessive Scores

• pRec: 0.165

Intolerance Scores

• loftool: 0.304
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.76

Haploinsufficiency Scores

• pHI: 0.171
• hipred: Y
• hipred_score: 0.825
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.645

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Klhl2

Gene ontology

• Biological process: protein ubiquitination;post-translational protein modification
• Cellular component: ruffle;cytoplasm;cytosol;actin cytoskeleton;lamellipodium;Cul3-RING ubiquitin ligase complex
• Molecular function: actin binding;protein binding;identical protein binding