KLHL8

kelch like family member 8, the group of Kelch like|BTB domain containing

Basic information

Region (hg38): 4:87160102-87240314

Links

ENSG00000145332 ∙ NCBI:57563 ∙ OMIM:611967 ∙ HGNC:18644 ∙ Uniprot:Q9P2G9 ∙ 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 KLHL8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL8 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						0
missense			23			23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	23	0	0

Variants in KLHL8

This is a list of pathogenic ClinVar variants found in the KLHL8 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-87163953-T-C		not specified	Uncertain significance (Dec 14, 2023)
4-87164025-C-T		not specified	Uncertain significance (Jan 23, 2023)
4-87164028-C-T		not specified	Uncertain significance (Feb 16, 2023)
4-87164040-C-T		not specified	Uncertain significance (Aug 13, 2021)
4-87164047-C-T		not specified	Uncertain significance (Jun 10, 2024)
4-87170219-C-A		not specified	Uncertain significance (Jan 09, 2024)
4-87170220-C-T		not specified	Uncertain significance (Sep 22, 2022)
4-87170237-T-C		not specified	Uncertain significance (Aug 22, 2023)
4-87170461-A-G		not specified	Uncertain significance (Nov 17, 2023)
4-87170550-G-C		not specified	Uncertain significance (Oct 05, 2023)
4-87170551-T-A		not specified	Uncertain significance (Jun 22, 2023)
4-87176845-G-A		not specified	Uncertain significance (Jul 12, 2022)
4-87178492-C-A		not specified	Uncertain significance (Apr 27, 2023)
4-87178532-G-C		not specified	Uncertain significance (Jul 20, 2022)
4-87178609-A-G		not specified	Uncertain significance (Apr 18, 2023)
4-87183319-T-C		not specified	Uncertain significance (Dec 06, 2021)
4-87183334-T-C		not specified	Uncertain significance (Aug 17, 2022)
4-87183355-A-G		not specified	Uncertain significance (Apr 18, 2023)
4-87185316-C-T		not specified	Uncertain significance (Apr 13, 2022)
4-87185457-T-C		not specified	Uncertain significance (Dec 02, 2022)
4-87185670-C-T		not specified	Uncertain significance (Jul 06, 2021)
4-87185699-G-A		not specified	Uncertain significance (Jan 26, 2022)
4-87195439-C-A		not specified	Uncertain significance (Oct 05, 2023)
4-87195532-G-A		not specified	Uncertain significance (Oct 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL8	protein_coding	protein_coding	ENST00000273963	9	80212

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000312	0.997	125677	0	69	125746	0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.23	222	337	0.659	0.0000166	4091
Missense in Polyphen		76	140.88	0.53947		1648
Synonymous	1.01	102	116	0.880	0.00000569	1184
Loss of Function	2.63	14	29.4	0.476	0.00000177	332

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000754	0.000753
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000165	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000284	0.000281
Middle Eastern	0.000165	0.000163
South Asian	0.000299	0.000294
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for The BCR(KLHL8) ubiquitin ligase complex mediates ubiquitination and degradation of RAPSN. {ECO:0000269|PubMed:19158078}.

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.596
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.12

Haploinsufficiency Scores

• pHI: 0.118
• hipred: Y
• hipred_score: 0.575
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.846

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Klhl8
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;protein ubiquitination
• Cellular component: nucleoplasm;Cul3-RING ubiquitin ligase complex