KLHL10

kelch like family member 10, the group of Kelch like|BTB domain containing

Basic information

Region (hg38): 17:41835685-41848384

Links

ENSG00000161594 ∙ NCBI:317719 ∙ OMIM:608778 ∙ HGNC:18829 ∙ Uniprot:Q6JEL2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• male infertility with azoospermia or oligozoospermia due to single gene mutation (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 11	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary	17047026

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHL10 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL10 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				2	2	4
missense			17	3		20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					12	12
Total	0	0	17	5	14

Variants in KLHL10

This is a list of pathogenic ClinVar variants found in the KLHL10 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-41835888-G-C		not specified	Uncertain significance (Jan 08, 2024)
17-41837496-T-C			Benign (Nov 12, 2018)
17-41837519-G-A			Benign (Nov 12, 2018)
17-41837948-G-A			Uncertain significance (Jan 01, 2024)
17-41837952-C-T		not specified	Uncertain significance (Oct 27, 2022)
17-41837954-G-A		not specified	Uncertain significance (Apr 01, 2024)
17-41838005-G-A		not specified	Likely benign (Apr 07, 2023)
17-41838049-C-T		not specified	Likely benign (Jun 10, 2024)
17-41841604-C-A			Benign (Nov 12, 2018)
17-41841793-C-T			Benign (Jun 20, 2021)
17-41841851-A-G		not specified	Uncertain significance (May 25, 2022)
17-41841870-A-T		Non-obstructive azoospermia • KLHL10-related disorder	Uncertain significance (Jun 07, 2020)
17-41841889-C-T		Spermatogenic failure 11	Benign (Aug 19, 2021)
17-41841932-G-A			Uncertain significance (Feb 01, 2023)
17-41842061-T-C		not specified	Uncertain significance (Apr 18, 2024)
17-41842082-T-C		not specified	Uncertain significance (Apr 20, 2023)
17-41842091-G-A		not specified	Uncertain significance (Feb 22, 2023)
17-41842092-A-G		not specified	Uncertain significance (Feb 22, 2023)
17-41842210-G-C		not specified	Uncertain significance (May 17, 2023)
17-41842275-A-C		Spermatogenic failure 11	Benign/Likely benign (Mar 02, 2022)
17-41844867-G-A			Benign (Nov 12, 2018)
17-41845300-C-T		not specified	Uncertain significance (Jan 03, 2022)
17-41845328-T-C		Non-obstructive azoospermia • KLHL10-related disorder	Conflicting classifications of pathogenicity (Mar 01, 2023)
17-41845364-T-C		Spermatogenic failure 11	Uncertain significance (Aug 27, 2019)
17-41845378-G-A		Spermatogenic failure 11	Uncertain significance (Nov 01, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL10	protein_coding	protein_coding	ENST00000293303	5	12700

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.979	0.0215	124799	0	5	124804	0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.72	213	358	0.595	0.0000209	4081
Missense in Polyphen		35	112.21	0.31192		1229
Synonymous	-0.789	143	131	1.09	0.00000831	1130
Loss of Function	3.80	2	20.6	0.0972	0.00000104	267

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000935	0.0000935
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000177
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be a substrate-specific adapter of a CUL3-based E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins during spermatogenesis.
• Disease: DISEASE: Spermatogenic failure 11 (SPGF11) [MIM:615081]: An infertility disorder caused by spermatogenesis defects. It results in decreased sperm motility, concentration, and multiple sperm structural defects. Oligozoospermia is usually observed in SPGF11 patients. In addition to oligozoospermia, teratozoospermia and moderate asthenozoospermia is observed in some cases. {ECO:0000269|PubMed:17047026}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.327
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.517
• hipred: Y
• hipred_score: 0.825
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.200

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Klhl10
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: cell morphogenesis;spermatid development;male gonad development;fertilization;protein ubiquitination;male genitalia morphogenesis;homeostasis of number of cells within a tissue
• Cellular component: cytoplasm