KLHL7

kelch like family member 7, the group of Kelch like|BTB domain containing

Basic information

Region (hg38): 7:23105758-23177914

Links

ENSG00000122550 ∙ NCBI:55975 ∙ OMIM:611119 ∙ HGNC:15646 ∙ Uniprot:Q8IXQ5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 42 (Moderate), mode of inheritance: AD
• PERCHING syndrome (Moderate), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• cold-induced sweating syndrome (Supportive), mode of inheritance: AR
• PERCHING syndrome (Definitive), mode of inheritance: AR
• retinitis pigmentosa 42 (Strong), mode of inheritance: AD
• retinitis pigmentosa 42 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Perching syndrome (Crisponi/Cold-induced sweating syndrome 3)	AR	Musculoskeletal	In the neonatal/early childhood period, the condition can be lethal unless advanced care is instituted; Later, it has been described that cold-induced sweating was alleviated by medical treatment (eg, with clonidine)	Musculoskeletal; Neurologic; Ophthalmologic	1872134; 19520207; 20547956; 22084217; 27392078

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHL7 gene.

• not provided (11 variants)
• PERCHING syndrome (4 variants)
• Retinitis pigmentosa 42 (2 variants)
• Neurodevelopmental delay (2 variants)
• Bohring-Opitz syndrome (1 variants)
• not specified (1 variants)
• Retinitis pigmentosa (1 variants)
• Inborn genetic diseases (1 variants)
• Retinal dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL7 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	87	4	93
missense	2	6	110			118
nonsense	8	2	2			12
start loss						0
frameshift	7	4	1			12
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		6				6
splice region		1	7	14	1	23
non coding		1	17	34	7	59
Total	17	20	133	121	11

Highest pathogenic variant AF is 0.00000658

Variants in KLHL7

This is a list of pathogenic ClinVar variants found in the KLHL7 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-23105792-G-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
7-23105796-G-C		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
7-23105812-T-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-23105821-C-T		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
7-23105882-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
7-23105989-G-A		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
7-23106011-A-G		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
7-23106030-G-A			Uncertain significance (Jun 30, 2023)
7-23106036-T-G			Uncertain significance (Jun 06, 2023)
7-23106040-G-T			Uncertain significance (May 06, 2022)
7-23106041-G-A			Likely benign (Nov 01, 2021)
7-23106042-G-A			Uncertain significance (Nov 01, 2022)
7-23106052-G-A			Uncertain significance (Apr 28, 2023)
7-23106054-A-G			Uncertain significance (Nov 27, 2023)
7-23106059-G-A			Likely benign (May 27, 2023)
7-23106077-A-G			Likely benign (Dec 20, 2019)
7-23106078-C-T			Uncertain significance (Apr 03, 2023)
7-23106079-T-C			Uncertain significance (Sep 30, 2023)
7-23106081-G-C			Uncertain significance (May 23, 2023)
7-23106095-A-G			Likely benign (Sep 04, 2019)
7-23106107-G-A			Likely benign (Aug 26, 2021)
7-23106109-C-T			Uncertain significance (Aug 04, 2023)
7-23106116-C-T			Likely benign (Aug 09, 2022)
7-23106120-G-T			Uncertain significance (Jul 05, 2022)
7-23106123-G-A			Uncertain significance (Apr 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL7	protein_coding	protein_coding	ENST00000339077	11	72181

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000456	1.00	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.91	123	320	0.385	0.0000166	3872
Missense in Polyphen		29	87.734	0.33054		998
Synonymous	0.837	101	112	0.899	0.00000620	1089
Loss of Function	3.13	13	32.1	0.404	0.00000196	357

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000329	0.000329
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000981	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex. The BCR(KLHL7) complex acts by mediating ubiquitination and subsequent degradation of substrate proteins. Probably mediates 'Lys-48'-linked ubiquitination. {ECO:0000269|PubMed:21828050}.
• Disease: DISEASE: Retinitis pigmentosa 42 (RP42) [MIM:612943]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:19520207, ECO:0000269|PubMed:20547956, ECO:0000269|PubMed:21828050, ECO:0000269|PubMed:22084217}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.646
• rvis_EVS: -0.76
• rvis_percentile_EVS: 13.33

Haploinsufficiency Scores

• pHI: 0.330
• hipred: Y
• hipred_score: 0.639
• ghis: 0.648

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.296

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Klhl7

Gene ontology

• Biological process: protein ubiquitination
• Cellular component: nucleus;nucleoplasm;nucleolus;cytosol;plasma membrane;Cul3-RING ubiquitin ligase complex;perinuclear region of cytoplasm
• Molecular function: protein binding;identical protein binding;protein homodimerization activity