GeneBe

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
  • PERCHING syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Perching syndrome (Crisponi/Cold-induced sweating syndrome 3)ARMusculoskeletalIn 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; Ophthalmologic1872134; 19520207; 20547956; 22084217; 27392078

ClinVar

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

  • not_provided (314 variants)
  • Inborn_genetic_diseases (29 variants)
  • PERCHING_syndrome (24 variants)
  • Retinitis_pigmentosa (19 variants)
  • Retinal_dystrophy (18 variants)
  • Retinitis_pigmentosa_42 (12 variants)
  • KLHL7-related_disorder (9 variants)
  • Cold-induced_sweating_syndrome_1 (4 variants)
  • Ulnar_deviation_of_the_wrist (3 variants)
  • Neurodevelopmental_delay (2 variants)
  • not_specified (2 variants)
  • Bohring-Opitz_syndrome (1 variants)
  • Bohring-Opitz-like_syndrome (1 variants)
  • Distal_arthrogryposis (1 variants)
  • Retinitis_Pigmentosa,_Dominant (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. These statistics are base on transcript: NM_001031710.3. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
106
clinvar
3
clinvar
 112
missense
5
clinvar
9
clinvar
142
clinvar
1
clinvar
 157
nonsense
8
clinvar
3
clinvar
3
clinvar
 14
start loss
0
frameshift
9
clinvar
6
clinvar
 15
splice donor/acceptor (+/-2bp)
6
clinvar
 6
Total 22 24 148 107 3

Highest pathogenic variant AF is 0.0000254333

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KLHL7protein_codingprotein_codingENST00000339077 1172181
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.00004561.001257130351257480.000139
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.911233200.3850.00001663872
Missense in Polyphen2987.7340.33054998
Synonymous0.8371011120.8990.000006201089
Loss of Function3.131332.10.4040.00000196357

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003290.000329
Ashkenazi Jewish0.00009920.0000992
East Asian0.00005440.0000544
Finnish0.0002770.000277
European (Non-Finnish)0.0001410.000141
Middle Eastern0.00005440.0000544
South Asian0.00009810.0000980
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Klhl7
Phenotype

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