KLHL24

kelch like family member 24, the group of BTB domain containing|Kelch like

Basic information

Region (hg38): 3:183635610-183684519

Links

ENSG00000114796NCBI:54800OMIM:611295HGNC:25947Uniprot:Q6TFL4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • epidermolysis bullosa simplex 6, generalized, with scarring and hair loss (Strong), mode of inheritance: AD
  • epidermolysis bullosa simplex 6, generalized, with scarring and hair loss (Moderate), mode of inheritance: AD
  • epidermolysis bullosa simplex 6, generalized, with scarring and hair loss (Strong), mode of inheritance: AD
  • epidermolysis bullosa simplex 6, generalized, with scarring and hair loss (Supportive), mode of inheritance: AD
  • epidermolysis bullosa simplex 6, generalized, with scarring and hair loss (Strong), mode of inheritance: AD
  • cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies (Strong), mode of inheritance: AR
  • cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies (Limited), mode of inheritance: AR
  • hypertrophic cardiomyopathy (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Epidermolysis bullosa simplex 6, generalized intermediate, with or without cardiomyopathy; Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodiesAD/ARCardiovascularThe condition can involve severe, early-onset cardiomyopathy, and awareness may allow early interventions and management; heart transplant has been describedCardiovascular; Dermatologic27798626; 27889062; 29779254; 30226531; 30579426; 30715372; 31649980

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHL24 gene.

  • Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss (5 variants)
  • Epidermolysis bullosa simplex, Koebner type (4 variants)
  • not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL24 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
6
clinvar
5
clinvar
11
missense
27
clinvar
1
clinvar
1
clinvar
29
nonsense
0
start loss
6
clinvar
6
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
1
clinvar
16
clinvar
17
Total 6 0 27 8 22

Variants in KLHL24

This is a list of pathogenic ClinVar variants found in the KLHL24 region.

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

Position Type Phenotype Significance ClinVar
3-183650149-T-C Benign (May 12, 2021)1222273
3-183650217-G-A Benign (May 12, 2021)1288159
3-183650357-A-G Epidermolysis bullosa simplex, Koebner type • Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss • KLHL24-related disorder Pathogenic (Nov 02, 2023)264648
3-183650357-A-T Pathogenic (May 17, 2017)432253
3-183650358-T-C Epidermolysis bullosa simplex, Koebner type • Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss Pathogenic (Aug 01, 2016)370042
3-183650359-G-A Epidermolysis bullosa simplex, Koebner type • Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss Pathogenic (Sep 01, 2016)264646
3-183650359-G-C Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss Pathogenic (Jul 01, 2019)931095
3-183650359-G-T Epidermolysis bullosa simplex, Koebner type • Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss Pathogenic (Sep 01, 2016)264647
3-183650364-T-C Inborn genetic diseases Uncertain significance (Feb 21, 2024)3115572
3-183650369-T-C Benign (Sep 11, 2023)1599275
3-183650375-C-T Inborn genetic diseases Uncertain significance (May 30, 2023)2515916
3-183650376-G-A Inborn genetic diseases Uncertain significance (Jul 19, 2023)2613084
3-183650406-G-A Inborn genetic diseases Uncertain significance (Feb 05, 2024)3115568
3-183650409-A-G KLHL24-related disorder Uncertain significance (May 15, 2024)3354026
3-183650427-G-A Inborn genetic diseases Uncertain significance (Mar 14, 2023)2496145
3-183650428-A-T Benign (Jan 29, 2024)1302789
3-183650503-C-T Likely benign (Mar 01, 2023)2919801
3-183650504-G-A Inborn genetic diseases Uncertain significance (Dec 28, 2023)3115566
3-183650535-G-A Inborn genetic diseases Uncertain significance (Jun 22, 2023)2605299
3-183650544-G-A Inborn genetic diseases Uncertain significance (May 03, 2023)2522468
3-183650723-T-C Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss Uncertain significance (Mar 26, 2024)3065341
3-183650739-A-G Inborn genetic diseases • Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies Uncertain significance (Oct 08, 2024)3115567
3-183650798-A-G Uncertain significance (Jun 13, 2017)450020
3-183650938-T-A Benign (Apr 22, 2022)1600773
3-183650946-A-C Benign (Oct 17, 2022)1601787

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KLHL24protein_codingprotein_codingENST00000454652 648910
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.001670.9971257320161257480.0000636
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.881903400.5600.00001873939
Missense in Polyphen46120.690.381141414
Synonymous0.05371171180.9940.000006231157
Loss of Function2.86924.20.3730.00000134306

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002510.000243
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00006160.0000615
Middle Eastern0.000.00
South Asian0.00009820.0000980
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity (PubMed:27889062). As part of the BCR(KLHL24) E3 ubiquitin ligase complex, mediates ubiquitination of KRT14 and controls its levels during keratinocytes differentiation (PubMed:27798626). Specifically reduces kainate receptor-mediated currents in hippocampal neurons, most probably by modulating channel properties (By similarity). {ECO:0000250|UniProtKB:Q56A24, ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:27889062}.;
Disease
DISEASE: Epidermolysis bullosa simplex, generalized, with scarring and hair loss (EBSSH) [MIM:617294]: A form of epidermolysis bullosa, a group of mechano-bullous disorders characterized by structural skin fragility, recurrent blister formation and erosion of the skin and mucous membranes occurring spontaneously or after mild trauma. Epidermolysis bullosa simplex is characterized by intraepidermal tissue separation that occurs within the basal keratinocytes at the bottom layer of epidermis. EBSSH is an autosomal dominant epidermolysis bullosa simplex, presenting at birth with extensive skin defects on the extremities, leaving behind hypopigmentation and atrophy with a whirled pattern. Cutaneous fragility and generalized blistering persist during childhood and decrease in adulthood. Adult patients have dyspigmentation and atrophy of the skin, scars, follicular atrophoderma, sparse body hair, progressive diffuse alopecia of the scalp, diffuse palmoplantar keratoderma, and nail changes. {ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:27889062}. Note=The disease is caused by mutations affecting the gene represented in this entry. Gain-of-function mutations that lead to excessive ubiquitination and degradation of KRT14 result in compromised mechanical integrity of basal keratinocytes. Under this pathological condition, trivial mechanical stress can induce blister formation at the basal layer of skin. {ECO:0000269|PubMed:27798626}.;

Recessive Scores

pRec
0.113

Intolerance Scores

loftool
0.391
rvis_EVS
-0.78
rvis_percentile_EVS
12.77

Haploinsufficiency Scores

pHI
0.214
hipred
Y
hipred_score
0.822
ghis
0.613

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.578

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Klhl24
Phenotype

Gene ontology

Biological process
protein ubiquitination;intermediate filament organization;protein autoubiquitination;regulation of kainate selective glutamate receptor activity
Cellular component
cytoplasm;adherens junction;desmosome;axon;Cul3-RING ubiquitin ligase complex;perikaryon
Molecular function
protein binding