KLHL24
Basic information
Region (hg38): 3:183635610-183684519
Links
Phenotypes
GenCC
Source:
- 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:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Epidermolysis bullosa simplex 6, generalized intermediate, with or without cardiomyopathy; Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies | AD/AR | Cardiovascular | The condition can involve severe, early-onset cardiomyopathy, and awareness may allow early interventions and management; heart transplant has been described | Cardiovascular; Dermatologic | 27798626; 27889062; 29779254; 30226531; 30579426; 30715372; 31649980 |
ClinVar
This is a list of variants' phenotypes submitted to
- 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 | 11 | |||||
missense | 27 | 29 | ||||
nonsense | 0 | |||||
start loss | 6 | |||||
frameshift | 0 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 0 | |||||
non coding | 16 | 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) | |||
3-183650217-G-A | Benign (May 12, 2021) | |||
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) | ||
3-183650357-A-T | Pathogenic (May 17, 2017) | |||
3-183650358-T-C | Epidermolysis bullosa simplex, Koebner type • Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss | Pathogenic (Aug 01, 2016) | ||
3-183650359-G-A | Epidermolysis bullosa simplex, Koebner type • Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss | Pathogenic (Sep 01, 2016) | ||
3-183650359-G-C | Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss | Pathogenic (Jul 01, 2019) | ||
3-183650359-G-T | Epidermolysis bullosa simplex, Koebner type • Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss | Pathogenic (Sep 01, 2016) | ||
3-183650364-T-C | Inborn genetic diseases | Uncertain significance (Feb 21, 2024) | ||
3-183650369-T-C | Benign (Sep 11, 2023) | |||
3-183650375-C-T | Inborn genetic diseases | Uncertain significance (May 30, 2023) | ||
3-183650376-G-A | Inborn genetic diseases | Uncertain significance (Jul 19, 2023) | ||
3-183650406-G-A | Inborn genetic diseases | Uncertain significance (Feb 05, 2024) | ||
3-183650409-A-G | KLHL24-related disorder | Uncertain significance (May 15, 2024) | ||
3-183650427-G-A | Inborn genetic diseases | Uncertain significance (Mar 14, 2023) | ||
3-183650428-A-T | Benign (Jan 29, 2024) | |||
3-183650503-C-T | Likely benign (Mar 01, 2023) | |||
3-183650504-G-A | Inborn genetic diseases | Uncertain significance (Dec 28, 2023) | ||
3-183650535-G-A | Inborn genetic diseases | Uncertain significance (Jun 22, 2023) | ||
3-183650544-G-A | Inborn genetic diseases | Uncertain significance (May 03, 2023) | ||
3-183650723-T-C | Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss | Uncertain significance (Mar 26, 2024) | ||
3-183650739-A-G | Inborn genetic diseases • Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies | Uncertain significance (Oct 08, 2024) | ||
3-183650798-A-G | Uncertain significance (Jun 13, 2017) | |||
3-183650938-T-A | Benign (Apr 22, 2022) | |||
3-183650946-A-C | Benign (Oct 17, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
KLHL24 | protein_coding | protein_coding | ENST00000454652 | 6 | 48910 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.00167 | 0.997 | 125732 | 0 | 16 | 125748 | 0.0000636 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 2.88 | 190 | 340 | 0.560 | 0.0000187 | 3939 |
Missense in Polyphen | 46 | 120.69 | 0.38114 | 1414 | ||
Synonymous | 0.0537 | 117 | 118 | 0.994 | 0.00000623 | 1157 |
Loss of Function | 2.86 | 9 | 24.2 | 0.373 | 0.00000134 | 306 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000251 | 0.000243 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00 | 0.00 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.0000616 | 0.0000615 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.0000982 | 0.0000980 |
Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- 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
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
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