KLHL20
kelch like family member 20, the group of Kelch like|BTB domain containing
Basic information
Region (hg38): 1:173714941-173786692
Links
Phenotypes
GenCC
Source:
- complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
- neurodevelopmental disorder (Strong), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (35 variants)
- not_provided (18 variants)
- KLHL20-related_disorder (2 variants)
- See_cases (2 variants)
- Prostate_cancer (1 variants)
- Neurodevelopmental_disorder (1 variants)
- Seizure (1 variants)
- Global_developmental_delay (1 variants)
- Intellectual_disability (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL20 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014458.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 48 | 53 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 4 | 50 | 1 | 1 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KLHL20 | protein_coding | protein_coding | ENST00000209884 | 11 | 71761 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00941 | 0.991 | 125714 | 0 | 31 | 125745 | 0.000123 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.61 | 168 | 361 | 0.465 | 0.0000203 | 3967 |
| Missense in Polyphen | 41 | 165.35 | 0.24796 | 1826 | ||
| Synonymous | -0.0246 | 122 | 122 | 1.00 | 0.00000621 | 1209 |
| Loss of Function | 3.73 | 10 | 33.2 | 0.301 | 0.00000206 | 348 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000277 | 0.000275 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000663 | 0.000653 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.0000708 | 0.0000703 |
| Middle Eastern | 0.000663 | 0.000653 |
| South Asian | 0.0000656 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis (PubMed:20389280). The BCR(KLHL20) E3 ubiquitin ligase complex also specifically mediates 'Lys-33'- linked ubiquitination (PubMed:24768539). Involved in anterograde Golgi to endosome transport by mediating 'Lys-33'-linked ubiquitination of CORO7, promoting interaction between CORO7 and EPS15, thereby facilitating actin polymerization and post-Golgi trafficking (PubMed:24768539). Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. The BCR(KLHL20) E3 ubiquitin ligase complex acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11 (PubMed:21670212). In case of tumor, the BCR(KLHL20) E3 ubiquitin ligase complex is involved in tumor hypoxia: following hypoxia, the BCR(KLHL20)complex mediates ubiquitination and degradation of PML, potentiating HIF-1 signaling and cancer progression (PubMed:21840486). {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:17395875, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:24768539}.;
- Pathway
- Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation;E-cadherin signaling in the nascent adherens junction
(Consensus)
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- loftool
- 0.443
- rvis_EVS
- -0.38
- rvis_percentile_EVS
- 27.69
Haploinsufficiency Scores
- pHI
- 0.203
- hipred
- Y
- hipred_score
- 0.580
- ghis
- 0.666
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.809
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Klhl20
- Phenotype
- reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- Golgi to endosome transport;cytoskeleton organization;protein transport;protein ubiquitination;response to interferon-alpha;negative regulation of apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;protein K33-linked ubiquitination
- Cellular component
- cytoplasm;Golgi apparatus;trans-Golgi network;cytosol;actin cytoskeleton;PML body;axon;dendrite;Cul3-RING ubiquitin ligase complex;perinuclear region of cytoplasm
- Molecular function
- actin binding;ubiquitin-protein transferase activity;protein binding;interferon-gamma binding