KLHL3
Basic information
Region (hg38): 5:137617500-137736089
Links
Phenotypes
GenCC
Source:
- pseudohypoaldosteronism type 2D (Strong), mode of inheritance: AD
- pseudohypoaldosteronism type 2D (Supportive), mode of inheritance: AD
- pseudohypoaldosteronism type 2D (Strong), mode of inheritance: AR
- pseudohypoaldosteronism type 2D (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Pseudohypoaldosteronism, type IID | AD/AR | Renal | Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective | Renal | 22266938 |
ClinVar
This is a list of variants' phenotypes submitted to
- Pseudohypoaldosteronism_type_2D (114 variants)
- not_provided (99 variants)
- Inborn_genetic_diseases (57 variants)
- Pseudohypoaldosteronism_type_2A (26 variants)
- Autosomal_dominant_pseudohypoaldosteronism_type_1 (11 variants)
- not_specified (8 variants)
- KLHL3-related_disorder (8 variants)
- Cerebral_palsy (1 variants)
- Renal_tubulopathies (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017415.3. 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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 27 | 35 | ||||
missense | 15 | 140 | 164 | |||
nonsense | 6 | |||||
start loss | 0 | |||||
frameshift | 2 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
Total | 22 | 11 | 144 | 27 | 4 |
Highest pathogenic variant AF is 0.0000154899
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
KLHL3 | protein_coding | protein_coding | ENST00000309755 | 15 | 118591 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.945 | 0.0552 | 125740 | 0 | 8 | 125748 | 0.0000318 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 2.99 | 206 | 367 | 0.561 | 0.0000224 | 3862 |
Missense in Polyphen | 61 | 148.48 | 0.41082 | 1420 | ||
Synonymous | 0.751 | 134 | 146 | 0.921 | 0.00000957 | 1118 |
Loss of Function | 4.35 | 5 | 31.2 | 0.160 | 0.00000141 | 366 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.0000578 | 0.0000578 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.00000902 | 0.00000879 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.000131 | 0.000131 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (PubMed:14528312, PubMed:22406640, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney (By similarity). {ECO:0000250|UniProtKB:E0CZ16, ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:22406640, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:23665031}.;
- Disease
- DISEASE: Pseudohypoaldosteronism 2D (PHA2D) [MIM:614495]: A disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. PHA2D inheritance is autosomal dominant or recessive. {ECO:0000269|PubMed:22266938, ECO:0000269|PubMed:22406640, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:23665031, ECO:0000269|PubMed:26435498, ECO:0000269|PubMed:27026694, ECO:0000269|PubMed:27780982, ECO:0000269|PubMed:28052936, ECO:0000269|PubMed:28511177}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- 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
(Consensus)
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- loftool
- 0.199
- rvis_EVS
- -0.87
- rvis_percentile_EVS
- 10.65
Haploinsufficiency Scores
- pHI
- 0.288
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.648
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.818
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Klhl3
- Phenotype
- hematopoietic system phenotype; 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); renal/urinary system phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- ubiquitin-dependent protein catabolic process;protein ubiquitination;post-translational protein modification;ion homeostasis;selective autophagy;renal sodium ion absorption;protein K48-linked ubiquitination;distal tubule morphogenesis
- Cellular component
- cytosol;cytoskeleton;Cul3-RING ubiquitin ligase complex
- Molecular function
- actin binding;structural molecule activity;protein binding