KLHL22
kelch like family member 22, the group of Kelch like|BTB domain containing
Basic information
Region (hg38): 22:20441519-20495844
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (60 variants)
- not_provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL22 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032775.4. 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 | 59 | 60 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 59 | 2 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KLHL22 | protein_coding | protein_coding | ENST00000328879 | 6 | 66643 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.424 | 0.576 | 125736 | 0 | 12 | 125748 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.41 | 267 | 403 | 0.662 | 0.0000263 | 4128 |
| Missense in Polyphen | 65 | 138.95 | 0.46778 | 1327 | ||
| Synonymous | 0.167 | 175 | 178 | 0.984 | 0.0000126 | 1287 |
| Loss of Function | 3.77 | 6 | 27.2 | 0.221 | 0.00000140 | 276 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000177 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000796 | 0.0000791 |
| Middle Eastern | 0.000177 | 0.000163 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for chromosome alignment and localization of PLK1 at kinetochores. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. Monoubiquitination of PLK1 does not lead to PLK1 degradation (PubMed:19995937, PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex- mediated inhibition of the TORC1 pathway. It is therefore an amino acid-dependent activator within the amino acid-sensing branch of the TORC1 pathway, indirectly regulating different cellular processes including cell growth and autophagy (PubMed:29769719). {ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:29769719}.;
- Disease
- DISEASE: Note=Defects in KLHL22 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.;
- 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
- 0.112
Intolerance Scores
- loftool
- 0.159
- rvis_EVS
- -1.2
- rvis_percentile_EVS
- 5.76
Haploinsufficiency Scores
- pHI
- 0.526
- hipred
- Y
- hipred_score
- 0.851
- ghis
- 0.663
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Klhl22
- Phenotype
Gene ontology
- Biological process
- mitotic sister chromatid segregation;protein monoubiquitination;mitotic spindle assembly checkpoint;negative regulation of autophagy;positive regulation of cell growth;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;cell division;cellular response to leucine;positive regulation of TORC1 signaling
- Cellular component
- nucleus;cytoplasm;lysosome;centrosome;polar microtubule;cytosol;Cul3-RING ubiquitin ligase complex;mitotic spindle
- Molecular function
- protein binding;14-3-3 protein binding