KLHL22

kelch like family member 22, the group of Kelch like|BTB domain containing

Basic information

Region (hg38): 22:20441519-20495844

Links

ENSG00000099910NCBI:84861OMIM:618020HGNC:25888Uniprot:Q53GT1AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHL22 gene.

  • 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
missense
59
clinvar
1
clinvar
60
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total 0 0 59 2 0
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KLHL22protein_codingprotein_codingENST00000328879 666643
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.4240.5761257360121257480.0000477
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.412674030.6620.00002634128
Missense in Polyphen65138.950.467781327
Synonymous0.1671751780.9840.00001261287
Loss of Function3.77627.20.2210.00000140276

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.0001770.000163
Finnish0.000.00
European (Non-Finnish)0.00007960.0000791
Middle Eastern0.0001770.000163
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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