KLHL22

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

Basic information

Region (hg38): 22:20441518-20495844

Links

ENSG00000099910 ∙ NCBI:84861 ∙ OMIM:618020 ∙ HGNC:25888 ∙ Uniprot:Q53GT1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (17 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.

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						0
missense			17			17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	0	0

Variants in KLHL22

This is a list of pathogenic ClinVar variants found in the KLHL22 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-20442311-C-T		not specified	Uncertain significance (Dec 28, 2022)
22-20442312-G-A		not specified	Uncertain significance (Aug 07, 2023)
22-20442349-G-T		not specified	Uncertain significance (Aug 10, 2021)
22-20446523-C-T		not specified	Uncertain significance (Sep 17, 2021)
22-20446537-C-T		not specified	Uncertain significance (Sep 16, 2021)
22-20457882-T-C		not specified	Uncertain significance (Feb 01, 2023)
22-20464919-C-T		not specified	Uncertain significance (Dec 27, 2022)
22-20464924-T-A		not specified	Uncertain significance (Feb 28, 2024)
22-20464927-T-C		not specified	Uncertain significance (Dec 27, 2023)
22-20464957-C-T		not specified	Uncertain significance (May 01, 2022)
22-20464958-G-A		not specified	Uncertain significance (Mar 31, 2023)
22-20465035-G-C		not specified	Uncertain significance (Jan 16, 2024)
22-20465072-C-T		not specified	Uncertain significance (Nov 15, 2021)
22-20465137-C-A		not specified	Uncertain significance (Feb 15, 2023)
22-20465153-C-T		not specified	Uncertain significance (Feb 15, 2023)
22-20465255-T-G		not specified	Uncertain significance (May 15, 2023)
22-20465260-G-T		not specified	Uncertain significance (Dec 26, 2023)
22-20465359-C-T		not specified	Uncertain significance (Jun 07, 2023)
22-20465543-G-A		not specified	Uncertain significance (Apr 26, 2023)
22-20471495-A-G		not specified	Uncertain significance (Oct 13, 2023)
22-20471498-C-T		not specified	Uncertain significance (Oct 13, 2023)
22-20489028-C-G		not specified	Uncertain significance (Jan 18, 2022)
22-20489201-T-C		not specified	Uncertain significance (Jun 21, 2023)

GnomAD

Source: gnomAD

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: 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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Klhl22

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