KLHL25

kelch like family member 25, the group of BTB domain containing|Kelch like|MicroRNA protein coding host genes

Basic information

Region (hg38): 15:85759326-85794925

Links

ENSG00000183655

∙ NCBI:64410 ∙ OMIM:619893 ∙ HGNC:25732 ∙ Uniprot:Q9H0H3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHL25 gene.

not_specified (116 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL25 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022480.4. 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						0
missense			115 clinvar	1 clinvar		116
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	115	1	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL25	protein_coding	protein_coding	ENST00000337975	1	35708

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.59e-15	0.000966	125661	2	85	125748	0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.43	478	398	1.20	0.0000279	3855
Missense in Polyphen		236	197.33	1.196		1883
Synonymous	-1.63	208	180	1.15	0.0000137	1221
Loss of Function	-1.61	19	12.8	1.49	5.53e-7	155

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000548	0.000547
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000163	0.000163
Finnish	0.0000974	0.0000924
European (Non-Finnish)	0.000291	0.000290
Middle Eastern	0.000163	0.000163
South Asian	0.00114	0.00108
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for translational homeostasis. The BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination of hypophosphorylated EIF4EBP1 (4E-BP1): ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) probably serves as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. The BCR(KLHL25) complex does not target EIF4EBP1 (4E-BP1) when it is hyperphosphorylated or associated with eIF4E. {ECO:0000269|PubMed:22578813}.;
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: 0.502
rvis_EVS: -1.57
rvis_percentile_EVS: 3.19

Haploinsufficiency Scores

pHI: 0.222
hipred: N
hipred_score: 0.282
ghis: 0.540

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.852

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Klhl25
Phenotype: skeleton phenotype; craniofacial phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: regulation of translational initiation;ubiquitin-dependent protein catabolic process;protein ubiquitination;post-translational protein modification
Cellular component: cytoplasm;cytosol;Cul3-RING ubiquitin ligase complex
Molecular function