KLHL12

kelch like family member 12, the group of BTB domain containing|Kelch like

Basic information

Region (hg38): 1:202891116-202928636

Links

ENSG00000117153

∙ NCBI:59349 ∙ OMIM:614522 ∙ HGNC:19360 ∙ Uniprot:Q53G59 ∙ 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 KLHL12 gene.

not_specified (40 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021633.4. 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			40 clinvar			40
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	40	0	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL12	protein_coding	protein_coding	ENST00000367261	11	37537

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0303	0.970	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.83	186	331	0.562	0.0000181	3716
Missense in Polyphen		48	116.67	0.41142		1284
Synonymous	0.374	111	116	0.956	0.00000596	1109
Loss of Function	3.45	8	27.6	0.290	0.00000145	321

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000324	0.000323
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is also involved in neural crest specification: in response to cytosolic calcium increase, interacts with the heterodimer formed with PEF1 and PDCD6/ALG-2, leading to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export (PubMed:27716508). As part of the BCR(KLHL12) complex, also acts as a negative regulator of the Wnt signaling pathway by mediating ubiquitination and subsequent proteolysis of DVL3 (PubMed:16547521). The BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and PEF1, without leading to degradation of these proteins (PubMed:18303015, PubMed:20100572, PubMed:27716508). {ECO:0000269|PubMed:16547521, ECO:0000269|PubMed:18303015, ECO:0000269|PubMed:20100572, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27716508}.;
Pathway: Signaling by WNT;Signal Transduction;Degradation of DVL;TCF dependent signaling in response to WNT;Canonical Wnt signaling pathway (Consensus)

Recessive Scores

pRec: 0.124

Intolerance Scores

loftool: 0.390
rvis_EVS: -0.45
rvis_percentile_EVS: 24

Haploinsufficiency Scores

pHI: 0.251
hipred: Y
hipred_score: 0.756
ghis: 0.691

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Klhl12
Phenotype

Gene ontology

Biological process: protein monoubiquitination;endoplasmic reticulum to Golgi vesicle-mediated transport;neural crest formation;neural crest cell development;Wnt signaling pathway;COPII vesicle coating;negative regulation of canonical Wnt signaling pathway
Cellular component: Golgi membrane;microtubule organizing center;cytosol;COPII vesicle coat;COPII-coated ER to Golgi transport vesicle;Cul3-RING ubiquitin ligase complex;intracellular membrane-bounded organelle
Molecular function: protein binding;identical protein binding