KLB

klotho beta, the group of MicroRNA protein coding host genes|Glycoside hydrolase family 1

Basic information

Region (hg38): 4:39406929-39451533

Links

ENSG00000134962 ∙ NCBI:152831 ∙ OMIM:611135 ∙ HGNC:15527 ∙ Uniprot:Q86Z14 ∙ 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 KLB gene.

• not provided (60 variants)
• Inborn genetic diseases (44 variants)
• Martsolf syndrome 1 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLB 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				16	8	24
missense			54	10	10	74
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1	1	2
non coding				1		1
Total	0	0	56	27	18

Variants in KLB

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

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

Position	Type	Phenotype	Significance	ClinVar
4-39406966-C-T		not specified	Uncertain significance (Jan 04, 2022)
4-39406975-C-A		KLB-related disorder	Benign/Likely benign (Jan 14, 2024)
4-39407008-A-G		not specified	Uncertain significance (Apr 07, 2022)
4-39407023-G-A			Uncertain significance (Jul 17, 2023)
4-39407033-T-C			Likely benign (Apr 14, 2023)
4-39407038-T-C			Uncertain significance (Dec 09, 2023)
4-39407045-C-T			Likely benign (Jul 18, 2022)
4-39407050-GA-AC			Uncertain significance (Aug 02, 2023)
4-39407057-A-T		not specified	Uncertain significance (Sep 25, 2023)
4-39407061-T-C		not specified	Uncertain significance (Aug 17, 2021)
4-39407067-A-G			Uncertain significance (Oct 03, 2023)
4-39407079-C-T			Likely benign (Dec 01, 2023)
4-39407115-G-A		KLB-related disorder	Likely benign (May 31, 2022)
4-39407142-C-G			Benign (Dec 09, 2023)
4-39407155-C-T		not specified	Uncertain significance (Jul 12, 2023)
4-39407182-A-G			Uncertain significance (Sep 25, 2022)
4-39407292-C-T		not specified	Uncertain significance (Sep 16, 2021)
4-39407369-C-G			Benign (Jul 06, 2023)
4-39407394-T-C		not specified	Uncertain significance (Jun 21, 2023)
4-39407397-C-G			Uncertain significance (Apr 02, 2023)
4-39407413-G-T		not specified	Uncertain significance (Dec 21, 2022)
4-39407442-A-G			Benign (Dec 26, 2023)
4-39407446-T-C		KLB-related disorder	Benign/Likely benign (Sep 26, 2023)
4-39407454-G-A		Amenorrhea	Uncertain significance (Mar 08, 2021)
4-39407476-G-A		not specified	Conflicting classifications of pathogenicity (Apr 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLB	protein_coding	protein_coding	ENST00000257408	5	44684

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0364	0.964	125636	0	112	125748	0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.88	477	608	0.785	0.0000343	6833
Missense in Polyphen		136	237.34	0.57302		2823
Synonymous	0.351	251	258	0.972	0.0000164	2069
Loss of Function	4.62	12	45.7	0.263	0.00000270	451

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000568	0.000551
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000327	0.000326
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000450	0.000448
Middle Eastern	0.000327	0.000326
South Asian	0.00132	0.00131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of FGFR1 and FGFR4 to bind FGF21 (By similarity). {ECO:0000250}.
• Pathway: Thermogenesis - Homo sapiens (human);PI-3K cascade:FGFR4;Disease;betaKlotho-mediated ligand binding;FGFR4 ligand binding and activation;Signal Transduction;FRS-mediated FGFR4 signaling;SHC-mediated cascade:FGFR4;Downstream signaling of activated FGFR4;Negative regulation of FGFR4 signaling;Signaling by FGFR4;Signaling by FGFR;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Diseases of signal transduction;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);FGF signaling pathway;Phospholipase C-mediated cascade; FGFR4 (Consensus)

Recessive Scores

• pRec: 0.0983

Intolerance Scores

• loftool: 0.618
• rvis_EVS: 0.34
• rvis_percentile_EVS: 73.71

Haploinsufficiency Scores

• pHI: 0.222
• hipred: Y
• hipred_score: 0.621
• ghis: 0.416

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.219

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Klb
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; skeleton phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: MAPK cascade;carbohydrate metabolic process;positive regulation of cell population proliferation;fibroblast growth factor receptor signaling pathway;phosphatidylinositol-3-phosphate biosynthetic process;phosphatidylinositol phosphorylation;positive regulation of protein kinase B signaling;positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: hydrolase activity, hydrolyzing O-glycosyl compounds;Ras guanyl-nucleotide exchange factor activity;fibroblast growth factor receptor binding;protein binding;1-phosphatidylinositol-3-kinase activity;fibroblast growth factor binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity