Incidental Mutation 'P0016:Klb'
ID7619
Institutional Source Beutler Lab
Gene Symbol Klb
Ensembl Gene ENSMUSG00000029195
Gene Nameklotho beta
SynonymsbetaKlotho
MMRRC Submission 038269-MU
Accession Numbers

Genbank: NM_031180.2; Ensembl: ENSMUST00000031096;

MGI:1932466

Is this an essential gene? Possibly essential (E-score: 0.561) question?
Stock #P0016 (G1)
Quality Score
Status Validated
Chromosome5
Chromosomal Location65348314-65384007 bp(+) (GRCm38)
Type of Mutationnonsense
DNA Base Change (assembly) G to A at 65379923 bp
ZygosityHeterozygous
Amino Acid Change Tryptophan to Stop codon at position 865 (W865*)
Ref Sequence ENSEMBL: ENSMUSP00000031096 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000031096] [ENSMUST00000205084]
Predicted Effect probably null
Transcript: ENSMUST00000031096
AA Change: W865*
SMART Domains Protein: ENSMUSP00000031096
Gene: ENSMUSG00000029195
AA Change: W865*

DomainStartEndE-ValueType
Pfam:Glyco_hydro_1 77 385 8.8e-96 PFAM
Pfam:Glyco_hydro_1 374 506 1.7e-31 PFAM
Pfam:Glyco_hydro_1 515 965 6.3e-80 PFAM
transmembrane domain 995 1017 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000205084
SMART Domains Protein: ENSMUSP00000145091
Gene: ENSMUSG00000029195

DomainStartEndE-ValueType
Pfam:Glyco_hydro_1 77 360 8.6e-94 PFAM
Meta Mutation Damage Score 0.712 question?
Coding Region Coverage
  • 1x: 85.6%
  • 3x: 81.0%
  • 10x: 66.8%
  • 20x: 50.1%
Validation Efficiency 96% (97/101)
MGI Phenotype Strain: 3587748
PHENOTYPE: Homozygous null mice display increased bile acid synthesis and excretion, resistance to gallstone formation, and slightly decreased body weight. Mice homozygous for a knock-out allele or a conditional allele activated in adipose tissue exhibit resistanceto FGF21-induced metabolic disruptions. [provided by MGI curators]
Allele List at MGI

All alleles(5) : Targeted(2) Gene trapped(3)

Other mutations in this stock
Total: 18 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700123K08Rik A T 5: 138,562,938 L154* probably null Het
4930432E11Rik T C 7: 29,563,112 noncoding transcript Het
Arap3 T A 18: 37,984,348 T892S probably benign Het
Ctnnd2 G A 15: 30,966,938 V987I probably benign Het
Dennd6b T C 15: 89,186,977 I351V probably benign Het
Kif27 G A 13: 58,303,452 Q1021* probably null Het
Mbd1 C T 18: 74,274,538 R130* probably null Het
Mroh7 T A 4: 106,707,857 probably null Het
Myo16 C T 8: 10,400,596 probably benign Het
Rbm22 T A 18: 60,570,770 probably benign Het
Rnaseh2a C G 8: 84,959,800 D206H probably damaging Het
Slain1 A G 14: 103,685,674 T187A probably benign Het
Slamf6 A G 1: 171,936,501 T154A probably damaging Het
Traip A G 9: 107,968,656 D316G possibly damaging Het
Ttn T C 2: 76,811,183 D5196G probably damaging Het
Ubr5 C T 15: 38,000,578 V1569M probably damaging Het
Zfp750 T A 11: 121,513,978 K24* probably null Het
Zfp799 T C 17: 32,819,357 E645G possibly damaging Het
Other mutations in Klb
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00425:Klb APN 5 65372374 missense possibly damaging 0.90
IGL00821:Klb APN 5 65372149 missense probably damaging 1.00
IGL01082:Klb APN 5 65375940 missense possibly damaging 0.71
IGL01637:Klb APN 5 65375679 critical splice acceptor site probably null
IGL02098:Klb APN 5 65379885 missense probably benign 0.21
IGL03113:Klb APN 5 65383470 missense probably benign 0.00
1mM(1):Klb UTSW 5 65348650 missense probably damaging 1.00
R0268:Klb UTSW 5 65348837 missense probably benign 0.02
R0383:Klb UTSW 5 65372499 intron probably null
R0676:Klb UTSW 5 65379055 missense probably damaging 1.00
R0735:Klb UTSW 5 65379727 missense probably benign
R0972:Klb UTSW 5 65348746 missense possibly damaging 0.70
R1051:Klb UTSW 5 65379327 missense probably damaging 1.00
R1168:Klb UTSW 5 65378974 missense probably damaging 1.00
R1372:Klb UTSW 5 65348746 missense possibly damaging 0.70
R1403:Klb UTSW 5 65348746 missense possibly damaging 0.70
R1403:Klb UTSW 5 65348746 missense possibly damaging 0.70
R1446:Klb UTSW 5 65348995 missense probably damaging 1.00
R1696:Klb UTSW 5 65348746 missense possibly damaging 0.70
R1743:Klb UTSW 5 65375861 missense probably damaging 0.99
R1801:Klb UTSW 5 65349235 missense probably null 0.90
R1804:Klb UTSW 5 65379853 missense probably damaging 1.00
R1848:Klb UTSW 5 65348837 missense probably benign 0.02
R1967:Klb UTSW 5 65372074 missense probably damaging 0.98
R3420:Klb UTSW 5 65372142 missense probably damaging 1.00
R4397:Klb UTSW 5 65380039 missense probably damaging 1.00
R4490:Klb UTSW 5 65375794 missense probably benign 0.02
R4491:Klb UTSW 5 65375794 missense probably benign 0.02
R4547:Klb UTSW 5 65379928 missense probably benign 0.00
R4878:Klb UTSW 5 65348490 missense probably damaging 0.99
R5269:Klb UTSW 5 65348797 missense probably damaging 1.00
R5418:Klb UTSW 5 65383470 missense probably benign 0.00
R5453:Klb UTSW 5 65383385 missense probably benign 0.08
R5541:Klb UTSW 5 65379234 missense probably benign 0.27
R5672:Klb UTSW 5 65379949 missense possibly damaging 0.82
R5841:Klb UTSW 5 65379324 nonsense probably null
R6088:Klb UTSW 5 65349013 missense probably benign 0.07
R6807:Klb UTSW 5 65379534 missense probably damaging 1.00
R6955:Klb UTSW 5 65379088 nonsense probably null
R7068:Klb UTSW 5 65379340 missense probably damaging 1.00
R7284:Klb UTSW 5 65383478 missense probably benign 0.01
R7322:Klb UTSW 5 65383364 missense probably benign 0.44
R7346:Klb UTSW 5 65348631 nonsense probably null
R7366:Klb UTSW 5 65372431 missense probably damaging 1.00
Protein Function and Prediction

The Klb gene encodes a 1043 amino acid single-pass type III membrane protein that contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis.Beta-Klotho is a member of the Klotho family of proteins and functions as a cofactor in FGF21 signaling in the process of glucose and lipid uptake in adipocytes (1). Klb contains an N-terminal signal sequence, followed by 2 tandemly repeated glycosidase-like domains (residues 77-506 and 515-965), a C-terminal transmembrane domain, and a short cytoplasmic tail. The protein is unlikely to have glycosidase activity as it lacks 2 key glutamates in the predicted active centers of the glycosidase-like domains (Uniprot Q99N32).

Expression/Localization

Northern blot analysis showed that Klb is predominantly expressed in liver and pancreas, with lower levels in skin and weak expression in stomach, skeletal muscle, small intestine, and lung. In mouse embryos, Klb expression became detectable at day 11 and increased in intensity as development progressed. In situ hybridization of mouse embryos revealed strong Klb expression in yolk sac, gut, brown and white adipose tissue, liver, and pancreas (2).

Background

Klbtm1Yin/tm1Yin; MGI:3587748

involves: C57BL/6 * CBA

Homozygous null mice are viable, fertile, and appeared grossly normal, but display increased bile acid synthesis and excretion, resistance to gallstone formation, and slightly decreased body weight (3).

References
Posted On2012-10-05
Science WriterAnne Murray