Incidental Mutation 'R0071:Folr1'
ID17002
Institutional Source Beutler Lab
Gene Symbol Folr1
Ensembl Gene ENSMUSG00000001827
Gene Namefolate receptor 1 (adult)
SynonymsFolbp-1, folate receptor [a], Folbp1, folate-binding protein 1, FBP1
MMRRC Submission 038362-MU
Accession Numbers

Ncbi RefSeq: NM_001252552.1, NM_008034.3, NM_001252553.1, NM_001252554.1; MGI:95568

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #R0071 (G1)
Quality Score
Status Validated
Chromosome7
Chromosomal Location101858331-101870788 bp(-) (GRCm38)
Type of Mutationcritical splice donor site (2 bp from exon)
DNA Base Change (assembly) A to G at 101863923 bp
ZygosityHeterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000115077 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000106981] [ENSMUST00000106982] [ENSMUST00000106983] [ENSMUST00000106985] [ENSMUST00000106986] [ENSMUST00000123321] [ENSMUST00000123630] [ENSMUST00000124026] [ENSMUST00000126204] [ENSMUST00000134145] [ENSMUST00000140068] [ENSMUST00000140584] [ENSMUST00000150184] [ENSMUST00000151706] [ENSMUST00000155311] [ENSMUST00000209334]
Predicted Effect probably null
Transcript: ENSMUST00000001882
SMART Domains Protein: ENSMUSP00000001882
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 209 2.4e-61 PFAM
low complexity region 242 251 N/A INTRINSIC
Predicted Effect probably null
Transcript: ENSMUST00000106981
SMART Domains Protein: ENSMUSP00000102594
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 209 2.4e-61 PFAM
low complexity region 242 251 N/A INTRINSIC
Predicted Effect probably null
Transcript: ENSMUST00000106982
SMART Domains Protein: ENSMUSP00000102595
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 209 2.4e-61 PFAM
low complexity region 242 251 N/A INTRINSIC
Predicted Effect probably null
Transcript: ENSMUST00000106983
SMART Domains Protein: ENSMUSP00000102596
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 209 4.2e-68 PFAM
low complexity region 242 251 N/A INTRINSIC
Predicted Effect probably null
Transcript: ENSMUST00000106985
SMART Domains Protein: ENSMUSP00000102598
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 209 2.4e-61 PFAM
low complexity region 242 251 N/A INTRINSIC
Predicted Effect probably null
Transcript: ENSMUST00000106986
SMART Domains Protein: ENSMUSP00000102599
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 209 2.4e-61 PFAM
low complexity region 242 251 N/A INTRINSIC
Predicted Effect probably null
Transcript: ENSMUST00000123321
SMART Domains Protein: ENSMUSP00000114167
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
PDB:4LRH|H 21 54 6e-13 PDB
Predicted Effect silent
Transcript: ENSMUST00000123630
SMART Domains Protein: ENSMUSP00000121947
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
PDB:4LRH|H 21 54 4e-13 PDB
Predicted Effect probably benign
Transcript: ENSMUST00000124026
Predicted Effect noncoding transcript
Transcript: ENSMUST00000125298
Predicted Effect probably null
Transcript: ENSMUST00000126204
SMART Domains Protein: ENSMUSP00000117175
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 137 2.9e-38 PFAM
Predicted Effect probably null
Transcript: ENSMUST00000134145
SMART Domains Protein: ENSMUSP00000118547
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 104 2.6e-25 PFAM
Predicted Effect probably null
Transcript: ENSMUST00000140068
SMART Domains Protein: ENSMUSP00000114633
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 160 9.5e-47 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000140584
Predicted Effect probably benign
Transcript: ENSMUST00000150184
Predicted Effect probably null
Transcript: ENSMUST00000151706
SMART Domains Protein: ENSMUSP00000115077
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
Pfam:Folate_rec 34 157 8.9e-47 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000155311
SMART Domains Protein: ENSMUSP00000115360
Gene: ENSMUSG00000001827

DomainStartEndE-ValueType
signal peptide 1 19 N/A INTRINSIC
PDB:4LRH|H 21 53 3e-12 PDB
Predicted Effect probably benign
Transcript: ENSMUST00000209334
Meta Mutation Damage Score 0.9488 question?
Coding Region Coverage
  • 1x: 88.2%
  • 3x: 84.4%
  • 10x: 70.8%
  • 20x: 43.5%
Validation Efficiency 93% (94/101)
MGI Phenotype Strain: 2383986
Lethality: E8-E10
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]
PHENOTYPE: Embryos homozygous for a knock-out allele are growth retarded and malformed, show multiple developmental anomalies, including neural and craniofacial defects, and die by E10. Folate supplementation of pregnant dams reduces embryonic mortality and improves many of the adverse developmental effects. [provided by MGI curators]
Allele List at MGI

All alleles(359) : Targeted(3) Gene trapped(356)

Other mutations in this stock
Total: 51 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2900011O08Rik A G 16: 14,088,954 D11G probably damaging Het
Acrbp T C 6: 125,050,952 probably benign Het
AI481877 A G 4: 59,059,643 Y1006H possibly damaging Het
Amotl1 G A 9: 14,548,773 A890V probably benign Het
Aox3 T A 1: 58,171,891 C931* probably null Het
Apob T A 12: 8,002,111 V1184E probably damaging Het
Bbx C T 16: 50,280,392 E47K probably benign Het
Bccip A G 7: 133,714,231 D72G probably damaging Het
Bckdha A T 7: 25,630,443 probably null Het
Cald1 C T 6: 34,758,134 probably benign Het
Cdk11b T C 4: 155,649,423 probably benign Het
Cebpe G T 14: 54,710,604 R261S probably damaging Het
Cep95 C T 11: 106,790,728 probably benign Het
Chil1 T C 1: 134,185,279 Y150H probably benign Het
Chrnd T C 1: 87,192,837 probably benign Het
Cog2 T C 8: 124,548,668 probably benign Het
Coro7 A T 16: 4,670,527 L93Q probably damaging Het
Csmd3 T C 15: 47,596,821 T3525A probably benign Het
Fam227b T A 2: 126,124,074 N144Y probably benign Het
Fhod1 A T 8: 105,337,225 probably null Het
Glis3 C T 19: 28,263,855 probably benign Het
Golgb1 G A 16: 36,915,503 R1704Q probably benign Het
Helz2 T C 2: 181,236,407 Y866C probably damaging Het
Kcnma1 C T 14: 23,526,767 R236H probably damaging Het
Lct C T 1: 128,292,018 W1631* probably null Het
Limk1 G T 5: 134,661,391 Q104K probably benign Het
Ly75 T C 2: 60,321,819 K1130R probably benign Het
Mdm1 A G 10: 118,146,796 E112G probably damaging Het
Myo7a A T 7: 98,056,830 Y1836N probably damaging Het
Nsun7 A G 5: 66,264,045 Y118C probably benign Het
Olfr53 A T 7: 140,652,257 I93F probably benign Het
Olfr716 A G 7: 107,147,712 Y132C probably damaging Het
Osbpl11 T C 16: 33,214,338 probably benign Het
Pik3cb A T 9: 99,044,865 D886E probably benign Het
Pkhd1 T A 1: 20,201,344 Y2995F probably benign Het
Raver2 C T 4: 101,120,445 probably benign Het
Sec22c A G 9: 121,692,913 F44L probably damaging Het
Sephs1 A G 2: 4,899,560 T250A probably benign Het
Sobp A G 10: 43,157,997 L111P probably damaging Het
Sparcl1 G T 5: 104,085,841 Y547* probably null Het
Spata31d1b G A 13: 59,715,349 A104T probably benign Het
Spsb3 A G 17: 24,887,904 D184G probably damaging Het
Sptan1 A T 2: 30,003,342 K1148* probably null Het
Tdrd12 A G 7: 35,529,246 V17A possibly damaging Het
Tlr9 A G 9: 106,223,578 T23A probably benign Het
Tra2b A T 16: 22,254,401 probably benign Het
Tspan15 A G 10: 62,203,070 probably benign Het
Ttc41 A G 10: 86,736,846 N694S probably benign Het
Ube3b G A 5: 114,419,497 G1014D probably damaging Het
Unc5d A G 8: 28,719,826 V422A possibly damaging Het
Vmn2r80 C T 10: 79,171,732 T514I possibly damaging Het
Other mutations in Folr1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01916:Folr1 APN 7 101858740 missense probably benign 0.00
IGL02423:Folr1 APN 7 101858525 missense probably benign 0.00
R0071:Folr1 UTSW 7 101863923 critical splice donor site probably null
R1022:Folr1 UTSW 7 101858603 missense probably damaging 0.98
R1024:Folr1 UTSW 7 101858603 missense probably damaging 0.98
R1562:Folr1 UTSW 7 101858594 missense probably damaging 0.98
R2299:Folr1 UTSW 7 101863992 missense probably damaging 1.00
R3690:Folr1 UTSW 7 101858538 missense probably benign 0.06
R4746:Folr1 UTSW 7 101863977 missense probably damaging 1.00
R4747:Folr1 UTSW 7 101863977 missense probably damaging 1.00
R5319:Folr1 UTSW 7 101863977 missense probably damaging 1.00
R6243:Folr1 UTSW 7 101863965 missense probably damaging 1.00
R6275:Folr1 UTSW 7 101859535 missense probably damaging 0.99
R7284:Folr1 UTSW 7 101859470 missense possibly damaging 0.67
Protein Function and Prediction

Folr1 encodes the GPI-anchored folate receptor [alternatively, folate-binding protein (FBP)] (1). FOLR1 binds with high affinity to folic acid and other folic acid derivatives to mediate the delivery of 5’methyltetrahydrofolate to the interior of cells. Steinfeld et al. found that FOLR1 is the major human folate transporter across the blood-brain barrier and is essential for cerebral folate supply (2). Studies have shown that FOLR1 is critical for embryonic development (3). Disruption of both Folr1 alleles in mice leads to malformations and embryonic lethality at the time of neural tube closure (3). Studies have shown that, in response to folic acid, FOLR1 translocates to the nucleus and acts as a transcription factor (4). FOLR1 binds to Hes1 and Fgfr4, indicating that FOLR1 is involved in stem cell maintenance and skeletal muscle differentiation, respectively (4). Other putative Folr1 targets indicate that FOLR1 may also regulate developmental genes involved in myogenesis, skeletonogenesis, cell mobility, neural crest cell migration, cranial and cardiac neural crest formation, hair morphogenesis, oligodendrogenesis, spermatogenesis, melanogenesis, and epithelial to mesenchymal transformation (4). FOLR1 has been identified as a tumor antigen/biomarker (5).

Expression/Localization

Northern blot analysis revealed a 1.1-kb FOLR1 mRNA in human KB cells, placenta, thymic epithelium, and brain, but not in liver (6). Real-time PCR of human tissues detected significant FOLR1 expression in the kidney (2). Membrane-bound and soluble forms of FOLR1 have been found in kidney, placenta, serum, milk, and in several cell lines.

Background

Mutations in FOLR1 are linked to neurodegeneration due to cerebral folate transport deficiency [OMIM: 613068; (2;7)].

 

Folr1tm1Fnn/tm1Fnn; MGI: 2383986

involves: 129 * C57BL/6J

Homozygotes have a decreased level of folate in the plasma and colonic mucosa (8).

 

Folr1tm1Fnn/tm1Fnn; MGI: 2383986

involves: 129P2/OlaHsd * C57BL/6J

Embryos homozygous for a knock-out allele are growth retarded and malformed, show multiple developmental anomalies, including neural and craniofacial defects, and die by E10. Folate supplementation of pregnant dams reduces embryonic mortality and improves many of the adverse developmental effects (3).

References
Posted On2013-01-20
Science WriterAnne Murray