Folate receptor 1

Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia

Folate receptor 1

Folate receptor 1 (Folate receptor alpha, FOLR1) is a protein that in humans is encoded by the FOLR1 gene.[5][6]

Quick Facts FOLR1, Available structures ...
FOLR1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFOLR1, FBP, FOLR, Folate receptor 1, folate receptor 1 (adult), folate receptor alpha, FRalpha, NCFTD
External IDsOMIM: 136430; MGI: 95568; HomoloGene: 7322; GeneCards: FOLR1; OMA:FOLR1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_016730
NM_000802
NM_016724
NM_016725
NM_016729

NM_001252552
NM_001252553
NM_001252554
NM_008034

RefSeq (protein)

NP_000793
NP_057936
NP_057937
NP_057941

NP_001239481
NP_001239482
NP_001239483
NP_032060

Location (UCSC)Chr 11: 72.19 – 72.2 MbChr 7: 101.51 – 101.52 Mb
PubMed search[3][4]
Wikidata
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The protein encoded by this gene is a member of the folate receptor (FOLR) family. Members of this family have a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells.

Functions

Summarize
Perspective

This receptor is responsible for binding to folic acid and its derivatives, which becomes crucial during fetal development. By adding folate supplementation during pregnancy, neural tube defects in the fetus are prevented. Folate derivatives are necessary for important metabolic processes such as DNA, protein and lipid methylation. More importantly, folate plays a major role in DNA replication and cell division, which are common characteristics of rapid growth. Even though it is unclear how folate affects neural tube formation, scientists are certain that without appropriate folate levels, neural tube defects can develop through human and mice studies. Neural tube defects refer to the improper development of the neural tube by not being sealed correctly. This results in exencephaly or spina bifida, both nervous system abnormalities.[7]

This gene is composed of 7 exons; exons 1 through 4 encode the 5' UTR and exons 4 through 7 encode the open reading frame. Due to the presence of 2 promoters, multiple transcription start sites, and alternative splicing of exons, several transcript variants are derived from this gene. These variants differ in the lengths of 5' and 3' UTR, but they encode an identical amino acid sequence.[6]

Clinical significance

Summarize
Perspective
Thumb
Schematic model of FRα used as a target in cancer therapy.[8]

FRα, due to its high expression in some tumors, is an attractive therapeutic target for the development of novel anti-cancer agents in order to limit toxic side-effects on off-target tissues.[8]

FRa can be overexpressed by a number of epithelial-derived tumors including ovarian, breast, renal, lung, colorectal, and brain. According to a review published in 2020, elevated expression of FRa was noted in mesotheliomas (72-100% of cases), triple-negative breast cancer (35-68% of cases) and epithelial ovarian cancer (76-89% of cases).[9]

Therefore, antibodies to FRa are being developed for use in targeted therapies, with one example being farletuzumab, in a phase III trial for ovarian cancer. Further, FRa-binding markers have been created in an attempt to visualise FRa-expressing tumors. In 2021, the fluorescent marker pafolacianine was approved for identification of malignant lesions during surgeries. Mirvetuximab soravtansine-gynx/Elahere is an ADC that was approved in 2022 by FDA for the treatment of platinum-resistant epithelial ovarian carcinoma.

Autoantibodies to the FRA have been linked to neurodevelopmental diseases,[10] particularly cerebral folate deficiency[11] schizophrenia[11] and autism spectrum disorder.[12] Recent studies have shown that these neurodevelopmental disorders can be treated with folinic acid.[12][13]

Figures

Thumb
Crystallographic structure of FRα protein. The folate is in green, the folate binding site is colored in orange. A Cys66Tyr substitution position induced by a pathogenic variant is represented in red while the disulfide bond between Cys66 and Cys109 is in dark blue. Figure from Mafi et al., 2020[14]
Thumb
Identification of ovarian cancer metastases located on the intestine and mesentery using fluorescence imaging of the folate receptor alpha-binding marker EC17. From Tummers et al., 2016.[15]

See also

References

Further reading

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