Folate receptor 1 (Folate receptor alpha, FOLR1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''FOLR1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The protein encoded by this gene is a member of the

folate receptor Folate receptors bind folate and reduced folic acid derivatives and mediates delivery of tetrahydrofolate to the interior of cells. It is then converted from monoglutamate to polyglutamate forms - such as 5-methyltetrahydrofolate - as only monog ...

(FOLR) family. Members of this family have a high affinity for

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

and for several reduced folic acid derivatives, and mediate delivery of

5-methyltetrahydrofolate Levomefolic acid (INN, also known as L-5-MTHF, L-methylfolate and L-5-methyltetrahydrofolate and (6''S'')-5-methyltetrahydrofolate, and (6''S'')-5-MTHF) is the primary biologically active form of folate used at the cellular level for DNA reproduc ...

to the interior of cells.

Functions

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. This gene is composed of 7

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

s; exons 1 through 4 encode the 5' UTR and exons 4 through 7 encode the

open reading frame In molecular biology, reading frames are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible reading frames ...

. Due to the presence of 2 promoters, multiple

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, often th ...

start sites, and

alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

sequence.

Clinical significance

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. 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

mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The area most commonly affected is the lining of the lungs and chest wall. Less commonly the lini ...

s (72-100% of cases),

triple-negative breast cancer Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification (i.e ...

(35-68% of cases) and epithelial

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

(76-89% of cases). Therefore, antibodies to FRa are being developed for use in targeted therapies, with one example being

farletuzumab Farletuzumab (MORAb-003) is a humanized monoclonal antibodies, monoclonal antibody of IgG1/κ which is being investigated for the treatment of ovarian cancer. This drug was developed by Morphotek, Inc. It is targeted at Folate receptor 1, folate ...

, in a phase III trial for

. Further, FRa-binding markers have been created in an attempt to visualise FRa-expressing tumors. In 2021, the fluorescent marker

pafolacianine Pafolacianine, sold under the brand name Cytalux, is an optical imaging agent used in fluorescence-guided surgery. Pafolacianine is a fluorescent medication that binds to folate receptor (FR)-expressing cells. The most common side effects ...

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, particularly

cerebral folate deficiency Cerebral may refer to: * Of or relating to the brain * Cerebrum, the largest and uppermost part of the brain * Cerebral cortex, the outer layer of the cerebrum * Retroflex consonant, also referred to as a cerebral consonant, a type of consonant so ...

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

and

autism spectrum disorder Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing di ...

. Recent studies have shown that these neurodevelopmental disorders can be treated with

folinic acid Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to ...

Figures

Functions

Clinical significance

Figures

See also

References

Further reading