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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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FOLR3
folate receptor gamma
Chromosome 11 · 11q13.4
NCBI Gene: 2352Ensembl: ENSG00000110203.11HGNC: HGNC:3795UniProt: P41439
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsignaling receptor activityfolic acid receptor activityfolic acid transportneurodegenerative diseaseAlzheimer diseaseParkinson diseasemultiple sclerosis
✦AI Summary

FOLR3 (folate receptor gamma) mediates cellular delivery of folate and reduced folic acid derivatives, with a secreted isoform that lacks folate-binding capacity 1. The protein functions as both a membrane-bound receptor and a secreted factor with distinct pathophysiological roles. Cellularly, FOLR3 enhances folic acid uptake and promotes cell growth in a folate-dependent manner 1. The secreted form of FOLR3 amplifies transforming growth factor-β (TGFβ) signaling in hepatic stellate cells through interaction with the serine protease HTRA1, driving extracellular matrix production and fibrosis progression in metabolic dysfunction-associated steatohepatitis (MASH) 2. FOLR3 expression correlates positively with fibrosis stage and is selectively elevated in MASH but absent in related metabolic disorders 2. Clinically, FOLR3 dysregulation associates with multiple diseases. Expression is downregulated in chr11 obstructive pulmonary disease monocyte/macrophages 3 and enriched in moderate-to-severe pediatric acute respiratory distress syndrome 4. FOLR3 is highly expressed in ovarian carcinoma compared to breast carcinoma and mesothelioma, supporting its utility as a therapeutic target 5. Blood FOLR3 hypomethylation specifically associates with lung squamous carcinoma diagnosis 6. Vitamin D supplementation upregulates FOLR3 expression, potentially improving COVID-19 outcomes through immunomodulation 7.

Sources cited
1
FOLR3 is secreted, enhances folic acid intake into cells, and protects against homocysteine-induced cytotoxicity
PMID: 32581311
2
Secreted FOLR3 amplifies TGFβ signaling in hepatic stellate cells and drives fibrosis in MASH
PMID: 37756380
3
FOLR3 is downregulated in monocyte/macrophages of COPD patients
PMID: 39810158
4
FOLR3 is enriched in moderate or severe pediatric acute respiratory distress syndrome
PMID: 37391405
5
FOLR3 mRNA is significantly higher in ovarian carcinoma compared to breast carcinoma and mesothelioma
PMID: 19454358
6
Blood FOLR3 hypomethylation associates with lung squamous carcinoma diagnosis with high diagnostic accuracy
PMID: 38273401
7
Vitamin D supplementation upregulates FOLR3 expression potentially through a negative VDRE element in FOLR3
PMID: 36192006
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.39Weak
Alzheimer diseaseOpen Targets
0.28Weak
Parkinson diseaseOpen Targets
0.28Weak
lysosomal storage diseaseOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.27Weak
neuroinflammatory disorderOpen Targets
0.22Weak
neoplasmOpen Targets
0.11Weak
thyroid cancerOpen Targets
0.07Suggestive
cancerOpen Targets
0.07Suggestive
lung adenocarcinomaOpen Targets
0.07Suggestive
urinary bladder carcinomaOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
prostate cancerOpen Targets
0.04Suggestive
chronic myelogenous leukemiaOpen Targets
0.04Suggestive
SepsisOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
acute myeloid leukemiaOpen Targets
0.03Suggestive
Crohn's diseaseOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
bladder transitional cell carcinomaOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FOLH1Protein interaction80%SLC25A32Shared pathway33%FOLR2Shared pathway20%SLC19A2Shared pathway20%SLC46A1Shared pathway17%FOLR1Shared pathway10%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
16%
Liver
1%
Brain
0%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
FOLR3FOLH1SLC25A32FOLR2SLC19A2SLC46A1FOLR1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P41439
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.76LoF Tolerant
pLIⓘ
0.35Tolerant
Observed/Expected LoF0.40 [0.23–0.76]
RankingsWhere FOLR3 stands among ~20K protein-coding genes
  • #13,419of 20,598
    Most Researched23
  • #6,031of 17,882
    Most Constrained (LOEUF)0.76
Genes detectedFOLR3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Single cell transcriptomics in blood of patients with chronic obstructive pulmonary disease.
PMID: 39810158
BMC Pulm Med · 2025
1.00
2
Secreted folate receptor γ drives fibrogenesis in metabolic dysfunction-associated steatohepatitis by amplifying TGFβ signaling in hepatic stellate cells.
PMID: 37756380
Sci Transl Med · 2023
0.90
3
Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome.
PMID: 37391405
Nat Commun · 2023
0.80
4
Landscape of Immune Cells Heterogeneity in Liver Transplantation by Single-Cell RNA Sequencing Analysis.
PMID: 35619708
Front Immunol · 2022
0.70
5
Plasma Homocysteine Concentration is Associated with the Expression Level of Folate Receptor 3.
PMID: 32581311
Sci Rep · 2020
0.60