FOLR1

Chr 11

folate receptor alpha

NCBI Gene: 2348ENSG00000110195UniProt: P15328

Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114, PubMed:8567728). Has high affinity for folate and folic acid analogs at neutral pH (PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114, PubMed:8567728). Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release (PubMed:8567728). Required for normal embryonic development and normal cell proliferation (By similarity)

Primary Disease Associations & Inheritance

UniProtNeurodegeneration due to cerebral folate transport deficiency
301
ClinVar variants
42
Pathogenic / LP
0.13
pLI score
4
Active trials
Clinical Summary— FOLR1
🧬
Gene-Disease Validity (ClinGen)
neurodegenerative syndrome due to cerebral folate transport deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 126 VUS of 301 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.65LOEUF
pLI 0.126
Z-score 2.48
OE 0.29 (0.14–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.67Z-score
OE missense 0.84 (0.72–0.98)
117 obs / 139.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.14–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.72–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 4 / 14.0Missense obs/exp: 117 / 139.4Syn Z: 0.71

ClinVar Variant Classifications

301 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic13
VUS126
Likely Benign102
Benign12
Conflicting19
29
Pathogenic
13
Likely Pathogenic
126
VUS
102
Likely Benign
12
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
2
20
0
29
Likely Pathogenic
5
5
3
0
13
VUS
1
111
14
0
126
Likely Benign
0
4
39
59
102
Benign
0
0
11
1
12
Conflicting
—19
Total131228760301

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FOLR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

FOLR1-related neurodegeneration due to cerebral folate transport deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — FOLR1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Folate Receptor Alpha-A Novel Approach to Cancer Therapy.
Gonzalez T et al.·Int J Mol Sci
2024Review
Therapeutic strategies targeting folate receptor α for ovarian cancer.
Mai J et al.·Front Immunol
2023Review
Cerebral Folate Deficiency Syndrome: Early Diagnosis, Intervention and Treatment Strategies.
Ramaekers VT et al.·Nutrients
2022Review
Hypomyelination caused by a novel homozygous pathogenic variant in FOLR1: complete clinical and radiological recovery with oral folinic acid therapy and review of the literature.
Potic A et al.·Orphanet J Rare Dis
2023Review
Optimizing efficacy and safety of T cell bispecific antibodies: the interdependence of CD3 and tumor antigen binder affinities in FOLR1 and CEACAM5 2 + 1 TCBs.
Abdelmotaleb O et al.·MAbs
2025
Folate Receptor Alpha in Advanced Epithelial Ovarian Cancer: Diagnostic Role and Therapeutic Implications of a Clinically Validated Biomarker.
Zannoni GF et al.·Int J Mol Sci
2025Review
Folate Receptor Immunohistochemical Staining and Gynecologic Tumors: Initial Experience With 216 Cases.
Lawson BC et al.·Int J Gynecol Pathol
2025Cohort
CBFA2T3-GLIS2 model of pediatric acute megakaryoblastic leukemia identifies FOLR1 as a CAR T cell target.
Le Q et al.·J Clin Invest
2022Functional
Analysis of real world FRα testing in ovarian, fallopian tube, and primary peritoneal cancers.
Previs RA et al.·Gynecol Oncol
2025
Cerebral folate deficiency.
Hyland K et al.·J Inherit Metab Dis
2010Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Advanced OsteosarcomaRecurrent OsteosarcomaRefractory Osteosarcoma

Genetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Refractory or Recurrent/Progressive Osteosarcoma, FIERCe Trial

RECRUITING
NCT07227571Phase PHASE1Fred Hutchinson Cancer CenterStarted 2026-01-16
FH FOLR1 ST CAR T-cellsLeukapheresisFludarabine
Ovary CancerPeritoneal CancerFallopian Tube Cancer

An Evaluation of Maintenance Therapy Combination Mirvetuximab Soravtansine and Olaparib

RECRUITING
NCT05887609Phase PHASE2University of Colorado, DenverStarted 2023-10-03
Mirvetuximab Soravtansine-gynxOlaparib
Ovarian CancerFallopian TubePrimary Peritoneal Cancer

Study of Carboplatin and Mirvetuximab Soravtansine in First-Line Treatment of Patients Receiving Neoadjuvant Chemotherapy With Advanced-Stage Ovarian, Fallopian Tube or Primary Peritoneal Cancer

RECRUITING
NCT04606914Phase PHASE2University of Alabama at BirminghamStarted 2021-05-27
mirvetuximab soravtansine (MIRV; IMGN853)
Recurrent Childhood Acute Myeloid LeukemiaRefractory Childhood Acute Myeloid Leukemia

FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for Treating Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia

RECRUITING
NCT06609928Phase PHASE1Fred Hutchinson Cancer CenterStarted 2025-02-24
FOLR1 CAR T-cellsBiospecimen CollectionBone Marrow Aspiration

External Resources

Links to major genomics databases and tools