FOLR1

Chr 11AR

folate receptor alpha

Also known as: FBP, FOLR, FR-alpha, FRalpha, NCFTD

NCBI Gene: 2348ENSG00000110195UniProt: P15328OMIM: 136430

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]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.651 OMIM phenotype
Clinical Summary— FOLR1
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Gene-Disease Validity (ClinGen)
neurodegenerative syndrome due to cerebral folate transport deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 120 VUS of 294 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — FOLR1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.65LOEUF
pLI 0.126
Z-score 2.48
OE 0.29 (0.14–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.67Z-score
OE missense 0.84 (0.72–0.98)
117 obs / 139.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.29 (0.14–0.65)
0≤0.351.4
Missense OE?0.84 (0.72–0.98)
0≤0.61.4
Synonymous OE?0.88
0≤1.21.6
LoF obs/exp: 4 / 14.0Missense obs/exp: 117 / 139.4Syn Z: 0.71

ClinVar Variant Classifications

294 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic14
VUS120
Likely Benign102
Benign12
Conflicting20
20
Pathogenic
14
Likely Pathogenic
120
VUS
102
Likely Benign
12
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
2
2
0
20
Likely Pathogenic
8
6
0
0
14
VUS
3
110
7
0
120
Likely Benign
0
4
39
59
102
Benign
0
0
11
1
12
Conflicting
—20
Total271225960288

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap FOLR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

FOLR1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients