FOLR3

Chr 11

folate receptor gamma

Also known as: FR-G, FR-gamma, FRgamma, gamma-hFR

NCBI Gene: 2352 ENSG00000110203 UniProt: P41439 OMIM: 602469

The protein binds folate and reduced folic acid derivatives and mediates cellular delivery of 5-methyltetrahydrofolate. Mutations cause autosomal recessive neurodegeneration due to cerebral folate deficiency, presenting with developmental regression, seizures, and movement disorders typically in early childhood. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the folate receptor (FOLR) family of proteins, which 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. Expression of this gene may be elevated in ovarian and primary peritoneal carcinoma. This gene is present in a gene cluster on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.10

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.015

Z-score 1.39

OE 0.48 (0.23–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.00Z-score

OE missense 1.00 (0.89–1.13)

176 obs / 175.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.48 (0.23–1.10)

0≤0.351.4

Missense OE?1.00 (0.89–1.13)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 4 / 8.3Missense obs/exp: 176 / 175.8Syn Z: -0.67

Background carrier burden — how many people carry a rare variant somewhere in FOLR3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

324 rare PASS variants

Rare truncating (LoF)

1 in 520

49 rare PASS variants

Rare synonymous (reference)

1 in 200

135 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FOLR3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 630
South Asian	~43k	1 in 110	1 in 1,800
Remaining (unassigned)	~30k	1 in 78	1 in 910
European (Finnish)	~27k	1 in 420	1 in 2,700
Admixed American	~22k	1 in 140	1 in 1,900
African / African American	~21k	1 in 100	1 in 780
East Asian	~20k	1 in 110	1 in 1,200
Ashkenazi Jewish	~13k	1 in 1,900	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 96	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓