FOLR2
protein-codingfolate receptor beta
Gene summary
The protein encoded by this gene is a member of the folate receptor (FOLR) family, and these genes exist in a cluster on chromosome 11. Members of this gene family have a high affinity for folic acid and for several reduced folic acid derivatives, and they mediate delivery of 5-methyltetrahydrofolate to the interior of cells. This protein has a 68% and 79% sequence homology with the FOLR1 and FOLR3 proteins, respectively. Although this protein was originally thought to be specific to placenta, it can also exist in other tissues, and it may play a role in the transport of methotrexate in synovial macrophages in rheumatoid arthritis patients. Multiple transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FOLR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000803.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 33 | 2 | 2 | 37 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 34 | 3 | 2 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000794.3 | 4 | MANE Select | |
| Ensembl | ENSP00000298223.6 | 4 | MANE Select | |
| RefSeq | NP_001107006.1 | 4 | Standard | |
| RefSeq | NP_001107007.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Folate Metabolism
- Post-translational modification: synthesis of GPI-anchored proteins
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- monocyte chemotaxis
- receptor-mediated endocytosis
- inflammatory response
- cell adhesion
- fusion of sperm to egg plasma membrane involved in single fertilization
Molecular Function
- folic acid binding
- drug binding
- signaling receptor activity
- methotrexate binding
- folic acid receptor activity
Cellular Component
- extracellular region
- plasma membrane
- cell surface
- anchored component of external side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000298223
- Coding exons
- 4
- Length
- 5350
- Individuals with no LoFs
- 125633
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 26
- Defined
- 125660
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.123 | 145 | 149 | 0.972 | 0.00000817 | 1700 |
| Missense (PolyPhen) | 46 | 43.161 | 1.0658 | 536 | ||
| Synonymous | 0.194 | 52 | 53.8 | 0.966 | 0.00000287 | 452 |
| Loss of Function | 0.556 | 9 | 11.0 | 0.819 | 4.69e-7 | 121 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00060 | 0.00050 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release. {ECO:0000269|PubMed:23934049, ECO:0000269|PubMed:2605182, ECO:0000269|PubMed:4066659}.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.568
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.209
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |