GFRA2
protein-codingGDNF family receptor alpha 2
Gene summary
Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This encoded protein acts preferentially as a receptor for NTN compared to its other family member, GDNF family receptor alpha 1. This gene is a candidate gene for RET-associated diseases. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~122.0 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 GFRA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001495.5. 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 | 2 | |||
| missense | 65 | 1 | 1 | 67 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 66 | 1 | 2 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001486.4 | 9 | MANE Select | |
| Ensembl | ENSP00000428518.1 | 9 | MANE Select | |
| RefSeq | NP_001158510.1 | 8 | Standard | |
| RefSeq | NP_001158511.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Developmental Biology
- Signal Transduction
- RAF/MAP kinase cascade
- MAPK1/MAPK3 signaling
- MAPK family signaling cascades
Biological Process
- MAPK cascade
- transmembrane receptor protein tyrosine kinase signaling pathway
- nervous system development
- axon guidance
- glial cell-derived neurotrophic factor receptor signaling pathway
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- glial cell-derived neurotrophic factor receptor activity
Cellular Component
- plasma membrane
- external side of plasma membrane
- extrinsic component of membrane
- anchored component of membrane
- receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000524240
- Coding exons
- 9
- Length
- 121955
- Individuals with no LoFs
- 124646
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 124652
- p
- 0.0000241
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.141 | 191 | 197 | 0.972 | 0.0000129 | 3011 |
| Missense (PolyPhen) | 49 | 68.737 | 0.71287 | 1014 | ||
| Synonymous | -1.44 | 100 | 83.3 | 1.20 | 0.00000568 | 914 |
| Loss of Function | 2.36 | 4 | 13.3 | 0.302 | 7.27e-7 | 237 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000059 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000028 | 0.000027 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor.;
Recessive Scores
- pRec
- 0.145
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.865
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | Medium | High |