GFRA2
Chr 8GDNF family receptor alpha 2
Also known as: GDNFRB, NRTNR-ALPHA, NTNRA, RETL2, TRNR2
The protein is a GPI-linked cell surface receptor that binds neurturin and GDNF to activate the RET tyrosine kinase receptor, supporting survival of sympathetic neurons. GFRA2 mutations cause congenital central hypoventilation syndrome and Hirschsprung disease through autosomal dominant inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.69), and these conditions affect the autonomic nervous system with onset in the neonatal period.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
ClinVar Variant Classifications
161 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 77 | 0 | 77 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 61 | 8 | 0 | 69 |
Likely Benign | 0 | 1 | 1 | 0 | 2 |
Benign | 0 | 1 | 0 | 1 | 2 |
| Total | 0 | 63 | 89 | 1 | 153 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GFRA2 · 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools