GFRA2

Chr 8

GDNF family receptor alpha 2

ENSG00000168546 UniProt: O00451 OMIM: 601956

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.

OMIM ResearchSummary from RefSeq, UniProt

Receptor for neurturin (NRTN), a growth factor that supports the survival of sympathetic neurons (PubMed:10829012, PubMed:29414779, PubMed:31535977, PubMed:9182803). NRTN-binding leads to autophosphorylation and activation of the RET receptor (PubMed:31535977). Also able to mediate GDNF signaling through the RET tyrosine kinase receptor (PubMed:9182803)

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.69

LOEUF

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Mechanism

Some data sources returned errors (1)

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