Disease relevance of GFRA4

• We postulated that mutations of GFRA4 contribute to MEN 2 in the absence of RET mutations or modify the RET mutation phenotype [1].
• A model for GFR alpha 4 function and a potential modifying role in multiple endocrine neoplasia 2 [1].

High impact information on GFRA4

• PSPN, but not other GDNF family ligands, promotes the survival of cultured sympathetic neurons microinjected with GFRA4 [2].
• We identified different splice forms of human GFRA4 mRNA encoding for two glycosylphosphatidylinositol-linked and one putative soluble isoform that were predominantly expressed in the thyroid gland [2].
• Our data suggest a model of wild-type GFR alpha 4 isoform expression that includes both activating and inhibiting co-receptors for RET [1].
• The second was a 7 bp insertion, which results in a change in reading frame for all three GFR alpha 4 isoforms [1].
• One of these was a single-base substitution upstream of the GFR alpha 4 coding region, where it may alter gene expression [1].

Biological context of GFRA4

• We screened patients with MEN 2 or MEN 2-like phenotypes, with and without RET mutations, for variants of GFRA4 [1].

Other interactions of GFRA4

• This would cause a relative shift in membrane bound and soluble forms of GFR alpha 4, which would significantly alter the formation of RET signalling complexes [1].

References