The detailed entries of the Imprinted Gene Catalogue database were created by Benjamin Tycko, Columbia University, New York and are updated by Ian Morison


Detailed entry for Gene:



Human Chr7p11-p12
Mouse Chr11 (proximal)


OMIM    David Thomas' GRB site


Paternal allele is silent; maternal allele active in mice (Miyoshi N et al, 1998). In humans the data are more variable. There are several Meg1 splice variants, most of which are expressed from both alleles. However, in the fetal brain the beta/zeta, gamma1, gamma6, epsilon, and sigma isoforms were reported to be paternally expressed, whereas in fetal muscle the gamma1 isoform was maternally expressed (Blagitko N et al, 2000).

Gene Product:

SH2-domain and PH-domain-containing cytoplasmic adaptor protein involved in growth factor signaling (Ooi J et al, 1995).

Functional Data:

Data from transfected cells support a role for the Grb10 protein in modulating growth signals from numerous membrane receptors. These including those for insulin, insulin-like growth factor, vascular endothelial growth factor, and others - see, for example (Dey BR et al, 1996; Hansen H et al, 1996; He W et al, 1998; Morrione A, 2000; Moutoussamy S et al, 1998; Pandey A et al, 1995). Grb10 binds to the cytoplasmic domain of the activated receptors and has been reported to either inhibit or stimulate their tyrosine kinase activity - for example (Giorgetti-Peraldi S et al, 2001; Mounier C et al, 2001; Stein EG et al, 2001; Wang J et al, 1999).
Mice with maternal and paternal disomy for the chromosomal region containing Grb10 show growth retarded and overgrowth phenotypes, respectively (Cattanach BM et al, 1998), but it is not known whether Grb10 is causal in this phenotype. GRB10 is a candidate for causing or contributing to the growth retardation of Silver-Russell syndrome, which can be caused by maternal UPD7 (Kotzot D et al, 1995; Kotzot D, 1999) Some studies have found no mutations (Hitchins MP et al, 2001), but two mutations (or polymorphisms) were reported in one study (Yoshihashi H et al, 2000). Duplication of the region containing GRB10 was found in one patient (Monk et al., 2000), but another report of regional UPD7 in a case of SRS concluded that the critical region was on 7q, and that the 7p11-p13 region containing GRB10 was outside of this region (Hannula K et al, 2001).


Click here to search again.

Return to the Imprinted Gene Catalogue home page.