AGGF1 gene

The AGGF1 gene (AGGF1 stands for: Angiogenic Factor With G-Patch And FHA Domains 1) is a protein-coding gene localized on chromosome 5q13.3. Pseudogenes of this gene are found on chromosomes 3, 4, 10 and 16.

The AGGF1 gene encodes an angiogenic factor of the same name that promotes the proliferation of endothelial cells. The protein is able to bind to endothelial cells and promote cell proliferation, suggesting that it may have an autocrine effect.

Mutations in this gene are associated with Klippel-Trénaunay syndrome.

Diseases associated with AGGF1 include:

• non-syndromic syndactyly

and

• Klippel-Trénaunaysyndrome. Aggf1 is the first gene identified for Klippel-Trénaunay syndrome (KTS). The encoded angiogenic factor is important for physiological angiogenesis as well as for pathological tumor angiogenesis. Mechanistically, AGGF1 promotes angiogenesis by activating the catalytic p110α subunit and the regulatory p85α subunit of PI3K, leading to activation of AKT, GSK3β and p70S6K. AKT activation is significantly reduced in heterozygous KO mice and isolated KO-ECs, which can be restored by exogenous AGGF1.

AGGF1 is the first gene to be identified for Klippel-Trénaunay syndrome (KTS). The encoded angiogenic factor is important for physiological angiogenesis as well as for pathological tumor angiogenesis. Mechanistically, AGGF1 promotes angiogenesis by activating the catalytic p110α subunit and the regulatory p85α subunit of PI3K, leading to activation of AKT, GSK3β and p70S6K. AKT activation is significantly reduced in heterozygous KO mice and isolated KO-ECs, which can be restored by exogenous AGGF1.

1. Chen D et al. (2013) Functional characterization of Klippel-Trenaunay syndrome gene AGGF1 identifies a novel angiogenic signaling pathway for specification of vein differentiation and angiogenesis during embryogenesis. Hum Mol Genet 22(5):963-76.
2. Pavone P et al. (2023) Klippel-Trenaunay Syndrome, Segmental/Focal Overgrowth Malformations: A Review. Children (Basel). 2023 Aug 21;10(8):1421
3. Zhang T et al. (2016) Haploinsufficiency of Klippel-Trenaunay syndrome gene Aggf1 inhibits developmental and pathological angiogenesis by inactivating PI3K and AKT and disrupts vascular integrity by activating VE-cadherin. Hum Mol Genet 25:5094-5110.