Recombinant Human Growth/differentiation factor 6 (GDF6) (Active)

Function

Growth factor that controls proliferation and cellular differentiation in the retina and bone formation. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal-ventral positional information in the retina and controls the formation of the retinotectal map (PubMed:23307924). Required for normal formation of bones and joints in the limbs, skull, digits and axial skeleton. Plays a key role in establishing boundaries between skeletal elements during development. Regulation of GDF6 expression seems to be a mechanism for evolving species-specific changes in skeletal structures. Seems to positively regulate differentiation of chondrogenic tissue through the growth factor receptors subunits BMPR1A, BMPR1B, BMPR2 and ACVR2A, leading to the activation of SMAD1-SMAD5-SMAD8 complex. The regulation of chondrogenic differentiation is inhibited by NOG (PubMed:26643732). Also involved in the induction of adipogenesis from mesenchymal stem cells. This mechanism acts through the growth factor receptors subunits BMPR1A, BMPR2 and ACVR2A and the activation of SMAD1-SMAD5-SMAD8 complex and MAPK14/p38 (By similarity)

Subcellular Location

Secreted

Disease Association

Klippel-Feil syndrome 1, autosomal dominant (KFS1) : A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. Deafness is a feature in some cases and may be of sensorineural, conductive, or mixed type. [The disease is caused by variants affecting the gene represented in this entry] | [A chromosomal aberration involving GDF6 has been found in a patient with Klippel-Feil syndrome (KFS). Paracentric inv(8)(q22;2q23.3)] | Microphthalmia, isolated, 4 (MCOP4) : A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. [The disease is caused by variants affecting the gene represented in this entry] | Leber congenital amaurosis 17 (LCA17) : A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or almost absent pupillary responses, photophobia, high hyperopia and keratoconus. [The disease is caused by variants affecting the gene represented in this entry] | Multiple synostoses syndrome 4 (SYNS4) : A bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism. SYNS4 inheritance is autosomal dominant. [The disease is caused by variants affecting the gene represented in this entry] | Deafness, autosomal recessive, 118, with cochlear aplasia (DFNB118) : A form of non-syndromic deafness characterized by congenital profound sensorineural hearing loss and cochlear aplasia. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. [The gene represented in this entry is involved in disease pathogenesis. Homozygous deletions on chromosome 8 removing putative enhancers of GDF6, segregate with the disease in families with congenital deafness and cochlear aplasia]

Subunit

Homodimer; disulfide-linked

• Guo J.H. et al. Cloning of human GDF16 and functional associated analysis. (JAN-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Tassabehji M. et al. Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. — Hum. Mutat. (2008)
• Asai-Coakwell M. et al. Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. — Hum. Mol. Genet. (2013)
• Bademci G. et al. Long-range cis-regulatory elements controlling GDF6 expression are essential for ear development. — J. Clin. Invest. (2020)
• Asai-Coakwell M. et al. Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. — Hum. Mol. Genet. (2009)
• Ye M. et al. Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. — Hum. Mol. Genet. (2010)
• Chassaing N. et al. Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia. — Clin. Genet. (2014)