GDF5

The protein encoded by this gene is a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. This group of proteins is characterized by a polybasic proteolytic processing site which is cleaved to produce a mature protein containing seven conserved cysteine residues. The members of this family are regulators of cell growth and differentiation in both embryonic and adult tissues. Mutations in this gene are associated with acromesomelic dysplasia, Hunter-Thompson type; brachydactyly, type C; and chondrodysplasia, Grebe type. These associations confirm that the gene product plays a role in skeletal development. [provided by RefSeq]

growth differentiation factor 5

Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction (PubMed:24098149, PubMed:21976273, PubMed:15530414, PubMed:25092592).

Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (PubMed:21976273).

Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (By similarity).

Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205).

BMP signaling pathway Source: GO_Central
Cell-cell signaling Source: ProtInc
Chondroblast differentiation Source: UniProtKB
Embryonic limb morphogenesis Source: Ensembl
Forelimb morphogenesis Source: Ensembl
Hindlimb morphogenesis Source: Ensembl
Negative regulation of chondrocyte differentiation Source: UniProtKB
Negative regulation of epithelial cell proliferation Source: BHF-UCL
Negative regulation of mesenchymal cell apoptotic process Source: Ensembl
Negative regulation of neuron apoptotic process Source: Ensembl
Ossification involved in bone remodeling Source: Ensembl
Positive regulation of BMP signaling pathway Source: UniProtKB
Positive regulation of chondrocyte differentiation Source: UniProtKB
Positive regulation of neuron differentiation Source: Ensembl
Positive regulation of pathway-restricted SMAD protein phosphorylation Source: GO_Central
Regulation of multicellular organism growth Source: Ensembl
Regulation of SMAD protein signal transduction Source: UniProtKB
Response to mechanical stimulus Source: Ensembl
SMAD protein signal transduction Source: UniProtKB
Transforming growth factor beta receptor signaling pathway Source: ProtInc

Cell membrane; Secreted

Acromesomelic chondrodysplasia, Grebe type (AMDG):
An autosomal recessive acromesomelic chondrodysplasia. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDG is characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.
Acromesomelic chondrodysplasia, Hunter-Thompson type (AMDH):
An autosomal recessive form of dwarfism. Patients have limb abnormalities, with the middle and distal segments being most affected and the lower limbs more affected than the upper. AMDH is characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.
Brachydactyly C (BDC):
The disease is caused by variants affecting the gene represented in this entry. Some BDC patients with GDF5 mutations also manifest clinical features of ASPED angel-shaped phalango-epiphyseal dysplasia (ASPED), an autosomal dominant skeletal abnormality characterized by a typical angel-shaped phalanx, brachydactyly, specific radiological findings, abnormal dentition, hip dysplasia, and delayed bone age. This suggests that BDC and ASPED are part of the same clinical spectrum (PubMed:22828468). A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type C is characterized by deformity of the middle and proximal phalanges of the second and third fingers, sometimes with hypersegmentation of the proximal phalanx. The ring finger may be essentially normal and project beyond the others.
Du Pan syndrome (DUPANS):
An autosomal recessive chondrodysplasia characterized by acromesomelic limb shortening, severe reduction or absence of the fibula, and severe hand and feet abnormalities including complex brachydactyly.
Symphalangism, proximal 1B (SYM1B):
A disease characterized by the hereditary absence of the proximal interphalangeal joints. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conductive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone.
Multiple synostoses syndrome 2 (SYNS2):
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.
Brachydactyly A2 (BDA2):
A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially.
Osteoarthritis 5 (OS5):
A degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement.
Brachydactyly A1, C (BDA1C):
A form of brachydactyly type A1. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. BDA1C inheritance can be autosomal dominant or autosomal recessive. Autosomal dominant BDA1C has a milder phenotype.