GDF5

Highest pathogenic variant AF is 0.000013141295

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000374372

Coding exons

2

Length

21424

Individuals with no LoFs

125734

Homozygous LoFs

0

Heterozygous LoFs

7

Defined

125741

p

0.0000278

Function

FUNCTION: 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). {ECO:0000250|UniProtKB:P43027, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:15530414, ECO:0000269|PubMed:19229295, ECO:0000269|PubMed:19956691, ECO:0000269|PubMed:21976273, ECO:0000269|PubMed:24098149, ECO:0000269|PubMed:25092592}.;

Disease

DISEASE: Acromesomelic chondrodysplasia, Hunter-Thompson type (AMDH) [MIM:201250]: 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. {ECO:0000269|PubMed:8589725}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brachydactyly C (BDC) [MIM:113100]: 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. {ECO:0000269|PubMed:14735582, ECO:0000269|PubMed:22828468, ECO:0000269|PubMed:25092592, ECO:0000269|PubMed:25820810}. Note=The disease is caused by mutations 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). {ECO:0000269|PubMed:22828468}.; DISEASE: Du Pan syndrome (DPS) [MIM:228900]: Rare autosomal recessive condition characterized by absence of the fibulae and severe acromesomelic limb shortening with small, non-functional toes. Although milder, the phenotype resembles the autosomal recessive Hunter-Thompson and Grebe types of acromesomelic chondrodysplasia. {ECO:0000269|PubMed:12121354, ECO:0000269|PubMed:16222676, ECO:0000269|PubMed:18629880}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Symphalangism, proximal 1B (SYM1B) [MIM:615298]: 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. {ECO:0000269|PubMed:16127465, ECO:0000269|PubMed:16892395, ECO:0000269|PubMed:18283415}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiple synostoses syndrome 2 (SYNS2) [MIM:610017]: 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. {ECO:0000269|PubMed:16532400, ECO:0000269|PubMed:19956691, ECO:0000269|PubMed:21976273, ECO:0000269|PubMed:24098149, ECO:0000269|Ref.18}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brachydactyly A2 (BDA2) [MIM:112600]: 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. {ECO:0000269|PubMed:16127465, ECO:0000269|PubMed:18203755, ECO:0000269|PubMed:21976273}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Osteoarthritis 5 (OS5) [MIM:612400]: 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. {ECO:0000269|PubMed:17384641}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Brachydactyly A1, C (BDA1C) [MIM:615072]: 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. {ECO:0000269|PubMed:20683927, ECO:0000269|PubMed:24098149}. Note=The disease is caused by mutations affecting the gene represented in this entry.;