GDF5 (growth differentiation factor 5)

Gene

• Entrez ID: 8200
• Gene name: Growth differentiation factor 5
• Gene symbol: GDF5
• Synonyms: BDA1C, BMP-14, BMP14, CDMP1, DUPANS, LAP-4, LAP4, OS5, SYM1B, SYNS2
• Chromosome: 20
• Chromosome location: 20q11.22
• Summary: This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs143383	G>A	Risk-factor, benign	Intron variant, 5 prime UTR variant
rs28936397	T>C,G	Pathogenic	Missense variant, coding sequence variant
rs753691079	CCC>-,CCCC	Pathogenic	Coding sequence variant, inframe deletion, frameshift variant
rs761962752	->G	Pathogenic	Coding sequence variant, frameshift variant
rs778834209	G>-,GG	Pathogenic	Coding sequence variant, frameshift variant
rs886042462	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1194065564	G>A,T	Likely-pathogenic	Stop gained, synonymous variant, coding sequence variant
rs1555823599	G>-	Risk-factor, benign	Intron variant, 5 prime UTR variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017506	hsa-miR-335-5p	Microarray	18185580
MIRT054572	hsa-miR-21-5p	Luciferase reporter assay, qRT-PCR, Western blot	24577233
MIRT054572	hsa-miR-21-5p	Luciferase reporter assay, qRT-PCR, Western blot	24577233
MIRT732384	hsa-miR-7-5p	Luciferase reporter assay, qRT-PCR, Western blot	27583982
MIRT732384	hsa-miR-7-5p	Luciferase reporter assay, qRT-PCR, Western blot	27583982
MIRT1015726	hsa-miR-132	CLIP-seq
MIRT1015727	hsa-miR-150	CLIP-seq
MIRT1015728	hsa-miR-212	CLIP-seq
MIRT1015729	hsa-miR-214	CLIP-seq
MIRT1015730	hsa-miR-3156-3p	CLIP-seq
MIRT1015731	hsa-miR-342-3p	CLIP-seq
MIRT1015732	hsa-miR-3619-5p	CLIP-seq
MIRT1015733	hsa-miR-4279	CLIP-seq
MIRT1015734	hsa-miR-4291	CLIP-seq
MIRT1015735	hsa-miR-4301	CLIP-seq
MIRT1015736	hsa-miR-4687-5p	CLIP-seq
MIRT1015737	hsa-miR-4713-5p	CLIP-seq
MIRT1015738	hsa-miR-4768-5p	CLIP-seq
MIRT1015739	hsa-miR-483-3p	CLIP-seq
MIRT1015740	hsa-miR-483-5p	CLIP-seq
MIRT1015741	hsa-miR-532-3p	CLIP-seq
MIRT1015742	hsa-miR-761	CLIP-seq
MIRT1015743	hsa-miR-922	CLIP-seq
MIRT1015744	hsa-miR-942	CLIP-seq
MIRT2234192	hsa-miR-1253	CLIP-seq
MIRT2234193	hsa-miR-125a-3p	CLIP-seq
MIRT2234194	hsa-miR-21	CLIP-seq
MIRT2234195	hsa-miR-224	CLIP-seq
MIRT2234196	hsa-miR-3150b-3p	CLIP-seq
MIRT2234197	hsa-miR-3691-3p	CLIP-seq
MIRT2234198	hsa-miR-3919	CLIP-seq
MIRT2234199	hsa-miR-3929	CLIP-seq
MIRT2234200	hsa-miR-4251	CLIP-seq
MIRT2234201	hsa-miR-4419b	CLIP-seq
MIRT2234202	hsa-miR-4478	CLIP-seq
MIRT2234203	hsa-miR-4493	CLIP-seq
MIRT2234204	hsa-miR-4689	CLIP-seq
MIRT2234205	hsa-miR-4710	CLIP-seq
MIRT2234206	hsa-miR-4726-3p	CLIP-seq
MIRT2234207	hsa-miR-4756-3p	CLIP-seq
MIRT2234208	hsa-miR-4784	CLIP-seq
MIRT2234209	hsa-miR-590-5p	CLIP-seq
MIRT2538226	hsa-miR-1200	CLIP-seq
MIRT2538227	hsa-miR-1261	CLIP-seq
MIRT2538228	hsa-miR-1286	CLIP-seq
MIRT1015727	hsa-miR-150	CLIP-seq
MIRT2538229	hsa-miR-1915	CLIP-seq
MIRT2538230	hsa-miR-1976	CLIP-seq
MIRT2234194	hsa-miR-21	CLIP-seq
MIRT1015729	hsa-miR-214	CLIP-seq
MIRT2234195	hsa-miR-224	CLIP-seq
MIRT1015730	hsa-miR-3156-3p	CLIP-seq
MIRT2538231	hsa-miR-3157-5p	CLIP-seq
MIRT1015732	hsa-miR-3619-5p	CLIP-seq
MIRT2234197	hsa-miR-3691-3p	CLIP-seq
MIRT2538232	hsa-miR-3691-5p	CLIP-seq
MIRT2234198	hsa-miR-3919	CLIP-seq
MIRT2538233	hsa-miR-4252	CLIP-seq
MIRT1015733	hsa-miR-4279	CLIP-seq
MIRT1015734	hsa-miR-4291	CLIP-seq
MIRT1015735	hsa-miR-4301	CLIP-seq
MIRT2538234	hsa-miR-4324	CLIP-seq
MIRT2538235	hsa-miR-4433	CLIP-seq
MIRT2538236	hsa-miR-4471	CLIP-seq
MIRT2538237	hsa-miR-4474-3p	CLIP-seq
MIRT2538238	hsa-miR-4476	CLIP-seq
MIRT2538239	hsa-miR-4677-3p	CLIP-seq
MIRT2538240	hsa-miR-4679	CLIP-seq
MIRT1015736	hsa-miR-4687-5p	CLIP-seq
MIRT2538241	hsa-miR-4691-3p	CLIP-seq
MIRT1015737	hsa-miR-4713-5p	CLIP-seq
MIRT2538242	hsa-miR-4722-5p	CLIP-seq
MIRT2234206	hsa-miR-4726-3p	CLIP-seq
MIRT2538243	hsa-miR-4752	CLIP-seq
MIRT2234207	hsa-miR-4756-3p	CLIP-seq
MIRT1015738	hsa-miR-4768-5p	CLIP-seq
MIRT1015739	hsa-miR-483-3p	CLIP-seq
MIRT1015740	hsa-miR-483-5p	CLIP-seq
MIRT2538244	hsa-miR-513c	CLIP-seq
MIRT2538245	hsa-miR-514b-5p	CLIP-seq
MIRT1015741	hsa-miR-532-3p	CLIP-seq
MIRT2538246	hsa-miR-544b	CLIP-seq
MIRT2234209	hsa-miR-590-5p	CLIP-seq
MIRT2538247	hsa-miR-618	CLIP-seq
MIRT2538248	hsa-miR-665	CLIP-seq
MIRT2538249	hsa-miR-760	CLIP-seq
MIRT1015742	hsa-miR-761	CLIP-seq
MIRT1015743	hsa-miR-922	CLIP-seq
MIRT1015744	hsa-miR-942	CLIP-seq
MIRT1015729	hsa-miR-214	CLIP-seq
MIRT2538231	hsa-miR-3157-5p	CLIP-seq
MIRT1015732	hsa-miR-3619-5p	CLIP-seq
MIRT2538233	hsa-miR-4252	CLIP-seq
MIRT1015734	hsa-miR-4291	CLIP-seq
MIRT2538241	hsa-miR-4691-3p	CLIP-seq
MIRT1015740	hsa-miR-483-5p	CLIP-seq
MIRT1015742	hsa-miR-761	CLIP-seq
MIRT1015743	hsa-miR-922	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
DEAF1	Unknown	24861163
SP1	Unknown	24861163
SP3	Unknown	24861163

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005125	Function	Cytokine activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	16127465, 18339631, 19229295, 21543859, 21976273, 24098149
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005886	Component	Plasma membrane	IEA
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS	7961761
GO:0007267	Process	Cell-cell signaling	TAS	8589725
GO:0008083	Function	Growth factor activity	IEA
GO:0009612	Process	Response to mechanical stimulus	IEA
GO:0010862	Process	Positive regulation of pathway-restricted SMAD protein phosphorylation	IBA	21873635
GO:0030326	Process	Embryonic limb morphogenesis	IEA
GO:0030509	Process	BMP signaling pathway	IBA	21873635
GO:0030513	Process	Positive regulation of BMP signaling pathway	IDA	21976273, 24098149
GO:0032331	Process	Negative regulation of chondrocyte differentiation	IDA	21976273
GO:0032332	Process	Positive regulation of chondrocyte differentiation	IDA	21976273, 24098149
GO:0035136	Process	Forelimb morphogenesis	IEA
GO:0035137	Process	Hindlimb morphogenesis	IEA
GO:0036122	Function	BMP binding	IPI	21976273
GO:0040014	Process	Regulation of multicellular organism growth	IEA
GO:0042802	Function	Identical protein binding	IPI	25174448
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0043932	Process	Ossification involved in bone remodeling	IEA
GO:0045666	Process	Positive regulation of neuron differentiation	IEA
GO:0050680	Process	Negative regulation of epithelial cell proliferation	IDA	9950587
GO:0060390	Process	Regulation of SMAD protein signal transduction	IDA	21976273
GO:0060395	Process	SMAD protein signal transduction	IBA	21873635
GO:0060395	Process	SMAD protein signal transduction	IDA	21976273, 25092592
GO:0060591	Process	Chondroblast differentiation	IDA	25092592
GO:2001054	Process	Negative regulation of mesenchymal cell apoptotic process	IEA

Other IDs

• MIM: 601146
• HGNC: 4220
• e!Ensembl: ENSG00000125965

Protein

• UniProt ID: P43026
• Protein name: Growth/differentiation factor 5 (GDF-5) (Bone morphogenetic protein 14) (BMP-14) (Cartilage-derived morphogenetic protein 1) (CDMP-1) (Lipopolysaccharide-associated protein 4) (LAP-4) (LPS-associated protein 4) (Radotermin)
• Protein 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
• PDB: 1WAQ, 2BHK, 3EVS, 3QB4, 5HK5, 6Z3G, 6Z3H, 6Z3J, 6Z3L, 6Z3M, 7ZJF, 8BWL, 8BWM, 8BWN, 8E3G
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00688	TGFb_propeptide	143 → 345	TGF-beta propeptide	Family
  PF00019	TGF_beta	399 → 500	Transforming growth factor beta like domain	Domain

• Sequence:

  MRLPKLLTFLLWYLAWLDLEFICTVLGAPDLGQRPQGTRPGLAKAEAKERPPLARNVFRP
  GGHSYGGGATNANARAKGGTGQTGGLTQPKKDEPKKLPPRPGGPEPKPGHPPQTRQATAR
  TVTPKGQLPGGKAPPKAGSVPSSFLLKKAREPGPPREPKEPFRPPPITPHEYMLSLYRTL
  SDADRKGGNSSVKLEAGLANTITSFIDKGQDDRGPVVRKQRYVFDISALEKDGLLGAELR
  ILRKKPSDTAKPAAPGGGRAAQLKLSSCPSGRQPASLLDVRSVPGLDGSGWEVFDIWKLF
  RNFKNSAQLCLELEAWERGRAVDLRGLGFDRAARQVHEKALFLVFGRTKKRDLFFNEIKA
  RSGQDDKTVYEYLFSQRRKRRAPLATRQGKRPSKNLKARCSRKALHVNFKDMGWDDWIIA
  PLEYEAFHCEGLCEFPLRSHLEPTNHAVIQTLMNSMDPESTPPTCCVPTRLSPISILFID
  SANNVVYKQYEDMVVESCGCR

• Sequence length: 501

Pathways

KEGG:

Cytokine-cytokine receptor interaction
TGF-beta signaling pathway
Hippo signaling pathway

Reactome:

Molecules associated with elastic fibres

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Acromesomelic dysplasia	Acromesomelic dysplasia Hunter-Thompson type, Acromesomelic dysplasia, Hunter-Thompson type, Acromesomelic dysplasia, Grebe type	rs863223287, rs28936683, rs121909350, rs121909351, rs28931582, rs28929479, rs121912739, rs879255257, rs863225041, rs863225042, rs745854387, rs1057519324, rs1057519335, rs1057519334, rs1057519333, rs1057519336, rs1177728492, rs753644648, rs771373457, rs749952755, rs1828106198, rs1311857509, rs1828226013, rs1827867580, rs1828356952, rs1828565145, rs1828107536	8589725, 2703235
Arthritis	Degenerative polyarthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470	30664745, 18830904
Brachydactyly	Brachydactyly, Brachydactyly syndrome type C, BRACHYDACTYLY, TYPE A2, Brachydactyly type C, BRACHYDACTYLY, TYPE A1 (disorder), BRACHYDACTYLY, TYPE A1, C, Brachydactyly type A1, Brachydactyly type A2	rs121908949, rs28937580, rs121909082, rs104894122, rs863223289, rs863223290, rs104894121, rs1587657302, rs863223292, rs74315386, rs74315387, rs28936397, rs753691079, rs121909348, rs121917852, rs121917853, rs121917854, rs121917855, rs121917859, rs121917861, rs267606873, rs267606872, rs267606985, rs267606986, rs267606987, rs267606988, rs28933082, rs397514519, rs869025613, rs869025614, rs886039878, rs1553540620, rs1057518333, rs1948841937, rs1948868228, rs1948842030, rs1948842142	12357473, 16127465, 21976273, 2703235, 16014698, 18203755, 25820810, 2703235, 22828468, 14735582, 25092592, 12357473, 20683927, 2703235, 24098149, 20683927
Chondrodysplasia punctata	Chondrodysplasia, Grebe type	rs80338714, rs398122843, rs121434599, rs121434604, rs2107055197, rs2089231699	2703235, 9288098, 12900894
Hearing loss	Conductive hearing loss, Sensorineural Hearing Loss (disorder)	rs267607135, rs267606855, rs779841884, rs267606854, rs28942097, rs121908073, rs121908076, rs74315289, rs121908144, rs111033313, rs74315437, rs121908348, rs121908349, rs121908350, rs397515359, rs180177151, rs180177154, rs180177153, rs35689081, rs35887622, rs80338944, rs104894396, rs104894398, rs80338947, rs80338948, rs80338942, rs104894402, rs104894403, rs80338945, rs28931594, rs80338940, rs80338941, rs80356590, rs80338950, rs387906706, rs387906707, rs387906708, rs398122848, rs387907016, rs587776894, rs387907088, rs397515411, rs370965183, rs398122930, rs199897298, rs111033187, rs111033448, rs199606180, rs111033284, rs397516413, rs111033305, rs111033220, rs111033256, rs111033297, rs111033253, rs104894408, rs111033295, rs397516874, rs76434661, rs111033335, rs397517323, rs111033247, rs367928692, rs374793617, rs143939430, rs397515605, rs80338939, rs200656442, rs779748859, rs587781261, rs587781262, rs143343083, rs200147906, rs730880338, rs797044491, rs146281367, rs756484720, rs869025593, rs201306709, rs540895576, rs777777359, rs879255246, rs1554358720, rs142498437, rs377145777, rs1057517519, rs779077039, rs952741388, rs1060499797, rs764139009, rs1060499590, rs1064794012, rs1064797115, rs756790858, rs775633137, rs1554952443, rs1554952193, rs782063761, rs1199012623, rs756147087, rs1555648043, rs1555661490, rs1553196233, rs781546107, rs111033190, rs775428246, rs782539587, rs537227442, rs148695069, rs1554835827, rs953422571, rs1554834186, rs1554834161, rs1554835103, rs1554577339, rs1554577402, rs768471577, rs782279338, rs781951909, rs998045226, rs375759781, rs755804651, rs1557458426, rs767797828, rs538027448, rs1559366084, rs367688416, rs1558480402, rs1558490542, rs1559870857, rs1560690591, rs1561299289, rs1562817224, rs1562817529, rs1562822565, rs1562835391, rs1564113368, rs1564554255, rs773851192, rs1564555240, rs761261855, rs1564805114, rs1565522273, rs1565127413, rs781790246, rs1565430886, rs1565469959, rs746667217, rs1565819402, rs1565855932, rs150529554, rs1567939793, rs201866631, rs754472294, rs1559372512, rs1558464965, rs1558488902, rs775062249, rs1226171550, rs1561590396, rs765574676, rs762876554, rs757327146, rs1564949059, rs1565519673, rs368050948, rs1565541888, rs781989117, rs1565402473, rs750358148, rs1386887007, rs1209665716, rs1567641234, rs1237955948, rs1569042782, rs752672077, rs146689036, rs1560070780, rs149712664, rs1564556995, rs762226905, rs773573968, rs1568528171, rs1198256157, rs377267777, rs370564476, rs1577876794, rs747787770, rs759432278, rs1043716893, rs1581138934, rs2033773650, rs1421964916, rs771766431, rs780917129, rs1895773215, rs1895769400, rs761543680, rs1565920060
Multiple synostoses syndrome	Multiple synostoses syndrome, Multiple synostoses syndrome 1, MULTIPLE SYNOSTOSES SYNDROME 2, Multiple synostosis syndrome	rs74315386, rs74315388, rs121909347, rs121918322, rs1555223925, rs1554571213	16532400, 2703235, 24098149, 16532400, 19956691, 21976273
Osteochondrodysplasia	Osteochondrodysplasias	rs386833498, rs104893919, rs104893916, rs386833492, rs121908078, rs386833497, rs386833507, rs200963884, rs121908077, rs786204675, rs763198695, rs1554095433, rs766836061
Polydactyly	Polydactyly	rs1583729398, rs121917709, rs1583734240, rs121917714, rs397507422, rs398122899, rs587776959, rs386833752, rs1057518698, rs1060499558, rs755938967, rs1375768446, rs1309855392, rs1565601979, rs748321474, rs368652620, rs1562587032, rs760694987
Proximal symphalangism	SYMPHALANGISM, PROXIMAL	rs104894602, rs121908948, rs104894608, rs104894609, rs104894611, rs104894612, rs104894613, rs28937580, rs1567745111	18283415, 16892395
Rheumatoid arthritis	Rheumatoid Arthritis	rs3766379, rs3792876, rs2071592, rs3087456, rs587776843, rs1566328963, rs2240340, rs1557787212	18830904
Sarcoma	Sarcoma	rs11540652, rs104886003, rs137852790, rs1555927374
Scoliosis	Scoliosis, unspecified	rs1057518828, rs147296805, rs758163506, rs1555613564, rs1596852902, rs1596853067, rs1596853085
Skeletal dysplasia	Skeletal dysplasia	rs121912632, rs121912633, rs121912634, rs121912636, rs121912637, rs267607147, rs387906324, rs267607150, rs397514473, rs398123438, rs515726153, rs515726154, rs515726162, rs515726163, rs515726172, rs757011098
Symphalangism	SYMPHALANGISM, PROXIMAL, 1A, SYMPHALANGISM, PROXIMAL, 1B	rs28936683, rs74315388, rs74315389, rs121909349	2703235, 16127465, 18283415, 16892395

Unknown
Disease name	Disease term	dbSNP ID	References
Mallet finger	Acquired deformity of finger
Elbow ankylosis	Ankylosis of the elbow joint
Camptodactyly of fingers	Clinodactyly of the 5th finger
Carpal synostosis	Carpal synostosis
Talipes equinovalgus	Talipes Equinovalgus
Congenital clubfoot	Congenital clubfoot
Short femur	Congenital hypoplasia of femur
Congenital hypoplasia of radius	Congenital hypoplasia of radius
Developmental dysplasia	DEVELOPMENTAL DYSPLASIA OF THE HIP 1		18947434
Dwarfism	Dwarfism
Fibular aplasia-complex brachydactyly syndrome	Fibular aplasia-complex brachydactyly syndrome
Fibular hypoplasia and complex brachydactyly	Fibular hypoplasia and complex brachydactyly		16222676, 2703235, 18629880, 12121354
Congenital hip dislocation	Hip Dysplasia, Congenital, Nonsyndromic		30273415
Hypodontia	Hypodontia
Hypoplasia of thumb	Hypoplasia of thumb
Impaired cognition	Impaired cognition
Knee osteoarthritis	Osteoarthritis, Knee		30374069, 30664745
Madelung deformity	Madelung Deformity
Micromelia	Micromelia
Osteoarthritis of hip	Osteoarthritis of hip
Osteoarthrosis deformans	Osteoarthrosis Deformans		18830904, 30664745
Phalangoepiphyseal dysplasia	Angel shaped phalangoepiphyseal dysplasia, Angel-shaped phalango-epiphyseal dysplasia		15173244
Ramer ladda syndrome	Ramer Ladda syndrome
Rhizomelia	Rhizomelia
Short-limb dwarfism	Severe short-limb dwarfism
Speech disorders	Speech Disorders
Strabismus	Strabismus
Syndactyly of fingers	Syndactyly of fingers
Syndactyly of the toes	2-3 toe syndactyly
Tarsal coalition	Tarsal Coalition
Postaxial hand polydactyly	Ulnar polydactyly of fingers