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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P43026: Variant p.Ser475Asn

Growth/differentiation factor 5
Gene: GDF5
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Variant information Variant position: help 475 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Serine (S) to Asparagine (N) at position 475 (S475N, p.Ser475Asn). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from small size and polar (S) to medium size and polar (N) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In SYNS2; reduction in binding affinity with BMPR2; no change in binding affinity with BMPR1A; no change in binding affinity with BMPR1B; decreases induction of SMAD1-SMAD5-SMAD8 protein complex phosphorylation; delay of phosphotylated SMAD1-SMAD5-SMAD8 protein complex nuclear translocation; strong reduction of SMAD protein signal transduction; reduction of chondrocyte differentiation; strong improvement of chondrogenesis; decrease of NOG binding; resistant to NOG inhibition; no chondrogenesis inhibition. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 475 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 501 The length of the canonical sequence.
Location on the sequence: help SMDPESTPPTCCVPTRLSPI S ILFIDSANNVVYKQYEDMVV The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         SMDPESTPPTCCVPTRLSPISILFIDSANNVVYKQYEDMVV

Mouse                         SMDPESTPPTCCVPTRLSPISILFIDSANNVVYKQYEDMVV
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 382 – 501 Growth/differentiation factor 5
Disulfide bond 429 – 498
Disulfide bond 433 – 500
Disulfide bond 465 – 465 Interchain
Mutagenesis 490 – 490 Y -> N. Resitant to NOG inhibition.
Beta strand 465 – 479



Literature citations
New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance.
Schwaerzer G.K.; Hiepen C.; Schrewe H.; Nickel J.; Ploeger F.; Sebald W.; Mueller T.; Knaus P.;
J. Bone Miner. Res. 27:429-442(2012)
Cited for: INTERACTION WITH BMPR2; NOG; BMPR1A AND BMPR1B; FUNCTION; VARIANT BDA2 PRO-441; VARIANT SYNS2 ASN-475; CHARACTERIZATION OF VARIANT SYNS2 ASN-475; CHARACTERIZATION OF VARIANT BDA2 PRO-441; Multiple synostosis type 2 (SYNS2) maps to 20q11.2 and caused by a missense mutation in the growth/differentiation factor 5 (GDF5).
Akarsu A.N.; Rezaie T.; Demirtas M.; Farhud D.D.; Sarfarazi M.;
Cited for: VARIANT SYNS2 ASN-475;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.