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UniProtKB/Swiss-Prot P43026: Variant p.Arg438Leu

Growth/differentiation factor 5
Gene: GDF5
Variant information

Variant position:  438
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Arginine (R) to Leucine (L) at position 438 (R438L, p.Arg438Leu).
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:  Change from large size and basic (R) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  In SYNS2 and SYM1B; increased biological activity when compared to wild-type; normal binding to BMPR1B ectodomain but increased binding to that of BMPR1A.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  438
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  501
The length of the canonical sequence.

Location on the sequence:   IIAPLEYEAFHCEGLCEFPL  R SHLEPTNHAVIQTLMNSMDP
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         IIAPLEYEAFHCEGLCEFPLRSHLEPTNHAVIQTLMNSMDP

Mouse                         IIAPLEYEAFHCEGLCEFPLRSHLEPTNHAVIQTLMNSMDP

Sequence annotation in neighborhood:  
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 400 – 466
Disulfide bond 429 – 498
Disulfide bond 433 – 500


Literature citations

Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2.
Seemann P.; Schwappacher R.; Kjaer K.W.; Krakow D.; Lehmann K.; Dawson K.; Stricker S.; Pohl J.; Ploeger F.; Staub E.; Nickel J.; Sebald W.; Knaus P.; Mundlos S.;
J. Clin. Invest. 115:2373-2381(2005)
Cited for: VARIANT SYM1B LEU-438; VARIANT BDA2 PRO-441; CHARACTERIZATION OF VARIANT SYM1B LEU-438; CHARACTERIZATION OF VARIANT BDA2 PRO-441;

GDF5 is a second locus for multiple-synostosis syndrome.
Dawson K.; Seeman P.; Sebald E.; King L.; Edwards M.; Williams J. III; Mundlos S.; Krakow D.;
Am. J. Hum. Genet. 78:708-712(2006)
Cited for: VARIANT SYNS2 LEU-438;

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.