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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43541: Variant p.Cys484Phe

Mothers against decapentaplegic homolog 6
Gene: SMAD6
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Variant information Variant position: help 484 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 Cysteine (C) to Phenylalanine (F) at position 484 (C484F, p.Cys484Phe). 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 medium size and polar (C) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In AOVD2; decreased inhibition of BMP signaling pathway. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 484 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 496 The length of the canonical sequence.
Location on the sequence: help VRISFAKGWGPCYSRQFITS C PCWLEILLNNPR 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                         VRISFAKGWGPCYSRQFITSCPCWLEILLNNPR

Mouse                         VRISFAKGWGPCYSRQFITSCPCWLEILLNNHR

Chicken                       VRISFAKGWGPCYSRQFITSCPCWLEILLSNNR
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 1 – 496 Mothers against decapentaplegic homolog 6
Domain 331 – 496 MH2
Alternative sequence 339 – 496 Missing. In isoform D.
Mutagenesis 471 – 471 G -> S. Loss of SMAD1-binding and of inhibition of BMP-SMAD1 signaling. No effect on interaction with BMPR1B and TGFBR1.
Mutagenesis 478 – 496 Missing. Loss of interaction with BMPR1B, TGFBR1 and SMAD1.



Literature citations
Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation.
Tan H.L.; Glen E.; Topf A.; Hall D.; O'Sullivan J.J.; Sneddon L.; Wren C.; Avery P.; Lewis R.J.; ten Dijke P.; Arthur H.M.; Goodship J.A.; Keavney B.D.;
Hum. Mutat. 33:720-727(2012)
Cited for: INVOLVEMENT IN CONGENITAL CARDIOVASCULAR MALFORMATIONS; INVOLVEMENT IN AOVD2; VARIANT THR-325; VARIANTS AOVD2 LEU-415 AND PHE-484; CHARACTERIZATION OF VARIANTS AOVD2 LEU-415 AND PHE-484; FUNCTION; A novel SMAD6 variant in a patient with severely calcified bicuspid aortic valve and thoracic aortic aneurysm.
Park J.E.; Park J.S.; Jang S.Y.; Park S.H.; Kim J.W.; Ki C.S.; Kim D.K.;
Mol. Genet. Genomic Med. 7:e620-e620(2019)
Cited for: VARIANT AOVD2 GLY-ILE-391 INS; CHARACTERIZATION OF AOVD2 GLY-ILE-391 INS AND PHE-484; FUNCTION;
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.