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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8IUQ4: Variant p.Cys128Phe

E3 ubiquitin-protein ligase SIAH1
Gene: SIAH1
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Variant information Variant position: help 128 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 128 (C128F, p.Cys128Phe). 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 BURHAS; loss of function in Wnt signaling pathway. Any additional useful information about the variant.


Sequence information Variant position: help 128 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 282 The length of the canonical sequence.
Location on the sequence: help TLPHTEKADHEELCEFRPYS C PCPGASCKWQGSLDAVMPHL 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                         TLPHTEKADHEELCEFRPYSCPCPGASCKWQGSLDAVMPHL

Rat                           TLPHTEKAEHEELCEFRPYSCPCPGASCKWQGSLDAVMPHL

Zebrafish                     TLPHTDKAEHEELCEFRPYSCPCPGASCKWQGSLDAVMPHL

Caenorhabditis elegans        NFHHADKTEHEELCEFRPYCCPCPGASCKWQGGLSDVMEHL
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 – 282 E3 ubiquitin-protein ligase SIAH1
Zinc finger 93 – 153 SIAH-type
Region 90 – 282 SBD
Binding site 117 – 117
Binding site 121 – 121
Binding site 128 – 128
Binding site 135 – 135
Binding site 147 – 147
Mutagenesis 124 – 124 R -> A. In D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-214; A-215; A-231 and A-232.
Mutagenesis 142 – 142 D -> A. In E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-151.



Literature citations
De novo variants in SIAH1, encoding an E3 ubiquitin ligase, are associated with developmental delay, hypotonia and dysmorphic features.
Buratti J.; Ji L.; Keren B.; Lee Y.; Booke S.; Erdin S.; Kim S.Y.; Palculict T.B.; Meiner V.; Chae J.H.; Woods C.G.; Tam A.; Heron D.; Cong F.; Harel T.;
J. Med. Genet. 58:205-212(2021)
Cited for: VARIANTS BURHAS GLY-41; LEU-50; PHE-128; ALA-168 AND ARG-174; CHARACTERIZATION OF VARIANTS BURHAS GLY-41; LEU-50; PHE-128; ALA-168 AND ARG-174; 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.