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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y3Q4: Variant p.Ser672Arg

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Gene: HCN4
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Variant information Variant position: help 672 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 Arginine (R) at position 672 (S672R, p.Ser672Arg). 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 large size and basic (R) 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 SSS2; results in decreased affinity for cAMP but does not abolish channel activation; shifts the current activation range to hyperpolarized voltages; slows channel opening and speeds up channel closure. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 672 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1203 The length of the canonical sequence.
Location on the sequence: help LADGSYFGEICLLTRGRRTA S VRADTYCRLYSLSVDNFNEV 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                         LADGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDNFNEV

Mouse                         LADGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDNFNEV

Rat                           LADGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDNFNEV

Rabbit                        LADGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDNFNEV
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 – 1203 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Topological domain 518 – 1203 Cytoplasmic
Binding site 659 – 659
Binding site 660 – 660
Binding site 662 – 662
Binding site 669 – 669
Binding site 670 – 670
Binding site 673 – 673
Mutagenesis 680 – 680 R -> E. Abolishes cyclic-dinucleotide modulation of HCN4 channels.
Beta strand 670 – 677



Literature citations
Local and global interpretations of a disease-causing mutation near the ligand entry path in hyperpolarization-activated cAMP-gated channel.
Xu X.; Marni F.; Wu S.; Su Z.; Musayev F.; Shrestha S.; Xie C.; Gao W.; Liu Q.; Zhou L.;
Structure 20:2116-2123(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 521-724 IN COMPLEX WITH 3',5'-CYCLIC AMP; CHARACTERIZATION OF VARIANT SSS2 ARG-672; Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel.
Milanesi R.; Baruscotti M.; Gnecchi-Ruscone T.; DiFrancesco D.;
N. Engl. J. Med. 354:151-157(2006)
Cited for: VARIANT SSS2 ARG-672; FUNCTION; ACTIVITY REGULATION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT SSS2 ARG-672;
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.