UniProtKB/Swiss-Prot Q9Y3Q4: Variant p.Ala485Val

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Gene: HCN4
Chromosomal location: 15q24.1
Variant information

Variant position:  485
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Alanine (A) to Valine (V) at position 485 (A485V, p.Ala485Val).
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 small size and hydrophobic (A) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Involvement in disease:  Sick sinus syndrome 2 (SSS2) [MIM:163800]: The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS2 onset is in utero or at birth. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In SSS2; results in a significant reduction of current density compared to wild-type.
Any additional useful information about the variant.



Sequence information

Variant position:  485
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1203
The length of the canonical sequence.

Location on the sequence:   YSYALFKAMSHMLCIGYGRQ  A PVGMSDVWLTMLSMIVGATC
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                         YSYALFKAMSHMLCIGYGRQAPVGMSDVWLTMLSMIVGATC

Mouse                         YSYALFKAMSHMLCIGYGRQAPVGMSDVWLTMLSMIVGATC

Rat                           YSYALFKAMSHMLCIGYGRQAPVGMSDVWLTMLSMIVGATC

Rabbit                        YSYALFKAMSHMLCIGYGRQAPMGMSDVWLTMLSMIVGATC

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 1 – 1203 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Intramembrane 465 – 486 Pore-forming; Name=Segment H5;


Literature citations

A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews.
Laish-Farkash A.; Glikson M.; Brass D.; Marek-Yagel D.; Pras E.; Dascal N.; Antzelevitch C.; Nof E.; Reznik H.; Eldar M.; Luria D.;
J. Cardiovasc. Electrophysiol. 21:1365-1372(2010)
Cited for: VARIANT SSS2 VAL-485; CHARACTERIZATION OF VARIANT SSS2 VAL-485;

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.