UniProtKB/Swiss-Prot Q9Y3Q4: Variant p.Arg550Cys

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Gene: HCN4
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Variant information Variant position:

550 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Cysteine (C) at position 550 (R550C, p.Arg550Cys). 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 polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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:

Risk factor for EIG18; alters the channel kinetics by causing a leftward shift in the voltage dependence of the channel activation curve; neurons expressing mutant channels present lower current thresholds to firing and higher firing rates. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs150691273 [ dbSNP | Ensembl ]

Sequence information Variant position:

550 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:

KYKQVEQYMSFHKLPPDTRQ R IHDYYEHRYQGKMFDEESIL 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                         KYKQVEQYMSFHKLPPDTRQRIHDYYEHRYQGKMFDEESIL

Mouse                         KYKQVEQYMSFHKLPPDTRQRIHDYYEHRYQGKMFDEESIL

Rat                           KYKQVEQYMSFHKLPPDTRQRIHDYYEHRYQGKMFDEESIL

Rabbit                        KYKQVEQYMSFHKLPPDTRQRIHDYYEHRYQGKMFDEESIL

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.

Type	Positions	Description
Chain	1 – 1203	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Topological domain	518 – 1203	Cytoplasmic
Binding site	559 – 559
Binding site	562 – 562
Binding site	564 – 564
Binding site	566 – 566
Mutagenesis	559 – 559	Y -> T. Alters the channel response to c-di-GMP.
Mutagenesis	564 – 564	F -> T. Alters the channel response to c-di-GMP.
Mutagenesis	566 – 566	E -> K. Alters the channel response to c-di-GMP.
Helix	545 – 559

Literature citations
A loss-of-function HCN4 mutation associated with familial benign myoclonic epilepsy in infancy causes increased neuronal excitability.
Campostrini G.; DiFrancesco J.C.; Castellotti B.; Milanesi R.; Gnecchi-Ruscone T.; Bonzanni M.; Bucchi A.; Baruscotti M.; Ferrarese C.; Franceschetti S.; Canafoglia L.; Ragona F.; Freri E.; Labate A.; Gambardella A.; Costa C.; Gellera C.; Granata T.; Barbuti A.; DiFrancesco D.;
Front. Mol. Neurosci. 11:269-269(2018)
Cited for: VARIANT CYS-550; CHARACTERIZATION OF VARIANT CYS-550; INVOLVEMENT IN EIG18;

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.