UniProtKB/Swiss-Prot O60741: Variant p.Glu85Ala

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Gene: HCN1
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Variant information Variant position:

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

US 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 Glutamate (E) to Alanine (A) at position 85 (E85A, p.Glu85Ala). 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 medium size and acidic (E) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-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:

In GEFSP10; uncertain significance. Any additional useful information about the variant.

Sequence information Variant position:

85 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

890 The length of the canonical sequence.
Location on the sequence:

GGGGGGGGGGEEPAGGFEDA E GPRRQYGFMQRQFTSMLQPG 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                         GGGGGGGGGGEEPAGGFEDAEGPRRQYGFMQRQFTSMLQPG

Mouse                         G--------GEEPAGSFEDAEGPRRQYGFMQRQFTSMLQPG

Rat                           G--------GEEPAGSFEDAEGPRRQYGFMQRQFTSMLQPG

Rabbit                        -------------ARGLEDAEGPRRQYGFMQRQFTSMLQPG

Fission yeast                 ----------------------------MLRRNPTAI----

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 – 890	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Topological domain	1 – 142	Cytoplasmic
Region	1 – 93	Disordered

Literature citations
HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond.
Marini C.; Porro A.; Rastetter A.; Dalle C.; Rivolta I.; Bauer D.; Oegema R.; Nava C.; Parrini E.; Mei D.; Mercer C.; Dhamija R.; Chambers C.; Coubes C.; Thevenon J.; Kuentz P.; Julia S.; Pasquier L.; Dubourg C.; Carre W.; Rosati A.; Melani F.; Pisano T.; Giardino M.; Innes A.M.; Alembik Y.; Scheidecker S.; Santos M.; Figueiroa S.; Garrido C.; Fusco C.; Frattini D.; Spagnoli C.; Binda A.; Granata T.; Ragona F.; Freri E.; Franceschetti S.; Canafoglia L.; Castellotti B.; Gellera C.; Milanesi R.; Mancardi M.M.; Clark D.R.; Kok F.; Helbig K.L.; Ichikawa S.; Sadler L.; Neupauerova J.; Lassuthova P.; Sterbova K.; Laridon A.; Brilstra E.; Koeleman B.; Lemke J.R.; Zara F.; Striano P.; Soblet J.; Smits G.; Deconinck N.; Barbuti A.; DiFrancesco D.; LeGuern E.; Guerrini R.; Santoro B.; Hamacher K.; Thiel G.; Moroni A.; DiFrancesco J.C.; Depienne C.;
Brain 141:3160-3178(2018)
Cited for: VARIANTS GEFSP10 ALA-85; ARG-171; PRO-172; ARG-243; ILE-260; SER-329; CYS-391; SER-391; MET-414; GLN-590; TYR-680 AND GLY-715; VARIANTS DEE24 TYR-143; ILE-153; GLU-261; LEU-305; ASP-391; LEU-397 AND PRO-399; CHARACTERIZATION OF VARIANTS DEE24 ILE-153; LEU-305; ASP-391; LEU-397 AND PRO-399; CHARACTERIZATION OF VARIANTS GEFSP10 ARG-243; SER-329; CYS-391; SER-391; MET-414 AND GLN-590; VARIANTS CYS-264; THR-275 AND ARG-379; INVOLVEMENT IN DEE24; INVOLVEMENT IN GEFSP10; SUBCELLULAR LOCATION; FUNCTION; Contribution of HCN1 variant to sinus bradycardia: A case report.
Yu H.; Gall B.; Newman M.; Hathaway Q.; Brundage K.; Ammer A.; Mathers P.; Siderovski D.; Hull R.W.;
J. Arrhythm. 37:1337-1347(2021)
Cited for: VARIANTS 72-GLY--GLY-74 DEL AND ALA-851; CHARACTERIZATION OF VARIANT ALA-851;

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.