UniProtKB/Swiss-Prot P23415: Variant p.Lys304Glu

Glycine receptor subunit alpha-1
Gene: GLRA1
Chromosomal location: 5q31-q35
Variant information

Variant position:  304
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 Lysine (K) to Glutamate (E) at position 304 (K304E, p.Lys304Glu).
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 (K) to medium size and acidic (E)
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

Involvement in disease:  Hyperekplexia 1 (HKPX1) [MIM:149400]: A neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli. {ECO:0000269|PubMed:10514101, ECO:0000269|PubMed:24108130, ECO:0000269|PubMed:7611730, ECO:0000269|PubMed:7881416, ECO:0000269|PubMed:7981700, ECO:0000269|PubMed:8298642, ECO:0000269|PubMed:8571969, ECO:0000269|PubMed:8733061, ECO:0000269|PubMed:9067762, ECO:0000269|PubMed:9920650, ECO:0000269|Ref.18}. 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 HKPX1; requires much higher glycine levels for channel activation.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  304
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  457
The length of the canonical sequence.

Location on the sequence:   GITTVLTMTTQSSGSRASLP  K VSYVKAIDIWMAVCLLFVFS
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                         GITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCLLFVFS

Mouse                         GITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCLLFVFS

Rat                           GITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCLLFVFS

Bovine                        GITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCLLFVFS

Zebrafish                     GITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCLLFVFS

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 29 – 457 Glycine receptor subunit alpha-1
Topological domain 299 – 309 Extracellular
Site 289 – 289 Important for obstruction of the ion pore in the closed conformation
Mutagenesis 304 – 304 K -> C. Decreases channel conductance; the mutant channel requires much higher glycine concentrations for activation.


Literature citations

Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis.
Elmslie F.V.; Hutchings S.M.; Spencer V.; Curtis A.; Covanis T.; Gardiner R.M.; Rees M.;
J. Med. Genet. 33:435-436(1996)
Cited for: VARIANT HKPX1 GLU-304;

Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel.
Lynch J.W.; Rajendra S.; Pierce K.D.; Handford C.A.; Barry P.H.; Schofield P.R.;
EMBO J. 16:110-120(1997)
Cited for: CHARACTERIZATION OF VARIANTS HKPX1 ASN-272; LEU-299; GLN-299; GLU-304 AND CYS-307; FUNCTION; SUBCELLULAR LOCATION; BIOPHYSICOCHEMICAL PROPERTIES;

Startle disease in an Italian family by mutation (K276E): the alpha-subunit of the inhibiting glycine receptor.
Seri M.; Bolino A.; Galietta L.J.V.; Lerone M.; Silengo M.; Romeo G.;
Hum. Mutat. 9:185-187(1997)
Cited for: VARIANT HKPX1 GLU-304;

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.