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UniProtKB/Swiss-Prot Q99972: Variant p.Glu323Lys

Myocilin
Gene: MYOC
Chromosomal location: 1q23-q24
Variant information

Variant position:  323
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glutamate (E) to Lysine (K) at position 323 (E323K, p.Glu323Lys).
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 large size and basic (K)
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:  Glaucoma 1, open angle, A (GLC1A) [MIM:137750]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. {ECO:0000269|PubMed:10196380, ECO:0000269|PubMed:10330365, ECO:0000269|PubMed:10340788, ECO:0000269|PubMed:10644174, ECO:0000269|PubMed:10798654, ECO:0000269|PubMed:10819638, ECO:0000269|PubMed:10873982, ECO:0000269|PubMed:10916185, ECO:0000269|PubMed:10980537, ECO:0000269|PubMed:11004290, ECO:0000269|PubMed:11774072, ECO:0000269|PubMed:12189160, ECO:0000269|PubMed:12356829, ECO:0000269|PubMed:12362081, ECO:0000269|PubMed:12442283, ECO:0000269|PubMed:12860809, ECO:0000269|PubMed:12872267, ECO:0000269|PubMed:15025728, ECO:0000269|PubMed:15255110, ECO:0000269|PubMed:15534471, ECO:0000269|PubMed:15795224, ECO:0000269|PubMed:16401791, ECO:0000269|PubMed:17210859, ECO:0000269|PubMed:17499207, ECO:0000269|PubMed:25524706, ECO:0000269|PubMed:9005853, ECO:0000269|PubMed:9328473, ECO:0000269|PubMed:9345106, ECO:0000269|PubMed:9361308, ECO:0000269|PubMed:9490287, ECO:0000269|PubMed:9510647, ECO:0000269|PubMed:9521427, ECO:0000269|PubMed:9535666, ECO:0000269|PubMed:9697688, ECO:0000269|PubMed:9792882, ECO:0000269|PubMed:9863594}. 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 GLC1A; inhibits endoproteolytic processing; mainly accumulates as insoluble aggregates inside the endoplasmic reticulum.
Any additional useful information about the variant.



Sequence information

Variant position:  323
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  504
The length of the canonical sequence.

Location on the sequence:   LISQFMQGYPSKVHILPRPL  E STGAVVYSGSLYFQGAESRT
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                         LISQFMQGY-----------------------------------------------------------------PSKVHILPRPLESTGA------VVYSGSLYF---------------------------------------QGAESRT

                              LASQFLQGY--------------------------------

Mouse                         QISQFEQGY--------------------------------

Rat                           QISQFEQGY--------------------------------

Bovine                        HIRKFTQGY--------------------------------

Rabbit                        RISQFVQGY--------------------------------

Cat                           LSSQFLQGY--------------------------------

Slime mold                    RCAQTIQGYFRAWKQASPFFDLRMQNEQLFQGRKERNRFSM

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 33 – 504 Myocilin
Chain 227 – 504 Myocilin, C-terminal fragment
Domain 244 – 503 Olfactomedin-like
Disulfide bond 245 – 433


Literature citations

Myocilin mutations causing glaucoma inhibit the intracellular endoproteolytic cleavage of myocilin between amino acids Arg226 and Ile227.
Aroca-Aguilar J.D.; Sanchez-Sanchez F.; Ghosh S.; Coca-Prados M.; Escribano J.;
J. Biol. Chem. 280:21043-21051(2005)
Cited for: PROTEIN SEQUENCE OF 227-233; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS GLC1A LYS-323; LEU-370 AND GLY-380; PROTEOLYTIC PROCESSING;

Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma.
Shimizu S.; Lichter P.R.; Johnson A.T.; Zhou Z.; Higashi M.; Gottfredsdottir M.; Othman M.; Moroi S.E.; Rozsa F.W.; Schertzer R.M.; Clarke M.S.; Schwartz A.L.; Downs C.A.; Vollrath D.; Richards J.E.;
Am. J. Ophthalmol. 130:165-177(2000)
Cited for: VARIANTS GLC1A ARG-252; GLY-272; LYS-323; LEU-370; MET-377; PHE-426; ASN-477 AND SER-499; VARIANTS ASP-57; LYS-76; MET-329 AND ARG-398; CHARACTERIZATION OF VARIANTS GLC1A ARG-252; GLY-272; LYS-323; LEU-370; MET-377; PHE-426; ASN-477 AND SER-499; CHARACTERIZATION OF VARIANTS ASP-57; LYS-76; MET-329 AND ARG-398;

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.