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UniProtKB/Swiss-Prot Q99972: Variant p.Pro370Leu

Myocilin
Gene: MYOC
Variant information

Variant position:  370
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 Proline (P) to Leucine (L) at position 370 (P370L, p.Pro370Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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

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; severe form; inhibits endoproteolytic processing; produced the highest inhibition of the endoproteolytic processing; mainly accumulates as insoluble aggregates inside the endoplasmic reticulum; inhibits neurite outgrowth.
Any additional useful information about the variant.

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



Sequence information

Variant position:  370
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:   NTETVKAEKEIPGAGYHGQF  P YSWGGYTDIDLAVDEAGLWV
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                         NTETVKAEKEIPGAGYHGQFPYSW------GGYTDIDLAVDE---------------AGLWV

                              TAETVKAEREIPGAGYHGQFPYSW------GGYTDIDLAVD

Mouse                         DTETVKAEKEIPGAGYHGHFPYAW------GGYTDIDLAVD

Rat                           NTETVKAEKEIPGAGYHGQFPYAW------GGYTDIDLAVD

Bovine                        RTETLKAEKEIPGAGYHGQFPYSW------GGYTDIDLAVD

Rabbit                        NTETVKAEKEIPGAGYRGQFPYSW------GGYTDIDLAVD

Cat                           NTETVKAEKEIPGAGYHGQFPYSW------GGYTDIDLAVD

Slime mold                    KTELVALINKQKGTTLAVNFGQSIQYFKKKGSNNTVTFLKD

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
Metal binding 380 – 380 Calcium
Disulfide bond 245 – 433


Literature citations

Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma.
Adam M.F.; Belmouden A.; Binisti P.; Brezin A.P.; Valtot F.; Bechetoille A.; Dascotte J.-C.; Copin B.; Gomez L.; Chaventre A.; Bach J.-F.; Garchon H.-J.;
Hum. Mol. Genet. 6:2091-2097(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS GLC1A ARG-246; LEU-370; SER-477; LYS-480 AND PHE-499;

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;

Mutations in the TIGR gene in familial primary open-angle glaucoma in Japan.
Suzuki Y.; Shirato S.; Taniguchi F.; Ohara K.; Nishimaki K.; Ohta S.;
Am. J. Hum. Genet. 61:1202-1204(1997)
Cited for: VARIANTS GLC1A ARG-367 AND LEU-370;

Prevalence of mutations in TIGR/Myocilin in patients with adult and juvenile primary open-angle glaucoma.
Wiggs J.L.; Allingham R.R.; Vollrath D.; Jones K.H.; De La Paz M.; Kern J.; Patterson K.; Babb V.L.; Del Bono E.A.; Broomer B.W.; Pericak-Vance M.A.; Haines J.L.;
Am. J. Hum. Genet. 63:1549-1552(1998)
Cited for: VARIANTS GLC1A LYS-352; LEU-370; MET-377 AND HIS-437;

Juvenile open angle glaucoma: fine mapping of the TIGR gene to 1q24.3-q25.2 and mutation analysis.
Michels-Rautenstrauss K.G.; Mardin C.Y.; Budde W.M.; Liehr T.; Polansky J.R.; Nguyen T.; Timmerman V.; van Broeckhoven C.; Naumann G.O.H.; Pfeiffer R.A.; Rautenstrauss B.W.;
Hum. Genet. 102:103-106(1998)
Cited for: VARIANTS GLC1A ARG-367 AND LEU-370;

Novel TIGR/MYOC mutations in families with juvenile onset primary open angle glaucoma.
Stoilova D.; Child A.; Brice G.; Desai T.; Barsoum-Homsy M.; Ozdemir N.; Chevrette L.; Adam M.F.; Garchon H.-J.; Pitts Crick R.; Sarfarazi M.;
J. Med. Genet. 35:989-992(1998)
Cited for: VARIANTS GLC1A LEU-370; ALA-380 AND PRO-502; VARIANT LYS-76;

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;

Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene.
Vincent A.L.; Billingsley G.; Buys Y.; Levin A.V.; Priston M.; Trope G.; Williams-Lyn D.; Heon E.;
Am. J. Hum. Genet. 70:448-460(2002)
Cited for: VARIANTS GLC1A ARG-252; LYS-293; ARG-367; LEU-370; LYS-377; VAL-399 AND VAL-445; VARIANT ARG-398;

Novel mutations in the MYOC/GLC1A gene in a large group of glaucoma patients.
Michels-Rautenstrauss K.; Mardin C.; Wakili N.; Juenemann A.M.; Villalobos L.; Mejia C.; Soley G.C.; Azofeifa J.; Oezbey S.; Naumann G.O.H.; Reis A.; Rautenstrauss B.;
Hum. Mutat. 20:479-480(2002)
Cited for: VARIANTS GLC1A ALA-251; MET-345; ARG-367; LEU-370; ASN-393; SER-434; ASP-450 AND CYS-470; VARIANT LYS-76;

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.