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UniProtKB/Swiss-Prot Q99972: Variant p.Ala445Val

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

Variant position:  445
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 Alanine (A) to Valine (V) at position 445 (A445V, p.Ala445Val).
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 small size and hydrophobic (A) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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; no effect on protein stability.
Any additional useful information about the variant.

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



Sequence information

Variant position:  445
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:   SVANAFIICGTLYTVSSYTS  A DATVNFAYDTGTGISKTLTI
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                         SVA---------NAFIICGTLYTVSSYTSADATVNFAYDTGTG------------------------------------ISKTLTI

                              SVA---------NAFVICGHLYTISSYSSPDATVNFAYDTG

Mouse                         SVA---------NAFVICGILYTVSSYSSAHATVNFAYDTK

Rat                           SVA---------NAFVICGILYTVSSYSSVHATINFAYDTN

Bovine                        SVA---------NAFIICGTLYTVSSYSSPDATVNFAYDTG

Rabbit                        SVA---------NAFIICGTLYTVSSYSSADATVNFAYDTG

Cat                           SVA---------NAFIICGRLYTVSSYSAPDATINFAYDTG

Slime mold                    APAPGGAPMMKKPAPVPGGPAPGGSAIMKPAGGVSKPLPSP

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 428 – 428 Calcium
Metal binding 429 – 429 Calcium; via carbonyl oxygen
Beta strand 435 – 454


Literature citations

Structural basis for misfolding in myocilin-associated glaucoma.
Donegan R.K.; Hill S.E.; Freeman D.M.; Nguyen E.; Orwig S.D.; Turnage K.C.; Lieberman R.L.;
Hum. Mol. Genet. 24:2111-2124(2015)
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 228-504 IN COMPLEX WITH CALCIUM; DISULFIDE BONDS; CHARACTERIZATION OF VARIANTS GLC1A LYS-293; ILE-353 AND VAL-445; CHARACTERIZATION OF VARIANTS MET-329; CYS-422; PRO-425 AND CYS-473;

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;

Founder TIGR/myocilin mutations for glaucoma in the Quebec population.
Faucher M.; Anctil J.-L.; Rodrigue M.-A.; Duchesne A.; Bergeron D.; Blondeau P.; Cote G.; Dubois S.; Bergeron J.; Arseneault R.; Morissette J.; Raymond V.;
Hum. Mol. Genet. 11:2077-2090(2002)
Cited for: VARIANTS GLC1A TRP-126; LYS-293; LYS-352; ARG-367; GLU-423; THR-427; VAL-445 AND LEU-481; VARIANTS LYS-76; GLU-77 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.