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UniProtKB/Swiss-Prot Q96CV9: Variant p.Met98Lys

Optineurin
Gene: OPTN
Chromosomal location: 10p14-p15
Variant information

Variant position:  98
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Methionine (M) to Lysine (K) at position 98 (M98K, p.Met98Lys).
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 hydrophobic (M) 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

Variant description:  Polymorphism; may modify intraocular pressure and increase risk of GLC1E and NPG; induces TFRC degradation leading to autophagic death in retinal ganglion cells.
Any additional useful information about the variant.

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



Sequence information

Variant position:  98
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  577
The length of the canonical sequence.

Location on the sequence:   KQKEERQFFEIQSKEAKERL  M ALSHENEKLKEELGKLKGKS
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                         KQKEERQFFEIQSKEAKERLMALSHENEKLKEELGKLKGKS

Rhesus macaque                KQKEERQFFETQSKEAKERLMALSHENEKLKEELGKLKGKS

Mouse                         KQKEERLLFEMQSKEVKERLKALTHENERLKEELGKFKEKS

Rat                           KQKEERQLFEIQSKEAKERLKALSHENERLKEELGKLKEKS

Pig                           KQKEERLFFETQSKEAKERLTALSLENEKLKQELGKLKGKT

Chicken                       KQKEEREFYETKFKEAKQCLLAKCVENEQLQQQLQSLKERE

Xenopus laevis                ------------LKRHNQHLLDLNSANEVLRKELQSLKEKI

Zebrafish                     KQKEERDFLEQRLEEARTRLNTMDVENEALKNQVKELEKSG

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 1 – 577 Optineurin
Region 58 – 209 Interaction with Rab8
Coiled coil 38 – 170
Helix 37 – 98


Literature citations

Adult-onset primary open-angle glaucoma caused by mutations in optineurin.
Rezaie T.; Child A.; Hitchings R.; Brice G.; Miller L.; Coca-Prados M.; Heon E.; Krupin T.; Ritch R.; Kreutzer D.; Crick R.P.; Sarfarazi M.;
Science 295:1077-1079(2002)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; VARIANTS GLC1E LYS-50 AND GLN-545; VARIANTS LYS-98; SER-201; HIS-213; ARG-216 AND PRO-357;

The M98K variant of the OPTINEURIN (OPTN) gene modifies initial intraocular pressure in patients with primary open angle glaucoma.
Melki R.; Belmouden A.; Akhayat O.; Brezin A.; Garchon H.-J.;
J. Med. Genet. 40:842-844(2003)
Cited for: VARIANT LYS-98;

M98K-OPTN induces transferrin receptor degradation and RAB12-mediated autophagic death in retinal ganglion cells.
Sirohi K.; Chalasani M.L.; Sudhakar C.; Kumari A.; Radha V.; Swarup G.;
Autophagy 9:510-527(2013)
Cited for: CHARACTERIZATION OF VARIANT LYS-98; INTERACTION WITH RAB12;

Analysis of optineurin (OPTN) gene mutations in subjects with and without glaucoma: the blue mountains eye study.
Baird P.N.; Richardson A.J.; Craig J.E.; Mackey D.A.; Rochtchina E.; Mitchell P.;
Clin. Exp. Ophthalmol. 32:518-522(2004)
Cited for: VARIANT LYS-98;

Variants in optineurin gene and their association with tumor necrosis factor-alpha polymorphisms in Japanese patients with glaucoma.
Funayama T.; Ishikawa K.; Ohtake Y.; Tanino T.; Kurosaka D.; Kimura I.; Suzuki K.; Ideta H.; Nakamoto K.; Yasuda N.; Fujimaki T.; Murakami A.; Asaoka R.; Hotta Y.; Tanihara H.; Kanamoto T.; Mishima H.; Fukuchi T.; Abe H.; Iwata T.; Shimada N.; Kudoh J.; Shimizu N.; Mashima Y.;
Invest. Ophthalmol. Vis. Sci. 45:4359-4367(2004)
Cited for: VARIANTS GLC1E ASP-26 AND GLN-545; VARIANT LYS-98;

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.