UniProtKB/Swiss-Prot O43405: Variant p.Gly88Glu

Gene: COCH
Chromosomal location: 14q11.2-q13
Variant information

Variant position:  88
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 Glycine (G) to Glutamate (E) at position 88 (G88E, p.Gly88Glu).
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 glycine (G) to medium size and acidic (E)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Deafness, autosomal dominant, 9 (DFNA9) [MIM:601369]: A form of non-syndromic hearing loss characterized by onset in the fourth or fifth decade of life and initially involves the high frequencies. Hearing loss is progressive and usually complete by the sixth decade. In addition to cochlear involvement, DFNA9 patients also exhibit a spectrum of vestibular dysfunctions. Penetrance of the vestibular symptoms is often incomplete, and some patients are minimally affected, whereas others suffer from severe balance disturbances and episodes of vertigo. Affected individuals have mucopolysaccharide depositions in the channels of the cochlear and vestibular nerves. These depositions apparently cause strangulation and degeneration of dendritic fibers. {ECO:0000269|PubMed:10400989, ECO:0000269|PubMed:11295836, ECO:0000269|PubMed:12928864, ECO:0000269|PubMed:14512963, ECO:0000269|PubMed:16835921, ECO:0000269|PubMed:17561763, ECO:0000269|PubMed:18312449, ECO:0000269|PubMed:22610276, ECO:0000269|PubMed:22931125, ECO:0000269|PubMed:23993205, ECO:0000269|PubMed:25388789, ECO:0000269|PubMed:9806553, ECO:0000269|PubMed:9931344}. 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 DFNA9; affects protein deposition to the extracellular matrix.
Any additional useful information about the variant.

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

Sequence information

Variant position:  88
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  550
The length of the canonical sequence.

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.





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.

Chain 25 – 550 Cochlin
Domain 28 – 121 LCCL
Glycosylation 100 – 100 N-linked (GlcNAc...) asparagine
Beta strand 88 – 95

Literature citations

Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction.
Robertson N.G.; Lu L.; Heller S.; Merchant S.N.; Eavey R.D.; McKenna M.; Nadol J.B. Jr.; Miyamoto R.T.; Linthicum F.H. Jr.; Neto J.F.L.; Hudspeth A.J.; Seidman C.E.; Morton C.C.; Seidman J.G.;
Nat. Genet. 20:299-303(1998)
Cited for: VARIANTS DFNA9 GLY-66; GLU-88 AND ARG-117;

Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin.
Grabski R.; Szul T.; Sasaki T.; Timpl R.; Mayne R.; Hicks B.; Sztul E.;
Hum. Genet. 113:406-416(2003)

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.