UniProtKB/Swiss-Prot O75838: Variant p.Cys99Trp

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] The variants are classified into three categories: LP/P, LB/B and US.

• LP/P: likely pathogenic or pathogenic.
• LB/B: likely benign or benign.
• US: uncertain significance

Residue change: From Cysteine (C) to Tryptophan (W) at position 99 (C99W, p.Cys99Trp). 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 polar (C) to large size and aromatic (W) 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
Variant description: In DFNB48; inhibits the ability to decrease ATP-induced calcium release; decreases interaction with TMC1 and TMC2. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs370965183 [ dbSNP | Ensembl ]

Sequence information

Variant position: 99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 187 The length of the canonical sequence.
Location on the sequence: SEDGEGNLTFNDFVDMFSVL C ESAPRELKANYAFKIYDFNT 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.
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.

Type	Positions	Description
Chain	1 – 187	Calcium and integrin-binding family member 2
Domain	66 – 101	EF-hand 1
Binding site	116 – 116
Binding site	118 – 118

Literature citations

Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48.
Riazuddin S.; Belyantseva I.A.; Giese A.P.; Lee K.; Indzhykulian A.A.; Nandamuri S.P.; Yousaf R.; Sinha G.P.; Lee S.; Terrell D.; Hegde R.S.; Ali R.A.; Anwar S.; Andrade-Elizondo P.B.; Sirmaci A.; Parise L.V.; Basit S.; Wali A.; Ayub M.; Ansar M.; Ahmad W.; Khan S.N.; Akram J.; Tekin M.; Riazuddin S.; Cook T.; Buschbeck E.K.; Frolenkov G.I.; Leal S.M.; Friedman T.B.; Ahmed Z.M.;
Nat. Genet. 44:1265-1271(2012)
Cited for: VARIANTS DFNB48 SER-91; TRP-99 AND THR-123; VARIANT USH1J ASP-64; FUNCTION; SUBUNIT; INTERACTION WITH WHRN AND MYO7A; TISSUE SPECIFICITY; CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells.
Giese A.P.J.; Tang Y.Q.; Sinha G.P.; Bowl M.R.; Goldring A.C.; Parker A.; Freeman M.J.; Brown S.D.M.; Riazuddin S.; Fettiplace R.; Schafer W.R.; Frolenkov G.I.; Ahmed Z.M.;
Nat. Commun. 8:43-43(2017)
Cited for: CHARACTERIZATION OF VARIANTS DFNB48 ASP-64; SER-91 AND TRP-99; INTERACTION WITH TMC1 AND TMC2; CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of hair cells.
Liang X.; Qiu X.; Dionne G.; Cunningham C.L.; Pucak M.L.; Peng G.; Kim Y.H.; Lauer A.; Shapiro L.; Mueller U.;
Neuron 109:2131-2149(2021)
Cited for: CHARACTERIZATION OF VARIANTS DFNB48 ASP-64; TRP-66; SER-91; TRP-99; THR-123 AND TRP-186; INTERACTION WITH TMC1 AND TMC2;