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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75838: Variant p.Cys99Trp

Calcium and integrin-binding family member 2
Gene: CIB2
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Variant information Variant position: help 99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help 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: help 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: help -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: help 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: help Links to websites of interest for the variant.


Sequence information Variant position: help 99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 187 The length of the canonical sequence.
Location on the sequence: help 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: help 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 – 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;
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.