This report describes deafness, autosomal recessive 48. The human gene implicated in this disease is CIB2, which encodes a calcium-binding protein that plays a role in intracellular calcium homeostasis; in humans, it is highly expressed in the inner ear and retina. There is a single orthologous gene in Drosophila, Dmel\Cib2, for which RNAi targeting constructs have been generated. Dmel\Cib2 is also orthologous to a second human gene, CIB3.
The human gene Hsap\CIB2 has been introduced into flies, but has not been analyzed in the context of human disease. The human gene CIB3 has not been introduced into flies.
Work in flies addresses the retinal-dysfunction aspect of this disease. Adult flies with reduced function of Dmel\Cib2 in the eye, effected by RNAi, exhibit defects in photoresponse; when this genotype is raised in conditions of constant light, significant photoreceptor degeneration is observed.
[updated Jan. 2026 by FlyBase; FBrf0222196]
Usher syndrome is a condition characterized by partial or total hearing loss and vision loss that worsens over time. The hearing loss is classified as sensorineural, which means that it is caused by abnormalities of the inner ear. The loss of vision is caused by a type of retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue in the retina. [from Genetics Home Reference, Usher syndrome; 2017.01.09]
Usher syndrome is characterized by congenital hearing impairment and varying degrees of unintelligible speech, early retinitis pigmentosa, and vestibular dysfunction; autosomal recessive inheritance is usually observed. Type I is distinguished from type II on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989; pubmed:2909824). Patients with type III have progressive hearing loss. [from MIM:601067; 2017.01.09]
[DEAFNESS, AUTOSOMAL RECESSIVE 48; DFNB48](https://omim.org/entry/609439)
[CALCIUM- AND INTEGRIN-BINDING PROTEIN 2; CIB2](https://omim.org/entry/605564)
DFNB48 is an autosomal recessive form of deafness. Affected individuals have prelingual onset of severe to profound sensorineural hearing loss affecting all frequencies (summary by Riazuddin et al., 2012; pubmed:23023331). [from MIM:609439; 2026.01.13]
Autosomal recessive deafness-48 (DFNB48) is caused by homozygous mutation in the CIB2 gene (605564) on chromosome 15q25. [from MIM:609439; 2026.01.13]
Experiments in human and mouse have shown CIB2 to be highly expressed in the inner ear and retina. (Riazuddin et al., 2012; pubmed:23023331). [from MIM:605564; 2026.01.13]
CIB2 encodes a calcium-binding regulatory protein that plays a role in intracellular calcium homeostasis by decreasing ATP-induced calcium release; it plays a critical role in photoreceptor cell maintenance and function. [Gene Cards, CIB2; 2018.09.27]
The CIB2 gene encodes a protein belonging to a family of calcium- and integrin-binding proteins containing 3 or 4 EF-hand domains that change conformation upon binding of calcium and presumably mediate intracellular calcium signaling. CIB2 has conserved roles in calcium homeostasis (summary by Riazuddin et al., 2012; pubmed:23023331). [from MIM:605564; 2018.09.27]
Many to one (2 human to 1 Drosophila); the human genes are CIB2 and CIB3.
High-scoring ortholog of human CIB2 and CIB3 (1 Drosophila to 2 human). Dmel\Cib2 shares 55-57% identity and 70-73% similarity with the human genes.
