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URL of this page: https://medlineplus.gov/genetics/gene/ush2a/

USH2A gene

usherin

Normal Function

The USH2A gene provides instructions for making a protein called usherin. Usherin is an important component of basement membranes, which are thin, sheet-like structures in many tissues that separate and support cells. Usherin is found in basement membranes in the inner ear and in the retina, which is the layer of light-sensitive tissue at the back of the eye.

The usherin protein often works as one of a group of proteins (a protein complex). Different versions (isoforms) of the usherin protein are produced from the USH2A gene, which suggests that this protein may have different functions. Studies suggest that one of these isoforms plays an important role in the development of sensory cells in the inner ear. These cells convert sound into electrical signals. Another isoform of usherin supports the development and function of specialized light receptor cells (photoreceptors) in the retina.

Usherin may also be involved in the function of synapses. Synapses are the junctions between nerve cells, such as the cells in the retina, where cell-to-cell communication occurs.

Health Conditions Related to Genetic Changes

Retinitis pigmentosa

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the USH2A gene can cause retinitis pigmentosa, which is characterized by vision loss that worsens over time. Retinitis pigmentosa affects the retina.  USH2A gene variants are the most common cause of the autosomal recessive form of retinitis pigmentosa. Autosomal recessive means that pathogenic variants in both copies of the USH2A gene in each cell are needed to cause the condition. This form of the disorder is described as nonsyndromic, which means that it is not associated with signs and symptoms that affect other parts of the body. Syndromic forms of retinitis pigmentosa, such as Usher syndrome (described below), have many other features.

Many of the pathogenic variants that cause retinitis pigmentosa lead to the substitution of one protein building block (amino acid) for another in the usherin protein. This causes cells to make a version of the protein that does not function properly, disrupting the structural organization and maintenance of photoreceptor cells. As a result, photoreceptor cells in the retina gradually break down, which causes the progressive vision loss that is seen in people with retinitis pigmentosa.

More About This Health Condition

Usher syndrome

Hundreds of pathogenic variants in the USH2A gene have been identified in people with Usher syndrome type IIA. Affected individuals typically have hearing loss that is present from birth and vision loss that develops later and worsens over time. The vision loss in people with Usher syndrome type IIA is caused by retinitis pigmentosa.

The pathogenic variants that cause Usher syndrome type IIA typically lead to a lack of functional usherin protein, which impairs the assembly and development of the sensory cells in the ear. The lack of usherin also disrupts the structural organization and maintenance of photoreceptor cells in the retina. These changes lead to the hearing and vision loss seen in individuals with Usher syndrome type IIA.

More About This Health Condition

Other Names for This Gene

  • US2
  • USH2
  • USH2A

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Bhattacharya G, Miller C, Kimberling WJ, Jablonski MM, Cosgrove D. Localization and expression of usherin: a novel basement membrane protein defective in people with Usher's syndrome type IIa. Hear Res. 2002 Jan;163(1-2):1-11. doi: 10.1016/s0378-5955(01)00344-6. Citation on PubMed
  • Blanco-Kelly F, Jaijo T, Aller E, Avila-Fernandez A, Lopez-Molina MI, Gimenez A, Garcia-Sandoval B, Millan JM, Ayuso C. Clinical aspects of Usher syndrome and the USH2A gene in a cohort of 433 patients. JAMA Ophthalmol. 2015 Feb;133(2):157-64. doi: 10.1001/jamaophthalmol.2014.4498. Citation on PubMed
  • Bujakowska KM, Liu Q, Pierce EA. Photoreceptor Cilia and Retinal Ciliopathies. Cold Spring Harb Perspect Biol. 2017 Oct 3;9(10):a028274. doi: 10.1101/cshperspect.a028274. Citation on PubMed
  • Chen X, Sheng X, Liu X, Li H, Liu Y, Rong W, Ha S, Liu W, Kang X, Zhao K, Zhao C. Targeted next-generation sequencing reveals novel USH2A mutations associated with diverse disease phenotypes: implications for clinical and molecular diagnosis. PLoS One. 2014 Aug 18;9(8):e105439. doi: 10.1371/journal.pone.0105439. eCollection 2014. Citation on PubMed or Free article on PubMed Central
  • Koenekoop R, Arriaga M, Trzupek KM, Lentz J. Usher Syndrome Type II. 1999 Dec 10 [updated 2023 Mar 23]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1341/ Citation on PubMed
  • Liu X, Bulgakov OV, Darrow KN, Pawlyk B, Adamian M, Liberman MC, Li T. Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4413-8. doi: 10.1073/pnas.0610950104. Epub 2007 Mar 5. Citation on PubMed or Free article on PubMed Central
  • McGee TL, Seyedahmadi BJ, Sweeney MO, Dryja TP, Berson EL. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. J Med Genet. 2010 Jul;47(7):499-506. doi: 10.1136/jmg.2009.075143. Epub 2010 May 27. Citation on PubMed or Free article on PubMed Central
  • O'Neal TB, Tripathy K, Luther EE. Retinitis Pigmentosa. 2024 Feb 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK519518/ Citation on PubMed
  • Sandberg MA, Rosner B, Weigel-DiFranco C, McGee TL, Dryja TP, Berson EL. Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene. Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5532-9. doi: 10.1167/iovs.08-2009. Epub 2008 Jul 18. Citation on PubMed or Free article on PubMed Central
  • Toualbi L, Toms M, Moosajee M. USH2A-retinopathy: From genetics to therapeutics. Exp Eye Res. 2020 Dec;201:108330. doi: 10.1016/j.exer.2020.108330. Epub 2020 Oct 27. Citation on PubMed
  • van Wijk E, Pennings RJ, te Brinke H, Claassen A, Yntema HG, Hoefsloot LH, Cremers FP, Cremers CW, Kremer H. Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II. Am J Hum Genet. 2004 Apr;74(4):738-44. doi: 10.1086/383096. Epub 2004 Mar 10. Citation on PubMed or Free article on PubMed Central

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.