ArticleHuman molecular genetics2014
Adenylate cyclase 1 (ADCY1) mutations cause recessive hearing impairment in humans and defects in hair cell function and hearing in zebrafish.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 60 citations in OpenAlex.
- cAMP-MFN2 signaling suppresses cochlear cell senescence and age-related hearing loss.Frontiers in immunology · 2025Article
- Autosomal recessive non-syndromic hearing loss genes in Pakistan during the previous three decades.Journal of cellular and molecular medicine · 2024Review
- Molecular adaptations underlying high-frequency hearing in the brain of CF bats species.BMC genomics · 2024Article
- Analysis of the Selection Signal of the Tibetan Black Chicken Genome Based on Whole-Genome Sequencing.Genes · 2023Article
- Adenylyl cyclase 6 plays a minor role in the mouse inner ear and retina.Scientific reports · 2023Article
- Two Loci Contribute to Age-Related Hearing Loss Resistance in the Japanese Wild-Derived Inbred MSM/Ms Mice.Biomedicines · 2022Article
- ARNSHL gene identification: past, present and future.Molecular genetics and genomics : MGG · 2022Review
- cAMP and voltage modulate rat auditory mechanotransduction by decreasing the stiffness of gating springs.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Expression and functions of adenylyl cyclases in the CNS.Fluids and barriers of the CNS · 2022Review
- Structural basis of adenylyl cyclase 9 activation.Nature communications · 2022Article
- Small fish, big prospects: using zebrafish to unravel the mechanisms of hereditary hearing loss.Hearing research · 2020Article
- Growth factor and receptor malfunctions associated with human genetic deafness.Clinical genetics · 2020Review
- Water Waves to Sound Waves: Using Zebrafish to Explore Hair Cell Biology.Journal of the Association for Research in Otolaryngology : JARO · 2019Review
- A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer.Journal of Cancer · 2019Review
- Genetic Hearing Loss and Gene Therapy.Genomics & informatics · 2018Article
- Curating Clinically Relevant Transcripts for the Interpretation of Sequence Variants.The Journal of molecular diagnostics : JMD · 2018Article
- Suxiao Jiuxin Pill protects cardiomyocytes against mitochondrial injury and alters gene expression during ischemic injury.Experimental and therapeutic medicine · 2017Article
- Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population.Scientific reports · 2017Article
- Enhanced expression of ADCY1 underlies aberrant neuronal signalling and behaviour in a syndromic autism model.Nature communications · 2017Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Cyclic AMP (cAMP) production, which is important for mechanotransduction within the inner ear, is catalyzed by adenylate cyclases (AC). However, knowledge of the role of ACs in hearing is limited. Previously, a novel autosomal recessive non-syndromic hearing impairment locus DFNB44 was mapped to chromosome 7p14.1-q11.22 in a consanguineous family from Pakistan. Through whole-exome sequencing of DNA samples from hearing-impaired family members, a nonsense mutation c.3112C>T (p.Arg1038*) within adenylate cyclase 1 (ADCY1) was identified. This stop-gained mutation segregated with hearing impairment within the family and was not identified in ethnically matched controls or within variant databases. This mutation is predicted to cause the loss of 82 amino acids from the carboxyl tail, including highly conserved residues within the catalytic domain, plus a calmodulin-stimulation defect, both of which are expected to decrease enzymatic efficiency. Individuals who are homozygous for this mutation had symmetric, mild-to-moderate mixed hearing impairment. Zebrafish adcy1b morphants had no FM1-43 dye uptake and lacked startle response, indicating hair cell dysfunction and gross hearing impairment. In the mouse, Adcy1 expression was observed throughout inner ear development and maturation. ADCY1 was localized to the cytoplasm of supporting cells and hair cells of the cochlea and vestibule and also to cochlear hair cell nuclei and stereocilia. Ex vivo studies in COS-7 cells suggest that the carboxyl tail of ADCY1 is essential for localization to actin-based microvilli. These results demonstrate that ADCY1 has an evolutionarily conserved role in hearing and that cAMP signaling is important to hair cell function within the inner ear.
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