ArticleHuman molecular genetics2015
Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Impact of AOC1 and HNMT Variants on the Therapeutic Outcomes of a Histamine Reducing Diet in Autism Spectrum Disorder.Journal of molecular neuroscience : MN · 2025Article
- Spatial multiomics atlas reveals smooth muscle phenotypic transformation and metabolic reprogramming in diabetic macroangiopathy.Cardiovascular diabetology · 2024Article
- Prevalence and Clinical Picture of Diamine Oxidase Gene Variants in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study.Journal of clinical medicine · 2024Article
- The monoaminergic system is a bilaterian innovation.Nature communications · 2023Article
- Article
- Histamine: A Key Neuromodulator of Memory Consolidation and Retrieval.Current topics in behavioral neurosciences · 2022Review
- Changes in Histaminergic System in Neuropsychiatric Disorders and the Potential Treatment Consequences.Current neuropharmacology · 2022Review
- Identification of two novel homozygous nonsense mutations in TRAPPC9 in two unrelated consanguineous families with intellectual Disability from Iran.Molecular genetics & genomic medicine · 2021Article
- Histamine can be Formed and Degraded in the Human and Mouse Heart.Frontiers in pharmacology · 2021Article
- Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene.BMJ case reports · 2020Article
- Proteomics analysis indicated the protein expression pattern related to the development of fetal conotruncal defects.Journal of cellular physiology · 2019Article
- Genetics of intellectual disability in consanguineous families.Molecular psychiatry · 2019Article
- HistamineInternational journal of molecular sciences · 2019Review
- Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.Molecular psychiatry · 2018Article
- Mapping of the binding sites of human histamine N-methyltransferase (HNMT) monoclonal antibodies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability.BMC genomics · 2017Article
- The Use of Next-Generation Sequencing for Research and Diagnostics for Intellectual Disability.Cold Spring Harbor perspectives in medicine · 2017Review
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Authors and funding
34 authors at 17 institutions in 8 countries.
Funding
Abstract
Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability.
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