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    HNMT histamine N-methyltransferase [ Homo sapiens (human) ]

    Gene ID: 3176, updated on 10-Dec-2024

    Summary

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    Official Symbol
    HNMTprovided by HGNC
    Official Full Name
    histamine N-methyltransferaseprovided by HGNC
    Primary source
    HGNC:HGNC:5028
    See related
    Ensembl:ENSG00000150540 MIM:605238; AllianceGenome:HGNC:5028
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HMT; MRT51; HNMT-S1; HNMT-S2
    Summary
    In mammals, histamine is metabolized by two major pathways: N(tau)-methylation via histamine N-methyltransferase and oxidative deamination via diamine oxidase. This gene encodes the first enzyme which is found in the cytosol and uses S-adenosyl-L-methionine as the methyl donor. In the mammalian brain, the neurotransmitter activity of histamine is controlled by N(tau)-methylation as diamine oxidase is not found in the central nervous system. A common genetic polymorphism affects the activity levels of this gene product in red blood cells. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in liver (RPKM 20.0), fat (RPKM 16.4) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HNMT in Genome Data Viewer
    Location:
    2q22.1
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (137964473..138016364)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (138410245..138462150)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (138722043..138773934)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene thrombospondin type 1 domain containing 7B Neighboring gene RNA, 5S ribosomal pseudogene 105 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:138464785-138465284 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:138465941-138466440 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16592 Neighboring gene uncharacterized LOC101928273 Neighboring gene uncharacterized LOC107985948 Neighboring gene uncharacterized LOC105373636 Neighboring gene NANOG hESC enhancer GRCh37_chr2:138829640-138830141 Neighboring gene long intergenic non-protein coding RNA 1832

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Genotype-phenotype correlation for histamine N-methyltransferase in a Chinese Han population. Chen GL, et al. Clin Chim Acta, 2003 Aug. PMID 12867290
    2. Association of myasthenia gravis with polymorphisms in the gene of histamine N-methyltransferase. Kellermayer B, et al. Hum Immunol, 2013 Dec. PMID 23932992
    3. Human histamine N-methyltransferase pharmacogenetics: gene resequencing, promoter characterization, and functional studies of a common 5'-flanking region single nucleotide polymorphism (SNP). Wang L, et al. Biochem Pharmacol, 2002 Aug 15. PMID 12167489
    4. Membrane-bound histamine N-methyltransferase in mouse brain: possible role in the synaptic inactivation of neuronal histamine. Barnes WG, et al. J Neurochem, 2002 Sep. PMID 12358773
    5. Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson's disease. Palada V, et al. Neurobiol Aging, 2012 Apr. PMID 21794955

    See all (80) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Thr105Ile Variant (rs11558538) of the Histamine N-methyltransferase Gene may be associated with Reduced Risk of Parkinson Disease: A Meta-analysis.
      Title: The Thr105Ile Variant (rs11558538) of the Histamine N-methyltransferase Gene may be associated with Reduced Risk of Parkinson Disease: A Meta-analysis.
    2. HNMT Upregulation Induces Cancer Stem Cell Formation and Confers Protection against Oxidative Stress through Interaction with HER2 in Non-Small-Cell Lung Cancer.
      Title: HNMT Upregulation Induces Cancer Stem Cell Formation and Confers Protection against Oxidative Stress through Interaction with HER2 in Non-Small-Cell Lung Cancer.
    3. Inhibition of Astrocytic Histamine N-Methyltransferase as a Possible Target for the Treatment of Alzheimer's Disease.
      Title: Inhibition of Astrocytic Histamine N-Methyltransferase as a Possible Target for the Treatment of Alzheimer's Disease.
    4. Histamine N-methyltransferase plays a central role in the degradation of the neurotransmitter histamine. Leucine 208 is a critical amino acid residue to maintain the structural integrity of the protein. Replacements by other amino acid residues have profound effects on stability and catalytic activity.
      Title: Leucine 208 in human histamine N-methyltransferase emerges as a hotspot for protein stability rationalizing the role of the L208P variant in intellectual disability.
    5. NHMT polymorphisms are not associated with Parkinson's disease, ALS and multiple system atrophy in Chinese population.
      Title: Determining the Effect of the HNMT, STK39, and NMD3 Polymorphisms on the Incidence of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple System Atrophy in Chinese Populations.
    6. miR-223 participates in the pathogenesis of atopic dermatitis through upregulating HNMT indirectly to degrade the excessive histamine.
      Title: MicroRNA-223 is involved in the pathogenesis of atopic dermatitis by affecting histamine-N-methyltransferase.
    7. The C allele for the HNMT polymorphism was associated with a lower degree of disability due to migraine (OR, 10.0; 95% CI, 2.65-37.6). In contrast, presence of the T allele (in heterozygous individuals) was associated with higher degree of disability (OR, 37.1; 95% CI, 4.37-315.2)
      Title: Association of diamine oxidase and histamine N-methyltransferase polymorphisms with presence of migraine in a group of Mexican mothers of children with allergies.
    8. This study shown that eight linked SNPs (r(2) = 1) in the HNMT gene were associated with sedation according to the generalized linear model, adjusted for age, gender and BMI (false-discovery-rate-adjusted p = 0.013).
      Title: Histaminergic gene polymorphisms associated with sedation in clozapine-treated patients.
    9. Genotype and allelic variant frequencies of HNMT rs11558538 SNP 205 restless legs syndrome (RLS) patients and 410 controls using a TaqMan assay: HNMT rs11558538 genotypes allelic variants frequencies were similar between RLS patients and controls and not influenced by gender, family history of RLS, or RLS severity. Some evidence that RLS patients carrying the genotype rs11558538TT had an earlier age at onset.
      Title: Thr105Ile (rs11558538) polymorphism in the histamine-1-methyl-transferase (HNMT) gene and risk for restless legs syndrome.
    10. The present meta-analysis confirms published evidence suggesting that the HNMT rs11558538 minor allele is related to a reduced risk of developing Parkinson disease
      Title: Thr105Ile (rs11558538) polymorphism in the histamine N-methyltransferase (HNMT) gene and risk for Parkinson disease: A PRISMA-compliant systematic review and meta-analysis.
    Submit: New GeneRIF Correction See all GeneRIFs (42)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Inherited susceptibility to asthma
    MedGen: C1869116 OMIM: 600807 GeneReviews: Not available
    		Compare labs
    Intellectual disability, autosomal recessive 51
    MedGen: C4225220 OMIM: 616739 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables histamine N-methyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables histamine N-methyltransferase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in L-histidine catabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in histamine catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in histamine metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in methylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in respiratory gaseous exchange by respiratory system TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in centrosome IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    histamine N-methyltransferase
    NP_001019245.1
    NP_001019246.1
    NP_008826.1
    XP_011509366.1
    XP_016859437.1
    XP_016859438.1
    XP_054197622.1
    XP_054197623.1
    XP_054197624.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012966.1 RefSeqGene

      Range
      5236..57127
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001024074.3 → NP_001019245.1  histamine N-methyltransferase isoform 2

      See identical proteins and their annotated locations for NP_001019245.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternate exon in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus compared to isoform 1. This transcript is supported by multiple mRNAs and ESTs, but the predicted ORF has not yet been experimentally confirmed.
      Source sequence(s)
      AC093674
      Consensus CDS
      CCDS33297.1
      UniProtKB/Swiss-Prot
      P50135
      Related
      ENSP00000280096.5, ENST00000280096.5

    2. NM_001024075.3 → NP_001019246.1  histamine N-methyltransferase isoform 3

      See identical proteins and their annotated locations for NP_001019246.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), also called HNMT-S, includes an alternate exon in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AF523357
      Consensus CDS
      CCDS33296.1
      UniProtKB/Swiss-Prot
      P50135
      Related
      ENSP00000333259.4, ENST00000329366.8

    3. NM_006895.3 → NP_008826.1  histamine N-methyltransferase isoform 1

      See identical proteins and their annotated locations for NP_008826.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and it encodes the longest protein (isoform 1).
      Source sequence(s)
      AA935821, AC093674, AF523358, AF523360
      Consensus CDS
      CCDS2181.1
      UniProtKB/Swiss-Prot
      B2R9J3, P50135, Q546Z6, Q7Z7I2, Q8IU56, Q8WW98, Q9BRW6
      Related
      ENSP00000280097.3, ENST00000280097.5
      Conserved Domains (1) summary
      pfam13489
      Location:32 → 217
      Methyltransf_23; Methyltransferase domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      137964473..138016364
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011511064.3 → XP_011509366.1  histamine N-methyltransferase isoform X2

      Conserved Domains (1) summary
      pfam13489
      Location:1 → 91
      Methyltransf_23; Methyltransferase domain

    2. XM_017003949.3 → XP_016859438.1  histamine N-methyltransferase isoform X3

      UniProtKB/TrEMBL
      B4DWC1
      Conserved Domains (1) summary
      cl17173
      Location:32 → 148
      AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...

    3. XM_017003948.2 → XP_016859437.1  histamine N-methyltransferase isoform X1

      Conserved Domains (1) summary
      pfam13489
      Location:2 → 183
      Methyltransf_23; Methyltransferase domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      138410245..138462150
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054341648.1 → XP_054197623.1  histamine N-methyltransferase isoform X2

    2. XM_054341649.1 → XP_054197624.1  histamine N-methyltransferase isoform X3

      UniProtKB/TrEMBL
      B4DWC1

    3. XM_054341647.1 → XP_054197622.1  histamine N-methyltransferase isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P50135.1 GenPept UniProtKB/Swiss-Prot:P50135

    Gene LinkOut

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