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

Gene ID: 3176, updated on 5-Mar-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (137964473..138016364)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (138410245..138462150)
105.20220307 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: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The Thr105Ile Variant (rs11558538) of the Histamine N-methyltransferase Gene may be associated with Reduced Risk of Parkinson Disease: A Meta-analysis. Lu Y, et al. Genet Test Mol Biomarkers, 2022 Nov. PMID 36378841
  2. Inhibition of Astrocytic Histamine N-Methyltransferase as a Possible Target for the Treatment of Alzheimer's Disease. Flores-Clemente C, et al. Biomolecules, 2021 Sep 26. PMID 34680041, Free PMC Article
  3. Thr105Ile (rs11558538) polymorphism in the histamine-1-methyl-transferase (HNMT) gene and risk for restless legs syndrome. Jiménez-Jiménez FJ, et al. J Neural Transm (Vienna), 2017 Mar. PMID 27837280
  4. Leucine 208 in human histamine N-methyltransferase emerges as a hotspot for protein stability rationalizing the role of the L208P variant in intellectual disability. Tongsook C, et al. Biochim Biophys Acta Mol Basis Dis, 2017 Jan. PMID 27769936
  5. Thr105Ile (rs11558538) polymorphism in the histamine N-methyltransferase (HNMT) gene and risk for Parkinson disease: A PRISMA-compliant systematic review and meta-analysis. Jiménez-Jiménez FJ, et al. Medicine (Baltimore), 2016 Jul. PMID 27399132, Free PMC Article

See all (79) 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 Variation Viewer (GRCh37.p13)

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 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 histidine catabolic process TAS
Traceable Author Statement
more info
  
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_2023_10

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

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