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)-methylatio... See more...

Aliases for HNMT Gene

Aliases for HNMT Gene

  • Histamine N-Methyltransferase 2 3 4 5
  • EC 4 50
  • HMT 3 4
  • HNMT-S1 3
  • HNMT-S2 3
  • MRT51 3
  • HNMT 5

External Ids for HNMT Gene

Previous GeneCards Identifiers for HNMT Gene

  • GC02P136386
  • GC02P137029
  • GC02P138744
  • GC02P138932
  • GC02P138555
  • GC02P138438
  • GC02P130713

Summaries for HNMT Gene

Entrez Gene Summary for HNMT Gene

  • 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]

GeneCards Summary for HNMT Gene

HNMT (Histamine N-Methyltransferase) is a Protein Coding gene. Diseases associated with HNMT include Mental Retardation, Autosomal Recessive 51 and Asthma. Among its related pathways are Viral mRNA Translation and Histidine metabolism. Gene Ontology (GO) annotations related to this gene include N-methyltransferase activity and histamine N-methyltransferase activity.

UniProtKB/Swiss-Prot Summary for HNMT Gene

  • Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.

Tocris Summary for HNMT Gene

  • Protein arginine methyltransferases are enyzmes that catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to the arginine residues on histones and other proteins. The dysregulation of this methylation is critical in the development of certain cancers.

No data available for CIViC Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HNMT Gene

Genomics for HNMT Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HNMT Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J137962 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 256.5 +1.0 1021 4.3 NCOR1 IKZF1 SSRP1 ZMYM3 KLF9 CEBPA ATF3 POLR2A NFIC CHD4 HNMT HSALNG0019145 lnc-NXPH2-12 ENSG00000260059 RPL15P5 ENSG00000228043 SPOPL FJ601684-256
GH02J137939 Enhancer 1.3 Ensembl ENCODE CraniofacialAtlas 20.8 -21.5 -21501 7 SSRP1 KLF9 CEBPA CHD4 YY1 FOXA1 ZFP64 HOMEZ THAP11 FOXA2 HSALNG0019142 HNMT SPOPL LOC101928273
GH02J138071 Enhancer 1 Ensembl ENCODE 10.3 +108.1 108095 2.2 ZNF600 ATF2 ZNF10 BRCA1 CEBPB FEZF1 ZNF639 ZEB1 MAX ZNF217 HNMT HSALNG0019155 LOC105373636 lnc-NXPH2-4 SPOPL
GH02J138121 Enhancer 0.9 Ensembl ENCODE 9.8 +159.9 159891 4.6 ZNF600 ATF2 ZNF10 FEZF1 ZNF639 ZNF217 CTBP1 CUX1 RFX5 ZNF843 HNMT piR-38351-271 lnc-NXPH2-4 ENSG00000228043 SPOPL
GH02J138028 Enhancer 0.9 Ensembl ENCODE 10.5 +64.3 64281 2.6 MYC IKZF1 MNT NKRF SPI1 HDAC2 BATF EP400 ZNF384 TCF12 HNMT HSALNG0019146 LOC107985948 FJ601684-256 SPOPL
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HNMT on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HNMT

Top Transcription factor binding sites by QIAGEN in the HNMT gene promoter:
  • ATF-2
  • Cdc5
  • E47
  • Hand1
  • HFH-1
  • POU2F1
  • POU2F1a
  • POU2F1b
  • SRF
  • SRF (504 AA)

Genomic Locations for HNMT Gene

Latest Assembly
52,345 bases
Plus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
51,892 bases
Plus strand

(GRCh37/hg19 by Ensembl)
52,341 bases
Plus strand

Genomic View for HNMT Gene

Genes around HNMT on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HNMT Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HNMT Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HNMT Gene

Proteins for HNMT Gene

  • Protein details for HNMT Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Histamine N-methyltransferase
    Protein Accession:
    Secondary Accessions:
    • B2R9J3
    • Q546Z6
    • Q7Z7I2
    • Q8IU56
    • Q8WW98
    • Q9BRW6

    Protein attributes for HNMT Gene

    292 amino acids
    Molecular mass:
    33295 Da
    Quaternary structure:
    • Monomer.
    • [Isoform 2]: Has no histamine-methylating activity.

    Three dimensional structures from OCA and Proteopedia for HNMT Gene

    Alternative splice isoforms for HNMT Gene


neXtProt entry for HNMT Gene

Selected DME Specific Peptides for HNMT Gene


Post-translational modifications for HNMT Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for HNMT Gene

Gene Families for HNMT Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for HNMT Gene

Suggested Antigen Peptide Sequences for HNMT Gene

GenScript: Design optimal peptide antigens:
  • Histamine N-methyltransferase (HNMT_HUMAN)
  • Histamine N-methyltransferase (Q9P1Y0_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the class I-like SAM-binding methyltransferase superfamily. HNMT family.
  • Belongs to the class I-like SAM-binding methyltransferase superfamily. HNMT family.
genes like me logo Genes that share domains with HNMT: view

Function for HNMT Gene

Molecular function for HNMT Gene

UniProtKB/Swiss-Prot Function:
Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=histamine + S-adenosyl-L-methionine = H(+) + N(tau)-methylhistamine + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:19301, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:58432, ChEBI:CHEBI:58600, ChEBI:CHEBI:59789; EC=; Evidence={ECO:0000255|PROSITE-ProRule:PRU00929, ECO:0000269|PubMed:26206890};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=5.47 uM for histamine (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:26206890};
GENATLAS Biochemistry:
histamine N-methyltransferase,S-adenosyl-L-methionine dependent cytosolic enzyme

Enzyme Numbers (IUBMB) for HNMT Gene

Phenotypes From GWAS Catalog for HNMT Gene

Gene Ontology (GO) - Molecular Function for HNMT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008168 methyltransferase activity IEA --
GO:0008170 N-methyltransferase activity IEA --
GO:0016740 transferase activity IEA --
GO:0046539 histamine N-methyltransferase activity TAS --
genes like me logo Genes that share ontologies with HNMT: view
genes like me logo Genes that share phenotypes with HNMT: view

Human Phenotype Ontology for HNMT Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HNMT Gene

MGI Knock Outs for HNMT:
  • Hnmt Hnmt<tm1a(KOMP)Wtsi>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HNMT

No data available for miRNA , Transcription Factor Targets and HOMER Transcription for HNMT Gene

Localization for HNMT Gene

Subcellular locations from UniProtKB/Swiss-Prot for HNMT Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HNMT gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 4
cytoskeleton 4
plasma membrane 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Centrosome (1)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HNMT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA,IDA 26206890
GO:0005813 centrosome IDA --
GO:0005829 cytosol TAS --
GO:0043005 neuron projection IEA --
genes like me logo Genes that share ontologies with HNMT: view

Pathways & Interactions for HNMT Gene

genes like me logo Genes that share pathways with HNMT: view

Gene Ontology (GO) - Biological Process for HNMT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001692 histamine metabolic process IMP 23505051
GO:0001695 histamine catabolic process IDA 26206890
GO:0002347 response to tumor cell IEA --
GO:0006548 histidine catabolic process TAS --
GO:0006972 hyperosmotic response IEA --
genes like me logo Genes that share ontologies with HNMT: view

No data available for SIGNOR curated interactions for HNMT Gene

Drugs & Compounds for HNMT Gene

(20) Drugs for HNMT Gene - From: DrugBank, PharmGKB, ApexBio, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Amodiaquine Approved, Investigational Pharma Target, inhibitor 119
Histamine Approved, Investigational Pharma Enzyme, substrate 1228
Aspirin Approved, Vet_approved Pharma 1600
Chlorhexidine Approved, Vet_approved Pharma 789
s-adenosylhomocysteine Experimental Pharma Target, Enzyme, inhibitor, binder 0

(9) Additional Compounds for HNMT Gene - From: Novoseek, HMDB, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • (3S)-5'-[(3-Amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine, inner salt
  • [1-(Adenin-9-yl)-1,5-dideoxy-beta-D-ribofuranos-5-yl][(3S)-3-amino-3-carboxypropyl](methyl)sulfonium
  • Acylcarnitine
  • AdoMet
  • S-(5'-Deoxyadenosin-5'-yl)-L-methionine
  • 1-Methyl-1H-imidazole-4-ethanamine
  • 1-Methyl-4-(2-aminoethyl)imidazole
  • 3-Methylhistamine
  • 4-(1-Aminoethyl)-1-methyl-1H-imidazole
  • Methylhistamine
Furamidine dihydrochloride
SGC 707
UNC 2327

(5) Tocris Compounds for HNMT Gene

Compound Action Cas Number
C 21 Selective PRMT1 inhibitor 1229236-78-5
Furamidine dihydrochloride Selective PRMT1 inhibitor 55368-40-6
SGC 707 Potent and selective allosteric inhibitor of PRMT3
TC-E 5003 Selective PRMT1 inhibitor 17328-16-4
UNC 2327 Allosteric inhibitor of PRMT3 1426152-53-5

(1) ApexBio Compounds for HNMT Gene

Compound Action Cas Number
SKF 91488 dihydrochloride 68941-21-9
genes like me logo Genes that share compounds with HNMT: view

Drug products for research

Transcripts for HNMT Gene

mRNA/cDNA for HNMT Gene

12 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HNMT

Alternative Splicing Database (ASD) splice patterns (SP) for HNMT Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10
SP1: - - - -
SP2: -
SP3: - - -
SP4: -
SP5: - -

Relevant External Links for HNMT Gene

GeneLoc Exon Structure for

Expression for HNMT Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HNMT Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for HNMT Gene

This gene is overexpressed in Uterus (9.8) and Spleen (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HNMT Gene

Protein tissue co-expression partners for HNMT Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HNMT

SOURCE GeneReport for Unigene cluster for HNMT Gene:


Evidence on tissue expression from TISSUES for HNMT Gene

  • Nervous system(4.6)
  • Liver(4.6)
  • Kidney(4.6)
  • Intestine(2.6)
  • Skin(2.4)
  • Lung(2.4)
  • Eye(2.3)
  • Blood(2.3)
  • Muscle(2.3)
  • Heart(2.2)
  • Lymph node(2.2)
  • Stomach(2.1)
  • Spleen(2.1)
genes like me logo Genes that share expression patterns with HNMT: view

Primer products for research

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for HNMT Gene

Orthologs for HNMT Gene

This gene was present in the common ancestor of chordates.

Orthologs for HNMT Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HNMT 29 30
  • 99.54 (n)
(Canis familiaris)
Mammalia HNMT 29 30
  • 90.53 (n)
(Bos Taurus)
Mammalia HNMT 29 30
  • 89.38 (n)
(Mus musculus)
Mammalia Hnmt 29 16 30
  • 86.76 (n)
(Rattus norvegicus)
Mammalia Hnmt 29
  • 86.3 (n)
(Monodelphis domestica)
Mammalia HNMT 30
  • 69 (a)
(Ornithorhynchus anatinus)
Mammalia HNMT 30
  • 56 (a)
(Gallus gallus)
Aves HNMT 29 30
  • 67.58 (n)
(Anolis carolinensis)
Reptilia HNMT 30
  • 57 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hnmt 29
  • 61.4 (n)
African clawed frog
(Xenopus laevis)
Amphibia hnmt-prov 29
(Danio rerio)
Actinopterygii hnmt 29 30
  • 55.37 (n)
Dr.17340 29
Species where no ortholog for HNMT was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for HNMT Gene

Gene Tree for HNMT (if available)
Gene Tree for HNMT (if available)
Evolutionary constrained regions (ECRs) for HNMT: view image
Alliance of Genome Resources:
Additional Orthologs for HNMT

Paralogs for HNMT Gene

No data available for Paralogs for HNMT Gene

Variants for HNMT Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HNMT Gene

Variant Ile-105 has a reduced activity and seems to be linked with a predisposition to asthma.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HNMT Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
1032500 Uncertain Significance: Mental retardation, autosomal recessive 51 138,002,082(+) C/T
NM_006895.3(HNMT):c.317C>T (p.Ser106Leu)
rs112342775 Likely Benign: not provided 138,014,001(+) T/C
NM_006895.3(HNMT):c.750T>C (p.Phe250=)
rs11558538 Risk Factor: Asthma, susceptibility to 138,002,079(+) C/Tp.Thr105Ile
NM_006895.3(HNMT):c.314C>T (p.Thr105Ile)
rs1316681747 Likely Benign: not provided 138,014,127(+) A/T
NM_006895.3(HNMT):c.876A>T (p.Ala292=)
rs143554428 Likely Benign: not provided 138,013,809(+) C/T
NM_006895.3(HNMT):c.558C>T (p.Tyr186=)

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HNMT Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HNMT Gene

Variant ID Type Subtype PubMed ID
esv2513921 CNV deletion 19546169
esv2671408 CNV deletion 23128226
esv34124 CNV loss 18971310
nsv583180 CNV gain 21841781
nsv583182 CNV loss 21841781
nsv7329 OTHER inversion 18451855

Variation tolerance for HNMT Gene

Residual Variation Intolerance Score: 59.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.01; 68.45% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HNMT Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

Disorders for HNMT Gene

MalaCards: The human disease database

(31) MalaCards diseases for HNMT Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
mental retardation, autosomal recessive 51
  • mrt51
  • asthma, susceptibility to
autosomal recessive non-syndromic intellectual disability
  • autosomal recessive mental retardation
suppression amblyopia
  • strabismic amblyopia
- elite association - COSMIC cancer census association via MalaCards
Search HNMT in MalaCards View complete list of genes associated with diseases


  • Mental retardation, autosomal recessive 51 (MRT51) [MIM:616739]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269 PubMed:26206890}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.

Additional Disease Information for HNMT

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HNMT: view

No data available for Genatlas for HNMT Gene

Publications for HNMT Gene

  1. Histamine N-methyltransferase pharmacogenetics: association of a common functional polymorphism with asthma. (PMID: 10803682) Yan L … Weinshilboum RM (Pharmacogenetics 2000) 3 4 22 40 72
  2. Lack of association of histamine-N-methyltransferase (HNMT) polymorphisms with asthma in the Indian population. (PMID: 16205835) Sharma S … Ghosh B (Journal of human genetics 2005) 3 22 40 72
  3. No association of histamine- N-methyltransferase polymorphism with asthma or bronchial hyperresponsiveness in two German pediatric populations. (PMID: 15693910) Deindl P … German Multicenter Atopy Study Group (Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 2005) 3 22 40 72
  4. Human histamine N-methyltransferase pharmacogenetics: common genetic polymorphisms that alter activity. (PMID: 9547362) Preuss CV … Weinshilboum RM (Molecular pharmacology 1998) 3 4 22 72
  5. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability. (PMID: 26206890) Heidari A … Vincent JB (Human molecular genetics 2015) 3 4 72

Products for HNMT Gene

Sources for HNMT Gene