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

Summary

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

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-AA036662 (e-PCR)
- UniSTS:80389

RH68885 (e-PCR)
- UniSTS:52490

RH70639 (e-PCR)
- UniSTS:59707

D2S2054 (e-PCR)
- UniSTS:3449

RH80835 (e-PCR)
- UniSTS:86231

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 more info	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

EC 2.1.1.8

NP_001019246.1

EC 2.1.1.8

NP_008826.1

EC 2.1.1.8

XP_011509366.1

EC 2.1.1.8

XP_016859437.1

EC 2.1.1.8

XP_016859438.1

EC 2.1.1.8

XP_054197622.1

EC 2.1.1.8

XP_054197623.1

EC 2.1.1.8

XP_054197624.1

EC 2.1.1.8

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

NG_012966.1 RefSeqGene

Range

5236..57127

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

137964473..138016364

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Conserved Domains (1) summary

pfam13489
Location:1 → 91

Methyltransf_23; Methyltransferase domain
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). ...
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

NC_060926.1 Alternate T2T-CHM13v2.0

Range

138410245..138462150

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054341648.1 → XP_054197623.1 histamine N-methyltransferase isoform X2
XM_054341649.1 → XP_054197624.1 histamine N-methyltransferase isoform X3

UniProtKB/TrEMBL

B4DWC1
XM_054341647.1 → XP_054197622.1 histamine N-methyltransferase isoform X1