HNMT

Protein identityUniProt · HPA

UniProt accession

P50135

Gene

HNMT

Ensembl

ENSG00000150540

Chromosome

2

Canonical length

292 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Centrosome,Cytosol

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

292 residues, UniProt reviewed canonical sequence.

>P50135|HNMT
     1  MASSMRSLFS DHGKYVESFR RFLNHSTEHQ CMQEFMDKKL PGIIGRIGDT KSEIKILSIG
    61  GGAGEIDLQI LSKVQAQYPG VCINNEVVEP SAEQIAKYKE LVAKTSNLEN VKFAWHKETS
   121  SEYQSRMLEK KELQKWDFIH MIQMLYYVKD IPATLKFFHS LLGTNAKMLI IVVSGSSGWD
   181  KLWKKYGSRF PQDDLCQYIT SDDLTQMLDN LGLKYECYDL LSTMDISDCF IDGNENGDLL
   241  WDFLTETCNF NATAPPDLRA ELGKDLQEPE FSAKKEGKVL FNNTLSFIVI EA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HNMT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

230 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HNMT.

Disease | AllUniProt

Conditions HNMT is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal recessive 51 (MRT51) MIM:616739

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 63 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, autosomal recessive 51
• Paediatric disorders

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.8

gnomAD pLI

0.02

gnomAD missense Z

0.66

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• chemical synaptic transmission
• histamine metabolic process
• L-histidine catabolic process
• methylation
• respiratory gaseous exchange by respiratory system
• histamine catabolic process

Molecular functions

• histamine N-methyltransferase activity

Cellular components

• centrosome
• cytoplasm
• cytosol
• extracellular exosome
• nucleoplasm
• synapse

Protein domainsUniProt · Pfam · InterPro

• S-adenosyl-L-methionine-dependent methyltransferase superfamily
• Methyltransferase domain
• Histamine N-methyltransferase-like

KeywordsUniProt

• Cytoplasm
• Intellectual disability
• Methyltransferase
• S-adenosyl-L-methionine
• Transferase