HNMT (histamine N-methyltransferase)

Gene

• Entrez ID: 3176
• Gene name: Histamine N-methyltransferase
• Gene symbol: HNMT
• Synonyms (NCBI Gene): HMT, HNMT-S1, HNMT-S2, MRT51
• Chromosome: 2
• Chromosome location: 2q22.1
• 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-methioni

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs758252808	G>A	Pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant, non coding transcript variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT756045	hsa-miR-33a-5p	Microarray, qRT-PCR	35899934
MIRT1050600	hsa-miR-1273f	CLIP-seq
MIRT1050601	hsa-miR-143	CLIP-seq
MIRT1050602	hsa-miR-2113	CLIP-seq
MIRT1050603	hsa-miR-221	CLIP-seq
MIRT1050604	hsa-miR-222	CLIP-seq
MIRT1050605	hsa-miR-323-3p	CLIP-seq
MIRT1050606	hsa-miR-4461	CLIP-seq
MIRT1050607	hsa-miR-4708-5p	CLIP-seq
MIRT1050608	hsa-miR-4770	CLIP-seq
MIRT1050609	hsa-miR-520f	CLIP-seq
MIRT1050610	hsa-miR-758	CLIP-seq
MIRT2011621	hsa-miR-3663-5p	CLIP-seq
MIRT2011622	hsa-miR-371-5p	CLIP-seq
MIRT2011623	hsa-miR-371b-5p	CLIP-seq
MIRT2243798	hsa-miR-129-5p	CLIP-seq
MIRT2243799	hsa-miR-21	CLIP-seq
MIRT2243800	hsa-miR-218	CLIP-seq
MIRT2243801	hsa-miR-300	CLIP-seq
MIRT2243802	hsa-miR-3160-3p	CLIP-seq
MIRT2243803	hsa-miR-3616-3p	CLIP-seq
MIRT2243804	hsa-miR-381	CLIP-seq
MIRT2243805	hsa-miR-4282	CLIP-seq
MIRT2243806	hsa-miR-4437	CLIP-seq
MIRT2243807	hsa-miR-4487	CLIP-seq
MIRT2243808	hsa-miR-450b-5p	CLIP-seq
MIRT2243809	hsa-miR-4666-3p	CLIP-seq
MIRT2243810	hsa-miR-4694-3p	CLIP-seq
MIRT2243811	hsa-miR-4704-3p	CLIP-seq
MIRT2243812	hsa-miR-4721	CLIP-seq
MIRT2243813	hsa-miR-4735-5p	CLIP-seq
MIRT2243814	hsa-miR-4775	CLIP-seq
MIRT2243815	hsa-miR-4781-3p	CLIP-seq
MIRT2243816	hsa-miR-4789-5p	CLIP-seq
MIRT2243817	hsa-miR-507	CLIP-seq
MIRT2243818	hsa-miR-556-5p	CLIP-seq
MIRT2243819	hsa-miR-557	CLIP-seq
MIRT2243820	hsa-miR-558	CLIP-seq
MIRT2243821	hsa-miR-590-3p	CLIP-seq
MIRT2243822	hsa-miR-590-5p	CLIP-seq
MIRT2243823	hsa-miR-596	CLIP-seq
MIRT2243824	hsa-miR-636	CLIP-seq
MIRT2546935	hsa-miR-1286	CLIP-seq
MIRT2546936	hsa-miR-148a	CLIP-seq
MIRT2546937	hsa-miR-148b	CLIP-seq
MIRT2546938	hsa-miR-152	CLIP-seq
MIRT2243802	hsa-miR-3160-3p	CLIP-seq
MIRT2243803	hsa-miR-3616-3p	CLIP-seq
MIRT2243806	hsa-miR-4437	CLIP-seq
MIRT2243807	hsa-miR-4487	CLIP-seq
MIRT2546939	hsa-miR-4493	CLIP-seq
MIRT2243812	hsa-miR-4721	CLIP-seq
MIRT2546940	hsa-miR-4722-5p	CLIP-seq
MIRT2546941	hsa-miR-485-3p	CLIP-seq
MIRT2546942	hsa-miR-487a	CLIP-seq
MIRT2546943	hsa-miR-516a-3p	CLIP-seq
MIRT2546944	hsa-miR-548aa	CLIP-seq
MIRT2243818	hsa-miR-556-5p	CLIP-seq
MIRT2243820	hsa-miR-558	CLIP-seq
MIRT2546945	hsa-miR-602	CLIP-seq
MIRT2243802	hsa-miR-3160-3p	CLIP-seq
MIRT2243803	hsa-miR-3616-3p	CLIP-seq
MIRT2243806	hsa-miR-4437	CLIP-seq
MIRT2243807	hsa-miR-4487	CLIP-seq
MIRT2546939	hsa-miR-4493	CLIP-seq
MIRT2243812	hsa-miR-4721	CLIP-seq
MIRT2546943	hsa-miR-516a-3p	CLIP-seq
MIRT2243818	hsa-miR-556-5p	CLIP-seq
MIRT2243820	hsa-miR-558	CLIP-seq
MIRT2546945	hsa-miR-602	CLIP-seq
MIRT1050610	hsa-miR-758	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001692	Process	Histamine metabolic process	IMP	23505051
GO:0001695	Process	Histamine catabolic process	IDA	26206890
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	26206890
GO:0005737	Component	Cytoplasm	IEA
GO:0005813	Component	Centrosome	IDA
GO:0005829	Component	Cytosol	IDA	23505051
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006548	Process	L-histidine catabolic process	TAS
GO:0007585	Process	Respiratory gaseous exchange by respiratory system	TAS	7943261
GO:0008168	Function	Methyltransferase activity	IEA
GO:0008170	Function	N-methyltransferase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0032259	Process	Methylation	IDA	26206890
GO:0032259	Process	Methylation	IEA
GO:0046539	Function	Histamine N-methyltransferase activity	IDA	26206890
GO:0046539	Function	Histamine N-methyltransferase activity	IEA
GO:0046539	Function	Histamine N-methyltransferase activity	TAS
GO:0070062	Component	Extracellular exosome	HDA	19056867

Other IDs

• MIM: 605238
• HGNC: 5028
• e!Ensembl: ENSG00000150540

Protein

• UniProt ID: P50135
• Protein name: Histamine N-methyltransferase (HMT) (EC 2.1.1.8)
• Protein function: Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
• PDB: 1JQD, 1JQE, 2AOT, 2AOU, 2AOV, 2AOW, 2AOX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13489	Methyltransf_23	27 → 217		Domain

• Sequence:

  MASSMRSLFSDHGKYVESFRRFLNHSTEHQCMQEFMDKKLPGIIGRIGDTKSEIKILSIG
  GGAGEIDLQILSKVQAQYPGVCINNEVVEPSAEQIAKYKELVAKTSNLENVKFAWHKETS
  SEYQSRMLEKKELQKWDFIHMIQMLYYVKDIPATLKFFHSLLGTNAKMLIIVVSGSSGWD
  KLWKKYGSRFPQDDLCQYITSDDLTQMLDNLGLKYECYDLLSTMDISDCFIDGNENGDLL
  WDFLTETCNFNATAPPDLRAELGKDLQEPEFSAKKEGKVLFNNTLSFIVIEA

• Sequence length: 292

Pathways

KEGG:

Histidine metabolism
Metabolic pathways

Reactome:

Histidine catabolism

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Intellectual disability, autosomal recessive 51	Pathogenic; Likely pathogenic	rs758252808, rs745756308	RCV000203518 RCV000203542	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTHMA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE NON-SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DERMATITIS, ATOPIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIGESTIVE SYSTEM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESSENTIAL TREMOR	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTROINTESTINAL DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HNMT-related disorder	Benign; risk factor; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Inherited susceptibility to asthma	Benign; risk factor; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 51	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LANGUAGE DEVELOPMENT DISORDERS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pulmonary arterial hypertension	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RHINITIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
URTICARIA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absence of septum pellucidum	Absence Of Septum Pellucidum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Acute Promyelocytic Leukemia	Promyelocytic Leukemia	BEFREE	31396278		★☆☆☆☆ Found in Text Mining only
Allergic rhinitis (disorder)	Allergic rhinitis	BEFREE	10051705		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	29564728		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	10803682, 15693910, 16205835, 17651147, 17672811, 25295384		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Asthma	Asthma	CTD_human_DG	17651147		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Asthma	Asthma	Pubtator	19025430, 25295384, 25909280	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Asthma	Asthma	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	33310825	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal recessive non-syndromic intellectual disability	Non-Syndromic Intellectual Disability	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bladder Neoplasm	Bladder Neoplasm	BEFREE	30984543		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	24835231, 25537518		★☆☆☆☆ Found in Text Mining only
Bronchial Hyperreactivity	Bronchial Hyperreactivity	BEFREE	15693910		★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	30984543		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	29099276	Associate	★☆☆☆☆ Found in Text Mining only
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood asthma	Asthma	GWASDB_DG	17611496		★☆☆☆☆ Found in Text Mining only
Chronic heart failure	Heart Failure	BEFREE	26989676		★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Ulcerative colitis	Pubtator	16489678	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	24925220		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	26989676		★☆☆☆☆ Found in Text Mining only
Cortical Dysplasia	Cortical Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deafness	Deafness	Pubtator	33524580	Associate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dermatitis Atopic	Atopic dermatitis	Pubtator	19025430	Associate	★☆☆☆☆ Found in Text Mining only
Dermatitis, Atopic	Dermatitis	BEFREE	19025430, 29506638		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dermatitis, Atopic	Dermatitis	LHGDN	19025430		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental Disabilities	Developmental disability	Pubtator	33310825	Associate	★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathy	Diabetic Nephropathy	BEFREE	28695133		★☆☆☆☆ Found in Text Mining only
Diffuse Large B-Cell Lymphoma	Diffuse Lymphoma	BEFREE	29623853		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	11880199		★☆☆☆☆ Found in Text Mining only
Duodenal Ulcer	Duodenal Ulcer	BEFREE	18086566		★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Eczema	Eczema	BEFREE	19025430, 29506638		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	32894095, 39326337	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	26004606	Associate	★☆☆☆☆ Found in Text Mining only
Essential Tremor	Tremor	BEFREE	18543121, 19773194		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric ulcer	Gastric ulcer	BEFREE	15551002		★☆☆☆☆ Found in Text Mining only
Generalized seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	26206890, 27769936		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	26206890, 33310825	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intestinal Diseases	Intestinal disease	Pubtator	33310825	Associate	★☆☆☆☆ Found in Text Mining only
Language Development Disorders	Language development disorders	Pubtator	33310825	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of breast	Breast Cancer	BEFREE	24835231, 25537518		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	30616239		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	30984543		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	21886846, 24047271		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 51	Mental retardation	UNIPROT_DG	26206890		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 51	Mental retardation	GENOMICS_ENGLAND_DG	30744146		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 51	Mental retardation	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 51	Mental retardation	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Migraine Disorders	Migraine	BEFREE	18266724, 27130307		★☆☆☆☆ Found in Text Mining only
Migraine Disorders	Migraine	Pubtator	27130307	Associate	★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Motion Sickness	Motion Sickness	BEFREE	29298819		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	BEFREE	18543121		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	19538200		★☆☆☆☆ Found in Text Mining only
Myasthenia Gravis	Myasthenia Gravis	BEFREE	23932992		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	28837224, 29113759		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	23807219	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	17985251, 18543121, 19773194, 21138759, 21794955, 25768024, 27399132, 27837280		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson Disease	Parkinson disease	Pubtator	25768024, 38027039	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pick Disease of the Brain	Pica	BEFREE	11880199		★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	29623853		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	30616239		★☆☆☆☆ Found in Text Mining only
Restless Legs Syndrome	Restless Legs Syndrome	BEFREE	27837280		★☆☆☆☆ Found in Text Mining only
Reticulosarcoma	Reticulosarcoma	BEFREE	29623853		★☆☆☆☆ Found in Text Mining only
Rhinitis	Rhinitis	BEFREE	17651147		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Rhinitis	Rhinitis	CTD_human_DG	17651147		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Rhinitis Allergic	Rhinitis	Pubtator	19025430	Associate	★☆☆☆☆ Found in Text Mining only
Salaam Seizures	Salaam Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	10898922, 25768024		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	Pubtator	25768024	Associate	★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	16489678		★☆☆☆☆ Found in Text Mining only
Urticaria	Urticaria	CTD_human_DG	20485159		★★☆☆☆ Found in Text Mining + Unknown/Other Associations