HNMT

histamine N-methyltransferase, the group of 7BS small molecule methyltransferases

Basic information

Region (hg38): 2:137964020-138016364

Links

ENSG00000150540 ∙ NCBI:3176 ∙ OMIM:605238 ∙ HGNC:5028 ∙ Uniprot:P50135 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 51 (Limited), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 51 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual development disorder, autosomal recessive 51	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	26206890

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HNMT gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNMT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	13		14
missense		1	14	2	1	18
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			1			1
Total	0	1	17	15	1

Variants in HNMT

This is a list of pathogenic ClinVar variants found in the HNMT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-137964494-G-A			Uncertain significance (Nov 02, 2023)
2-137964536-T-C			Likely benign (Jan 23, 2018)
2-137964616-G-A		not specified	Uncertain significance (Aug 13, 2021)
2-137964633-C-A			Likely benign (Dec 28, 2018)
2-137966915-G-A		Inherited susceptibility to asthma;Intellectual disability, autosomal recessive 51	Uncertain significance (Jun 10, 2022)
2-137970170-G-C			Uncertain significance (Nov 02, 2023)
2-137970171-A-T			Likely benign (Jun 13, 2018)
2-137970176-C-T		not specified	Uncertain significance (Jan 05, 2022)
2-137970206-G-A		Intellectual disability, autosomal recessive 51	Pathogenic (Oct 15, 2015)
2-137970207-C-T			Benign/Likely benign (Aug 01, 2023)
2-137970212-G-A		not specified	Uncertain significance (Oct 20, 2023)
2-137981259-G-A			Likely benign (Oct 01, 2021)
2-138000962-C-T		not specified	Uncertain significance (Aug 21, 2023)
2-138001003-T-C			Likely benign (Apr 01, 2024)
2-138002077-G-T		not specified	Uncertain significance (Dec 15, 2023)
2-138002079-C-T		Inherited susceptibility to asthma • HNMT-related disorder	Benign; risk factor (Nov 25, 2019)
2-138002082-C-T		Intellectual disability, autosomal recessive 51	Uncertain significance (Jul 31, 2018)
2-138002090-G-A		Intellectual disability, autosomal recessive 51	Conflicting classifications of pathogenicity (Dec 31, 2019)
2-138002096-G-A		not specified	Likely benign (Mar 08, 2024)
2-138002106-C-T		not specified	Uncertain significance (Aug 08, 2023)
2-138002119-G-A		HNMT-related disorder	Benign (Dec 31, 2019)
2-138002121-C-G		not specified	Uncertain significance (Feb 13, 2024)
2-138005156-C-T		not specified	Uncertain significance (Jun 06, 2023)
2-138005158-A-G			Likely benign (Jun 11, 2018)
2-138005175-TC-T		Inherited susceptibility to asthma;Intellectual disability, autosomal recessive 51 • not specified	Conflicting classifications of pathogenicity (Nov 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HNMT	protein_coding	protein_coding	ENST00000280097	6	52341

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0197	0.964	125671	0	64	125735	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.661	127	150	0.848	0.00000694	1957
Missense in Polyphen		41	40.362	1.0158		568
Synonymous	0.377	50	53.5	0.934	0.00000266	509
Loss of Function	2.09	5	13.2	0.379	5.57e-7	176

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000674	0.000674
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000336	0.000334
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine. {ECO:0000269|PubMed:26206890}.
• Disease: DISEASE: 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 mutations affecting distinct genetic loci, including the gene represented in this entry.
• Pathway: Histidine metabolism - Homo sapiens (human);Histidine Metabolism;Histidinemia;Amino Acid metabolism;Metapathway biotransformation Phase I and II;Methylation Pathways;Histidine catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;Selenoamino acid metabolism;Metabolism of ingested SeMet, Sec, MeSec into H2Se;histamine degradation;Histidine degradation (Consensus)

Recessive Scores

• pRec: 0.238

Intolerance Scores

• loftool: 0.483
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.0926
• hipred: N
• hipred_score: 0.218
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.884

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hnmt
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: histamine catabolic process;histidine catabolic process;brain development;respiratory gaseous exchange;methylation
• Cellular component: cytoplasm;cytosol;neuron projection;extracellular exosome
• Molecular function: histamine N-methyltransferase activity