Intellectual disability
Gene: HNMT

HNMT (histamine N-methyltransferase)
EnsemblGeneIds (GRCh38): ENSG00000150540
EnsemblGeneIds (GRCh37): ENSG00000150540
OMIM: 605238, Gene2Phenotype
HNMT is in 1 panel

5 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 14 Mar 2022, 2:22 p.m. | Last Modified: 14 Mar 2022, 2:22 p.m.

Panel Version: 3.1519

Created: 14 Mar 2022, 2:22 p.m.
Last Modified: 14 Mar 2022, 2:22 p.m.
Panel version: 3.1519

Ivone Leong (Genomics England Curator)

Green List (high evidence)

This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. Based on the expert reviews and available information, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Created: 17 Aug 2021, 10:12 a.m. | Last Modified: 17 Aug 2021, 10:12 a.m.

Panel Version: 3.1227

Created: 17 Aug 2021, 10:12 a.m.
Last Modified: 17 Aug 2021, 10:12 a.m.
Panel version: 3.1227

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Green List (high evidence)

In addition to the two unrelated families reported by Heidari et al. 2015 (PMID: 26206890), two further simplex cases with homozygous HNMT variants have been reported, providing sufficient evidence for a 'green' classification. Verhoeven et al. 2020 (PMID: 33310825) report an adult male patient with severe intellectual disability and autism, born to second cousins, with a homozygous nonsense variant (c.88C>T; p.Gln30*). Treatment with antihistaminergic medication and a histamine-restricted diet resulted in significant general improvement, supporting an etiological role for HNMT deficiency. Taskiran et al. 2021 (PMID: 33739554) report an adult male patient with severe intellectual disability, pervasive developmental disorder and ADHD, born to consanguineous parents, with a homozygous nonsense variant (c.100G>T; p.Glu34*).
Created: 13 Aug 2021, 9:10 a.m. | Last Modified: 13 Aug 2021, 9:10 a.m.

Panel Version: 3.1220

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; 616739

Publications

Created: 13 Aug 2021, 9:10 a.m.
Last Modified: 13 Aug 2021, 9:10 a.m.
Panel version: 3.1220

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Amber rating as additional unrelated pedigrees are required before inclusion of HNMT on a diagnostic panel (added to watchlist).
Created: 30 Jul 2020, 8:24 a.m. | Last Modified: 30 Jul 2020, 8:24 a.m.

Panel Version: 3.207

Heidari et al. 2015 (PMID: 26206890) described seven affected individuals from two unrelated Turkish and Kurdish consanguineous families presenting with nonsyndromic mild-profound ID (1 mild, 1 moderate, 3 severe, 2 severe-profound). Homozygous missense variants (c.179G>A; p.Gly60Asp) and (c.632T>C; p.Leu208Pro) were identified which segregated with the phenotype in each family. Functional data was supportive of defects in HNMT function.
Created: 30 Jul 2020, 8:21 a.m. | Last Modified: 30 Jul 2020, 8:21 a.m.

Panel Version: 3.206

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; Mental retardation, 616739

Publications

26206890

Created: 30 Jul 2020, 8:21 a.m.
Last Modified: 30 Jul 2020, 8:21 a.m.
Panel version: 3.206

Zornitza Stark (Australian Genomics)

Green List (high evidence)

7 individuals from two unrelated families, some functional evidence and other circumstantial evidence linking this gene to brain function. Borderline Amber/Green.
Sources: Expert list
Created: 7 Feb 2020, 2:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mental retardation, autosomal recessive 51, MIM#616739

Publications

Created: 7 Feb 2020, 2:31 a.m.

Panel version: 3.0

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green

Phenotypes

Mental retardation, autosomal recessive 51, OMIM:616739

OMIM

605238

Clinvar variants

Variants in HNMT

Penetrance

None

Publications

Panels with this gene

Intellectual disability