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Intellectual disability

Gene: TMLHE

Amber List (moderate evidence)
TMLHE (trimethyllysine hydroxylase, epsilon)
EnsemblGeneIds (GRCh38): ENSG00000185973
EnsemblGeneIds (GRCh37): ENSG00000185973
OMIM: 300777, Gene2Phenotype
TMLHE is in 1 panel

4 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Promoting to Amber as two unrelated families have been reported with moderate ID in association with this gene. This gene is otherwise linked to ASD susceptibility and the phenotype in these families may be explained by the more severe consequence (truncating) of their identified variants.

However, caution should be taken in the future if this gene is being considered for a diagnostic panel as pathogenicity remains unclear and it has been listed as non-disease gene.
Created: 27 Mar 2025, 2:43 p.m. | Last Modified: 27 Mar 2025, 2:43 p.m.
Panel Version: 8.234
Comment on publications: PMID: 39845198 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Created: 27 Mar 2025, 2:38 p.m. | Last Modified: 27 Mar 2025, 2:38 p.m.
Panel Version: 8.233
PMID: 39845198 (2025) - 46-year-old male patient with moderate intellectual disability and autism was found to have a hemizygous premature stop (c.14_16dup, p.(Leu6*)) in the TMHLE gene. Biochemical confirmation showed increased TML and decreased BB levels.

PMID: 23092983 (2012) - reported 4 boys, including 2 brothers, from 3 unrelated families with ASD. The two brothers harbouring a nonsense variant (c.229C>T, p.Arg77*) also had moderate intellectual disability and mild variable dysmorphic features.
Created: 27 Mar 2025, 2:36 p.m. | Last Modified: 27 Mar 2025, 2:36 p.m.
Panel Version: 8.230

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
{Autism, susceptibility to, X-linked 6}, OMIM:300872

Publications

Created: 27 Mar 2025, 2:36 p.m.
Last Modified: 27 Mar 2025, 2:36 p.m.
Panel version: 8.230

Caroline Wright (Sanger)

Red List (low evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

Rated red: Although MIM:300872 includes ID presentation, TMLHE is a susceptibility factor. Listed as non-disease gene in PMID:19377476.
Created: 31 Oct 2017, 9:24 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
{Autism, susceptibility to, X-linked 6}, 300872 (includes Intellectual disability)

Created: 31 Oct 2017, 9:24 a.m.

Panel version: Imported from Intellectual disability update Oct 2017 panel version 0.4

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:23 a.m.

Panel version: 0.306

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Amber
  • Victorian Clinical Genetics Services
Phenotypes
  • {Autism, susceptibility to, X-linked 6}, 300872 (includes Intellectual disability)
OMIM
300777
Clinvar variants
Variants in TMLHE
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

27 Mar 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: tmlhe has been classified as Amber List (Moderate Evidence).

27 Mar 2025, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: TMLHE were set to 39845198; 23092983

27 Mar 2025, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: TMLHE were set to

29 Sep 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to TMLHE.

12 Mar 2018, Gel status: 1

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 1

Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene TMLHE was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

TMLHE was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

TMLHE was added to Intellectual disabilitypanel. Sources: Expert Review Red