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Intellectual disability

Gene: TLK2

Green List (high evidence)

TLK2 (tousled like kinase 2)
EnsemblGeneIds (GRCh38): ENSG00000146872
EnsemblGeneIds (GRCh37): ENSG00000146872
OMIM: 608439, Gene2Phenotype
TLK2 is in 5 panels

2 reviews

Ellen McDonagh (Genomics England Curator)

Comment on list classification: New evidence to promote this gene from Red to Green has arisen. A publication (Reijnders & Miller et al, AJHG, published online May 31, 2018) reports heterozygous loss-of-function or missense variants in this gene in 38 unrelated individuals and two affected mothers. Affected individuals had mild-boderline neurodevelopmental delay, behavioral disorders, severe gastro-intestinal problems and facial dysmorphism. 6% of the individuals had normal IQ levels (85–100), 14% had borderline ID (IQ
70–85), and from the 72% diagnosed with ID (IQ < 70), most had mild ID (IQ 50–70). 3 individuals were too young for formal assessment of their neurodevelopmental phenotype, but all had language and motor delay. Five loss-of-function variants were identified in gnomAD at a frequency of around 0.00002. None of the missense were identified in Exac or an in-house database of healthy individuals. Only one missense variant was identified in gnomAD in one individual (an allele frequency of 0.000004). The pseudogenes similar to TLK2 were investigated, and the sequences at the site of each recurrent mutation corresponded to wild-type TLK2, excluding a gene conversion mechanism. Analysis of ExAC demonstrated TLK2 is extremely intolerant for LOF variants with a pLI score of 1. Tlk2-null mice have been previously reported as embryonically lethal, due to placental failure.
Created: 1 Jun 2018, 7:33 a.m.
Comment on mode of inheritance: Heterozygous de novo or maternally inherited variants reported in Reijnders & Miller et al, AJHG (2018).
Created: 1 Jun 2018, 7:08 a.m.
Comment on publications: New publication "De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder" Reijnders & Miller et al, AJHG, published Online: May 31, 2018. ( - PMID not yet available).
Created: 1 Jun 2018, 7:07 a.m.

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

Added gene to panel but insufficient evidence to rate as diagnostic-grade. Current evidence comes from PMID:27479843 (2016) who perform meta-analysis on 2,637 de novo mutations identified from the exomes of 2,104 patient-parent trios, and identify TLK2 as a candidate ID gene.
Created: 31 Oct 2017, 10:18 a.m.

intellectual disability



Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • Mental retardation, autosomal dominant 57, OMIM:618050
  • Mental retardation, autosomal dominant 57, MONDO:0054837
Clinvar variants
Variants in TLK2
  • 27479843
Panels with this gene

History Filter Activity

8 Jan 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TLK2 were changed from intellectual disability to Mental retardation, autosomal dominant 57, OMIM:618050; Mental retardation, autosomal dominant 57, MONDO:0054837

29 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to TLK2.

1 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: tlk2 has been classified as Green List (High Evidence).

1 Jun 2018, Gel status: 1

Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for gene: TLK2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

1 Jun 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: TLK2 were set to 27479843;

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

Added New Source

Ellen McDonagh (Genomics England Curator)

TLK2 was added to Intellectual disability panel. Sources: Expert Review Red

29 Nov 2017, Gel status: 1


Ellen McDonagh (Genomics England Curator)

TLK2 was created by Ellen McDonagh