protein
Serine/threonine-protein kinase tousled-like 2
Gene
TLK2
Organism
Homo sapiens(9606)
Length
772 aa
Mass
87,661 Da
TLK2 (tousled-like 2) is a serine/threonine-protein kinase of 772 amino acids that regulates chromatin assembly and associated DNA processes (UniProt: Q86UE8). The protein phosphorylates chromatin assembly factors ASF1A and ASF1B, with ASF1A phosphorylation preventing proteasomal degradation and promoting chromatin assembly. TLK2 also functions as a negative regulator of autophagy during amino acid starvation.
TLK2 is expressed in multiple tissues and participates in DNA replication, transcription, repair, and chromosome segregation. Pathogenic variants in TLK2 are associated with intellectual developmental disorder, autosomal dominant 57 (MRD57; MIM 618050), characterized by delayed psychomotor development, behavioral abnormalities, gastrointestinal dysfunction, and facial dysmorphism.
TLK2 is classified as SFARI category 1 with syndromic involvement (SFARI Cat 1), indicating strong evidence for association with autism spectrum disorder, particularly in the context of broader developmental and intellectual disability phenotypes.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037)
Disease associations
Intellectual developmental disorder, autosomal dominant 57MRD57
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD57 is characterized by delayed psychomotor development apparent in infancy or early childhood, and a variety of behavioral abnormalities. Affected individuals may have severe gastro-intestinal problems, and facial dysmorphism.
Sources
Last updated 5/6/2026, 5:25:12 AM