TLK2

tousled like kinase 2

Basic information

Region (hg38): 17:62458658-62615481

Links

ENSG00000146872 ∙ NCBI:11011 ∙ OMIM:608439 ∙ HGNC:11842 ∙ Uniprot:Q86UE8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 57 (Moderate), mode of inheritance: AD
• intellectual disability, autosomal dominant 57 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 57 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 57 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 57 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 57	AD	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	Craniofacial; Musculoskeletal; Neurologic	27479843; 29861108

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLK2 gene.

• not_provided (139 variants)
• Intellectual_disability,_autosomal_dominant_57 (77 variants)
• Inborn_genetic_diseases (43 variants)
• TLK2-related_disorder (9 variants)
• not_specified (7 variants)
• Neurodevelopmental_disorder (3 variants)
• Intellectual_disability (2 variants)
• See_cases (2 variants)
• Rare_genetic_intellectual_disability (1 variants)
• TLK2-related_neurodevelopmental_disorder (1 variants)
• Neurofibromatosis,_type_1 (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006852.6. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	13		14
missense		24	116	10		150
nonsense	15	14				29
start loss						0
frameshift	15	4	2			21
splice donor/acceptor (+/-2bp)	11	4	3			18
Total	41	46	122	23	0

Highest pathogenic variant AF is 0.00000657808

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLK2	protein_coding	protein_coding	ENST00000346027	21	156824

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.65e-8	125736	0	5	125741	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.49	148	401	0.369	0.0000217	4917
Missense in Polyphen		12	113.47	0.10575		1576
Synonymous	0.0259	145	145	0.997	0.00000802	1353
Loss of Function	6.62	2	55.0	0.0364	0.00000351	609

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation. Phosphorylates the chromatin assembly factors ASF1A AND ASF1B. Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly. Negative regulator of amino acid starvation-induced autophagy. {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:9427565}.
• Pathway: miRNA Regulation of DNA Damage Response;DNA Damage Response (Consensus)

Recessive Scores

• pRec: 0.0999

Intolerance Scores

• loftool: 0.156
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.367
• hipred: Y
• hipred_score: 0.817
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.451

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tlk2

Gene ontology

• Biological process: regulation of chromatin assembly or disassembly;chromatin organization;protein phosphorylation;cellular response to DNA damage stimulus;cell cycle;chromosome segregation;negative regulation of autophagy;peptidyl-serine phosphorylation;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;intracellular signal transduction;cellular response to gamma radiation
• Cellular component: nucleus;intermediate filament;perinuclear region of cytoplasm
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding