TTBK1

protein-coding

tau tubulin kinase 1, the group of Armadillo like helical domain containing

Gene summary

Summary:This gene belongs to the casein kinase 1 superfamily. The encoded protein is a neuron-specific, serine/threonine and tyrosine kinase, which regulates phosphorylation of tau, a protein that associates with microtubule assemblies and stabilizes them. Genetic variants in this gene are associated with Alzheimer's disease. [provided by RefSeq, Jul 2016]

MANE transcript

NM_032538.3

Inheritance

—

ClinVar variants

P:2U:219B:24

Top phenotype

Autism

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr6:43,243,481-43,288,258

External References & Databases

Ensembl (ENSG00000146216)

Transcript & Mutation Effects

hg38 • Region Span ~44.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTBK1 variants in ClinVar

11 Conditions Cataloged

not specifiedTotal: 222

not providedTotal: 16

AutismTotal: 1

Childhood-onset schizophreniaTotal: 1

AnxietyTotal: 1

Mild global developmental delayTotal: 1

Neurodevelopmental abnormalityTotal: 1

Joint laxityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032538.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar	4 clinvar	9
missense		1 clinvar	213 clinvar	14 clinvar		228
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar	3 clinvar			4
splice donor/acceptor (+/-2bp)			2 clinvar	1 clinvar		3
Total	0	2	219	20	4	245

Highest pathogenic variant AF is 0.000010260732

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032538.3	RefSeq	NP_115927.1	14	MANE Select
ENST00000259750.9	Ensembl	ENSP00000259750.4	14	MANE Select
ENST00000703836.1	Ensembl	ENSP00000515493.1	13	Standard
XM_011514947.3	RefSeq	XP_011513249.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ras Signaling

Biological Process

protein phosphorylation
learning or memory
positive regulation of gene expression
negative regulation of gene expression
peptidyl-serine phosphorylation

Molecular Function

protein serine/threonine kinase activity
ATP binding
tau protein binding
tau-protein kinase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
microtubule associated complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259750
Coding exons: 14
Length: 44580
Individuals with no LoFs: 125674
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125682
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.63	555	759	0.731	0.0000497	8269
Missense (PolyPhen)		199	363.52	0.54742		3816
Synonymous	0.169	335	339	0.988	0.0000230	2878
Loss of Function	5.53	5	45.0	0.111	0.00000259	522

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000061	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000036	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU. {ECO:0000269|PubMed:16923168}.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.276
RVIS EVS: -0.46
RVIS percentile EVS: 23.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.697

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High