TSKS

protein-coding

testis specific serine kinase substrate, the group of Protein phosphatase 1 regulatory subunits

Gene summary

This gene may play a role in testicular physiology, spermatogenesis or spermiogenesis. Expression of the encoded protein is highest in the testis and down-regulated in testicular cancer. The gene is localized to the region 19q13.3 among the related RAS viral oncogene homolog (RRAS) and interferon regulatory factor 3 (IRF3) genes, which are both involved in tumorigenesis pathways and progression. [provided by RefSeq, Jul 2008]

MANE transcript

NM_021733.2

Inheritance

—

ClinVar variants

U:97B:7

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr19:49,739,753-49,763,306

External References & Databases

Ensembl (ENSG00000126467)

Transcript & Mutation Effects

hg38 • Region Span ~23.6 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 TSKS variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 97

not providedTotal: 4

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021733.2. 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				4 clinvar		4
missense			95 clinvar	3 clinvar		98
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	97	7	0	104

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021733.2	RefSeq	NP_068379.1	11	MANE Select
ENST00000246801.8	Ensembl	ENSP00000246801.2	11	MANE Select
ENST00000358830.3	Ensembl	ENSP00000351691.2	7	Standard
ENST00001143489.1	Ensembl	ENSP00000802419.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of phosphatase activity

Molecular Function

protein binding
protein kinase binding

Cellular Component

centriole

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000246801
Coding exons: 11
Length: 23578
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.283	355	370	0.959	0.0000239	3769
Missense (PolyPhen)		145	159.87	0.90698		1693
Synonymous	0.491	165	173	0.953	0.0000120	1246
Loss of Function	4.56	3	29.9	0.100	0.00000159	316

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000084	0.000053	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in testicular physiology, most probably in the process of spermatogenesis or spermatid development.;

Intolerance Scores

LoFtool: 0.326
RVIS EVS: -0.33
RVIS percentile EVS: 30.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.447

Gene Damage Prediction

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