TSSK4
protein-codingtestis specific serine kinase 4
Gene summary
This gene encodes a member of the testis-specific serine/threonine kinase family. The encoded protein is thought to be involved in spermatogenesis via stimulation of the CREB/CRE responsive pathway through phosphorylation of the cAMP responsive element binding protein transcription factor. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
- C14orf20
- STK22E
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.7 kbGenCC 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 TSSK4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001184739.2. 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 | 0 | |||||
| missense | 35 | 4 | 39 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 35 | 4 | 0 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001171668.1 | 4 | MANE Select | |
| Ensembl | ENSP00000339179.5 | 4 | MANE Select | |
| RefSeq | NP_001294996.1 | 3 | Standard | |
| RefSeq | NP_777604.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein phosphorylation
- multicellular organism development
- spermatogenesis
- cell differentiation
- positive regulation of CREB transcription factor activity
Molecular Function
- magnesium ion binding
- protein serine/threonine kinase activity
- protein binding
- ATP binding
Cellular Component
- acrosomal vesicle
- nucleus
- cytoplasm
- motile cilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000339917
- Coding exons
- 4
- Length
- 2666
- Individuals with no LoFs
- 125565
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 182
- Defined
- 125748
- p
- 0.000728
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.06 | 148 | 189 | 0.782 | 0.0000102 | 2211 |
| Missense (PolyPhen) | 60 | 81.157 | 0.73931 | 999 | ||
| Synonymous | 0.954 | 63 | 73.4 | 0.858 | 0.00000378 | 670 |
| Loss of Function | 0.131 | 13 | 13.5 | 0.962 | 7.45e-7 | 155 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.0015 | 0.0015 | notable |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00056 | 0.00042 | rare |
| European (Non-Finnish) | 0.00057 | 0.00057 | rare |
| South Asian | 0.00098 | 0.00098 | rare |
| Other | 0.0018 | 0.0018 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine kinase which is involved in male germ cell development and in mature sperm function (By similarity). May be involved in the Cre/Creb signaling pathway (By similarity). Phosphorylates CREB1 on 'Ser-133' in vitro and can stimulate Cre/Creb pathway in cells (PubMed:15964553). Phosphorylates CREM on 'Ser-116' in vitro (By similarity). Phosphorylates ODF2 on 'Ser-95' (By similarity). {ECO:0000250|UniProtKB:Q9D411, ECO:0000269|PubMed:15964553}.;
Recessive Scores
- pRec
- 0.0929
Intolerance Scores
- LoFtool
- 0.912
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.218
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |