THNSL2
protein-codingthreonine synthase like 2
Gene summary
This gene encodes a threonine synthase-like protein. A similar enzyme in mouse can catalyze the degradation of O-phospho-homoserine to a-ketobutyrate, phosphate, and ammonia. This protein also has phospho-lyase activity on both gamma and beta phosphorylated substrates. In mouse an alternatively spliced form of this protein has been shown to act as a cytokine and can induce the production of the inflammatory cytokine IL6 in osteoblasts. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.3 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 THNSL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018271.5. 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 | 2 | 1 | 3 | |||
| missense | 78 | 3 | 81 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 82 | 4 | 0 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060741.3 | 8 | MANE Select | |
| Ensembl | ENSP00000501453.1 | 8 | MANE Select | |
| RefSeq | NP_001231605.1 | 7 | Standard | |
| RefSeq | NP_001231607.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| thnsl2 | Danio rerio | Structure: head Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- biological_process
- serine family amino acid catabolic process
- regulation of signaling receptor activity
- dephosphorylation
- 2-oxobutyrate biosynthetic process
Molecular Function
- molecular_function
- threonine synthase activity
- cytokine activity
- pyridoxal phosphate binding
- serine binding
Cellular Component
- cellular_component
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324166
- Coding exons
- 8
- Length
- 16312
- Individuals with no LoFs
- 124917
- Homozygous LoFs
- 13
- Heterozygous LoFs
- 818
- Defined
- 125748
- p
- 0.00331
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0881 | 273 | 277 | 0.985 | 0.0000158 | 3152 |
| Missense (PolyPhen) | 87 | 80.951 | 1.0747 | 951 | ||
| Synonymous | -0.426 | 123 | 117 | 1.05 | 0.00000722 | 974 |
| Loss of Function | 1.49 | 12 | 19.0 | 0.632 | 8.92e-7 | 219 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0020 | 0.0020 | notable |
| Latino/Admixed American | 0.0016 | 0.0016 | notable |
| Ashkenazi Jewish | 0.0025 | 0.0025 | notable |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00054 | 0.00054 | rare |
| South Asian | 0.021 | 0.021 | notable |
| Other | 0.0029 | 0.0028 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Isoform 1: Acts as a catabolic phospho-lyase on both gamma- and beta-phosphorylated substrates. Degrades O-phospho- threonine (PThr) to alpha-ketobutyrate, ammonia and phosphate (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.143
Intolerance Scores
- LoFtool
- 0.550
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 77.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.504
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |