THEMIS
protein-codingthymocyte selection associated
Gene summary
This gene encodes a protein that plays a regulatory role in both positive and negative T-cell selection during late thymocyte development. The protein functions through T-cell antigen receptor signaling, and is necessary for proper lineage commitment and maturation of T-cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
- C6orf207
- C6orf190
- TSEPA
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~210.6 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 THEMIS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001010923.3. 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 | 1 | 1 | ||||
| missense | 92 | 4 | 1 | 97 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 93 | 4 | 1 | 98 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001010923.1 | 6 | MANE Select | |
| Ensembl | ENSP00000357231.2 | 6 | MANE Select | |
| RefSeq | NP_001158157.1 | 7 | Standard | |
| RefSeq | NP_001158159.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- adaptive immune response
- positive T cell selection
- negative T cell selection
- T cell receptor signaling pathway
Molecular Function
- protein binding
Cellular Component
- nucleus
- cytoplasm
- cell-cell junction
- COP9 signalosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000543064
- Coding exons
- 7
- Length
- 210560
- Individuals with no LoFs
- 125701
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 47
- Defined
- 125748
- p
- 0.000187
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.583 | 381 | 350 | 1.09 | 0.0000182 | 4457 |
| Missense (PolyPhen) | 118 | 114.92 | 1.0268 | 1498 | ||
| Synonymous | -1.49 | 151 | 129 | 1.17 | 0.00000712 | 1308 |
| Loss of Function | 2.05 | 13 | 23.8 | 0.546 | 0.00000115 | 341 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00040 | 0.00028 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a central role in late thymocyte development by controlling both positive and negative T-cell selection. Required to sustain and/or integrate signals required for proper lineage commitment and maturation of T-cells. Regulates T-cell development through T-cell antigen receptor (TCR) signaling and in particular through the regulation of calcium influx and phosphorylation of Erk. {ECO:0000250|UniProtKB:Q8BGW0}.;
Intolerance Scores
- LoFtool
- 0.847
- RVIS EVS
- -0.35
- RVIS percentile EVS
- 29.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0298
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |