TLX2
protein-codingT cell leukemia homeobox 2, the group of NKL subclass homeoboxes and pseudogenes
Gene summary
This gene is a member of an orphan homeobox-containing transcription factor family. Studies of the mouse ortholog have shown that the encoded protein is crucial for the development of the enteric nervous system; in humans, loss-of-function may play a role in tumorigenesis of gastrointestinal stromal tumors. [provided by RefSeq, May 2010]
- HOX11L1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.7 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 TLX2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016170.5. 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 | 2 | ||||
| missense | 40 | 1 | 41 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 40 | 1 | 2 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057254.1 | 3 | MANE Select | |
| Ensembl | ENSP00000233638.6 | 3 | MANE Select | |
| Ensembl | ENSP00000482690.1 | 3 | Standard | |
| Ensembl | ENSP00000482690.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell Differentiation - Index expanded
- Cell Differentiation - Index
- Neural Crest Differentiation
- ALK1 signaling events
- ALK2 signaling events
Biological Process
- mesoderm formation
- positive regulation of transcription by RNA polymerase II
- enteric nervous system development
- negative regulation of dendrite morphogenesis
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- sequence-specific DNA binding
Cellular Component
- cellular_component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000233638
- Coding exons
- 3
- Length
- 3685
- Individuals with no LoFs
- 125573
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125576
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.495 | 135 | 152 | 0.887 | 0.00000699 | 1732 |
| Missense (PolyPhen) | 48 | 52.893 | 0.9075 | 594 | ||
| Synonymous | -0.948 | 83 | 72.7 | 1.14 | 0.00000342 | 661 |
| Loss of Function | 1.88 | 2 | 7.59 | 0.263 | 3.30e-7 | 88 |
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 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription activator that binds DNA elements with the consensus sequence 5'-CGGTAATTGG-3'. Binds DNA via its homeobox. Required for normal cell death of enteric neurons in the gastrointestinal tract. Required for normal development of the enteric nervous system, and for proper development of normal motility of the gastrointestinal tract (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.233
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.576
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |