TLX1
protein-codingT cell leukemia homeobox 1, the group of NKL subclass homeoboxes and pseudogenes
Gene summary
This gene encodes a nuclear transcription factor that belongs to the NK-linked or NK-like (NKL) subfamily of homeobox genes. The encoded protein is required for normal development of the spleen during embryogenesis. This protein is also involved in specification of neuronal cell fates. Ectopic expression of this gene due to chromosomal translocations is associated with certain T-cell acute lymphoblastic leukemias. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]
- TCL3
- HOX11
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.5 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 TLX1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005521.4. 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 | 42 | 2 | 44 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 42 | 2 | 0 | 44 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005512.1 | 3 | MANE Select | |
| Ensembl | ENSP00000359215.6 | 3 | MANE Select | |
| RefSeq | NP_001182446.1 | 3 | Standard | |
| Ensembl | ENSP00000434358.3 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transcriptional misregulation in cancer - Homo sapiens (human)
- Cell Differentiation - Index expanded
- Cell Differentiation - Index
Biological Process
- multicellular organism development
- positive regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- protein binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370196
- Coding exons
- 3
- Length
- 8289
- Individuals with no LoFs
- 123490
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 123492
- p
- 0.00000810
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.93 | 85 | 152 | 0.560 | 0.00000709 | 2053 |
| Missense (PolyPhen) | 19 | 52.994 | 0.35853 | 638 | ||
| Synonymous | 0.560 | 64 | 70.0 | 0.915 | 0.00000342 | 708 |
| Loss of Function | 2.44 | 1 | 8.80 | 0.114 | 3.81e-7 | 110 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000055 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000091 | 0.0000091 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Controls the genesis of the spleen. Binds to the DNA sequence 5'-GGCGGTAAGTGG-3'.;
- Disease
- DISEASE: Note=A chromosomal aberration involving TLX1 may be a cause of a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(10;14)(q24;q11) with TCRD. {ECO:0000269|PubMed:1676542, ECO:0000269|PubMed:1681546, ECO:0000269|PubMed:1717256}.;
Recessive Scores
- pRec
- 0.232
Intolerance Scores
- LoFtool
- 0.138
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.891
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |