HLX
protein-codingH2.0 like homeobox, the group of NKL subclass homeoboxes and pseudogenes
Gene summary
Enables sequence-specific DNA binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within several processes, including embryonic digestive tract morphogenesis; enteric nervous system development; and regulation of T-helper cell differentiation. Predicted to be located in chromatin. Implicated in childhood-onset asthma. [provided by Alliance of Genome Resources, Jun 2026]
- HLX1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.6 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 HLX variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021958.4. 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 | 2 | 2 | 4 | |||
| missense | 82 | 2 | 1 | 85 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 84 | 4 | 1 | 89 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_068777.1 | 4 | MANE Select | |
| Ensembl | ENSP00000355870.5 | 4 | MANE Select | |
| Ensembl | ENSP00000408248.1 | 2 | Standard | |
| Ensembl | ENSP00000614573.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hlx1 | Danio rerio | Structure: intersegmental vein Quality: shortened abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TYROBP Causal Network
- IL12-mediated signaling events
Biological Process
- liver development
- regulation of transcription by RNA polymerase II
- multicellular organism development
- skeletal muscle tissue development
- positive regulation of cell population proliferation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- protein binding
- sequence-specific DNA binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000366903
- Coding exons
- 4
- Length
- 6703
- Individuals with no LoFs
- 125743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125748
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.377 | 275 | 293 | 0.938 | 0.0000155 | 3110 |
| Missense (PolyPhen) | 73 | 86.88 | 0.84024 | 932 | ||
| Synonymous | -0.619 | 148 | 139 | 1.07 | 0.00000850 | 1052 |
| Loss of Function | 3.21 | 2 | 15.8 | 0.127 | 7.32e-7 | 157 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor required for TBX21/T-bet-dependent maturation of Th1 cells as well as maintenance of Th1-specific gene expression. Involved in embryogenesis and hematopoiesis (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.157
Intolerance Scores
- LoFtool
- 0.222
- RVIS EVS
- 0.62
- RVIS percentile EVS
- 83.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.412
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | High | High |