ARNT2: Aryl Hydrocarbon Receptor Nuclear Translocator 2
Key regulator of neurodevelopment, endocrine function, and cellular response to hypoxia.
Gene Information Card
| Symbol | ARNT2 |
|---|---|
| Full Name | Aryl Hydrocarbon Receptor Nuclear Translocator 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q25.1 |
| NCBI Gene ID | 9915 ncbi.nlm.nih.gov/gene/9915 |
| Ensembl ID | ENSG00000172379 |
| UniProt ID | Q9HBZ2 |
| OMIM ID | 606036 |
| HGNC ID | 702 |
| Aliases | bHLHe1, MGC138207, MGC138209 |
Description
ARNT2 encodes a member of the basic helix-loop-helix (bHLH) Per-Arnt-Sim (PAS) family of transcription factors. The protein forms heterodimers with other bHLH-PAS proteins, such as SIM1 and SIM2, to regulate gene expression in response to developmental and environmental signals. ARNT2 is critical for neurodevelopment, hypothalamic-pituitary axis function, and cellular adaptation to hypoxia. Loss-of-function mutations are associated with syndromic intellectual disability and endocrine abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| ARNT2-related neurodevelopmental disorder | Biallelic loss-of-function mutations disrupt ARNT2 dimerization with SIM1/SIM2, impairing hypothalamic development and function. | ClinVar, OMIM |
| Central diabetes insipidus (syndromic) | ARNT2 deficiency leads to abnormal development of the supraoptic and paraventricular nuclei, causing vasopressin deficiency. | ClinVar, OMIM |
| Pituitary stalk interruption syndrome | Disrupted ARNT2 signaling affects pituitary gland morphogenesis and hormone secretion. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Kidney | 8.2 | Low |
| Lung | 6.1 | Low |
| Liver | 3.4 | Not detected |
| Heart | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | Neuronal model |
| HEK293 (embryonic kidney) | 9.8 | Common expression |
| HeLa (cervical carcinoma) | 4.2 | Low expression |
| HepG2 (hepatocellular carcinoma) | 1.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1372C>T (p.Arg458*) | Nonsense | Rare | Loss of function – premature truncation |
| c.1120G>A (p.Gly374Arg) | Missense | Rare | Loss of function – impaired dimerization |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function – no translation |
Mutation functional classification
Loss of Function (LOF)
Most reported ARNT2 mutations are biallelic loss-of-function (nonsense, frameshift, start loss, missense) leading to truncated or non-functional protein.
Gain of Function (GOF)
No gain-of-function mutations have been reported in ARNT2.
Dominant Negative (DN)
No dominant-negative mutations have been characterized; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hypoxia-inducible factor (HIF) signaling pathway
• Aryl hydrocarbon receptor (AhR) signaling pathway
• Circadian rhythm (via CLOCK/BMAL1 interaction)
• Neuroactive ligand-receptor interaction (indirect)
Protein Summary
ARNT2 is a 712-amino-acid transcription factor containing bHLH and PAS domains. It heterodimerizes with SIM1, SIM2, or HIF1A to regulate target genes involved in neurogenesis, endocrine homeostasis, and oxygen sensing. The protein is predominantly expressed in the developing and adult brain, kidney, and lung. Structural integrity of the PAS domain is essential for dimerization and transcriptional activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARNT2 Knockout HEK293 Cell Line | EDJ-KQ6166 | Human | 9915 | Details Get a Quote |
| ARNT2 Knockout A-549 Cell Line | EDJ-KQ31341 | Human | 9915 | Details Get a Quote |
| ARNT2 Knockout HCT 116 Cell Line | EDJ-KQ31342 | Human | 9915 | Details Get a Quote |
| ARNT2 Knockout HeLa Cell Line | EDJ-KQ55278 | Human | 9915 | Details Get a Quote |
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