HESX1 Gene: Homeobox Expressed in ES Cells 1
Key regulator of forebrain and pituitary development; mutations linked to septo-optic dysplasia and combined pituitary hormone deficiency.
Gene Information Card
| Symbol | HESX1 |
|---|---|
| Full Name | Homeobox Expressed in ES Cells 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 3p14.3 |
| NCBI Gene ID | 8820 ncbi.nlm.nih.gov/gene/8820 |
| Ensembl ID | ENSG00000163666 |
| UniProt ID | Q9UBX0 |
| OMIM ID | 601802 |
| HGNC ID | 4877 |
| Aliases | ANF, CPHD5, RPX, HESX1/RPX |
Description
HESX1 encodes a homeobox-containing transcription factor essential for the development of the forebrain, eyes, and pituitary gland. It acts as a transcriptional repressor during early embryogenesis, regulating the formation of the anterior neural plate and Rathke's pouch. Loss-of-function mutations cause septo-optic dysplasia (SOD) and combined pituitary hormone deficiency (CPHD).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Septo-optic dysplasia (SOD) | Loss-of-function mutations impair forebrain and pituitary development, leading to optic nerve hypoplasia, midline brain defects, and pituitary hypoplasia. | ClinVar, OMIM |
| Combined pituitary hormone deficiency (CPHD) | Homozygous or compound heterozygous mutations disrupt pituitary organogenesis, resulting in deficiencies of GH, TSH, ACTH, and gonadotropins. | ClinVar, OMIM |
| Isolated growth hormone deficiency (IGHD) | Rare missense variants may partially impair HESX1 function, leading to isolated GH deficiency without other pituitary hormone deficits. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pituitary gland | 12.5 | Medium |
| Brain (cerebral cortex) | 8.2 | Low |
| Eye (retina) | 6.0 | Low |
| Testis | 3.1 | Low |
| Thyroid | 2.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | Neuronal lineage |
| NT2/D1 (embryonal carcinoma) | 10.8 | Stem cell model |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
| MCF7 (breast carcinoma) | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.449G>A (p.Arg150Gln) | Missense | Rare (SOD) | Loss of DNA-binding and transcriptional repression |
| c.306C>A (p.Tyr102*) | Nonsense | Rare (CPHD) | Premature truncation, loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare (SOD) | No protein translation |
| c.218_219del (p.Leu73Argfs*12) | Frameshift | Rare (CPHD) | Frameshift, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most HESX1 mutations are loss-of-function, leading to haploinsufficiency or complete loss of transcriptional repressor activity, causing SOD or CPHD.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg150Gln) may exert dominant-negative effects by interfering with wild-type HESX1 function in heterozygous carriers.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pituitary development and organogenesis
• Forebrain patterning (Shh signaling)
• Wnt signaling modulation
Protein Summary
HESX1 is a 185-amino-acid homeodomain transcription factor that localizes to the nucleus. It binds DNA via its homeodomain and represses target genes by recruiting co-repressors such as TLE1. The protein is critical for early forebrain and pituitary development. Mutations disrupt its repressor function, leading to congenital hypopituitarism and midline brain defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HESX1 Knockout HEK293 Cell Line | EDJ-KQ3186 | Human | 8820 | Details Get a Quote |
| HESX1 Knockout A-549 Cell Line | EDJ-KQ24622 | Human | 8820 | Details Get a Quote |
| HESX1 Knockout HCT 116 Cell Line | EDJ-KQ24623 | Human | 8820 | Details Get a Quote |
| HESX1 Knockout HeLa Cell Line | EDJ-KQ24624 | Human | 8820 | Details Get a Quote |
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