SIX6 Gene: Homeobox Transcription Factor in Ocular Development
SIX6: Genetic Insights into Eye Development and Anophthalmia/Microphthalmia
Gene Information Card
| Symbol | SIX6 |
|---|---|
| Full Name | SIX homeobox 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q23.1 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | O95476 |
| OMIM ID | 606326 |
| HGNC ID | 10891 |
| Aliases | ODR1, OPTX2, SIX9, six6 |
Description
The SIX6 gene encodes a homeobox-containing transcription factor that plays a critical role in the development of the eye, particularly in the formation of the optic cup, retina, and optic nerve. It is a member of the SIX family of homeodomain proteins, which are involved in organogenesis and cell fate determination. Mutations in SIX6 are associated with ocular developmental disorders such as anophthalmia and microphthalmia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Anophthalmia/Microphthalmia | Loss-of-function mutations in SIX6 disrupt retinal progenitor cell proliferation and optic cup formation, leading to reduced eye size or absence of ocular tissue. | ClinVar, OMIM |
| Optic Nerve Hypoplasia | SIX6 variants impair optic nerve development by altering transcription of downstream targets essential for retinal ganglion cell differentiation. | ClinVar, OMIM |
| Pituitary Stalk Interruption Syndrome | Rare association with SIX6 mutations affecting both ocular and pituitary development due to shared developmental pathways. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Eye | 15.2 | High |
| Brain | 3.1 | Low |
| Pituitary | 2.8 | Low |
| Testis | 1.5 | Not detected |
| Heart | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 12.4 | High expression |
| HMC3 (microglia) | 2.1 | Low expression |
| SH-SY5Y (neuroblastoma) | 1.8 | Low expression |
| HEK293 (embryonic kidney) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.328C>T (p.Arg110Trp) | Missense | Rare | Loss of DNA-binding ability, reduced transcriptional activity |
| c.346G>A (p.Gly116Arg) | Missense | Rare | Impaired protein stability and nuclear localization |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein expression |
| c.427_429del (p.Lys143del) | In-frame deletion | Rare | Altered homeodomain structure, reduced function |
Mutation functional classification
Loss of Function (LOF)
Most SIX6 mutations are loss-of-function, reducing or abolishing transcriptional activation of target genes involved in retinal progenitor cell proliferation and optic cup morphogenesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SIX6.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg110Trp) may act in a dominant-negative manner by interfering with wild-type SIX6 function in heterozygous state.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Retinal development and differentiation
• Optic cup morphogenesis
• SIX family signaling in organogenesis
Protein Summary
The SIX6 protein is a 246-amino-acid transcription factor containing a conserved SIX domain and a homeodomain. It binds DNA as a dimer and regulates genes essential for retinal progenitor cell proliferation, optic cup formation, and retinal ganglion cell differentiation. The protein is predominantly expressed in the developing and adult eye, with lower levels in brain and pituitary. Structural integrity of the homeodomain is critical for DNA binding and transcriptional activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIX6 Knockout HEK293 Cell Line | EDJ-KQ5383 | Human | 4990 | Details Get a Quote |
| SIX6 Knockout HeLa Cell Line | EDJ-KQ54051 | Human | 4990 | Details Get a Quote |
| SIX6 Knockout A-549 Cell Line | EDJ-KQ62539 | Human | 4990 | Details Get a Quote |
| SIX6 Knockout HCT 116 Cell Line | EDJ-KQ71011 | Human | 4990 | Details Get a Quote |
