SIX2 Gene
SIX Homeobox 2: A key regulator of kidney development and nephrogenesis
Gene Information Card
| Symbol | SIX2 |
|---|---|
| Full Name | SIX homeobox 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p21 |
| NCBI Gene ID | 10736 ncbi.nlm.nih.gov/gene/10736 |
| Ensembl ID | ENSG00000170577 |
| UniProt ID | Q9NPC8 |
| OMIM ID | 604994 |
| HGNC ID | 10889 |
| Aliases | SIX2 homeobox 2, sine oculis homeobox homolog 2 |
Description
SIX2 is a homeobox-containing transcription factor that plays a critical role in kidney development, specifically in the maintenance and proliferation of nephron progenitor cells. It is essential for the formation of the metanephric mesenchyme and the subsequent induction of nephrogenesis. Mutations in SIX2 are associated with congenital anomalies of the kidney and urinary tract (CAKUT).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital anomalies of the kidney and urinary tract (CAKUT) | Loss-of-function mutations in SIX2 disrupt nephron progenitor cell maintenance, leading to renal hypodysplasia or agenesis. | ClinVar, OMIM |
| Renal hypodysplasia | Heterozygous missense or nonsense variants impair SIX2 DNA-binding or transcriptional activity, reducing nephron endowment. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Testis | 2.1 | Low |
| Brain | 1.0 | Low |
| Lung | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | Embryonic kidney cell line |
| A-431 | 0.5 | Epidermoid carcinoma |
| Hep G2 | 0.2 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.445C>T (p.Arg149*) | Nonsense | Rare | Loss of function; truncated protein |
| c.527G>A (p.Arg176Gln) | Missense | Rare | Impaired DNA binding; reduced transcriptional activity |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein production |
Mutation functional classification
Loss of Function (LOF)
Most SIX2 mutations in CAKUT are loss-of-function, leading to haploinsufficiency or dominant-negative effects on nephrogenesis.
Gain of Function (GOF)
No gain-of-function mutations reported in SIX2.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg176Gln) may act as dominant-negative by dimerizing with wild-type SIX2 and blocking target gene activation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Kidney development (Reactome: R-HSA-983170)
• Transcriptional regulation by SIX2 (Reactome: R-HSA-5619507)
Protein Summary
SIX2 is a 290-amino acid homeodomain-containing transcription factor. It contains a SIX domain (SD) for protein-protein interactions and a homeodomain (HD) for DNA binding. SIX2 forms complexes with co-factors such as EYA1 and PAX2 to regulate genes involved in nephron progenitor cell self-renewal and differentiation. It is predominantly expressed in the metanephric mesenchyme during embryonic kidney development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIX2 Knockout HEK293 Cell Line | EDJ-KQ3875 | Human | 10736 | Details Get a Quote |
| SIX2 Knockout HeLa Cell Line | EDJ-KQ26084 | Human | 10736 | Details Get a Quote |
| SIX2 Knockout A-549 Cell Line | EDJ-KQ63961 | Human | 10736 | Details Get a Quote |
| SIX2 Knockout HCT 116 Cell Line | EDJ-KQ72415 | Human | 10736 | Details Get a Quote |
