SRY (Sex-Determining Region Y)
Master regulator of male sex determination and testis development
Gene Information Card
| Symbol | SRY |
|---|---|
| Full Name | Sex-Determining Region Y |
| Gene Type | Protein-coding |
| Chromosomal Location | Yp11.2 |
| NCBI Gene ID | 6736 ncbi.nlm.nih.gov/gene/6736 |
| Ensembl ID | ENSG00000184895 |
| UniProt ID | Q05066 |
| OMIM ID | 480000 |
| HGNC ID | 11311 |
| Aliases | TDF, TDY, testis-determining factor |
Description
The SRY gene (sex-determining region Y) is located on the Y chromosome and encodes the testis-determining factor (TDF), a transcription factor that initiates male sex determination by promoting the development of testes in the bipotential gonad. SRY expression in the genital ridge triggers a cascade of downstream genes (e.g., SOX9) leading to Sertoli cell differentiation and testis formation. Mutations in SRY are a major cause of 46,XY complete gonadal dysgenesis (Swyer syndrome) and other disorders of sex development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 46,XY Complete Gonadal Dysgenesis (Swyer Syndrome) | Loss-of-function mutations in SRY prevent testis development, leading to female external genitalia with streak gonads | ClinVar, OMIM |
| 46,XY Partial Gonadal Dysgenesis | Missense or regulatory mutations reduce SRY activity, causing ambiguous genitalia and partial testicular development | ClinVar, OMIM |
| 46,XX Testicular Disorder of Sex Development | Translocation of SRY to the X chromosome or autosomes causes testis development in XX individuals | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 0.0 | Not detected (adult; expressed only in fetal genital ridge) |
| Adrenal Gland | 0.0 | Not detected |
| Ovary | 0.0 | Not detected |
| Fetal Genital Ridge | N/A | High expression (critical developmental window) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Sertoli cells (fetal) | N/A | Primary site of SRY expression during development |
| HEK293 | 0.0 | No endogenous expression |
| NT2/D1 (embryonal carcinoma) | N/A | Low/inducible expression in some studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200A>G (p.Tyr67Cys) | Missense | Rare | Loss of DNA-binding activity; associated with Swyer syndrome |
| c.266G>A (p.Arg89Gln) | Missense | Rare | Reduced nuclear localization; partial gonadal dysgenesis |
| c.5C>T (p.Pro2Leu) | Missense | Rare | Impaired transactivation; 46,XY DSD |
| Complete gene deletion | Deletion | Very rare | Complete loss of SRY; Swyer syndrome |
Mutation functional classification
Loss of Function (LOF)
Most SRY mutations are loss-of-function, impairing DNA binding, nuclear localization, or transactivation, leading to 46,XY gonadal dysgenesis.
Gain of Function (GOF)
Gain-of-function is not typically described for SRY; ectopic expression (e.g., translocation) causes XX testicular DSD.
Dominant Negative (DN)
Dominant-negative effects are not well documented for SRY; haploinsufficiency is the primary mechanism.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Male sex determination (Reactome: R-HSA-447115)
• SOX9 activation cascade (KEGG: hsa04950)
Protein Summary
The SRY protein is a 204-amino acid transcription factor containing a high-mobility group (HMG) box domain that binds to specific DNA sequences (AACAAT). It is expressed transiently in the fetal genital ridge and activates SOX9 expression, which drives testis differentiation. The protein is predominantly nuclear and acts as an architectural factor bending DNA to regulate transcription. Mutations in the HMG box disrupt DNA binding and cause sex reversal.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SRY Knockout HEK293 Cell Line | EDJ-KQ5843 | Human | 6736 | Details Get a Quote |
| SRY Knockout HeLa Cell Line | EDJ-KQ54566 | Human | 6736 | Details Get a Quote |
| SRY Knockout A-549 Cell Line | EDJ-KQ63050 | Human | 6736 | Details Get a Quote |
| SRY Knockout HCT 116 Cell Line | EDJ-KQ71524 | Human | 6736 | Details Get a Quote |
