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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SRY
sex determining region Y
Chromosome Y Β· Yp11.2
NCBI Gene: 6736Ensembl: ENSG00000184895.8HGNC: HGNC:11311UniProt: A7WPU8
194PubMed Papers
22Diseases
0Drugs
42Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of gene expressionDNA-binding transcription factor activity, RNA polymerase II-specificDNA bindingpositive regulation of DNA-templated transcription46,XY sex reversal 146,XX sex reversal 146,XY complete gonadal dysgenesis46,XY partial gonadal dysgenesis
✦AI Summary

SRY (sex-determining region Y) is a master regulatory transcription factor located on the Y chromosome Y initiates male sex determination in mammals 1. Its primary function is to direct the development of supporting cell precursors (pre-Sertoli cells) toward a Sertoli cell fate rather than granulosa cells, thereby triggering the male developmental pathway while repressing female differentiation 1. Mechanistically, SRY functions as a DNA-binding transcription factor that recognizes the consensus sequence 5'-[AT]AACAA[AT]-3' through its HMG box domain, which promotes DNA bending via partial intercalation into the minor groove 2. SRY expression itself is regulated by steroidogenic factor-1 (NR5A1), which binds to a conserved enhancer element located upstream of the SRY transcription start site 3. Mutations in SRY or its regulatory elements cause sex reversal disorders (46,XY and 46,XX sex reversal), where individuals possess chrY of one sex but develop physical characteristics of the other 1. Clinical significance lies in understanding these disorders of sex development (DSD); recent transgenic mouse models with human SRY have enabled functional analysis of pathogenic variants and their effects on testis development 4. The rapid evolution of SRY across mammals and the identification of disease-causing enhancer variants suggest that both coding and regulatory regions are critical for proper sexual differentiation 3.

Sources cited
1
SRY is a master regulatory gene on the Y chromosome that initiates the male pathway or represses the female pathway by regulating downstream gene transcription; mutations cause sex reversal disorders
PMID: 11750731
2
SRY discoveries include sex-reversing mutations with variable penetrance and rapid sequence evolution
PMID: 7849739
3
NR5A1/SF-1 binds a conserved enhancer upstream of SRY to regulate its expression; disruption of this enhancer causes testis dysgenesis phenotypically similar to SRY coding variants
PMID: 38555298
4
Transgenic mouse model with human SRY enables functional analysis of mutations in SRY's three domains (N-terminal, HMG box, C-terminal) and their effects on testis development
PMID: 34918413
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜22
46,XY sex reversal 1Open Targets
0.83Strong
46,XX sex reversal 1Open Targets
0.61Moderate
46,XY complete gonadal dysgenesisOpen Targets
0.47Moderate
46,XY partial gonadal dysgenesisOpen Targets
0.40Weak
46,XX testicular disorder of sex developmentOpen Targets
0.40Weak
46,XX ovotesticular disorder of sex developmentOpen Targets
0.39Weak
46,XY disorder of sex developmentOpen Targets
0.27Weak
46,XY disorder of sex development due to isolated 17,20 lyase deficiencyOpen Targets
0.09Suggestive
Testicular regression syndromeOpen Targets
0.08Suggestive
precocious puberty, central, 2Open Targets
0.07Suggestive
acute lung injuryOpen Targets
0.07Suggestive
primary ovarian insufficiencyOpen Targets
0.07Suggestive
46,XX gonadal dysgenesisOpen Targets
0.07Suggestive
Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinomaOpen Targets
0.07Suggestive
palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndromeOpen Targets
0.07Suggestive
46,XY sex reversal 3Open Targets
0.07Suggestive
familial male-limited precocious pubertyOpen Targets
0.07Suggestive
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiencyOpen Targets
0.07Suggestive
46,XY sex reversal 6Open Targets
0.06Suggestive
46,XY ovotesticular disorder of sex developmentOpen Targets
0.06Suggestive
46,XX sex reversal 1UniProt
46,XY sex reversal 1UniProt
Pathogenic Variants42
NM_003140.3(SRY):c.338C>A (p.Ala113Glu)Likely pathogenic
Differences in sex development
β˜…β˜†β˜†β˜†2025β†’ Residue 113
NM_003140.3(SRY):c.301C>T (p.Leu101Phe)Likely pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2025β†’ Residue 101
NM_003140.3(SRY):c.188C>T (p.Pro63Leu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 63
NM_003140.3(SRY):c.380A>G (p.Tyr127Cys)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2024β†’ Residue 127
NM_003140.3(SRY):c.192G>A (p.Met64Ile)Likely pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2024β†’ Residue 64
NM_003140.3(SRY):c.22_23del (p.Met8fs)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2024β†’ Residue 8
NM_003140.3(SRY):c.174_175insC (p.Arg59fs)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2023β†’ Residue 59
NM_003140.3(SRY):c.179T>C (p.Val60Ala)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 60
NM_003140.3(SRY):c.145G>T (p.Gly49Ter)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2023β†’ Residue 49
NM_003140.3(SRY):c.305C>T (p.Thr102Ile)Likely pathogenic
46,XX sex reversal 1
β˜…β˜†β˜†β˜†2022β†’ Residue 102
NM_003140.3(SRY):c.263C>G (p.Ser88Ter)Likely pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2022β†’ Residue 88
NM_003140.3(SRY):c.178G>C (p.Val60Leu)Pathogenic
46,XY sex reversal 1|not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 60
NM_003140.3(SRY):c.212C>A (p.Ser71Tyr)Likely pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2021β†’ Residue 71
NM_003140.3(SRY):c.196G>C (p.Ala66Pro)Likely pathogenic
46,XY disorder of sex development
β˜…β˜†β˜†β˜†2021β†’ Residue 66
NM_003140.3(SRY):c.169C>T (p.Gln57Ter)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2018β†’ Residue 57
NM_003140.3(SRY):c.203T>C (p.Ile68Thr)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2018β†’ Residue 68
NM_003140.3(SRY):c.288C>G (p.Tyr96Ter)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2017β†’ Residue 96
NM_003140.3(SRY):c.263C>A (p.Ser88Ter)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2017β†’ Residue 88
NM_003140.3(SRY):c.264dup (p.Glu89fs)Pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2017β†’ Residue 89
NM_003140.3(SRY):c.227G>T (p.Arg76Leu)Likely pathogenic
46,XY sex reversal 1
β˜…β˜†β˜†β˜†2017β†’ Residue 76
View on ClinVar β†—
Related Genes
USP9YProtein interaction100%AMELYProtein interaction99%ZFYProtein interaction99%CTNNB1Protein interaction98%DDX3YProtein interaction97%KDM5DProtein interaction97%
Tissue Expression6 tissues
Brain
0%
Bone Marrow
0%
Ovary
0%
Heart
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
SRYUSP9YAMELYZFYCTNNB1DDX3YKDM5D
PROTEIN STRUCTURE
Preparing viewer…
PDB9BVD Β· 2.48 Γ… Β· X-ray
View on RCSB β†—
RankingsWhere SRY stands among ~20K protein-coding genes
  • #2,209of 20,598
    Most Researched194 Β· top quartile
  • #1,483of 5,498
    Most Pathogenic Variants42
Genes detectedSRY
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Sex determination.
PMID: 7849739
Hum Mol Genet Β· 1994
1.00
2
46,XX sex reversal.
PMID: 11750731
Arch Med Res Β· 2001
0.90
3
Generation and mutational analysis of a transgenic mouse model of human SRY.
PMID: 34918413
Hum Mutat Β· 2022
0.80
4
Whatever happened to SRY?
PMID: 11212323
Cell Mol Life Sci Β· 1999
0.70
5
Porcine SRY gene locus and genital ridge expression.
PMID: 8793057
Biol Reprod Β· 1996
0.64