GeneBe

SRY

protein-coding

sex determining region Y, the group of SRY-box transcription factors

Gene summary

This intronless gene encodes a transcription factor that is a member of the high mobility group (HMG)-box family of DNA-binding proteins. This protein is the testis-determining factor (TDF), which initiates male sex determination. Mutations in this gene give rise to XY females with gonadal dysgenesis (Swyer syndrome); translocation of part of the Y chromosome containing this gene to the X chromosome causes XX male syndrome. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003140.3

Inheritance

AD, XL, YL

ClinVar variants

P:47U:23B:4

Top phenotype

46,XY disorder of sex development; 46, XX disorder of sex development

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chrY:2,786,855-2,787,682

External References & Databases

Ensembl (ENSG00000184895)NCBI Gene (6736)OMIM (480000)HGNC:11311GenCCUniProt (Q05066)AlphaFoldClinVar (SRY)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~0.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

46,XY partial gonadal dysgenesisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016674

Submitter: Orphanet

46,XX sex reversal 1SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010766

Submitter: Orphanet

46,XX sex reversal 1STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0100250

Submitter: PanelApp Australia

46,XY sex reversal 1STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0020712

Submitter: PanelApp Australia

46,XY complete gonadal dysgenesisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010765

Submitter: Orphanet

46,XX ovotesticular disorder of sex developmentSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016281

Submitter: Orphanet

46,XX sex reversal 1DEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010766

Submitter: Ambry Genetics

46,XY sex reversal 1DEFINITIVE

Inheritance Pattern: YL

Disease ID:MONDO:0020712

Submitter: G2P

Clinical Genomic Database (CGD)

46,XY disorder of sex development; 46, XX disorder of sex developmentYL

Manifestation: Endocrine; Genitourinary; Oncologic

Intervention: Genitourinary; Oncologic

Rationale: In individuals with 46, XY, karyotype, due to increased risk for gonadal tumors, abdominal dysgenetic gonads and streak gonads should be surgically removed

Comments: Treatment depends on sex chromosome complement; Hormonal treatment may be beneficial (eg, with hormone replacement therapy at the onset of puberty)

Refs: 2247151; 7904700; 8472885; 1956279; 1734522; 1639410; 1570829; 20301714; 20301589Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SRY variants in ClinVar

8 Conditions Cataloged
46,XY sex reversal 1Total: 51
not providedTotal: 10
SRY-related disorderTotal: 8
46,XX sex reversal 1Total: 3
not specifiedTotal: 3
46 XY differences of sex developmentTotal: 2
Differences in sex developmentTotal: 2
46,XY TRUE HERMAPHRODITISMTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003140.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
 3
missense
14
clinvar
11
clinvar
20
clinvar
1
clinvar
 46
nonsense
12
clinvar
2
clinvar
2
clinvar
 16
start loss
0
frameshift
5
clinvar
3
clinvar
1
clinvar
 9
splice donor/acceptor (+/-2bp)
0
Total3116233174

Highest pathogenic variant AF is 0.000010082195

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_003140.3RefSeqNP_003131.11MANE Select
ENST00000383070.2EnsemblENSP00000372547.11MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Signaling by WNT
  • Signal Transduction
  • AndrogenReceptor
  • Deactivation of the beta-catenin transactivating complex
  • TCF dependent signaling in response to WNT

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • regulation of transcription, DNA-templated
  • central nervous system development
  • sex differentiation
  • cell differentiation

Molecular Function

  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • DNA binding
  • calmodulin binding
  • transcription factor binding

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm
  • nuclear speck
  • nuclear transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000383070
Coding exons
1
Length
845
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.1382422.21.080.000004781354
Missense (PolyPhen)87.61221.0509513
Synonymous0.34178.250.8490.00000199371
Loss of Function

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Transcriptional regulator that controls a genetic switch in male development. It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (By similarity). In male adult brain involved in the maintenance of motor functions of dopaminergic neurons (By similarity). Involved in different aspects of gene regulation including promoter activation or repression (By similarity). Promotes DNA bending. SRY HMG box recognizes DNA by partial intercalation in the minor groove. Also involved in pre-mRNA splicing. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'. {ECO:0000250, ECO:0000269|PubMed:11563911, ECO:0000269|PubMed:11818535, ECO:0000269|PubMed:15170344, ECO:0000269|PubMed:16762365}.;
Disease
DISEASE: 46,XY sex reversal 1 (SRXY1) [MIM:400044]: A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients manifest rapid and early degeneration of their gonads, which are present in the adult as 'streak gonads', consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female, and Muellerian structures are normal. {ECO:0000269|PubMed:10670762, ECO:0000269|PubMed:10721678, ECO:0000269|PubMed:10843173, ECO:0000269|PubMed:10852465, ECO:0000269|PubMed:11563911, ECO:0000269|PubMed:12107262, ECO:0000269|PubMed:12793612, ECO:0000269|PubMed:1339396, ECO:0000269|PubMed:1415266, ECO:0000269|PubMed:1483689, ECO:0000269|PubMed:1570829, ECO:0000269|PubMed:17063144, ECO:0000269|PubMed:2247149, ECO:0000269|PubMed:28030592, ECO:0000269|PubMed:7717397, ECO:0000269|PubMed:7776083, ECO:0000269|PubMed:7985018, ECO:0000269|PubMed:8019555, ECO:0000269|PubMed:8105086, ECO:0000269|PubMed:8353496, ECO:0000269|PubMed:8447323, ECO:0000269|PubMed:9450909, ECO:0000269|PubMed:9521592, ECO:0000269|PubMed:9678356, ECO:0000269|Ref.41, ECO:0000269|Ref.47}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A 45,X chromosomal aberration involving SRY is found in Turner syndrome, a disease characterized by gonadal dysgenesis with short stature, "streak gonads", variable abnormalities such as webbing of the neck, cubitus valgus, cardiac defects, low posterior hair line. The phenotype is female.; DISEASE: 46,XX sex reversal 1 (SRXX1) [MIM:400045]: A condition in which male gonads develop in a genetic female (female to male sex reversal). {ECO:0000269|PubMed:10602113, ECO:0000269|PubMed:9652903}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Indispensability pred.
N
Indispensability score
0.0208

Gene Damage Prediction

AllRecessiveDominant
MendelianLowLowLow
Primary ImmunodeficiencyLowLowLow
CancerLowLowLow
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.