SRY

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

Basic information

Region (hg38): Y:2786854-2787682

Links

ENSG00000184895 ∙ NCBI:6736 ∙ OMIM:480000 ∙ HGNC:11311 ∙ Uniprot:Q05066 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46,XX sex reversal 1 (Definitive), mode of inheritance: XLR
• 46,XY complete gonadal dysgenesis (Supportive), mode of inheritance: AD
• 46,XX ovotesticular disorder of sex development (Supportive), mode of inheritance: AD
• 46,XX sex reversal 1 (Supportive), mode of inheritance: AD
• 46,XY partial gonadal dysgenesis (Supportive), mode of inheritance: AD
• 46,XX sex reversal 1 (Definitive), mode of inheritance: XL
• 46,XX sex reversal 1 (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
46,XY disorder of sex development; 46, XX disorder of sex development	YL	Genitourinary; Oncologic	In individuals with 46, XY, karyotype, due to increased risk for gonadal tumors, abdominal dysgenetic gonads and streak gonads should be surgically removed	Endocrine; Genitourinary; Oncologic	2247151; 7904700; 8472885; 1956279; 1734522; 1639410; 1570829; 20301714; 20301589
Treatment depends on sex chromosome complement; Hormonal treatment may be beneficial (eg, with hormone replacement therapy at the onset of puberty)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRY gene.

• 46,XY sex reversal 1 (21 variants)
• not provided (4 variants)
• not specified (3 variants)
• 46,XY disorder of sex development (1 variants)
• 46,XX sex reversal 1;46,XY sex reversal 1 (1 variants)
• 46,XX sex reversal 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRY gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense	3	4	8			15
nonsense	4	1	2			7
start loss						0
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	9	5	11	3	1

Variants in SRY

This is a list of pathogenic ClinVar variants found in the SRY region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
Y-2786976-T-C		not specified	Likely benign (-)
Y-2787001-C-T			Uncertain significance (Jun 23, 2022)
Y-2787015-G-T		46,XY sex reversal 1	Uncertain significance (Sep 13, 2023)
Y-2787033-AG-A		46,XY sex reversal 1	Uncertain significance (Nov 02, 2022)
Y-2787132-G-A		46,XY sex reversal 1	Uncertain significance (Nov 28, 2023)
Y-2787139-G-A		46,XY sex reversal 1	Benign (Oct 13, 2022)
Y-2787207-G-A		46,XY sex reversal 1	Pathogenic (May 01, 1997)
Y-2787224-T-A		46,XY sex reversal 1	Pathogenic (Jul 01, 2002)
Y-2787224-T-C		46,XY sex reversal 1	Pathogenic (Jan 25, 2019)
Y-2787236-TTCTC-T		46,XY sex reversal 1	Pathogenic (Feb 01, 1992)
Y-2787258-A-G			Likely benign (Sep 13, 2018)
Y-2787265-T-C		46,XY sex reversal 1	Likely benign (Dec 31, 2019)
Y-2787267-C-T		46,XY sex reversal 1	Pathogenic (Aug 01, 1993)
Y-2787273-G-A		46,XX sex reversal 1;46,XY sex reversal 1	Pathogenic (Nov 03, 2015)
Y-2787278-A-G		46,XY sex reversal 1	Pathogenic (Dec 01, 1992)
Y-2787279-AT-A		46,XY sex reversal 1	Pathogenic (Jan 01, 1993)
Y-2787283-C-A		46,XY sex reversal 1	Uncertain significance (Aug 14, 2020)
Y-2787284-C-T		46,XY sex reversal 1	Pathogenic (Aug 01, 1994)
Y-2787287-T-A		46,XY sex reversal 1	Pathogenic (Jan 01, 1993)
Y-2787291-C-T		not specified	Uncertain significance (Sep 17, 2018)
Y-2787299-G-A		46,XX sex reversal 1	Likely pathogenic (Nov 09, 2022)
Y-2787310-C-T		SRY-related disorder	Pathogenic (Nov 13, 2023)
Y-2787313-C-CG		46,XY sex reversal 1	Pathogenic (Sep 02, 2021)
Y-2787316-G-C		46,XY sex reversal 1	Pathogenic (Dec 14, 2017)
Y-2787320-C-T		46,XY sex reversal 1	Pathogenic (Jun 01, 2000)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRY	protein_coding	protein_coding	ENST00000383070	1	845

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.138	24	22.2	1.08	0.00000478	1354
Missense in Polyphen		8	7.6122	1.0509		513
Synonymous	0.341	7	8.25	0.849	0.00000199	371
Loss of Function

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish
East Asian
Finnish
European (Non-Finnish)
Middle Eastern
South Asian
Other

dbNSFP

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.
• Pathway: Signaling by WNT;Signal Transduction;AndrogenReceptor;Deactivation of the beta-catenin transactivating complex;TCF dependent signaling in response to WNT;Regulation of Androgen receptor activity (Consensus)

Haploinsufficiency Scores

• pHI: 0.160
• hipred: N
• hipred_score: 0.213
• ghis: 0.448

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0208

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Sry
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;central nervous system development;sex differentiation;cell differentiation;neuron differentiation;male sex determination;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of male gonad development
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear speck;nuclear transcription factor complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;calmodulin binding;transcription factor binding