46,xy Sex Reversal disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: 46X082 MIFTS: 46	46,xy Sex Reversal Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases
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Aliases & Classifications for 46,xy Sex Reversal

MalaCards integrated aliases for 46,xy Sex Reversal:

Name: 46,xy Sex Reversal ¹² ²⁵ ¹⁵ ³⁹

Swyer Syndrome ¹² ⁷⁴ ⁵² ²⁵ ⁵⁸

Pure Gonadal Dysgenesis 46,xy ¹² ²⁵ ²⁹

Gonadal Dysgenesis, Xy Female Type ⁵² ²⁵

46,xy Complete Gonadal Dysgenesis ²⁵ ⁵⁸

Gonadal Dysgenesis, 46,xy ²⁵ ⁴³

46,xy Cgd ²⁵ ⁵⁸

46, Xy Complete Gonadal Dysgenesis ⁵²

46, Xy Pure Gonadal Dysgenesis ⁵²

46,xy Pure Gonadal Dysgenesis ⁵⁸

Xy Pure Gonadal Dysgenesis ²⁵

46 Xy Gonadal Dysgenesis ¹²

46,xy Gonadal Dysgenesis ³⁶

46, Xy Cgd ⁵²

Characteristics:

Orphanet epidemiological data:

⁵⁸

46,xy complete gonadal dysgenesis
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive,Y-linked; Age of onset: Adolescent,Adult; Age of death: normal life expectancy;

Classifications:

MalaCards categories:
Global: Rare diseases Fetal diseases Genetic diseases
Anatomical: Reproductive diseases Endocrine diseases

See all MalaCards categories (disease lists)

ICD10: ³³

Congenital malformations, deformations and chromosomal abnormalities

Chromosomal abnormalities, not elsewhere classified

Other chromosome abnormalities, not elsewhere classified

46,XX true hermaphrodite

Orphanet: ⁵⁸

Rare gynaecological and obstetric diseases

Rare endocrine diseases

Developmental anomalies during embryogenesis

External Ids:

Disease Ontology ¹² DOID:14448

KEGG ³⁶ H00607

MeSH ⁴³ D006061

NCIt ⁴⁹ C120198

ICD10 via Orphanet ³³ Q99.1

UMLS via Orphanet ⁷² C0018054 C2936694

Orphanet ⁵⁸ ORPHA242

SNOMED-CT via HPO ⁶⁸ 111332007 253847002 33927004 more

UMLS ⁷¹ C0018054

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Summaries for 46,xy Sex Reversal

Genetics Home Reference : ²⁵ Swyer syndrome is a condition that affects sexual development. Sexual development is usually determined by an individual's chromosomes; however, in Swyer syndrome, sexual development does not match the affected individual's chromosomal makeup. People usually have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Girls and women typically have two X chromosomes (46,XX karyotype), while boys and men usually have one X chromosome and one Y chromosome (46,XY karyotype). In Swyer syndrome, individuals with one X chromosome and one Y chromosome in each cell, the pattern typically found in boys and men, have female reproductive structures. People with Swyer syndrome have typical female external genitalia. The uterus and fallopian tubes are normally-formed, but the gonads (ovaries or testes) are not functional; affected individuals have undeveloped clumps of tissue called streak gonads. Because of the lack of development of the gonads, Swyer syndrome is also called 46,XY complete gonadal dysgenesis. The residual gonadal tissue often becomes cancerous, so it is usually removed surgically early in life. People with Swyer syndrome are typically raised as girls and have a female gender identity. Because they do not have functional ovaries, affected individuals usually begin hormone replacement therapy during adolescence to induce menstruation and development of female secondary sex characteristics such as breast enlargement and uterine growth. Hormone replacement therapy also helps reduce the risk of reduced bone density (osteopenia and osteoporosis). Women with this disorder do not produce eggs (ova), but they may be able to become pregnant with a donated egg or embryo. Swyer syndrome usually affects only sexual development; such cases are called isolated Swyer syndrome. However, depending on the genetic cause, Swyer syndrome may also occur along with health conditions such as nerve problems (neuropathy) or as part of a syndrome such as campomelic dysplasia, which causes severe skeletal abnormalities.

MalaCards based summary : 46,xy Sex Reversal, also known as swyer syndrome, is related to adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete and 46,xy sex reversal 9. An important gene associated with 46,xy Sex Reversal is NR5A1 (Nuclear Receptor Subfamily 5 Group A Member 1), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers and Diseases of metabolism. Affiliated tissues include ovary, testes and testis, and related phenotypes are polycystic ovaries and male pseudohermaphroditism

Disease Ontology : ¹² A gonadal dysgenesis that is characterized by a normal 46,XY karyotype along with a progressive loss of germ cells on the developing gonads of an embryo.

NIH Rare Diseases : ⁵² Swyer syndrome is a genetic condition affecting sexual organ development, classified as a disorder of sex development (DSD). In Swyer syndrome, people with one X chromosome and one Y chromosome , normally present in males, are born with female external genitalia and underdeveloped gonads (ovaries or testes ) known as streak gonads. Most people with Swyer syndrome are raised as females. Adolescents with this condition do not go through normal puberty and are infertile. Some cases of Swyer syndrome are caused by genetic alterations (mutations ) in one of several genes , but in some cases the cause is unknown. The inheritance pattern depends on the responsible gene. This condition is diagnosed based on the chromosome results, clinical examination, and imaging studies. Treatment includes removal of streak gonads to prevent cancer and hormone replacement therapy from puberty onward. While women with Swyer syndrome are infertile, they may become pregnant with the use of donated eggs.

KEGG : ³⁶ Gonadal dysgenesis (GD) is a disorder of sex development. Formerly, 46,XY GD was also known as 46,XY sex reversal (SRXY). In 46,XY GD, the gonadal histology can range from fibrous streak gonads to partial GD with presence of testicular tissue. The phenotype of patients with 46,XY GD can vary from normal female to genital ambiguity to an undervirilized male. Mutations involving the testis-determining gene SRY, and other genes involved in sex determination, such as the genes WT1, DHH, NR5A1, SOX9, FOG2/ZFPM2 and MAP3K1 have been identified.

Wikipedia : ⁷⁴ XY gonadal dysgenesis, also known as Swyer syndrome, is a type of hypogonadism in a person whose... more...

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Related Diseases for 46,xy Sex Reversal

Diseases in the 46,xx Sex Reversal 1 family:

46,xy Sex Reversal 4	46,xy Sex Reversal 7
46,xy Sex Reversal 11	46,xx Sex Reversal 2
46,xy Sex Reversal 2	46,xx Sex Reversal 3
46,xy Sex Reversal 1	46,xy Sex Reversal 3
46,xy Sex Reversal 5	46,xy Sex Reversal 6
46,xy Sex Reversal 8	46,xy Sex Reversal 9
46,xy Sex Reversal 10	46,xx Sex Reversal 4
46,xx Sex Reversal 5	46,xx Sex Reversal
46,xy Sex Reversal

Diseases related to 46,xy Sex Reversal via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 133)

#	Related Disease	Score	Top Affiliating Genes
1	adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete	35.5	STAR NR0B1 FDXR FDX1 CYP11A1
2	46,xy sex reversal 9	35.4	ZFPM2-AS1 ZFPM2 WT1 SOX9 NR5A1 GATA4
3	46,xy sex reversal 1	35.4	SRY SOX9
4	46,xy sex reversal 2	35.4	WT1 STAR SOX9 NR5A1 NR0B1 CYP11A1
5	46,xy sex reversal 3	35.3	NR5A1 GATA4
6	campomelic dysplasia	33.6	SRY SOX9 NR5A1
7	chondrodysplasia-pseudohermaphroditism syndrome	33.3	WT1 SOX9 NR5A1 NR0B1 MAP3K1
8	nonsyndromic disorders of testicular development	31.5	SRY NR5A1 NR0B1 MAP3K1 DMRT1 DHH
9	disorders of sexual development	31.5	WT1 STAR SOX9 NR5A1 NR0B1 DMRT1
10	hermaphroditism	31.4	ZFPM2 SRY SOX9 NR0B1 DMRT1
11	46,xx sex reversal	31.3	SRY SOX9 NR5A1 NR0B1 DMRT1 DHH
12	frasier syndrome	31.3	WT1 SRY SOX9 NR5A1
13	gonadoblastoma	31.3	WT1 SRY SOX9 NR5A1 DMRT3 DMRT1
14	anorchia	31.2	SRY NR5A1
15	gonadal dysgenesis	31.2	ZFPM2 WT1 SRY SOX9 NR5A1 NR0B1
16	wilms tumor 1	31.1	WT1 SRY SOX9 NR5A1 NR0B1 GATA4
17	cryptorchidism, unilateral or bilateral	31.0	ZFPM2 WT1 STAR SOX9 NR5A1 NR0B1
18	lipoid congenital adrenal hyperplasia	30.9	STAR NR5A1 NR0B1 FDXR CYP11A1
19	hypospadias	30.9	WT1 SRY SOX9 NR5A1 GATA4 CYP11A1
20	mixed gonadal dysgenesis	30.9	SRY SOX9 NR5A1 DHH
21	dysgerminoma	30.9	WT1 SRY DMRT1
22	pseudohermaphroditism	30.8	WT1 STAR SRY NR5A1 NR0B1 AKR1C2
23	chromosome 9p deletion syndrome	30.8	DOCK8 DMRT3 DMRT1
24	diaphragmatic hernia, congenital	30.7	ZFPM2 WT1 GATA4
25	46,xy partial gonadal dysgenesis	30.7	ZFPM2 WT1 SRY SOX9 NR5A1 NR0B1
26	46,xy sex reversal 6	12.9
27	46,xy sex reversal 7	12.9
28	46,xy sex reversal 5	12.9
29	46,xy sex reversal 4	12.9
30	46,xy sex reversal 8	12.9
31	46,xy sex reversal 10	12.9
32	46,xy gonadal dysgenesis, partial, with minifascicular neuropathy	12.7
33	46,xy sex reversal 11	12.6
34	gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy	11.7
35	genitopalatocardiac syndrome	11.5
36	45,x/46,xy mixed gonadal dysgenesis	10.7	SRY NR0B1 DMRT1 DHH
37	46,xx sex reversal 1	10.7	SRY SOX9 NR5A1 NR0B1
38	adrenal cortical hypofunction	10.7	STAR NR5A1 NR0B1 CYP11A1
39	adrenal cortex disease	10.7	STAR NR5A1 NR0B1 CYP11A1
40	leydig cell tumor	10.7	STAR NR5A1 NR0B1 CYP11A1
41	corticosterone methyloxidase type i deficiency	10.7	NR5A1 NR0B1 FDX1
42	intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies	10.7	NR5A1 NR0B1 CYP11A1
43	hypoadrenocorticism, familial	10.7	STAR NR5A1 NR0B1 CYP11A1
44	ovarian gonadoblastoma	10.7	WT1 SOX9 NR0B1 DMRT1
45	diaphragmatic hernia 3	10.6	ZFPM2-AS1 ZFPM2
46	familial glucocorticoid deficiency	10.6	STAR NR5A1 NR0B1 CYP11A1
47	persistent mullerian duct syndrome	10.6	WT1 SOX9 NR5A1 NR0B1 DMRT1
48	adrenal gland disease	10.6	STAR NR5A1 NR0B1 CYP11A1
49	spermatogenic failure 8	10.6	NR5A1 DMRT3 DMRT1
50	steroid inherited metabolic disorder	10.6	STAR NR5A1 NR0B1 FDXR FDX1 CYP11A1

Graphical network of the top 20 diseases related to 46,xy Sex Reversal:

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Symptoms & Phenotypes for 46,xy Sex Reversal

Human phenotypes related to 46,xy Sex Reversal:

⁵⁸ ³¹

#	Description	HPO Frequency	Orphanet Frequency	HPO Source Accession
1	polycystic ovaries ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0000147
2	male pseudohermaphroditism ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0000037
3	testicular dysgenesis ⁵⁸ ³¹	hallmark (90%)	Very frequent (99-80%)	HP:0008715
4	hypogonadotropic hypogonadism ³¹	hallmark (90%)		HP:0000044
5	hypogonadotrophic hypogonadism ⁵⁸		Very frequent (99-80%)

GenomeRNAi Phenotypes related to 46,xy Sex Reversal according to GeneCards Suite gene sharing:

²⁶ (show all 12)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased shRNA abundance (Z-score < -2)	GR00366-A-100	9.55	CBX2
2	Decreased shRNA abundance (Z-score < -2)	GR00366-A-102	9.55	MAP3K1
3	Decreased shRNA abundance (Z-score < -2)	GR00366-A-130	9.55	FDX1
4	Decreased shRNA abundance (Z-score < -2)	GR00366-A-132	9.55	FDX1
5	Decreased shRNA abundance (Z-score < -2)	GR00366-A-152	9.55	DMRT3
6	Decreased shRNA abundance (Z-score < -2)	GR00366-A-167	9.55	DMRT3
7	Decreased shRNA abundance (Z-score < -2)	GR00366-A-204	9.55	CBX2
8	Decreased shRNA abundance (Z-score < -2)	GR00366-A-23	9.55	WT1
9	Decreased shRNA abundance (Z-score < -2)	GR00366-A-35	9.55	DMRT3 MAP3K1 WT1
10	Decreased shRNA abundance (Z-score < -2)	GR00366-A-4	9.55	FDX1
11	Decreased shRNA abundance (Z-score < -2)	GR00366-A-48	9.55	MAP3K1
12	Decreased shRNA abundance (Z-score < -2)	GR00366-A-83	9.55	NR5A1

MGI Mouse Phenotypes related to 46,xy Sex Reversal:

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	endocrine/exocrine gland	MP:0005379	9.7	CBX2 CYP11A1 DHH DMRT1 GATA4 NR0B1
2	reproductive system	MP:0005389	9.4	CBX2 CYP11A1 DHH DMRT1 DMRT3 GATA4

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Drugs & Therapeutics for 46,xy Sex Reversal

Search Clinical Trials , NIH Clinical Center for 46,xy Sex Reversal

Cochrane evidence based reviews: gonadal dysgenesis, 46,xy

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Genetic Tests for 46,xy Sex Reversal

Genetic tests related to 46,xy Sex Reversal:

#	Genetic test	Affiliating Genes
1	Pure Gonadal Dysgenesis 46,xy ²⁹

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Anatomical Context for 46,xy Sex Reversal

MalaCards organs/tissues related to 46,xy Sex Reversal:

⁴⁰

Ovary, Testes, Testis, Uterus, Breast, Bone, Lymph Node

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Publications for 46,xy Sex Reversal

Articles related to 46,xy Sex Reversal:

(show top 50) (show all 198)

#	Title	Authors	PMID	Year
1	A novel missense mutation (S18N) in the 5' non-HMG box region of the SRY gene in a patient with partial gonadal dysgenesis and his normal male relatives. ⁶ ⁶¹	Domenice S...Bilharinho Mendonca B	9521592	1998
2	A new de novo mutation (A113T) in HMG box of the SRY gene leads to XY gonadal dysgenesis. ⁶ ⁶¹	Zeng YT...Huang SZ	8105086	1993
3	Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene. ⁶	Biason-Lauber A...Schoenle EJ	19361780	2009
4	Nonsyndromic Disorders of Testicular Development ⁶	Mohnach L...Keegan CE	20301714	2008
5	Consensus statement on management of intersex disorders. ⁶	Hughes IA...Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus Group	18947601	2006
6	True hermaphroditism in an XY individual due to a familial point mutation of the SRY gene. ⁶	Maier EM...Kuhnle U	12793612	2003
7	Familial mutation in the testis-determining gene SRY shared by an XY female and her normal father. ⁶	Jordan BK...Vilain E	12107262	2002
8	Identification of a new missense mutation (Gly95Glu) in a highly conserved codon within the high-mobility group box of the sex-determining region Y gene: report on a 46,XY female with gonadal dysgenesis and yolk-sac tumor. ⁶	Schaffler A...Palitzsch KD	10852465	2000
9	A mutation in the 5' non-high mobility group box region of the SRY gene in patients with Turner syndrome and Y mosaicism. ⁶	Canto P...Mendez JP	10843173	2000
10	Independent observation of SRY mutation I90M in a patient with complete gonadal dysgenesis. ⁶	Dork T...Schmidtke J	9450909	1998
11	A de novo mutation (Gln2Stop) at the 5' end of the SRY gene leads to sex reversal with partial ovarian function. ⁶	Brown S...Stadtmauer L	9443877	1998
12	Mutations and sequence variants in the testis-determining region of the Y chromosome in individuals with a 46,XY female phenotype. ⁶	Veitia R...McElreavey K	9150734	1997
13	An SRY mutation causing human sex reversal resolves a general mechanism of structure-specific DNA recognition: application to the four-way DNA junction. ⁶	Peters R...Weiss MA	7718558	1995
14	Molecular basis of mammalian sexual determination: activation of Müllerian inhibiting substance gene expression by SRY. ⁶	Haqq CM...Weiss MA	7985018	1994
15	A novel nonsense mutation in the HMG box of the SRY gene in a patient with XY sex reversal. ⁶	Iida T...Nakagome Y	7987333	1994
16	Analysis of the SRY gene in 22 sex-reversed XY females identifies four new point mutations in the conserved DNA binding domain. ⁶	Affara NA...Ferguson-Smith MA	8353496	1993
17	Mutational analysis of SRY in XY females. ⁶	Hawkins JR	8257986	1993
18	A familial mutation in the testis-determining gene SRY shared by both sexes. ⁶	Jager RJ...Scherer G	1483689	1992
19	Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis. ⁶	Hawkins JR...Berkovitz GD	1415266	1992
20	XY sex reversal associated with a nonsense mutation in SRY. ⁶	McElreavey KD...Fellous M	1639410	1992
21	Analysis of the sex-determining region of the Y chromosome (SRY) in sex reversed patients: point-mutation in SRY causing sex-reversion in a 46,XY female. ⁶	Muller J...Skakkebaek NE	1619028	1992
22	Familial case with sequence variant in the testis-determining region associated with two sex phenotypes. ⁶	Vilain E...Fellous M	1570829	1992
23	Mutational analysis of SRY: nonsense and missense mutations in XY sex reversal. ⁶	Hawkins JR...Goodfellow PN	1339396	1992
24	DNA binding activity of recombinant SRY from normal males and XY females. ⁶	Harley VR...Goodfellow PN	1734522	1992
25	Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: its relevance to the understanding of sex differentiation. ⁶	Berkovitz GD...Perlman EJ	1956279	1991
26	Genetic evidence equating SRY and the testis-determining factor. ⁶	Berta P...Fellous M	2247149	1990
27	A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. ⁶	Jager RJ...Scherer G	2247151	1990
28	XY female mice resulting from a heritable mutation in the primary testis-determining gene, Tdy. ⁶	Lovell-Badge R...Robertson E	2401216	1990
29	A Case of 45,X/46,XY Mosaicism Presenting as Swyer Syndrome. ⁶¹	Chand MT...Misra VK	32565348	2020
30	Genetic analysis of a Taiwanese family identifies a DMRT3-OAS3 interaction that is involved in human sexual differentiation through the regulation of ESR1 expression. ⁶¹	Tsai CL...Chao A	32553473	2020
31	Inherited Missense Mutation Occurring in Arginine76 of the SRY Gene Does Not Account for Familial 46, XY Sex Reversal. ⁶¹	Wang N...Qiao J	32140723	2020
32	Dysgerminoma in a Prepubertal Girl with Complete 46XY Gonadal Dysgenesis: Case Report and Review of the Literature. ⁶¹	Bumbuliene Z...Geimanaite L	32380037	2020
33	Atypical Presentation of Swyer Syndrome. ⁶¹	Dural O...Akhan SE	31356871	2019
34	Swyer Syndrome with Heterotopic Adrenal Cortical Tissue in Streak Gonads: A Rare Case and Review of Literature. ⁶¹	Goyal M...Elhence P	32038087	2019
35	The XY female and SWYER syndrome. ⁶¹	Meyer KF...Souza MBM	31275808	2019
36	A Rare Case of Swyer Syndrome in Two Sisters with Successful Pregnancy Outcome in Both. ⁶¹	Gupta A...Jindal UN	31576088	2019
37	Gene dosage of DAX-1, determining in sexual differentiation: duplication of DAX-1 in two sisters with gonadal dysgenesis. ⁶¹	Garcia-Acero M...Rojas A	30879272	2019
38	Gonadoblastoma Y locus genes expressed in germ cells of individuals with dysgenetic gonads and a Y chromosome in their karyotypes include DDX3Y and TSPY. ⁶¹	Vogt PH...Strowitzki T	30753444	2019
39	'Size does matter': Prophylactic gonadectomy in a case of Swyer syndrome. ⁶¹	Mayur P...Arvind R	30690088	2019
40	XY oocytes of sex-reversed females with a Sry mutation deviate from the normal developmental process beyond the mitotic stage†. ⁶¹	Sakashita A...Kono T	30289439	2019
41	Causes Of Primary Amenorrhea At Tertiary Level Hospital. ⁶¹	Jabeen S...Nisar M	30868785	2019
42	Spontaneous virilization around puberty in NR5A1-related 46,XY sex reversal: additional case and a literature review. ⁶¹	Adachi M...Muroya K	30224582	2018
43	Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9. ⁶¹	Croft B...Sinclair A	30552336	2018
44	Twin gestation in a Swyer syndrome patient with superimposed pre-eclampsia. ⁶¹	Shah JS...Sibai B	29421927	2018
45	Unexpected diagnosis of stage IIA dysgerminoma in streak gonad in a patient with Swyer syndrome: a case report. ⁶¹	Yada-Hashimoto N...Kamiura S	29084462	2018
46	Familial Swyer syndrome: a rare genetic entity. ⁶¹	Banoth M...Chowhan AK	29069951	2018
47	Sensorineural hearing loss in a patient with Swyer syndrome. ⁶¹	Chen PJ...Chen HC	29200406	2018
48	Loss of DMRT1 gene in a Mos 45,XY,-9[8]/46,XY,r(9)[29]/47,XY,+idic r(9)× 2[1]/46,XY,idic r(9)[1]/46,XY[1] female presenting with short stature. ⁶¹	Marsudi BA...Marzuki NS	29760778	2018
49	A Case of Primary Amenorrhea with Swyer Syndrome. ⁶¹	Priya PK...Rizvi JS	29430160	2017
50	Clinical heterogeneity in children with gonadal dysgenesis associated with non-mosaic 46,XY karyotype. ⁶¹	Wong YS...Lee KH	28434637	2017

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Genes for 46,xy Sex Reversal

Genes related to 46,xy Sex Reversal (9 elite genes):

(show top 50) (show all 78)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence
1	NR5A1	Nuclear Receptor Subfamily 5 Group A Member 1	Protein Coding	388.64	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Publications Variants (show sections)
2	SRY	Sex Determining Region Y	Protein Coding	380.16	Causative germline mutation (loss of function) ⁵⁸ GeneCards inferred via : Disorders Publications Variants (show sections)
3	MAP3K1	Mitogen-Activated Protein Kinase Kinase Kinase 1	Protein Coding	375.62	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)
4	DHH	Desert Hedgehog Signaling Molecule	Protein Coding	375.22	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)
5	CBX2	Chromobox 2	Protein Coding	374.29	Causative germline mutation (loss of function) ⁵⁸ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)
6	SOX9	SRY-Box Transcription Factor 9	Protein Coding	365.31	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders (show sections)
7	DMRT1	Doublesex And Mab-3 Related Transcription Factor 1	Protein Coding	58.44	Candidate gene tested ⁵⁸ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Publications Variants (show sections)
8	NR0B1	Nuclear Receptor Subfamily 0 Group B Member 1	Protein Coding	53.35	Role in the phenotype ⁵⁸ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)
9	CYP11A1	Cytochrome P450 Family 11 Subfamily A Member 1	Protein Coding	47.25	DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Publications Pathways & Interactions Variants (show sections)
10	WT1	WT1 Transcription Factor	Protein Coding	31.61	Candidate gene tested ⁵⁸ DISEASES inferred ¹⁵
11	ZFPM2	Zinc Finger Protein, FOG Family Member 2	Protein Coding	25.6	DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)
12	AKR1C4	Aldo-Keto Reductase Family 1 Member C4	Protein Coding	21.86	DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)
13	AKR1C2	Aldo-Keto Reductase Family 1 Member C2	Protein Coding	18.63	GeneCards inferred via : Disorders Variants (show sections)
14	STAR	Steroidogenic Acute Regulatory Protein	Protein Coding	14.33	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
15	GATA4	GATA Binding Protein 4	Protein Coding	14.19	DISEASES inferred ¹⁵ GeneCards inferred via : Variants (show sections)
16	DMRT3	Doublesex And Mab-3 Related Transcription Factor 3	Protein Coding	12.14	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
17	FDXR	Ferredoxin Reductase	Protein Coding	11.73	DISEASES inferred ¹⁵ GeneCards inferred via : Pathways & Interactions (show sections)
18	FDX1	Ferredoxin 1	Protein Coding	11.59	DISEASES inferred ¹⁵ GeneCards inferred via : Pathways & Interactions (show sections)
19	DOCK8	Dedicator Of Cytokinesis 8	Protein Coding	10.23	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
20	ZFPM2-AS1	ZFPM2 Antisense RNA 1	RNA Gene	9.74	GeneCards inferred via : Variants (show sections)
21	H2AC18	H2A Clustered Histone 18	Protein Coding	8.78	DISEASES inferred ¹⁵ ¹⁵
22	DHX37	DEAH-Box Helicase 37	Protein Coding	8.58	GeneCards inferred via : Variants (show sections)
23	SMDT1	Single-Pass Membrane Protein With Aspartate Rich Tail 1	Protein Coding	8.48	DISEASES inferred ¹⁵
24	LCOR	Ligand Dependent Nuclear Receptor Corepressor	Protein Coding	8.47	DISEASES inferred ¹⁵ ¹⁵
25	LOC108964933	CYP11A1 Promoter Region	Biological Region	8.12	GeneCards inferred via : Variants (show sections)
26	FDX2	Ferredoxin 2	Protein Coding	7.88	GeneCards inferred via : Pathways & Interactions (show sections)
27	DDT	D-Dopachrome Tautomerase	Protein Coding	7.86	DISEASES inferred ¹⁵
28	NR5A2	Nuclear Receptor Subfamily 5 Group A Member 2	Protein Coding	6.99	DISEASES inferred ¹⁵
29	AMH	Anti-Mullerian Hormone	Protein Coding	6.55	DISEASES inferred ¹⁵
30	WNT4	Wnt Family Member 4	Protein Coding	6.54	DISEASES inferred ¹⁵
31	CYP17A1	Cytochrome P450 Family 17 Subfamily A Member 1	Protein Coding	6.53	DISEASES inferred ¹⁵
32	HSD3B2	Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- And Steroid Delta-Isomerase 2	Protein Coding	6.33	DISEASES inferred ¹⁵
33	NR0B2	Nuclear Receptor Subfamily 0 Group B Member 2	Protein Coding	6.26	DISEASES inferred ¹⁵
34	DMRT2	Doublesex And Mab-3 Related Transcription Factor 2	Protein Coding	6.22	DISEASES inferred ¹⁵
35	MC2R	Melanocortin 2 Receptor	Protein Coding	6.16	DISEASES inferred ¹⁵
36	FOXL2	Forkhead Box L2	Protein Coding	6.08	DISEASES inferred ¹⁵
37	INS	Insulin	Protein Coding	6.08	DISEASES inferred ¹⁵
38	PLEKHF1	Pleckstrin Homology And FYVE Domain Containing 1	Protein Coding	6.07	DISEASES inferred ¹⁵
39	FGF9	Fibroblast Growth Factor 9	Protein Coding	6.04	DISEASES inferred ¹⁵
40	CYP21A2	Cytochrome P450 Family 21 Subfamily A Member 2	Protein Coding	6.03	DISEASES inferred ¹⁵
41	CYP11B1	Cytochrome P450 Family 11 Subfamily B Member 1	Protein Coding	6.02	DISEASES inferred ¹⁵
42	HEXA	Hexosaminidase Subunit Alpha	Protein Coding	5.99	DISEASES inferred ¹⁵
43	DTWD1	DTW Domain Containing 1	Protein Coding	5.97	DISEASES inferred ¹⁵
44	CYP19A1	Cytochrome P450 Family 19 Subfamily A Member 1	Protein Coding	5.95	DISEASES inferred ¹⁵
45	HSD17B3	Hydroxysteroid 17-Beta Dehydrogenase 3	Protein Coding	5.89	DISEASES inferred ¹⁵
46	TSR3	TSR3 Ribosome Maturation Factor	Protein Coding	5.86	DISEASES inferred ¹⁵
47	DTWD2	DTW Domain Containing 2	Protein Coding	5.85	DISEASES inferred ¹⁵
48	HPSE	Heparanase	Protein Coding	5.76	DISEASES inferred ¹⁵
49	HSD3B1	Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- And Steroid Delta-Isomerase 1	Protein Coding	5.75	DISEASES inferred ¹⁵
50	AR	Androgen Receptor	Protein Coding	5.74	DISEASES inferred ¹⁵

Sources

Variations for 46,xy Sex Reversal

Sources

Expression for 46,xy Sex Reversal

Search GEO for disease gene expression data for 46,xy Sex Reversal.

Sources

Pathways for 46,xy Sex Reversal

Pathways related to 46,xy Sex Reversal according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers ⁶⁴	11.62	WT1 SOX9 GATA4
2	Diseases of metabolism ⁶⁵ Show member pathways Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD) ⁶⁵ Defective CD320 causes methylmalonic aciduria ⁶⁵ Defective CYP11A1 causes Adrenal insufficiency, congenital, with 46,XY sex reversal (AICSR) ⁶⁵ Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC ⁶⁵ Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD ⁶⁵ Defective TCN2 causes hereditary megaloblastic anemia ⁶⁵ Defects in cobalamin (B12) metabolism ⁶⁵ Defects in vitamin and cofactor metabolism ⁶⁵ Electron transport from NADPH to Ferredoxin ⁶⁵ Metabolic disorders of biological oxidation enzymes ⁶⁵	11.4	FDXR FDX1 CYP11A1
3	Steroid hormone biosynthesis ³⁶ Show member pathways allopregnanolone biosynthesis ¹	10.96	CYP11A1 AKR1C4 AKR1C2
4	Metabolism of steroid hormones ⁶⁵ Show member pathways Androgen biosynthesis ⁶⁵ Estrogen biosynthesis ⁶⁵ Glucocorticoid andamp; Mineralcorticoid Metabolism ¹ glucocorticoid biosynthesis ¹ Glucocorticoid biosynthesis ⁶⁵ mineralocorticoid biosynthesis ¹ Mineralocorticoid biosynthesis ⁶⁵ Pregnenolone biosynthesis ⁶⁵	10.87	STAR FDXR FDX1 CYP11A1
5	Naphthalene metabolism ²²	10.75	AKR1C4 AKR1C2
6	Mitochondrial iron-sulfur cluster biogenesis ⁶⁵	10.11	FDXR FDX1

Sources

GO Terms for 46,xy Sex Reversal

Cellular components related to 46,xy Sex Reversal according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	nuclear chromatin	GO:0000790	9.23	ZFPM2 SRY SOX9 NR5A1 NR0B1 GATA4

Biological processes related to 46,xy Sex Reversal according to GeneCards Suite gene sharing:

(show all 32)

#	Name	GO ID	Score	Top Affiliating Genes
1	regulation of transcription, DNA-templated	GO:0006355	10.21	WT1 SRY SOX9 NR5A1 NR0B1 GATA4
2	positive regulation of transcription by RNA polymerase II	GO:0045944	10.16	ZFPM2 WT1 SRY SOX9 NR5A1 GATA4
3	cell differentiation	GO:0030154	10.13	ZFPM2 SRY SOX9 NR5A1 NR0B1 DMRT3
4	negative regulation of transcription by RNA polymerase II	GO:0000122	10.11	ZFPM2 WT1 SRY SOX9 NR0B1 DMRT1
5	positive regulation of transcription, DNA-templated	GO:0045893	10.07	ZFPM2 WT1 SRY SOX9 NR5A1 GATA4
6	positive regulation of gene expression	GO:0010628	10.04	WT1 STAR SRY SOX9 NR5A1
7	steroid metabolic process	GO:0008202	9.88	FDXR FDX1 CYP11A1 AKR1C4 AKR1C2
8	cholesterol metabolic process	GO:0008203	9.85	STAR FDXR FDX1 CYP11A1
9	cellular response to cAMP	GO:0071320	9.77	WT1 STAR FDX1
10	sterol metabolic process	GO:0016125	9.73	FDXR FDX1 CYP11A1
11	steroid biosynthetic process	GO:0006694	9.72	STAR NR0B1 FDXR FDX1 CYP11A1
12	adrenal gland development	GO:0030325	9.71	WT1 NR5A1 NR0B1
13	sex differentiation	GO:0007548	9.71	SRY DMRT3 DMRT1 CBX2
14	male gonad development	GO:0008584	9.7	WT1 STAR SOX9 NR5A1 NR0B1 GATA4
15	C21-steroid hormone metabolic process	GO:0008207	9.69	CYP11A1 AKR1C4 AKR1C2
16	regulation of steroid biosynthetic process	GO:0050810	9.67	STAR NR5A1 DHH
17	cardiac muscle tissue development	GO:0048738	9.65	ZFPM2 GATA4
18	gonad development	GO:0008406	9.65	WT1 NR0B1
19	Sertoli cell development	GO:0060009	9.65	SOX9 DMRT1
20	Leydig cell differentiation	GO:0033327	9.64	NR0B1 DHH
21	progesterone metabolic process	GO:0042448	9.63	AKR1C4 AKR1C2
22	doxorubicin metabolic process	GO:0044598	9.63	AKR1C4 AKR1C2
23	sex determination	GO:0007530	9.63	WT1 NR5A1 NR0B1
24	daunorubicin metabolic process	GO:0044597	9.62	AKR1C4 AKR1C2
25	cellular response to gonadotropin stimulus	GO:0071371	9.61	WT1 STAR
26	Sertoli cell differentiation	GO:0060008	9.61	SOX9 NR0B1 DMRT1
27	cellular response to jasmonic acid stimulus	GO:0071395	9.58	AKR1C4 AKR1C2
28	male sex differentiation	GO:0046661	9.58	DMRT3 DMRT1
29	C21-steroid hormone biosynthetic process	GO:0006700	9.56	STAR FDXR FDX1 CYP11A1
30	negative regulation of female gonad development	GO:2000195	9.54	ZFPM2 WT1 NR5A1
31	male sex determination	GO:0030238	9.43	SRY SOX9 NR5A1 NR0B1 DMRT1 DHH
32	positive regulation of male gonad development	GO:2000020	9.1	ZFPM2 WT1 SRY SOX9 NR5A1 DMRT1

Molecular functions related to 46,xy Sex Reversal according to GeneCards Suite gene sharing:

(show all 14)

#	Name	GO ID	Score	Top Affiliating Genes
1	zinc ion binding	GO:0008270	9.95	ZFPM2 WT1 NR5A1 MAP3K1 GATA4 DHH
2	DNA binding	GO:0003677	9.85	ZFPM2 WT1 SRY SOX9 NR5A1 NR0B1
3	transcription regulatory region sequence-specific DNA binding	GO:0000976	9.84	WT1 SOX9 NR5A1 GATA4
4	DNA-binding transcription factor activity	GO:0003700	9.8	WT1 SRY SOX9 NR5A1 GATA4 DMRT3
5	proximal promoter sequence-specific DNA binding	GO:0000987	9.67	SOX9 GATA4 DMRT1
6	alcohol dehydrogenase (NADP+) activity	GO:0008106	9.52	AKR1C4 AKR1C2
7	alditol:NADP+ 1-oxidoreductase activity	GO:0004032	9.51	AKR1C4 AKR1C2
8	sequence-specific DNA binding	GO:0043565	9.5	WT1 SOX9 NR5A1 NR0B1 GATA4 DMRT3
9	bile acid binding	GO:0032052	9.46	AKR1C4 AKR1C2
10	oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	GO:0016655	9.43	AKR1C4 AKR1C2
11	steroid dehydrogenase activity	GO:0016229	9.4	AKR1C4 AKR1C2
12	androsterone dehydrogenase activity	GO:0047023	9.37	AKR1C4 AKR1C2
13	ketosteroid monooxygenase activity	GO:0047086	9.32	AKR1C4 AKR1C2
14	DNA-binding transcription factor activity, RNA polymerase II-specific	GO:0000981	9.28	ZFPM2 WT1 SRY SOX9 NR5A1 NR0B1

Sources

Sources for 46,xy Sex Reversal

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