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

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Aliases & Classifications for 46,xy Sex Reversal

MalaCards integrated aliases for 46,xy Sex Reversal:

Name: 46,xy Sex Reversal ¹¹ ⁴² ¹⁴

Swyer Syndrome ¹¹ ¹⁹ ⁴² ⁵⁸ ⁷⁵ ⁵³ ⁷¹ ³³

Pure Gonadal Dysgenesis 46,xy ¹¹ ⁴² ²⁸ ⁵

Gonadal Dysgenesis, Xy Female Type ¹⁹ ⁷⁵ ³³

Gonadal Dysgenesis, 46,xy ⁴² ⁴³ ⁷¹

46,xy Complete Gonadal Dysgenesis ⁴² ⁵⁸

46,xy Pure Gonadal Dysgenesis ⁵⁸ ³³

46,xy Cgd ⁴² ⁵⁸

46, Xy Complete Gonadal Dysgenesis ¹⁹

46, Xy Pure Gonadal Dysgenesis ¹⁹

Female with 46,xy Karyotype ³³

Xy Pure Gonadal Dysgenesis ⁴²

46 Xy Gonadal Dysgenesis ¹¹

46, Xy Cgd ¹⁹

Xy Females ³³

Characteristics:

Inheritance:

46,xy Complete Gonadal Dysgenesis: Autosomal dominant,Autosomal recessive,X-linked recessive,Y-linked ⁵⁸

Prevelance:

46,xy Complete Gonadal Dysgenesis: <1/1000000 (Denmark) 1-9/100000 (Denmark) ⁵⁸

Age Of Onset:

46,xy Complete Gonadal Dysgenesis: Adolescent,Adult ⁵⁸

Classifications:

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

See all MalaCards categories (disease lists)

ICD10: ³²

Congenital malformations, deformations and chromosomal abnormalities

Chromosomal abnormalities, not elsewhere classified

Other chromosome abnormalities, not elsewhere classified

46,XX true hermaphrodite

ICD11: ³³

Developmental anomalies

Multiple developmental anomalies or syndromes

Malformative disorders of sex development

46,XY gonadal dysgenesis

Orphanet: ⁵⁸

Rare gynaecological and obstetric diseases

Rare endocrine diseases

Developmental anomalies during embryogenesis

External Ids:

Disease Ontology ¹¹ DOID:14448

MeSH ⁴³ D006061

NCIt ⁴⁹ C120198

ICD10 via Orphanet ³² Q99.1

UMLS via Orphanet ⁷² C0018054 C2936694

Orphanet ⁵⁸ ORPHA242

SNOMED-CT via HPO ⁶⁹ 111332007 253847002 33927004 more

ICD11 ³³ 1844256276

UMLS ⁷¹ C0018054 C2936694

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Summaries for 46,xy Sex Reversal

MedlinePlus Genetics: ⁴² Swyer syndrome is a condition that affects sex development. Sex development usually follows a particular path based on an individual's chromosomes; however, in Swyer syndrome, sex development is not typical for the affected individual's chromosomal pattern. Chromosomes contain the genetic instructions for how the body develops and functions. 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 reproductive structures. Girls and women typically have two X chromosomes (46,XX karyotype), while boys and men typically have one X chromosome and one Y chromosome (46,XY karyotype). In Swyer syndrome, individuals have one X chromosome and one Y chromosome in each cell, which is the pattern typically found in boys and men; however, they have female reproductive structures. People with Swyer syndrome have female external genitalia and some female internal reproductive structures. These individuals usually have a uterus and fallopian tubes, but their gonads (ovaries or testes) are not functional. Instead, the gonads are small and underdeveloped and contain little gonadal tissue. These structures are called streak gonads. The streak gonadal tissue is at risk of developing cancer that is often hard-to-detect, so it is usually removed surgically. Swyer syndrome is also called 46,XY complete gonadal dysgenesis; the medical term “dysgenesis” means "abnormal development." Because they appear female on the outside, babies with Swyer syndrome are usually raised as girls and develop a female gender identity, which is a person's sense of their gender (girl, boy, a combination, or neither). Swyer syndrome may be identified before birth, at birth, or later when a child does not go through puberty as usual. Because they do not have functional ovaries that produce hormones, affected individuals often begin hormone replacement therapy during early adolescence to start puberty, causing the breasts and uterus to grow, and eventually leading to menstruation. Hormone replacement therapy is also important for bone health and helps reduce the risk of low bone density (osteopenia) and fragile bones (osteoporosis). Women with Swyer syndrome do not produce eggs (ova), but if they have a uterus, they may be able to become pregnant with a donated egg or embryo.

MalaCards based summary: 46,xy Sex Reversal, also known as swyer syndrome, is related to 46,xy sex reversal 9 and 46,xy sex reversal 2. An important gene associated with 46,xy Sex Reversal is AR (Androgen Receptor), and among its related pathways/superpathways are Nervous system development and Metabolism of steroids. Affiliated tissues include uterus, testes and bone, and related phenotypes are polycystic ovaries and male pseudohermaphroditism

GARD: ¹⁹ 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 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. While women with Swyer syndrome are infertile, they may become pregnant with the use of donated eggs.

Orphanet: ⁵⁸ A rare disorder/difference of sex development (DSD) associated with absence in gonadal development that results in the presence of female appearing external and internal genitalia in presence of a 46,XY karyotype.

Disease Ontology: ¹¹ 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.

Wikipedia: ⁷⁵ 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 194)

#	Related Disease	Score	Top Affiliating Genes
1	46,xy sex reversal 9	33.7	ZFPM2 WT1 SOX9 NR5A1 AR AMH
2	46,xy sex reversal 2	33.6	WT1 WNT4 STAR SOX9 NR5A2 NR5A1
3	adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete	33.5	STAR NR5A1 NR0B1 CYP11A1
4	46,xy sex reversal 11	33.4	SRY DHX37
5	campomelic dysplasia	33.1	SRY SOX9 NR5A1 DMRT1
6	46,xy sex reversal 8	33.0	AKR1C4 AKR1C2
7	gonadoblastoma	31.7	WT1 SRY SOX9 NR5A1 NR0B1 DMRT1
8	turner syndrome	31.4	SRY NR0B1 AR AMH
9	46,xx sex reversal 1	31.3	SRY SOX9 NR5A1 NR0B1
10	46,xy partial gonadal dysgenesis	31.2	ZFPM2 WT1 SRY SOX9 NR5A1 NR0B1
11	frasier syndrome	31.2	WT1 SRY SOX9 NR5A1 NR0B1
12	mixed gonadal dysgenesis	31.2	SRY SOX9 NR5A1 NR0B1 DMRT1 AMH
13	gonadal dysgenesis	31.1	ZFPM2 WT1 SRY SOX9 NR5A1 NR0B1
14	hermaphroditism	31.1	ZFPM2 WNT4 SOX9 NR5A1 NR0B1 DMRT1
15	wilms tumor 1	31.1	WT1 WNT4 SOX9 NR5A1 NR0B1
16	disorder of sexual development	31.1	ZFPM2 WT1 WNT4 STAR SRY SOX9
17	syndrome with 46,xy disorder of sex development	30.9	SRY NR5A1
18	androgen insensitivity syndrome	30.9	SRY NR5A1 NR0B1 DMRT1 AR AMH
19	cryptorchidism, unilateral or bilateral	30.9	ZFPM2 WT1 WNT4 STAR SOX9 NR5A1
20	renal hypodysplasia/aplasia 1	30.9	WT1 WNT4 AMH
21	gender incongruence	30.9	AR AMH
22	hypospadias	30.8	WT1 SRY SOX9 NR5A1 CYP11A1 AR
23	46,xx sex reversal	30.8	WT1 WNT4 SRY SOX9 NR5A1 NR0B1
24	azoospermia	30.8	WT1 NR5A1 NR0B1 AR AMH
25	mixed germ cell cancer	30.8	DMRT1 AMH
26	lipoid congenital adrenal hyperplasia	30.7	WNT4 STAR SRY NR5A1 NR0B1 DMRT1
27	premature menopause	30.7	WT1 WNT4 STAR SOX9 NR5A2 NR5A1
28	hypogonadotropic hypogonadism	30.6	STAR SOX9 NR5A1 NR0B1 DMRT1 AR
29	androgen insensitivity, partial	30.5	NR5A1 NR0B1 AR AMH
30	complete androgen insensitivity syndrome	30.5	SRY NR5A1 NR0B1 DMRT1 AR AMH
31	pseudohermaphroditism	30.3	WT1 WNT4 STAR SRY SOX9 NR5A1
32	46,xy sex reversal 5	12.1
33	46,xy sex reversal 6	12.1
34	46,xy sex reversal 1	12.0
35	46,xy sex reversal 7	12.0
36	46,xy sex reversal 3	12.0
37	46,xy sex reversal 4	12.0
38	46,xy sex reversal 10	12.0
39	46,xy gonadal dysgenesis with minifascicular neuropathy	11.9
40	genitopalatocardiac syndrome	11.6
41	nivelon-nivelon-mabille syndrome	11.4
42	down syndrome	10.7
43	dysgerminoma	10.6
44	spermatogenic failure 8	10.5	NR5A1 DMRT1 AR
45	testicular granulosa cell tumor	10.5	WT1 AMH
46	contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a	10.5
47	intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies	10.5	NR5A1 NR0B1 CYP11A1
48	corticosterone methyloxidase type i deficiency	10.5	STAR NR5A1 NR0B1 CYP11A1
49	adrenal cortical hypofunction	10.5	STAR NR5A1 NR0B1 CYP11A1
50	adrenal hypoplasia, congenital	10.5	STAR NR5A1 NR0B1 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 ³⁰

#	Description	HPO Frequency	Orphanet Frequency	HPO Source Accession
1	polycystic ovaries ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0000147
2	male pseudohermaphroditism ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0000037
3	testicular dysgenesis ⁵⁸ ³⁰	Hallmark (90%)	Very frequent (99-80%)	HP:0008715
4	hypogonadotropic hypogonadism ³⁰	Hallmark (90%)		HP:0000044
5	hypogonadotrophic hypogonadism ⁵⁸		Very frequent (99-80%)

MGI Mouse Phenotypes related to 46,xy Sex Reversal:

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	homeostasis/metabolism	MP:0005376	10.2	AKR1C2 AKR1C4 AMH AR CYP11A1 DHH
2	endocrine/exocrine gland	MP:0005379	10.13	AMH AR CBX2 CYP11A1 DHH DMRT1
3	cellular	MP:0005384	9.9	AR CBX2 CYP11A1 DMRT1 MAP3K1 NR0B1
4	reproductive system	MP:0005389	9.83	AMH AR CBX2 CYP11A1 DHH DMRT1
5	mortality/aging	MP:0010768	9.47	AR CBX2 CYP11A1 DHX37 LCOR MAP3K1

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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 ²⁸

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Anatomical Context for 46,xy Sex Reversal

Organs/tissues related to 46,xy Sex Reversal:

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

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Publications for 46,xy Sex Reversal

Articles related to 46,xy Sex Reversal:

(show top 50) (show all 688)

#	Title	Authors	PMID	Year
1	Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. ⁵	Eggers S...Sinclair AH	27899157	2016
2	Genotype versus phenotype in families with androgen insensitivity syndrome. ⁵	Boehmer AL...Drop SL	11549642	2001
3	Identification of a new mutation in the SRY gene in a 46,XY woman with Swyer syndrome. ⁵³ ⁶²	Marchina E...Barlati S	18990383	2009
4	Identification of a novel mutation in the SRY gene in a 46, XY female patient. ⁵³ ⁶²	Salehi LB...Stuppia L	16675314	2006
5	Swyer syndrome with SRY + Y chromosome and rudimentary internal genitalia demonstrating temporary action of antimüllerian hormone in utero: a case report. ⁵³ ⁶²	Kahyaoglu S...Batioglu S	16846094	2006
6	A novel frame shift mutation in the HMG box of the SRY gene in a patient with complete 46,XY pure gonadal dysgenesis. ⁵³ ⁶²	Kellermayer R...Kosztolanyi G	16106197	2005
7	Description and molecular analysis of SRY and AR genes in a patient with 46,XY pure gonadal dysgenesis (Swyer syndrome). ⁵³ ⁶²	Iliopoulos D...Voyiatzis N	15183752	2004
8	Mutation analysis of subjects with 46, XX sex reversal and 46, XY gonadal dysgenesis does not support the involvement of SOX3 in testis determination. ⁵³ ⁶²	Lim HN...Hawkins JR	11153920	2000
9	A novel double nucleotide substitution in the HMG box of the SRY gene associated with Swyer syndrome. ⁵³ ⁶²	Battiloro E...D'Ambrosio E	9341876	1997
10	Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations. ⁵³ ⁶²	Meyer J...Scherer G	9002675	1997
11	A new de novo mutation (A113T) in HMG box of the SRY gene leads to XY gonadal dysgenesis. ⁵³ ⁶²	Zeng YT...Huang SZ	8105086	1993
12	The presence of the testicular determining sequence, SRY, in 46,XY females with gonadal dysgenesis (Swyer syndrome). ⁵³ ⁶²	Behzadian MA...McDonough PG	1750489	1991
13	FGF9 variant in 46,XY DSD patient suggests a role for dimerization in sex determination. ⁶²	Croft B...Harley VR	36349847	2022
14	Fertility in Individuals with Differences in Sex Development: Provider Knowledge Assessment. ⁶²	Finlayson C...Gomez-Lobo V	35296452	2022
15	Muscle spasms as presenting feature of Nivelon-Nivelon-Mabile syndrome. ⁶²	Saini N...Aggarwal S	36271814	2022
16	Novel mutation of MAP3K1 gene in 46,XY DSD with complete gonadal dysgenesis. ⁶²	Yu PH...Kuo PL	36088066	2022
17	Disruption of the topologically associated domain at Xp21.2 is related to 46,XY gonadal dysgenesis. ⁶²	Meinel JA...Werner R	36227713	2022
18	SOX9 in organogenesis: shared and unique transcriptional functions. ⁶²	Ming Z...Harley V	36114905	2022
19	Anomalies in Human Sex Determination: Usefulness of a Combined Cytogenetic Approach to Characterize an Additional Case with Xp Functional Disomy Associated to 46,XY Gonadal Dysgenesis. ⁶²	Rjiba K...Mougou-Zerelli S	35984215	2022
20	The Mysteries of Primary Amenorrhea: Swyer Syndrome. ⁶²	Cherukuri S...Andela M	36158407	2022
21	SOX9 and SRY binding sites on mouse mXYSRa/Enh13 enhancer redundantly regulate Sox9 expression to varying degrees. ⁶²	Ogawa Y...Takada S	35921234	2022
22	Ulerythema ophryogenes in association with MAP3K1-mutated Swyer syndrome. ⁶²	Nimgaonkar I...Milgraum SS	35755173	2022
23	Dysgerminoma in a 15 years old phenotypically female Swyer syndrome with 46, XY pure gonadal dysgenesis: A case report. ⁶²	Ashraf Ganjooei T...Hashemieh M	35846908	2022
24	A Successful New Case of Twin Pregnancy in a Patient with Swyer Syndrome-An Up-to-Date Review on the Incidence and Outcome of Twin/Multiple Gestations in the Pure 46,XY Gonadal Dysgenesis. ⁶²	Winkler I...Skrzypczak M	35564421	2022
25	Role of the X and Y Chromosomes in the Female Germ Cell Line Development in the Mouse (Mus musculus). ⁶²	Yamazaki W...Taketo T	35235936	2022
26	Novel androgen receptor gene variant containing a frameshift mutation in a patient with complete androgen insensitivity syndrome. ⁶²	Chen G...Qiao S	34700362	2022
27	A nonfunctional copy of the salmonid sex-determining gene (sdY) is responsible for the "apparent" XY females in Chinook salmon, Oncorhynchus tshawytscha. ⁶²	Bertho S...Guiguen Y	35100376	2022
28	WAGR, Sex Reversal, Bilateral Gonadoblastomas, and Intralobar Nephrogenic Rests: Uncertainties of Pre-Biopsy Chemotherapy in a High Risk Syndrome for Nephroblastoma. ⁶²	Craver R...C Roth C	35199613	2022
29	Expanding the spectrum of syndromic PPP2R3C-related XY gonadal dysgenesis to XX gonadal dysgenesis. ⁶²	Altunoglu U...Kayserili H	34750818	2022
30	Case Report: Novel Compound Heterozygotic Variants in PPP2R3C Gene Causing Syndromic 46, XY Gonadal Dysgenesis and Literature Review. ⁶²	Zhang W...Wu X	35812758	2022
31	Genetics of 46,XY gonadal dysgenesis. ⁶²	Elzaiat M...Bashamboo A	35249806	2022
32	DMRT1: An Ancient Sexual Regulator Required for Human Gonadogenesis. ⁶²	Zarkower D...Murphy MW	34515237	2022
33	Pathogenic Variants in MAP3K1 Cause 46,XY Gonadal Dysgenesis: A Review. ⁶²	Ostrer H	35290982	2022
34	A 15-20-year follow-up of mental health, psychosocial functioning and quality of life in a single center sample of individuals with differences in sex development. ⁶²	Waehre A...Diseth T	36105256	2022
35	DHX37 and 46,XY DSD: A New Ribosomopathy? ⁶²	McElreavey K...Bashamboo A	35835064	2022
36	A Homozygous Missense Variant in Hedgehog Acyltransferase (HHAT) Gene Associated with 46,XY Gonadal Dysgenesis. ⁶²	Mazen I...Abdel-Hamid MS	35045414	2022
37	Case Report: Long-term follow-up of desert hedgehog variant caused 46, XY gonadal dysgenesis with multiple complications in a Chinese child. ⁶²	Pan L...Wen P	36072668	2022
38	Gonadal tumor risk in pediatric and adolescent phenotypic females with disorders of sex development and Y chromosomal constitution with different genetic etiologies. ⁶²	Lu L...Wang X	35935368	2022
39	Tenuous Transcriptional Threshold of Human Sex Determination. I. SRY and Swyer Syndrome at the Edge of Ambiguity. ⁶²	Chen YS...Weiss MA	35957822	2022
40	The Desert Hedgehog Signalling Pathway in Human Gonadal Development and Differences of Sex Development. ⁶²	Pachernegg S...Ayers K	34518472	2022
41	Complete gonadal dysgenesis analysis in the population of Latvia: malignant outcomes and a review of literature. ⁶²	Jakovleva A...Kovalova Z	35720238	2022
42	Swyer Syndrome: A Case of Dysgerminoma Solely within the Fallopian Tube. ⁶²	Anwar A...Busby G	33989803	2021
43	Bilateral Gonadoblastoma Overgrown by Dysgerminoma of the Right Gonad in a Patient with Swyer Syndrome. ⁶²	Arafa M...Al-Kindi N	35261680	2021
44	Swyer Syndrome/46 XY Gonadal Dysgenesis: Remove the Tubes or Not? ⁶²	Fallat ME...Klipstein S	34742465	2021
45	Broad-spectrum XX and XY gonadal dysgenesis in patients with a homozygous L193S variant in PPP2R3C. ⁶²	Cicek D...Guran T	34714774	2021
46	Unusual Mammalian Sex Determination Systems: A Cabinet of Curiosities. ⁶²	Saunders PA...Veyrunes F	34828376	2021
47	Two successful pregnancies after in vitro fertilisation with oocyte donation in a patient with Swyer syndrome - a case report. ⁶²	Urban A...Smolarczyk R	34703418	2021
48	On the Form and Origins of the Bizarre Sex Chromosomal System of the Mandarin Vole. ⁶²	Roy SW	33884423	2021
49	A Novel Intronic Splice-Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development. ⁶²	Matusik P...Gawlik A	34281122	2021
50	Mode of delivery of women with Swyer syndrome in a German case series. ⁶²	Weisshaupt K...Weichert A	33725759	2021

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Genes for 46,xy Sex Reversal

Genes related to 46,xy Sex Reversal (11 elite genes):

(show top 50) (show all 74)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	AR	Androgen Receptor	Protein Coding	405.41	Pathogenic ⁵ DISEASES inferred ¹⁴	27899157 11549642
2	SRY	Sex Determining Region Y	Protein Coding	378.73	Causative germline mutation (loss of function) ⁵⁸ Novoseek inferred ⁵³ GeneCards inferred via : Disorders Publications (show sections)	20301714 15183752 9341876 (more) 16846094 10803875 11153920 16675314 8105086 1750489 9249610 16106197 18990383
3	NR5A1	Nuclear Receptor Subfamily 5 Group A Member 1	Protein Coding	376.09	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁴ GeneCards inferred via : Disorders Publications (show sections)	20301714
4	SOX9	SRY-Box Transcription Factor 9	Protein Coding	372.71	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁴ Novoseek inferred ⁵³ GeneCards inferred via : Disorders (show sections)	22051515 9002675
5	NR0B1	Nuclear Receptor Subfamily 0 Group B Member 1	Protein Coding	367.77	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)	30879272
6	DHH	Desert Hedgehog Signaling Molecule	Protein Coding	364.69	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)	20301714
7	MAP3K1	Mitogen-Activated Protein Kinase Kinase Kinase 1	Protein Coding	364.19	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)	21129722
8	CBX2	Chromobox 2	Protein Coding	363.97	Causative germline mutation (loss of function) ⁵⁸ DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)	19361780
9	DHX37	DEAH-Box Helicase 37	Protein Coding	362.91	Causative germline mutation ⁵⁸ DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)	31337883
10	DMRT1	Doublesex And Mab-3 Related Transcription Factor 1	Protein Coding	49.34	Role in the phenotype ⁵⁸ DISEASES inferred ¹⁴ GeneCards inferred via : Disorders Publications (show sections)	20685758
11	WT1	WT1 Transcription Factor	Protein Coding	31.44	Candidate gene tested ⁵⁸ DISEASES inferred ¹⁴	21314844
12	CYP11A1	Cytochrome P450 Family 11 Subfamily A Member 1	Protein Coding	24.9	DISEASES inferred ¹⁴ GeneCards inferred via : Disorders Publications (show sections)
13	ZFPM2	Zinc Finger Protein, FOG Family Member 2	Protein Coding	13.6	DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)
14	AKR1C4	Aldo-Keto Reductase Family 1 Member C4	Protein Coding	13.01	DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)
15	AKR1C2	Aldo-Keto Reductase Family 1 Member C2	Protein Coding	11.63	DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)
16	STAR	Steroidogenic Acute Regulatory Protein	Protein Coding	7.29	DISEASES inferred ¹⁴
17	NR5A2	Nuclear Receptor Subfamily 5 Group A Member 2	Protein Coding	6.78	DISEASES inferred ¹⁴
18	LCOR	Ligand Dependent Nuclear Receptor Corepressor	Protein Coding	6.72	DISEASES inferred ¹⁴ ¹⁴
19	AMH	Anti-Mullerian Hormone	Protein Coding	6.61	DISEASES inferred ¹⁴
20	WNT4	Wnt Family Member 4	Protein Coding	6.58	DISEASES inferred ¹⁴
21	MC2R	Melanocortin 2 Receptor	Protein Coding	6.58	DISEASES inferred ¹⁴
22	CYP17A1	Cytochrome P450 Family 17 Subfamily A Member 1	Protein Coding	6.45	DISEASES inferred ¹⁴
23	FOXL2	Forkhead Box L2	Protein Coding	6.38	DISEASES inferred ¹⁴
24	DMRT2	Doublesex And Mab-3 Related Transcription Factor 2	Protein Coding	6.36	DISEASES inferred ¹⁴
25	HSD3B2	Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- And Steroid Delta-Isomerase 2	Protein Coding	6.3	DISEASES inferred ¹⁴
26	NR0B2	Nuclear Receptor Subfamily 0 Group B Member 2	Protein Coding	6.14	DISEASES inferred ¹⁴
27	CYP11B1	Cytochrome P450 Family 11 Subfamily B Member 1	Protein Coding	6.12	DISEASES inferred ¹⁴
28	CYP21A2	Cytochrome P450 Family 21 Subfamily A Member 2	Protein Coding	6.03	DISEASES inferred ¹⁴
29	FGF9	Fibroblast Growth Factor 9	Protein Coding	5.92	DISEASES inferred ¹⁴
30	HSD17B3	Hydroxysteroid 17-Beta Dehydrogenase 3	Protein Coding	5.85	DISEASES inferred ¹⁴
31	POMC	Proopiomelanocortin	Protein Coding	5.78	DISEASES inferred ¹⁴
32	HSD3B1	Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- And Steroid Delta-Isomerase 1	Protein Coding	5.75	DISEASES inferred ¹⁴
33	CYP19A1	Cytochrome P450 Family 19 Subfamily A Member 1	Protein Coding	5.74	DISEASES inferred ¹⁴
34	RSPO1	R-Spondin 1	Protein Coding	5.72	DISEASES inferred ¹⁴
35	GATA4	GATA Binding Protein 4	Protein Coding	5.59	DISEASES inferred ¹⁴
36	LHCGR	Luteinizing Hormone/Choriogonadotropin Receptor	Protein Coding	5.59	DISEASES inferred ¹⁴
37	CYP11B2	Cytochrome P450 Family 11 Subfamily B Member 2	Protein Coding	5.58	DISEASES inferred ¹⁴
38	CITED2	Cbp/P300 Interacting Transactivator With Glu/Asp Rich Carboxy-Terminal Domain 2	Protein Coding	5.56	DISEASES inferred ¹⁴
39	NR4A1	Nuclear Receptor Subfamily 4 Group A Member 1	Protein Coding	5.54	DISEASES inferred ¹⁴
40	GNRH1	Gonadotropin Releasing Hormone 1	Protein Coding	5.51	DISEASES inferred ¹⁴
41	LHX9	LIM Homeobox 9	Protein Coding	5.5	DISEASES inferred ¹⁴
42	DMRT3	Doublesex And Mab-3 Related Transcription Factor 3	Protein Coding	5.43	DISEASES inferred ¹⁴
43	NR6A1	Nuclear Receptor Subfamily 6 Group A Member 1	Protein Coding	5.36	DISEASES inferred ¹⁴
44	SOX8	SRY-Box Transcription Factor 8	Protein Coding	5.31	DISEASES inferred ¹⁴
45	SRD5A2	Steroid 5 Alpha-Reductase 2	Protein Coding	5.31	DISEASES inferred ¹⁴
46	INSL3	Insulin Like 3	Protein Coding	5.3	DISEASES inferred ¹⁴
47	POR	Cytochrome P450 Oxidoreductase	Protein Coding	5.3	DISEASES inferred ¹⁴
48	SOX3	SRY-Box Transcription Factor 3	Protein Coding	5.28	DISEASES inferred ¹⁴
49	CST9L	Cystatin 9 Like	Protein Coding	5.23	DISEASES inferred ¹⁴
50	AMHR2	Anti-Mullerian Hormone Receptor Type 2	Protein Coding	5.18	DISEASES inferred ¹⁴

Sources

Variations for 46,xy Sex Reversal

ClinVar genetic disease variations for 46,xy Sex Reversal:

⁵

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	AR	NM_000044.6(AR):c.1462C>T (p.Gln488Ter)	SNV	Pathogenic	988321	rs1929774367	GRCh37: X:66766450-66766450 GRCh38: X:67546608-67546608
2	DMRT1	NM_021951.3(DMRT1):c.967G>A (p.Val323Ile)	SNV	Uncertain Significance	988653	rs746758951	GRCh37: 9:916907-916907 GRCh38: 9:916907-916907
3	CHD7	NM_017780.4(CHD7):c.4388T>C (p.Leu1463Pro)	SNV	Uncertain Significance	1344532		GRCh37: 8:61750669-61750669 GRCh38: 8:60838110-60838110

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 directly related to 46,xy Sex Reversal:

#	Pathway	Source
1	Hh mutants are degraded by ERAD	Reactome ⁶⁶
2	HHAT G278V doesn't palmitoylate Hh-Np	Reactome ⁶⁶

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

#	Super pathways	Score	Top Affiliating Genes
1	Nervous system development ⁶⁶ Show member pathways Axon guidance ⁶⁶ Developmental Biology ⁶⁶	13.42	ZFPM2 WT1 SRY SOX9 NR5A2 NR5A1
2	Metabolism of steroids ⁶⁶ Show member pathways Activation of gene expression by SREBF (SREBP) ⁶⁶ allopregnanolone biosynthesis ⁶¹ androgen biosynthesis ⁶¹ Cholesterol synthesis disorders ⁷⁴ Defective CYP17A1 causes AH5 ⁶⁶ Regulation of cholesterol biosynthesis by SREBP (SREBF) ⁶⁶ Sterol regulatory element-binding proteins (SREBP) signaling ⁷⁴ Vitamin D (calciferol) metabolism ⁶⁶	12.32	STAR CYP11A1 AKR1C4 AKR1C2
3	Nuclear receptors ⁷⁴ Show member pathways Nuclear Receptor transcription pathway ⁶⁶ SUMOylation of intracellular receptors ⁶⁶	11.64	NR5A2 NR5A1 NR0B1 AR
4	Prostaglandin synthesis and regulation ⁷⁴ Show member pathways Defective TBXAS1 causes GHDD ⁶⁶ Eicosanoid metabolism via cyclooxygenases (COX) ⁷⁴ Ibuprofen Pathway, Pharmacodynamics ⁶⁰	11.5	SOX9 CYP11A1 AKR1C2
5	Regulation of Androgen receptor activity ⁶¹	11.23	SRY NR0B1 AR
6	Kisspeptin/kisspeptin receptor system in the ovary ⁷⁴	11.08	AMH CYP11A1 STAR
7	Mammalian disorder of sexual development ⁷⁴ Show member pathways Somatic sex determination ⁷⁴ Transcriptional regulation of testis differentiation ⁶⁶	11.01	ZFPM2 WT1 WNT4 SRY SOX9 NR5A1
8	Naphthalene metabolism ²²	10.86	AKR1C4 AKR1C2
9	MAP3K1 role in promoting and blocking gonadal determination ⁷⁴	10.66	WNT4 SRY SOX9 MAP3K1
10	Alternative pathway of fetal androgen synthesis ⁷⁴	10.3	STAR CYP11A1 AKR1C4 AKR1C2

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	chromatin	GO:0000785	9.53	ZFPM2 SRY SOX9 NR5A2 NR5A1 NR0B1

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

(show all 29)

#	Name	GO ID	Score	Top Affiliating Genes
1	positive regulation of transcription by RNA polymerase II	GO:0045944	10.54	ZFPM2 WT1 SRY SOX9 NR5A2 NR5A1
2	negative regulation of transcription by RNA polymerase II	GO:0000122	10.46	AR CBX2 DMRT1 LCOR NR0B1 SOX9
3	positive regulation of gene expression	GO:0010628	10.38	AMH AR NR5A1 SOX9 SRY WT1
4	positive regulation of DNA-templated transcription	GO:0045893	10.37	ZFPM2 WT1 WNT4 SRY SOX9 NR5A2
5	cell differentiation	GO:0030154	10.3	ZFPM2 WNT4 SRY SOX9 DMRT1 CBX2
6	male gonad development	GO:0008584	10.13	AR DMRT1 NR0B1 NR5A1 SOX9 WNT4
7	branching involved in ureteric bud morphogenesis	GO:0001658	10.06	WT1 WNT4 SOX9
8	adrenal gland development	GO:0030325	10.06	NR0B1 NR5A1 WNT4 WT1
9	tissue development	GO:0009888	10.05	WT1 NR5A2 NR5A1
10	intracellular receptor signaling pathway	GO:0030522	10.04	NR5A2 NR5A1 AR
11	sex differentiation	GO:0007548	9.97	WNT4 SRY DMRT1 CBX2 AMH
12	Leydig cell differentiation	GO:0033327	9.96	NR5A1 NR0B1 DHH AR AMH
13	regulation of steroid biosynthetic process	GO:0050810	9.95	STAR NR5A1 DHH
14	sex determination	GO:0007530	9.95	WT1 NR5A1 NR0B1 AMH
15	Sertoli cell development	GO:0060009	9.94	SOX9 DMRT1
16	doxorubicin metabolic process	GO:0044598	9.93	AKR1C4 AKR1C2
17	progesterone metabolic process	GO:0042448	9.93	AKR1C4 AKR1C2
18	gonadal mesoderm development	GO:0007506	9.92	AMH ZFPM2
19	daunorubicin metabolic process	GO:0044597	9.92	AKR1C2 AKR1C4
20	mesenchymal to epithelial transition	GO:0060231	9.91	WNT4 WT1
21	negative regulation of female gonad development	GO:2000195	9.91	ZFPM2 WT1 NR5A1
22	negative regulation of steroid biosynthetic process	GO:0010894	9.89	WNT4 NR0B1
23	gonad development	GO:0008406	9.89	WT1 NR0B1 AMH
24	cellular response to jasmonic acid stimulus	GO:0071395	9.86	AKR1C2 AKR1C4
25	renal vesicle induction	GO:0072034	9.85	WNT4 SOX9
26	Sertoli cell differentiation	GO:0060008	9.85	DMRT1 NR0B1 NR5A1 SOX9 WNT4
27	tertiary branching involved in mammary gland duct morphogenesis	GO:0060748	9.84	WNT4 AR
28	male sex determination	GO:0030238	9.7	SRY SOX9 NR5A1 NR0B1 DMRT1 DHH
29	positive regulation of male gonad development	GO:2000020	9.47	ZFPM2 WT1 SRY SOX9 NR5A1 DMRT1

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

(show all 13)

#	Name	GO ID	Score	Top Affiliating Genes
1	zinc ion binding	GO:0008270	10.32	AR DHH MAP3K1 NR5A1 NR5A2 WT1
2	DNA-binding transcription factor activity	GO:0003700	10.16	WT1 SRY SOX9 NR5A2 NR5A1 AR
3	transcription corepressor activity	GO:0003714	10.11	ZFPM2 WNT4 NR0B1 LCOR
4	chromatin binding	GO:0003682	10.03	SOX9 NR5A2 NR5A1 DMRT1 CBX2 AR
5	DNA binding	GO:0003677	9.86	AR CBX2 DMRT1 LCOR NR5A1 NR5A2
6	alditol:NADP+ 1-oxidoreductase activity	GO:0004032	9.83	AKR1C4 AKR1C2
7	bile acid binding	GO:0032052	9.8	AKR1C4 AKR1C2
8	nuclear receptor activity	GO:0004879	9.8	AR NR5A2 NR5A1
9	androstan-3-alpha,17-beta-diol dehydrogenase activity	GO:0047044	9.73	AKR1C4 AKR1C2
10	oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	GO:0016655	9.71	AKR1C4 AKR1C2
11	androsterone dehydrogenase activity	GO:0047023	9.67	AKR1C4 AKR1C2
12	ketosteroid monooxygenase activity	GO:0047086	9.46	AKR1C4 AKR1C2
13	sequence-specific DNA binding	GO:0043565	9.32	WT1 SOX9 NR5A2 NR5A1 DMRT1 AR

Sources

Sources for 46,xy Sex Reversal

¹ BitterDB

² CDC

³ Cell Signaling Technology

⁴ ClinicalTrials

⁵ ClinVar

⁶ CNVD

⁷ Cochrane Library

⁸ Cosmic

⁹ dbSNP

¹⁰ DGIdb

¹¹ Disease Ontology

¹² diseasecard

¹³ DiseaseEnhancer

¹⁴ DISEASES

¹⁵ DrugBank

¹⁶ EFO

¹⁷ ExPASy

¹⁸ FMA

¹⁹ GARD

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ GenomeRNAi

²⁶ GEO DataSets

²⁷ GO

²⁸ GTR

²⁹ HMDB

³⁰ HPO

³¹ ICD10

³² ICD10 via Orphanet

³³ ICD11

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ LifeMap

³⁷ LncRNADisease

³⁸ LOVD

³⁹ MalaCards

⁴⁰ MedGen

⁴¹ MedlinePlus

⁴² MedlinePlus Genetics

⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NINDS

⁵³ Novoseek

⁵⁴ Novus Biologicals

⁵⁵ ODiseA

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 08-Dec-2022)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubChem

⁶² PubMed

⁶³ PubMed Health

⁶⁴ QIAGEN

⁶⁵ R&D Systems

⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ WikiPathways

⁷⁵ Wikipedia

MCID: 46X082 MIFTS: 50	46,xy Sex Reversal Categories: Bone diseases, Cancer diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases	Data Licensing For inquiries, contact: [email protected]
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