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SRXY1
MCID: 46X051
MIFTS: 38

46,xy Sex Reversal 1 (SRXY1)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes
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Aliases & Classifications for 46,xy Sex Reversal 1

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MalaCards integrated aliases for 46,xy Sex Reversal 1:

Name: 46,xy Sex Reversal 1 57 12 73
46,xy Gonadal Dysgenesis, Complete, Sry-Related 57 12 71
Srxy1 57 12 73
46,xy Sex Reversal, Sry-Related 57 12
46,xy Sex Reversal, Type 1 29 6
46xy Sex Reversal 1 57 13
Swyer Syndrome 73 71
46,xy Gonadal Dysgenesis Complete Sry-Related 73
46,xy True Hermaphroditism, Sry-Related 6
46,xy True Hermaphroditism Sry-Related 73
Gonadal Dysgenesis Xy Female Type 73
46,xy Sex Reversal Sry-Related 73
Sex Reversal, 46,xy, Type 1 39
Gonadal Dysgenesis, 46,xy 71
46, Xy Female 71
Xy Females 73

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
y-linked

Miscellaneous:
highly variable intrafamilial penetrance, with many 46,xy carriers developing into normal fertile males
some patients exhibit stigmata of turner syndrome
includes report of 1 patient designated as having true hermaphroditism


HPO:

31
46,xy sex reversal 1:
Inheritance y-linked inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Endocrine diseases Reproductive diseases
See all MalaCards categories (disease lists)


External Ids:

Disease Ontology 12 DOID:0111778
OMIM® 57 400044
OMIM Phenotypic Series 57 PS400044
MeSH 44 D006061
UMLS 71 C0018054 C0432470 C2748896 more
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Summaries for 46,xy Sex Reversal 1

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UniProtKB/Swiss-Prot : 73 46,XY sex reversal 1: 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.

MalaCards based summary : 46,xy Sex Reversal 1, also known as 46,xy gonadal dysgenesis, complete, sry-related, is related to 46,xy sex reversal and anorchia. An important gene associated with 46,xy Sex Reversal 1 is SRY (Sex Determining Region Y). Affiliated tissues include uterus, breast and testis, and related phenotypes are primary amenorrhea and gonadoblastoma

Disease Ontology : 12 A 46 XY sex reversal characterized by an XY karyotype, phenotypically female genitalia and failure to develop secondary sexual characteristics at puberty including menstruation that has material basis in hemizygous mutation in SRY on chromosome Yp11.2.

OMIM® : 57 Individuals with 46,XY complete gonadal dysgenesis are phenotypically female; however, they do not develop secondary sexual characteristics at puberty and do not menstruate. They have bilateral 'streak gonads,' which typically consist of fibrous tissue and variable amounts of wavy ovarian stroma. A uterus and fallopian tube are present and external genitalia are female (reviewed by Berkovitz et al., 1991). (400044) (Updated 05-Mar-2021)

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Related Diseases for 46,xy Sex Reversal 1

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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 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 54)
# Related Disease Score Top Affiliating Genes
1 46,xy sex reversal 11.9
2 anorchia 11.0
3 numeric sex chromosome variations 11.0
4 46,xy sex reversal 10 11.0
5 gonadal dysgenesis 10.7
6 amenorrhea 10.6
7 dysgerminoma 10.6
8 gonadoblastoma 10.5
9 disorder of sexual development 10.2
10 hypogonadism 10.2
11 germ cells tumors 10.2
12 47,xyy 10.2
13 campomelic dysplasia 10.0
14 male infertility 10.0
15 androgen insensitivity syndrome 10.0
16 germ cell cancer 10.0
17 teratoma 10.0
18 encephalitis 10.0
19 46, xy disorders of sexual development 10.0
20 hair whorl 9.9
21 androgen insensitivity, partial 9.9
22 tooth size 9.9
23 infertility 9.9
24 nonsyndromic 46,xx testicular disorders of sex development 9.9
25 nonsyndromic disorders of testicular development 9.9
26 diaphragmatic hernia, congenital 9.9
27 46,xy sex reversal 4 9.9
28 chromosome 9p deletion syndrome 9.9
29 ovarian cancer 9.9
30 lipoid congenital adrenal hyperplasia 9.9
31 46,xy sex reversal 7 9.9
32 hypogonadism, male 9.9
33 46,xy sex reversal 2 9.9
34 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.9
35 inflammatory bowel disease 9.9
36 ileitis 9.9
37 limbic encephalitis 9.9
38 antisynthetase syndrome 9.9
39 complete androgen insensitivity syndrome 9.9
40 sensorineural hearing loss 9.9
41 pre-eclampsia 9.9
42 eclampsia 9.9
43 mixed gonadal dysgenesis 9.9
44 endodermal sinus tumor 9.9
45 testicular cancer 9.9
46 turner syndrome 9.9
47 choriocarcinoma 9.9
48 hermaphroditism 9.9
49 pseudohermaphroditism 9.9
50 seminoma 9.9

Graphical network of the top 20 diseases related to 46,xy Sex Reversal 1:



Diseases related to 46,xy Sex Reversal 1
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Symptoms & Phenotypes for 46,xy Sex Reversal 1

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Human phenotypes related to 46,xy Sex Reversal 1:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 primary amenorrhea 31 HP:0000786
2 gonadoblastoma 31 HP:0000150
3 tall stature 31 HP:0000098
4 male pseudohermaphroditism 31 HP:0000037
5 ambiguous genitalia 31 HP:0000062
6 abnormality of female external genitalia 31 HP:0000055
7 gonadal dysgenesis 31 HP:0000133
8 sex reversal 31 HP:0012245
9 elevated circulating follicle stimulating hormone level 31 HP:0008232
10 elevated circulating luteinizing hormone level 31 HP:0011969
11 absence of secondary sex characteristics 31 HP:0008187

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Genitourinary Internal Genitalia Female:
primary amenorrhea
small to normal uterus
normal-appearing vagina
cervix present
fallopian tubes present (normal or filiform)
more
Growth Height:
tall stature

Chest Breasts:
normal-appearing breast development

Genitourinary External Genitalia Female:
infantile or normal female external genitalia

Neoplasia:
gonadoblastoma

Endocrine Features:
elevated luteinizing hormone (lh)
elevated follicle-stimulating hormone (fsh)
no elevation of androgens

Genitourinary External Genitalia Male:
ambiguous genitalia, severe (1 patient)
urogenital sinus (1 patient)

Genitourinary Internal Genitalia Male:
no testicular components in gonads
immature testicular tissue in gonads (1 patient)

Clinical features from OMIM®:

400044 (Updated 05-Mar-2021)

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Drugs & Therapeutics for 46,xy Sex Reversal 1

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Search Clinical Trials , NIH Clinical Center for 46,xy Sex Reversal 1

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Genetic Tests for 46,xy Sex Reversal 1

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Genetic tests related to 46,xy Sex Reversal 1:

# Genetic test Affiliating Genes
1 46,xy Sex Reversal, Type 1 29 SRY
Sources

Anatomical Context for 46,xy Sex Reversal 1

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MalaCards organs/tissues related to 46,xy Sex Reversal 1:

40
Uterus, Breast, Testis, Cervix, Lymph Node, Ovary
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Publications for 46,xy Sex Reversal 1

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Articles related to 46,xy Sex Reversal 1:

(show top 50) (show all 188)
# Title Authors PMID Year
1
True hermaphroditism in an XY individual due to a familial point mutation of the SRY gene. 57 6
12793612 2003
2
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. 57 6
1619028 1992
3
XY sex reversal associated with a nonsense mutation in SRY. 57 6
1639410 1992
4
Familial case with sequence variant in the testis-determining region associated with two sex phenotypes. 57 6
1570829 1992
5
DNA binding activity of recombinant SRY from normal males and XY females. 57 6
1734522 1992
6
Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: its relevance to the understanding of sex differentiation. 57 6
1956279 1991
7
A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. 57 6
2247151 1990
8
Genetic evidence equating SRY and the testis-determining factor. 6 57
2247149 1990
9
A new de novo mutation (A113T) in HMG box of the SRY gene leads to XY gonadal dysgenesis. 6 61
8105086 1993
10
Genetic heterogeneity of XY gonadal dysgenesis (Swyer syndrome): H-Y antigen-negative XY gonadal dysgenesis associated with inflammatory bowel disease. 57 61
7246614 1981
11
H-Y antigen in Swyer syndrome and the genetics of XY gonadal dysgenesis. 61 57
535902 1979
12
Novel candidate genes for 46,XY gonadal dysgenesis identified by a customized 1 M array-CGH platform. 57
24055526 2013
13
A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development. 57
22071891 2012
14
Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation. 57
21802064 2011
15
Isodicentric Y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes. 57
19737515 2009
16
Report of fertility in a woman with a predominantly 46,XY karyotype in a family with multiple disorders of sexual development. 57
18000096 2008
17
Consensus statement on management of intersex disorders. International Consensus Conference on Intersex. 57
16882788 2006
18
The makings of maleness: towards an integrated view of male sexual development. 57
16832429 2006
19
Familial mutation in the testis-determining gene SRY shared by an XY female and her normal father. 6
12107262 2002
20
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
10852465 2000
21
A mutation in the 5' non-high mobility group box region of the SRY gene in patients with Turner syndrome and Y mosaicism. 6
10843173 2000
22
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
9521592 1998
23
Independent observation of SRY mutation I90M in a patient with complete gonadal dysgenesis. 6
9450909 1998
24
A de novo mutation (Gln2Stop) at the 5' end of the SRY gene leads to sex reversal with partial ovarian function. 6
9443877 1998
25
X-linked sex-reversing genes. 57
9678362 1998
26
Mutations and sequence variants in the testis-determining region of the Y chromosome in individuals with a 46,XY female phenotype. 6
9150734 1997
27
An SRY mutation causing human sex reversal resolves a general mechanism of structure-specific DNA recognition: application to the four-way DNA junction. 6
7718558 1995
28
Molecular basis of mammalian sexual determination: activation of Müllerian inhibiting substance gene expression by SRY. 6
7985018 1994
29
A novel nonsense mutation in the HMG box of the SRY gene in a patient with XY sex reversal. 6
7987333 1994
30
SRVX, a sex reversing locus in Xp21.2-->p22.11. 57
8168809 1994
31
Analysis of the SRY gene in 22 sex-reversed XY females identifies four new point mutations in the conserved DNA binding domain. 6
8353496 1993
32
Mutational analysis of SRY in XY females. 6
8257986 1993
33
A familial mutation in the testis-determining gene SRY shared by both sexes. 6
1483689 1992
34
Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis. 6
1415266 1992
35
Mutational analysis of SRY: nonsense and missense mutations in XY sex reversal. 6
1339396 1992
36
Further evidence consistent with Yqh as an indicator of risk of gonadal blastoma in Y-bearing mosaic Turner syndrome. 57
1633643 1992
37
Sex and the single gene. 57
2028253 1991
38
Male development of chromosomally female mice transgenic for Sry. 57
2030730 1991
39
Expression of a candidate sex-determining gene during mouse testis differentiation. 57
2247150 1990
40
A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. 57
1695712 1990
41
XY female mice resulting from a heritable mutation in the primary testis-determining gene, Tdy. 6
2401216 1990
42
The sex-determining region of the human Y chromosome encodes a finger protein. 57
3690661 1987
43
Separation of the genetic loci for the H-Y antigen and for testis determination on human Y chromosome. 57
3494951 1987
44
Small deletions of the short arm of the Y chromosome in 46,XY females. 57
3464001 1986
45
Gonadoblastoma and Y-chromosome fluorescence. 57
3720008 1986
46
XY gonadal dysgenesis: genetic heterogeneity based upon clinical observations, H-Y antigen status and segregation analysis. 57
7286997 1981
47
The gonads of human true hermaphrodites. 57
6895206 1981
48
Abnormality of the X chromosome in human 46,XY female siblings with dysgenetic ovaries. 57
7352285 1980
49
A gene controlling H-Y antigen on the X chromosome. Tentative assignment by deletion mapping to Xp223. 57
7390489 1980
50
H-Y antigen in 46,XY gonadal dysgenesis. 57
7390478 1980
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Variations for 46,xy Sex Reversal 1

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ClinVar genetic disease variations for 46,xy Sex Reversal 1:

6 (show all 34)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SRY NM_003140.3(SRY):c.326T>C (p.Phe109Ser) SNV Pathogenic 9738 rs104894956 Y:2655319-2655319 Y:2787278-2787278
2 SRY NM_003140.3(SRY):c.178G>C (p.Val60Leu) SNV Pathogenic 9739 rs104894957 Y:2655467-2655467 Y:2787426-2787426
3 SRY NM_003140.3(SRY):c.277C>T (p.Gln93Ter) SNV Pathogenic 9740 rs104894958 Y:2655368-2655368 Y:2787327-2787327
4 SRY NM_003140.3(SRY):c.270C>G (p.Ile90Met) SNV Pathogenic 9741 rs104894959 Y:2655375-2655375 Y:2787334-2787334
5 SRY NM_003140.3(SRY):c.270C>G (p.Ile90Met) SNV Pathogenic 9741 rs104894959 Y:2655375-2655375 Y:2787334-2787334
6 SRY NM_003140.3(SRY):c.317A>T (p.Lys106Ile) SNV Pathogenic 9742 rs104894964 Y:2655328-2655328 Y:2787287-2787287
7 SRY NM_003140.3(SRY):c.324del (p.Phe109fs) Deletion Pathogenic 9743 rs606231179 Y:2655321-2655321 Y:2787280-2787280
8 SRY NM_003140.3(SRY):c.337G>A (p.Ala113Thr) SNV Pathogenic 9744 rs104894966 Y:2655308-2655308 Y:2787267-2787267
9 SRY NM_003140.3(SRY):c.320G>A (p.Trp107Ter) SNV Pathogenic 9745 rs104894967 Y:2655325-2655325 Y:2787284-2787284
10 SRY NM_003140.3(SRY):c.192G>A (p.Met64Ile) SNV Pathogenic 9747 rs104894969 Y:2655453-2655453 Y:2787412-2787412
11 SRY NM_003140.3(SRY):c.209G>A (p.Trp70Ter) SNV Pathogenic 9748 rs104894965 Y:2655436-2655436 Y:2787395-2787395
12 SRY NM_003140.3(SRY):c.274A>T (p.Lys92Ter) SNV Pathogenic 9749 rs104894970 Y:2655371-2655371 Y:2787330-2787330
13 SRY NM_003140.3(SRY):c.283G>C (p.Gly95Arg) SNV Pathogenic 9750 rs104894974 Y:2655362-2655362 Y:2787321-2787321
14 SRY NM_003140.3(SRY):c.12T>A (p.Tyr4Ter) SNV Pathogenic 9751 rs104894975 Y:2655633-2655633 Y:2787592-2787592
15 SRY NM_003140.3(SRY):c.397C>T (p.Arg133Trp) SNV Pathogenic 9752 rs104894976 Y:2655248-2655248 Y:2787207-2787207
16 SRY NM_003140.3(SRY):c.4C>T (p.Gln2Ter) SNV Pathogenic 9753 rs104894977 Y:2655641-2655641 Y:2787600-2787600
17 SRY NM_003140.3(SRY):c.53G>A (p.Ser18Asn) SNV Pathogenic 9754 rs104894971 Y:2655592-2655592 Y:2787551-2787551
18 SRY NM_003140.3(SRY):c.284G>A (p.Gly95Glu) SNV Pathogenic 9755 rs104894972 Y:2655361-2655361 Y:2787320-2787320
19 SRY NM_003140.3(SRY):c.380A>T (p.Tyr127Phe) SNV Pathogenic 9756 rs104894973 Y:2655265-2655265 Y:2787224-2787224
20 SRY NM_003140.3(SRY):c.380A>G (p.Tyr127Cys) SNV Pathogenic 470196 rs104894973 Y:2655265-2655265 Y:2787224-2787224
21 SRY NM_003140.3(SRY):c.89G>T (p.Arg30Ile) SNV Pathogenic 492908 rs1556370576 Y:2655556-2655556 Y:2787515-2787515
22 SRY NM_003140.3(SRY):c.169C>T (p.Gln57Ter) SNV Pathogenic 664404 rs1603308308 Y:2655476-2655476 Y:2787435-2787435
23 SRY NM_003140.3(SRY):c.203T>C (p.Ile68Thr) SNV Pathogenic 9746 rs104894968 Y:2655442-2655442 Y:2787401-2787401
24 SRY NM_003140.3(SRY):c.288C>G (p.Tyr96Ter) SNV Pathogenic 537738 rs1556370548 Y:2655357-2655357 Y:2787316-2787316
25 SRY NM_003140.3(SRY):c.263C>A (p.Ser88Ter) SNV Pathogenic 537739 rs1556370558 Y:2655382-2655382 Y:2787341-2787341
26 SRY NM_003140.3(SRY):c.362_363GA[1] (p.Glu122fs) Microsatellite Pathogenic 9737 rs606231178 Y:2655278-2655281 Y:2787237-2787240
27 SRY NM_003140.3(SRY):c.264dup (p.Glu89fs) Duplication Pathogenic 470195 rs1556370556 Y:2655380-2655381 Y:2787339-2787340
28 SRY NM_003140.3(SRY):c.331C>T (p.Gln111Ter) SNV Pathogenic 436871 rs1556370543 Y:2655314-2655314 Y:2787273-2787273
29 SRY NM_003140.3(SRY):c.227G>T (p.Arg76Leu) SNV Likely pathogenic 393470 rs1057519627 Y:2655418-2655418 Y:2787377-2787377
30 SRY NM_003140.3(SRY):c.248C>A (p.Pro83His) SNV Uncertain significance 949914 Y:2655397-2655397 Y:2787356-2787356
31 SRY NM_003140.3(SRY):c.266A>C (p.Glu89Ala) SNV Uncertain significance 492907 rs1556370554 Y:2655379-2655379 Y:2787338-2787338
32 SRY NM_003140.3(SRY):c.570del (p.Ser191fs) Deletion Uncertain significance 652674 rs1603308285 Y:2655075-2655075 Y:2787034-2787034
33 SRY NM_003140.3(SRY):c.339A>G (p.Ala113=) SNV Likely benign 752210 rs773247144 Y:2655306-2655306 Y:2787265-2787265
34 SRY NM_003140.3(SRY):c.465C>T (p.Ser155=) SNV Benign 703672 rs11575897 Y:2655180-2655180 Y:2787139-2787139

UniProtKB/Swiss-Prot genetic disease variations for 46,xy Sex Reversal 1:

73 (show all 27)
# Symbol AA change Variation ID SNP ID
1 SRY p.Ser18Asn VAR_003717 rs104894971
2 SRY p.Val60Ala VAR_003718 rs764249635
3 SRY p.Val60Leu VAR_003719 rs104894957
4 SRY p.Arg62Gly VAR_003720
5 SRY p.Met64Ile VAR_003721 rs104894969
6 SRY p.Ile68Thr VAR_003722 rs104894968
7 SRY p.Met78Thr VAR_003723
8 SRY p.Ile90Met VAR_003724 rs104894959
9 SRY p.Ser91Gly VAR_003725
10 SRY p.Gly95Arg VAR_003726 rs104894974
11 SRY p.Leu101His VAR_003727
12 SRY p.Lys106Ile VAR_003728 rs104894964
13 SRY p.Pro108Arg VAR_003729
14 SRY p.Phe109Ser VAR_003730 rs104894956
15 SRY p.Ala113Thr VAR_003731 rs104894966
16 SRY p.Pro125Leu VAR_003732
17 SRY p.Tyr127Cys VAR_003733 rs104894973
18 SRY p.Arg133Trp VAR_003734 rs104894976
19 SRY p.Met64Arg VAR_017298
20 SRY p.Phe67Val VAR_017299
21 SRY p.Arg76Ser VAR_017300
22 SRY p.Asn87Tyr VAR_017301
23 SRY p.Gly95Glu VAR_017302 rs104894972
24 SRY p.Tyr127Phe VAR_017303 rs104894973
25 SRY p.Pro131Arg VAR_017304
26 SRY p.Ser3Leu VAR_030019
27 SRY p.Arg75Met VAR_078433

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Expression for 46,xy Sex Reversal 1

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Search GEO for disease gene expression data for 46,xy Sex Reversal 1.
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Pathways for 46,xy Sex Reversal 1

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GO Terms for 46,xy Sex Reversal 1

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Sources for 46,xy Sex Reversal 1

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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