MCID: 46X055
MIFTS: 31

46,xy Sex Reversal 3

Categories: Genetic diseases, Endocrine diseases

Aliases & Classifications for 46,xy Sex Reversal 3

MalaCards integrated aliases for 46,xy Sex Reversal 3:

Name: 46,xy Sex Reversal 3 57 75 73
46,xy Sex Reversal, Type 3 29 6 40
46xy Sex Reversal 3 57 13
Srxy3 57 75
46,xy Gonadal Dysgenesis, Partial or Complete, with or Without Adrenal Failure 57
Complete or Partial 46,xy Gonadal Dysgenesis with or Without Adrenal Failure 75
46,xy Sex Reversal, Partial or Complete, Nr5a1-Related 57
46,xy Sex Reversal Partial or Complete Nr5a1-Related 75
Sex Reversal, Xy, with or Without Adrenal Failure 57
Disorder of Sex Development, 46,xy, Nr5a1-Related 57
Xy Sex Reversal with or Without Adrenal Failure 75
46,xy Disorders of Sex Development 37
46, Xy Disorder of Sex Development 29
46,xy Disorder of Sex Development 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
patients are 46,xy individuals who may be phenotypically female
familial cases may have affected 46,xx family members who exhibit premature ovarian failure (see pof7, )


HPO:

32
46,xy sex reversal 3:
Inheritance sex-limited autosomal dominant


Classifications:



Summaries for 46,xy Sex Reversal 3

UniProtKB/Swiss-Prot : 75 46,XY sex reversal 3: A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype.

MalaCards based summary : 46,xy Sex Reversal 3, also known as 46,xy sex reversal, type 3, is related to leydig cell hypoplasia, type i and hypogonadotropic hypogonadism 23 without anosmia. An important gene associated with 46,xy Sex Reversal 3 is NR5A1 (Nuclear Receptor Subfamily 5 Group A Member 1), and among its related pathways/superpathways are Hedgehog signaling pathway and Wnt signaling pathway. Affiliated tissues include testes, uterus and breast, and related phenotypes are hypoplasia of the uterus and ambiguous genitalia

Description from OMIM: 612965

Related Diseases for 46,xy Sex Reversal 3

Graphical network of the top 20 diseases related to 46,xy Sex Reversal 3:



Diseases related to 46,xy Sex Reversal 3

Symptoms & Phenotypes for 46,xy Sex Reversal 3

Symptoms via clinical synopsis from OMIM:

57
Genitourinary External Genitalia Male:
penoscrotal hypospadias
small phallus
ambiguous external genitalia (in some patients)

Chest Breasts:
small breasts (in some patients)

Genitourinary Internal Genitalia Female:
small uterus (in some patients)

Endocrine Features:
low testosterone
elevated follicle-stimulating hormone (fsh)
elevated luteinizing hormone (lh)

Genitourinary External Genitalia Female:
hypertrophic clitoris (in some patients)
female-appearing genitalia (in some patients)
labial rugosity (in some patients)
labioscrotal folds (in some patients)

GenitourinaryInternal GenitaliaMale:
labial or labioscrotal testes (in some patients)
high scrotal testes (in some patients)
inguinal testes (in some patients)
pelvic testes (in some patients)
testicular tissue on gonadal histology (in some patients)
more

Clinical features from OMIM:

612965

Human phenotypes related to 46,xy Sex Reversal 3:

32 (show all 9)
# Description HPO Frequency HPO Source Accession
1 hypoplasia of the uterus 32 occasional (7.5%) HP:0000013
2 ambiguous genitalia 32 occasional (7.5%) HP:0000062
3 gonadal dysgenesis 32 HP:0000133
4 penoscrotal hypospadias 32 HP:0000808
5 streaky metaphyseal sclerosis 32 HP:0005092
6 elevated circulating follicle stimulating hormone level 32 HP:0008232
7 clitoral hypertrophy 32 occasional (7.5%) HP:0008665
8 elevated circulating luteinizing hormone level 32 HP:0011969
9 sex reversal 32 HP:0012245

Drugs & Therapeutics for 46,xy Sex Reversal 3

Search Clinical Trials , NIH Clinical Center for 46,xy Sex Reversal 3

Genetic Tests for 46,xy Sex Reversal 3

Genetic tests related to 46,xy Sex Reversal 3:

# Genetic test Affiliating Genes
1 46,xy Sex Reversal, Type 3 29 NR5A1
2 46, Xy Disorder of Sex Development (dsd) 29

Anatomical Context for 46,xy Sex Reversal 3

MalaCards organs/tissues related to 46,xy Sex Reversal 3:

41
Testes, Uterus, Breast

Publications for 46,xy Sex Reversal 3

Articles related to 46,xy Sex Reversal 3:

# Title Authors Year
1
Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development. ( 27849622 )
2017
2
Biochemical analyses and molecular modeling explain the functional loss of 17beta-hydroxysteroid dehydrogenase 3 mutant G133R in three Tunisian patients with 46, XY Disorders of Sex Development. ( 26545797 )
2016
3
Androgen insensitivity syndrome in a cohort of Sri Lankan children with 46, XY disorders of sex development (46, XY DSD). ( 26778393 )
2015
4
Mutation analysis of NR5A1 encoding steroidogenic factor 1 in 77 patients with 46, XY disorders of sex development (DSD) including hypospadias. ( 22028768 )
2011
5
A novel heterozygous mutation of steroidogenic factor-1 (SF-1/Ad4BP) gene (NR5A1) in a 46, XY disorders of sex development (DSD) patient without adrenal failure. ( 19318730 )
2009

Variations for 46,xy Sex Reversal 3

UniProtKB/Swiss-Prot genetic disease variations for 46,xy Sex Reversal 3:

75 (show all 11)
# Symbol AA change Variation ID SNP ID
1 NR5A1 p.Gly35Glu VAR_004737 rs121918654
2 NR5A1 p.Arg92Gln VAR_016982 rs104894119
3 NR5A1 p.Cys33Ser VAR_039106
4 NR5A1 p.Arg84His VAR_039107 rs375469069
5 NR5A1 p.Val15Met VAR_063255 rs104894124
6 NR5A1 p.Met78Ile VAR_063256 rs104894125
7 NR5A1 p.Gly91Ser VAR_063257 rs104894126
8 NR5A1 p.Leu437Gln VAR_063258 rs104894120
9 NR5A1 p.Cys65Tyr VAR_078136
10 NR5A1 p.Arg92Trp VAR_078137 rs886039769
11 NR5A1 p.Thr40Pro VAR_079572

ClinVar genetic disease variations for 46,xy Sex Reversal 3:

6
(show all 43)
# Gene Variation Type Significance SNP ID Assembly Location
1 NR5A1 NM_004959.4(NR5A1): c.104_105delGCinsAA (p.Gly35Glu) indel Pathogenic rs121918654 GRCh37 Chromosome 9, 127265497: 127265498
2 NR5A1 NM_004959.4(NR5A1): c.104_105delGCinsAA (p.Gly35Glu) indel Pathogenic rs121918654 GRCh38 Chromosome 9, 124503218: 124503219
3 NR5A1 NM_004959.4(NR5A1): c.275G> A (p.Arg92Gln) single nucleotide variant Pathogenic rs104894119 GRCh37 Chromosome 9, 127262964: 127262964
4 NR5A1 NM_004959.4(NR5A1): c.275G> A (p.Arg92Gln) single nucleotide variant Pathogenic rs104894119 GRCh38 Chromosome 9, 124500685: 124500685
5 NR5A1 NR5A1, 8-BP DEL, NT1058 deletion Pathogenic
6 NR5A1 NM_004959.4(NR5A1): c.48C> A (p.Cys16Ter) single nucleotide variant Pathogenic rs104894123 GRCh37 Chromosome 9, 127265627: 127265627
7 NR5A1 NM_004959.4(NR5A1): c.48C> A (p.Cys16Ter) single nucleotide variant Pathogenic rs104894123 GRCh38 Chromosome 9, 124503348: 124503348
8 NR5A1 NM_004959.4(NR5A1): c.18delC (p.Asp6Glufs) deletion Pathogenic rs606231205 GRCh38 Chromosome 9, 124503378: 124503378
9 NR5A1 NM_004959.4(NR5A1): c.18delC (p.Asp6Glufs) deletion Pathogenic rs606231205 GRCh37 Chromosome 9, 127265657: 127265657
10 NR5A1 NM_004959.4(NR5A1): c.43G> A (p.Val15Met) single nucleotide variant Pathogenic rs104894124 GRCh37 Chromosome 9, 127265632: 127265632
11 NR5A1 NM_004959.4(NR5A1): c.43G> A (p.Val15Met) single nucleotide variant Pathogenic rs104894124 GRCh38 Chromosome 9, 124503353: 124503353
12 NR5A1 NM_004959.4(NR5A1): c.234G> A (p.Met78Ile) single nucleotide variant Pathogenic rs104894125 GRCh37 Chromosome 9, 127265368: 127265368
13 NR5A1 NM_004959.4(NR5A1): c.234G> A (p.Met78Ile) single nucleotide variant Pathogenic rs104894125 GRCh38 Chromosome 9, 124503089: 124503089
14 NR5A1 NM_004959.4(NR5A1): c.271G> A (p.Gly91Ser) single nucleotide variant Pathogenic rs104894126 GRCh37 Chromosome 9, 127262968: 127262968
15 NR5A1 NM_004959.4(NR5A1): c.271G> A (p.Gly91Ser) single nucleotide variant Pathogenic rs104894126 GRCh38 Chromosome 9, 124500689: 124500689
16 NR5A1 NM_004959.4(NR5A1): c.1310T> A (p.Leu437Gln) single nucleotide variant Pathogenic rs104894120 GRCh37 Chromosome 9, 127245113: 127245113
17 NR5A1 NM_004959.4(NR5A1): c.1310T> A (p.Leu437Gln) single nucleotide variant Pathogenic rs104894120 GRCh38 Chromosome 9, 124482834: 124482834
18 NR5A1 NM_004959.4(NR5A1): c.666delC (p.Asn222Lysfs) deletion Pathogenic rs606231206 GRCh38 Chromosome 9, 124500294: 124500294
19 NR5A1 NM_004959.4(NR5A1): c.666delC (p.Asn222Lysfs) deletion Pathogenic rs606231206 GRCh37 Chromosome 9, 127262573: 127262573
20 NR5A1 NM_004959.4(NR5A1): c.877G> A (p.Asp293Asn) single nucleotide variant Pathogenic rs121918655 GRCh37 Chromosome 9, 127255422: 127255422
21 NR5A1 NM_004959.4(NR5A1): c.877G> A (p.Asp293Asn) single nucleotide variant Pathogenic rs121918655 GRCh38 Chromosome 9, 124493143: 124493143
22 NR5A1 NM_004959.4(NR5A1): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs121918656 GRCh37 Chromosome 9, 127265672: 127265672
23 NR5A1 NM_004959.4(NR5A1): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs121918656 GRCh38 Chromosome 9, 124503393: 124503393
24 NR5A1 NM_004959.4(NR5A1): c.390delG (p.Pro131Argfs) deletion Pathogenic rs606231207 GRCh38 Chromosome 9, 124500570: 124500570
25 NR5A1 NM_004959.4(NR5A1): c.390delG (p.Pro131Argfs) deletion Pathogenic rs606231207 GRCh37 Chromosome 9, 127262849: 127262849
26 NR5A1 NM_004959.4(NR5A1): c.1210T> G (p.Tyr404Asp) single nucleotide variant Pathogenic rs863224904 GRCh37 Chromosome 9, 127245213: 127245213
27 NR5A1 NM_004959.4(NR5A1): c.1210T> G (p.Tyr404Asp) single nucleotide variant Pathogenic rs863224904 GRCh38 Chromosome 9, 124482934: 124482934
28 NR5A1 NM_004959.4(NR5A1): c.151G> T (p.Glu51Ter) single nucleotide variant Pathogenic rs775441984 GRCh37 Chromosome 9, 127265451: 127265451
29 NR5A1 NM_004959.4(NR5A1): c.151G> T (p.Glu51Ter) single nucleotide variant Pathogenic rs775441984 GRCh38 Chromosome 9, 124503172: 124503172
30 NR5A1 NM_004959.4(NR5A1): c.375G> A (p.Pro125=) single nucleotide variant Benign rs1110062 GRCh38 Chromosome 9, 124500585: 124500585
31 NR5A1 NM_004959.4(NR5A1): c.375G> A (p.Pro125=) single nucleotide variant Benign rs1110062 GRCh37 Chromosome 9, 127262864: 127262864
32 NR5A1 NM_004959.4(NR5A1): c.274C> T (p.Arg92Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs886039769 GRCh37 Chromosome 9, 127262965: 127262965
33 NR5A1 NM_004959.4(NR5A1): c.274C> T (p.Arg92Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs886039769 GRCh38 Chromosome 9, 124500686: 124500686
34 NR5A1 NM_004959.4(NR5A1): c.937C> T (p.Arg313Cys) single nucleotide variant Pathogenic/Likely pathogenic rs1057517779 GRCh37 Chromosome 9, 127255362: 127255362
35 NR5A1 NM_004959.4(NR5A1): c.937C> T (p.Arg313Cys) single nucleotide variant Pathogenic/Likely pathogenic rs1057517779 GRCh38 Chromosome 9, 124493083: 124493083
36 NR5A1 NM_004959.4(NR5A1): c.938G> T (p.Arg313Leu) single nucleotide variant Likely pathogenic GRCh38 Chromosome 9, 124493082: 124493082
37 NR5A1 NM_004959.4(NR5A1): c.938G> T (p.Arg313Leu) single nucleotide variant Likely pathogenic GRCh37 Chromosome 9, 127255361: 127255361
38 NR5A1 NM_004959.4(NR5A1): c.34_38delCTGTGinsGACCTGGACCTGT (p.Leu12Aspfs) indel Pathogenic GRCh37 Chromosome 9, 127265637: 127265641
39 NR5A1 NM_004959.4(NR5A1): c.34_38delCTGTGinsGACCTGGACCTGT (p.Leu12Aspfs) indel Pathogenic GRCh38 Chromosome 9, 124503358: 124503362
40 NR5A1 NM_004959.4(NR5A1): c.236_238delGCC (p.Arg79del) deletion Uncertain significance GRCh38 Chromosome 9, 124503085: 124503087
41 NR5A1 NM_004959.4(NR5A1): c.236_238delGCC (p.Arg79del) deletion Uncertain significance GRCh37 Chromosome 9, 127265364: 127265366
42 NR5A1 NC_000009.12: g.(?_124482420)_(124482928_?)del deletion Likely pathogenic GRCh38 Chromosome 9, 124482420: 124482928
43 NR5A1 NC_000009.12: g.(?_124482420)_(124482928_?)del deletion Likely pathogenic GRCh37 Chromosome 9, 127244699: 127245207

Expression for 46,xy Sex Reversal 3

Search GEO for disease gene expression data for 46,xy Sex Reversal 3.

Pathways for 46,xy Sex Reversal 3

Pathways related to 46,xy Sex Reversal 3 according to KEGG:

37
# Name Kegg Source Accession
1 Hedgehog signaling pathway hsa04340
2 Wnt signaling pathway hsa04310
3 Oocyte meiosis hsa04114
4 Steroid hormone biosynthesis hsa00140
5 Calcium signaling pathway hsa04020
6 Neuroactive ligand-receptor interaction hsa04080
7 Cytokine-cytokine receptor interaction hsa04060
8 TGF-beta signaling pathway hsa04350

GO Terms for 46,xy Sex Reversal 3

Sources for 46,xy Sex Reversal 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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