SRXY3
MCID: 46X055
MIFTS: 34

46,xy Sex Reversal 3 (SRXY3)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive 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 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). Affiliated tissues include testes, uterus and breast, and related phenotypes are ambiguous genitalia and sex reversal

Description from OMIM: 612965

Related Diseases for 46,xy Sex Reversal 3

Diseases in the 46,xx Sex Reversal 1 family:

46,xy Sex Reversal 4 46,xy Sex Reversal 7
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

Diseases related to 46,xy Sex Reversal 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 leydig cell hypoplasia, type i 11.9
2 hypogonadotropic hypogonadism 23 without anosmia 11.8
3 leydig cell hypoplasia 11.8
4 46,xy sex reversal 2 11.6
5 adrenal hyperplasia, congenital, due to 17-alpha-hydroxylase deficiency 11.5
6 17-beta hydroxysteroid dehydrogenase iii deficiency 11.5
7 pseudovaginal perineoscrotal hypospadias 11.5
8 adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete 11.5
9 46,xy sex reversal 8 11.5
10 46, xy disorders of sexual development 11.4
11 aromatase deficiency 11.1
12 testicular anomalies with or without congenital heart disease 11.1
13 lipoid congenital adrenal hyperplasia 10.1
14 gonadal dysgenesis 10.1
15 hypospadias 10.1
16 diaphragmatic hernia, congenital 10.0
17 adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency 10.0
18 ovarian dysgenesis 1 10.0
19 smith-lemli-opitz syndrome 10.0
20 opitz gbbb syndrome, type i 10.0
21 androgen insensitivity syndrome 10.0
22 premature ovarian failure 1 10.0
23 wilms tumor 6 10.0
24 male infertility 10.0
25 heart disease 10.0
26 46 xx gonadal dysgenesis 10.0
27 infertility 10.0

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)

Genitourinary Internal Genitalia Male:
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 ambiguous genitalia 32 occasional (7.5%) HP:0000062
2 sex reversal 32 HP:0012245
3 hypoplasia of the uterus 32 occasional (7.5%) HP:0000013
4 gonadal dysgenesis 32 HP:0000133
5 penoscrotal hypospadias 32 HP:0000808
6 clitoral hypertrophy 32 occasional (7.5%) HP:0008665
7 elevated circulating follicle stimulating hormone level 32 HP:0008232
8 elevated circulating luteinizing hormone level 32 HP:0011969
9 streaky metaphyseal sclerosis 32 HP:0005092

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, Heart

Publications for 46,xy Sex Reversal 3

Articles related to 46,xy Sex Reversal 3:

(show all 17)
# Title Authors Year
1
Long-term outcomes and molecular analysis of a large cohort of patients with 46,XY disorder of sex development due to partial gonadal dysgenesis. ( 29668062 )
2018
2
Novel DHCR7 mutation in a case of Smith-Lemli-Opitz syndrome showing 46,XY disorder of sex development. ( 28503313 )
2017
3
A novel variant of DHH in a familial case of 46,XY disorder of sex development: Insights from molecular dynamics simulations. ( 28708305 )
2017
4
Homozygous Mutation of the FGFR1 Gene Associated with Congenital Heart Disease and 46,XY Disorder of Sex Development. ( 27055092 )
2016
5
Phalloplasty: A panacea for 46,XY disorder of sex development conditions with penile deficiency? ( 25247659 )
2014
6
NR5A1 gene mutations: clinical, endocrine and genetic features in two girls with 46,XY disorder of sex development. ( 24434652 )
2014
7
Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling. ( 24784881 )
2014
8
46,XY disorder of sex development in a sudanese patient caused by a novel mutation in the HSD17B3 gene. ( 24941935 )
2014
9
Mutation analysis of mitogen activated protein kinase 1 gene in Indian cases of 46,XY disorder of sex development. ( 24497709 )
2013
10
The novel mutation p.Trp147Arg of the steroidogenic acute regulatory protein causes classic lipoid congenital adrenal hyperplasia with adrenal insufficiency and 46,XY disorder of sex development. ( 23920000 )
2013
11
Preserved fertility in a patient with a 46,XY disorder of sex development due to a new heterozygous mutation in the NR5A1/SF-1 gene: evidence of 46,XY and 46,XX gonadal dysgenesis phenotype variability in multiple members of an affected kindred. ( 22907560 )
2012
12
A missense mutation in the human cytochrome b5 gene causes 46,XY disorder of sex development due to true isolated 17,20 lyase deficiency. ( 22170710 )
2012
13
Identification by array-Comparative Genomic Hybridization (array-CGH) of a large deletion of luteinizing hormone receptor gene combined with a missense mutation in a patient diagnosed with a 46,XY disorder of sex development and application to prenatal diagnosis. ( 21720050 )
2011
14
Molecular diagnosis of 5I+-reductase type II deficiency in Brazilian siblings with 46,XY disorder of sex development. ( 22272144 )
2011
15
The role of SRY mutations in the etiology of gonadal dysgenesis in patients with 45,X/46,XY disorder of sex development and variants. ( 20699606 )
2011
16
Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development. ( 20150575 )
2010
17
Mutations in the TSPYL1 gene associated with 46,XY disorder of sex development and male infertility. ( 19463995 )
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 49)
# 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.516C> T (p.Ala172=) single nucleotide variant Benign rs113506523 GRCh38 Chromosome 9, 124500444: 124500444
27 NR5A1 NM_004959.4(NR5A1): c.516C> T (p.Ala172=) single nucleotide variant Benign rs113506523 GRCh37 Chromosome 9, 127262723: 127262723
28 NR5A1 NM_004959.4(NR5A1): c.1210T> G (p.Tyr404Asp) single nucleotide variant Pathogenic rs863224904 GRCh37 Chromosome 9, 127245213: 127245213
29 NR5A1 NM_004959.4(NR5A1): c.1210T> G (p.Tyr404Asp) single nucleotide variant Pathogenic rs863224904 GRCh38 Chromosome 9, 124482934: 124482934
30 NR5A1 NM_004959.4(NR5A1): c.151G> T (p.Glu51Ter) single nucleotide variant Pathogenic rs775441984 GRCh37 Chromosome 9, 127265451: 127265451
31 NR5A1 NM_004959.4(NR5A1): c.151G> T (p.Glu51Ter) single nucleotide variant Pathogenic rs775441984 GRCh38 Chromosome 9, 124503172: 124503172
32 NR5A1 NM_004959.4(NR5A1): c.375G> A (p.Pro125=) single nucleotide variant Benign rs1110062 GRCh38 Chromosome 9, 124500585: 124500585
33 NR5A1 NM_004959.4(NR5A1): c.375G> A (p.Pro125=) single nucleotide variant Benign rs1110062 GRCh37 Chromosome 9, 127262864: 127262864
34 NR5A1 NM_004959.4(NR5A1): c.274C> T (p.Arg92Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs886039769 GRCh37 Chromosome 9, 127262965: 127262965
35 NR5A1 NM_004959.4(NR5A1): c.274C> T (p.Arg92Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs886039769 GRCh38 Chromosome 9, 124500686: 124500686
36 NR5A1 NM_004959.4(NR5A1): c.937C> T (p.Arg313Cys) single nucleotide variant Pathogenic/Likely pathogenic rs1057517779 GRCh37 Chromosome 9, 127255362: 127255362
37 NR5A1 NM_004959.4(NR5A1): c.937C> T (p.Arg313Cys) single nucleotide variant Pathogenic/Likely pathogenic rs1057517779 GRCh38 Chromosome 9, 124493083: 124493083
38 NR5A1 NM_004959.4(NR5A1): c.938G> T (p.Arg313Leu) single nucleotide variant Likely pathogenic GRCh38 Chromosome 9, 124493082: 124493082
39 NR5A1 NM_004959.4(NR5A1): c.938G> T (p.Arg313Leu) single nucleotide variant Likely pathogenic GRCh37 Chromosome 9, 127255361: 127255361
40 NR5A1 NM_004959.4(NR5A1): c.34_38delCTGTGinsGACCTGGACCTGT (p.Leu12Aspfs) indel Pathogenic GRCh38 Chromosome 9, 124503358: 124503362
41 NR5A1 NM_004959.4(NR5A1): c.34_38delCTGTGinsGACCTGGACCTGT (p.Leu12Aspfs) indel Pathogenic GRCh37 Chromosome 9, 127265637: 127265641
42 NR5A1 NM_004959.4(NR5A1): c.236_238delGCC (p.Arg79del) deletion Uncertain significance GRCh37 Chromosome 9, 127265364: 127265366
43 NR5A1 NM_004959.4(NR5A1): c.236_238delGCC (p.Arg79del) deletion Uncertain significance GRCh38 Chromosome 9, 124503085: 124503087
44 NR5A1 NC_000009.12: g.(?_124482420)_(124482928_?)del deletion Likely pathogenic GRCh37 Chromosome 9, 127244699: 127245207
45 NR5A1 NC_000009.12: g.(?_124482420)_(124482928_?)del deletion Likely pathogenic GRCh38 Chromosome 9, 124482420: 124482928
46 NR5A1 NM_004959.4(NR5A1): c.1227C> G (p.Tyr409Ter) single nucleotide variant Likely pathogenic GRCh37 Chromosome 9, 127245196: 127245196
47 NR5A1 NM_004959.4(NR5A1): c.1227C> G (p.Tyr409Ter) single nucleotide variant Likely pathogenic GRCh38 Chromosome 9, 124482917: 124482917
48 NR5A1 NM_004959.4(NR5A1): c.88T> C (p.Cys30Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 9, 124503308: 124503308
49 NR5A1 NM_004959.4(NR5A1): c.88T> C (p.Cys30Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 9, 127265587: 127265587

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

GO Terms for 46,xy Sex Reversal 3

Sources for 46,xy Sex Reversal 3

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