Disorders of sex development

Gene: NR5A1

Green List (high evidence)

NR5A1 (nuclear receptor subfamily 5 group A member 1)
EnsemblGeneIds (GRCh38): ENSG00000136931
EnsemblGeneIds (GRCh37): ENSG00000136931
OMIM: 184757, Gene2Phenotype
NR5A1 is in 8 panels

3 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Created: 29 Apr 2019, 9:46 a.m.

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM and G2P / DD. Thirteen variants reported in 46XY sex reversal 3 612965.
Created: 12 Sep 2016, 10:53 a.m.
Comment on mode of inheritance: 46XY sex reversal 3 612965 and Premature ovarian failure 7 612964 are monogenic, Spermatogenic failure 8 613957 is biallelic and only on case of adrenocortical insufficiency has been reported to be associated with variants in this gene
Created: 12 Sep 2016, 10:41 a.m.

John Achermann (UCL Institute of Child Health)

Green List (high evidence)

Nuclear receptor that is a key regulator of reproductive function. Usually heterozygous (monoallellic) changes that are de novo or sex limited dominant from a mother who sometimes then develops primary ovarian insufficiency. Very rarely recessive partial loss of function. Severe forms usually cause 46,XY female with uterus and primary adrenal insufficiency, but this is very rare. Most changes cause 46,XY atypical genitalia with or without Mulllerian structures and normal adrenal function. Milder defects can be found in association with hypospadias, male factor infertility, and in 46,XX females with primary ovarian insufficiency. Phenotypes may vary within families, and sex-limited dominant inheritance may mimic X-linked, so often misdiagnosed as partial androgen insensitivity syndrome.
Created: 4 Feb 2016, 4:26 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Variable underandrogenization, occassionally adrenal insfficiency; may also be associated with hypospadias, infertility or primary ovarian insufficinecy

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN)
  • Endocrine disorders including disorders of sexual development (Emory)
  • 46XY sex reversal 3, 612965
  • Premature ovarian failure 7, 612964
  • Spermatogenic failure 8, 613957
OMIM
184757
Clinvar variants
Variants in NR5A1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 Dec 2016, Gel status: 4

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to V1 21/12/2016

12 Sep 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

12 Sep 2016, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for NR5A1 were set to 26303087

12 Sep 2016, Gel status: 3

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for NR5A1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

12 Sep 2016, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for NR5A1 were set to Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN); Endocrine disorders including disorders of sexual development (Emory); 46XY sex reversal 3, 612965; Premature ovarian failure 7, 612964; Spermatogenic failure 8, 613957;

20 May 2016, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene NR5A1 were set to Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN); 46XY sex reversal 3, 612965; Premature ovarian failure 7, 612964; Spermatogenic failure 8, 613957; Endocrine disorders including disorders of sexual development (Emory)

20 May 2016, Gel status: 3

Added New Source

Sarah Leigh (Genomics England Curator)

NR5A1 was added to Disorders of sex developmentpanel. Source: Radboud University Medical Center, Nijmegen

20 May 2016, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

NR5A1 was added to Disorders of sex developmentpanel. Source: Emory Genetics Laboratory

20 May 2016, Gel status: 1

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Model of inheritance for gene NR5A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

11 Jan 2016, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

NR5A1 was added to Disorders of sex developmentpanel. Sources: UKGTN

11 Jan 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

NR5A1 was created by ellenmcdonagh