SRD5A2

protein-coding

steroid 5 alpha-reductase 2, the group of Steroid 5-alpha reductase family

Gene summary

This gene encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The encoded protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride. Deficiencies in this gene can result in male pseudohermaphroditism, specifically pseudovaginal perineoscrotal hypospadias (PPSH). [provided by RefSeq, Jul 2008]

MANE transcript

NM_000348.4

Inheritance

ClinVar variants

P:102U:46B:83

Top phenotype

Steroid 5-alpha-reductase 2 deficiency

Max pathogenic AF

—

Genomic locus

chr2:31,522,480-31,580,938

External References & Databases

Ensembl (ENSG00000277893)

Transcript & Mutation Effects

hg38 • Region Span ~58.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

46,XY disorder of sex development due to 5-alpha-reductase 2 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009923

Submitter: PanelApp Australia

46,XY disorder of sex development due to 5-alpha-reductase 2 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009923

Submitter: Labcorp Genetics (formerly Invitae)

46,XY disorder of sex development due to 5-alpha-reductase 2 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009923

Submitter: Orphanet

Clinical Genomic Database (CGD)

Steroid 5-alpha-reductase 2 deficiencyAR

Manifestation: Endocrine; Genitourinary; Oncologic

Intervention: Endocrine; Genitourinary; Oncologic

Rationale: Hormonal treatment may be beneficial related to phenotypic gender characteristics; Due to risk of gonadal malignancy, prophlactic measures (related to gonadal tumors) may be beneficial

Refs: 4432067; 431680; 1944596; 1406794; 1522235; 8262007; 7554313; 8626825; 8768837; 8606628; 8723114; 8789759; 9208814; 9066886; 9467575; 9745434; 10564874; 10999800; 10718838; 11869378; 12576851; 12699446; 12713261; 12843198; 15813602; 16098368; 16181229; 17551467; 18391525; 17609295; 18717241; 18314109; 18350250; 20511729; 20019388; 20132346; 20395661; 21147889; 20850730; 22001134; 22453073

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SRD5A2 variants in ClinVar

10 Conditions Cataloged

3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiencyTotal: 244

not providedTotal: 63

SRD5A2-related disorderTotal: 22

not specifiedTotal: 19

Differences in sex developmentTotal: 4

Inborn genetic diseasesTotal: 3

MicropenisTotal: 2

Type 2 diabetes mellitusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000348.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	72 clinvar	1 clinvar	75
missense	22 clinvar	32 clinvar	43 clinvar	6 clinvar	3 clinvar	106
nonsense	12 clinvar	5 clinvar				17
start loss	1 clinvar					1
frameshift	18 clinvar	4 clinvar	1 clinvar	1 clinvar		24
splice donor/acceptor (+/-2bp)	3 clinvar	5 clinvar				8
Total	56	46	46	79	4	231

Highest pathogenic variant AF is 0.00028507438

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000348.4	RefSeq	NP_000339.2	5	MANE Select
ENST00000622030.2	Ensembl	ENSP00000477587.1	5	MANE Select
ENST00000882642.1	Ensembl	ENSP00000552701.1	6	Standard
ENST00000882642.2	Ensembl	ENSP00000552701.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Steroid hormone biosynthesis - Homo sapiens (human)
Prostate cancer - Homo sapiens (human)
Metabolism of lipids
Androgen and estrogen biosynthesis and metabolism
Metabolism

Biological Process

androgen biosynthetic process
steroid catabolic process
cell-cell signaling
androgen metabolic process
male gonad development

Molecular Function

3-oxo-5-alpha-steroid 4-dehydrogenase activity
sterol 5-alpha reductase activity
oxidoreductase activity
testosterone dehydrogenase [NAD(P)] activity
amide binding

Cellular Component

endoplasmic reticulum membrane
integral component of membrane
organelle membrane
neuronal cell body
cell body fiber

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Converts testosterone (T) into 5-alpha- dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology. {ECO:0000269|PubMed:10898110}.;
Disease: DISEASE: Pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600]: A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum. {ECO:0000269|PubMed:10718838, ECO:0000269|PubMed:10898110, ECO:0000269|PubMed:10999800, ECO:0000269|PubMed:12843198, ECO:0000269|PubMed:15064320, ECO:0000269|PubMed:1522235, ECO:0000269|PubMed:15528927, ECO:0000269|PubMed:15770495, ECO:0000269|PubMed:16098368, ECO:0000269|PubMed:16181229, ECO:0000269|PubMed:7554313, ECO:0000269|PubMed:8626825, ECO:0000269|PubMed:8768837, ECO:0000269|PubMed:9208814, ECO:0000269|PubMed:9745434, ECO:0000269|PubMed:9843052}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.319

Essentials

Indispensability pred.: N
Indispensability score: 0.00567