SRD5A2

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

Basic information

Region (hg38): 2:31522480-31580938

Links

ENSG00000277893 ∙ NCBI:6716 ∙ OMIM:607306 ∙ HGNC:11285 ∙ Uniprot:P31213 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency (Supportive), mode of inheritance: AR
• 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Steroid 5-alpha-reductase 2 deficiency	AR	Endocrine; Genitourinary; Oncologic	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	Endocrine; Genitourinary; Oncologic	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

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRD5A2 gene.

• 3-Oxo-5_alpha-steroid_delta_4-dehydrogenase_deficiency (230 variants)
• not_provided (58 variants)
• not_specified (15 variants)
• SRD5A2-related_disorder (10 variants)
• Inborn_genetic_diseases (3 variants)
• Micropenis (2 variants)
• Abnormality_of_the_genitourinary_system (1 variants)
• Autism_spectrum_disorder (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRD5A2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000348.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	68	2	73
missense	22	27	36	5	5	95
nonsense	13	2				15
start loss	1					1
frameshift	18	1	1		1	21
splice donor/acceptor (+/-2bp)	3	3				6
Total	57	33	40	73	8

Highest pathogenic variant AF is 0.000285074

GnomAD

Source: gnomAD

dbNSFP

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.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Metabolism of lipids;Androgen and estrogen biosynthesis and metabolism;Metabolism;allopregnanolone biosynthesis;Androgen biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;Bile acid biosynthesis;androgen biosynthesis;superpathway of steroid hormone biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.319

Haploinsufficiency Scores

• pHI: 0.0503

Essentials

• gene_indispensability_pred: N
• gene_indispensability_score: 0.00567

Mouse Genome Informatics

• Gene name: Srd5a2
• Phenotype: endocrine/exocrine gland phenotype; reproductive system phenotype

Gene ontology

• Biological process: androgen biosynthetic process;steroid catabolic process;cell-cell signaling;androgen metabolic process;male gonad development;biphenyl metabolic process;dibenzo-p-dioxin metabolic process;phthalate metabolic process;hippocampus development;hypothalamus development;cell differentiation;male genitalia development;female genitalia development;response to nutrient levels;response to follicle-stimulating hormone;response to testosterone;response to drug;response to peptide hormone;response to steroid hormone;oxidation-reduction process;bone development;testosterone biosynthetic process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane;organelle membrane;neuronal cell body;cell body fiber
• Molecular function: 3-oxo-5-alpha-steroid 4-dehydrogenase activity;sterol 5-alpha reductase activity;oxidoreductase activity;testosterone dehydrogenase [NAD(P)] activity;amide binding;cholestenone 5-alpha-reductase activity