SRD5A3

steroid 5 alpha-reductase 3, the group of Steroid 5-alpha reductase family

Basic information

Region (hg38): 4:55346212-55373100

Links

ENSG00000128039 ∙ NCBI:79644 ∙ OMIM:611715 ∙ HGNC:25812 ∙ Uniprot:Q9H8P0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• SRD5A3-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• SRD5A3-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• SRD5A3-congenital disorder of glycosylation (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Kahrizi syndrome; Congenital disorder of glycosylation, type Iq	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Neurologic; Ophthalmologic	18271001; 18781183; 20637498; 20700148
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRD5A3 gene.

• SRD5A3-congenital disorder of glycosylation (141 variants)
• not provided (57 variants)
• Inborn genetic diseases (16 variants)
• Congenital disorder of glycosylation (14 variants)
• not specified (12 variants)
• Abnormality of the nervous system (3 variants)
• SRD5A3-congenital disorder of glycosylation;Kahrizi syndrome (3 variants)
• Generalized hypotonia;Low-set ears;Hemangioma (1 variants)
• Kahrizi syndrome;SRD5A3-congenital disorder of glycosylation (1 variants)
• Kahrizi syndrome (1 variants)
• SRD5A3-related condition (1 variants)
• Autism;Global developmental delay;Cone dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRD5A3 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	17		20
missense		2	52	2		56
nonsense	5	1				6
start loss			1			1
frameshift	2	3				5
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				2		2
non coding			55	23	26	104
Total	7	7	111	42	26

Highest pathogenic variant AF is 0.0000525

Variants in SRD5A3

This is a list of pathogenic ClinVar variants found in the SRD5A3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-55346237-C-G		Congenital disorder of glycosylation	Uncertain significance (Jun 14, 2016)
4-55346253-G-C		SRD5A3-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
4-55346297-G-A		SRD5A3-congenital disorder of glycosylation • not specified	Benign (Feb 28, 2018)
4-55346307-C-A		SRD5A3-congenital disorder of glycosylation	Uncertain significance (Jan 12, 2018)
4-55346310-G-T		SRD5A3-congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
4-55346331-C-T		not specified	Likely benign (Sep 21, 2016)
4-55346338-T-C		SRD5A3-congenital disorder of glycosylation • SRD5A3-congenital disorder of glycosylation;Kahrizi syndrome	Uncertain significance (Jan 13, 2022)
4-55346343-C-T		Inborn genetic diseases	Uncertain significance (Jun 30, 2022)
4-55346356-C-T			Uncertain significance (Jan 18, 2023)
4-55346358-G-A		SRD5A3-congenital disorder of glycosylation	Uncertain significance (Aug 16, 2022)
4-55346365-C-A		SRD5A3-congenital disorder of glycosylation	Pathogenic (Jul 23, 2010)
4-55346374-A-C			Uncertain significance (Apr 17, 2019)
4-55346379-C-T		not specified • SRD5A3-congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Aug 16, 2022)
4-55346383-G-A		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
4-55346385-GCGGTGTGGCTC-G		SRD5A3-congenital disorder of glycosylation	Pathogenic (-)
4-55346386-C-T		SRD5A3-congenital disorder of glycosylation	Uncertain significance (Apr 19, 2022)
4-55346387-G-T		not specified • SRD5A3-congenital disorder of glycosylation • SRD5A3-related disorder	Conflicting classifications of pathogenicity (Feb 03, 2022)
4-55346392-G-T		SRD5A3-congenital disorder of glycosylation	Uncertain significance (Jul 21, 2023)
4-55346393-G-A		SRD5A3-congenital disorder of glycosylation • Autism;Global developmental delay;Cone dystrophy • Abnormality of the nervous system • Congenital disorder of glycosylation • Kahrizi syndrome	Pathogenic (Feb 09, 2024)
4-55346399-G-A		SRD5A3-congenital disorder of glycosylation	Likely benign (Sep 01, 2022)
4-55346400-C-G		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
4-55346401-T-G		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
4-55346401-TG-T			Pathogenic (Apr 05, 2019)
4-55346413-T-G		SRD5A3-congenital disorder of glycosylation	Uncertain significance (Aug 14, 2020)
4-55346419-T-G		SRD5A3-congenital disorder of glycosylation	Uncertain significance (May 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRD5A3	protein_coding	protein_coding	ENST00000264228	5	26988

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000249	0.932	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.760	136	163	0.833	0.00000827	2048
Missense in Polyphen		41	47.371	0.86551		632
Synonymous	0.804	65	73.8	0.881	0.00000413	644
Loss of Function	1.64	8	14.8	0.539	7.42e-7	152

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000118	0.000118
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000968	0.0000924
European (Non-Finnish)	0.000215	0.000211
Middle Eastern	0.0000544	0.0000544
South Asian	0.000102	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol. Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation. Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism. Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT). {ECO:0000269|PubMed:17986282, ECO:0000269|PubMed:20637498}.
• Disease: DISEASE: Kahrizi syndrome (KHRZ) [MIM:612713]: An autosomal recessive neurodevelopmental disorder characterized by mental retardation, cataracts, coloboma, kyphosis, and coarse facial features. {ECO:0000269|PubMed:20700148}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Metabolism of lipids;Post-translational protein modification;Metabolism of proteins;Androgen and estrogen biosynthesis and metabolism;Metabolism;dolichol and dolichyl phosphate biosynthesis;Androgen biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;Synthesis of Dolichyl-phosphate;Bile acid biosynthesis;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.586
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.82

Haploinsufficiency Scores

• pHI: 0.188
• hipred: N
• hipred_score: 0.230
• ghis: 0.430

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.575

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Srd5a3
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: dolichol-linked oligosaccharide biosynthetic process;dolichyl diphosphate biosynthetic process;androgen biosynthetic process;polyprenol catabolic process;dolichol metabolic process;dolichol biosynthetic process;oxidation-reduction process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
• Molecular function: 3-oxo-5-alpha-steroid 4-dehydrogenase activity;oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor;cholestenone 5-alpha-reductase activity;polyprenol reductase activity