HSD17B3

hydroxysteroid 17-beta dehydrogenase 3, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 9:96235306-96302176

Links

ENSG00000130948 ∙ NCBI:3293 ∙ OMIM:605573 ∙ HGNC:5212 ∙ Uniprot:P37058 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency (Strong), mode of inheritance: AR
• 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
17-Beta hydroxysteroid dehydrogenase III deficiency	AR	Endocrine; Genitourinary	Prepubertal diagnosis may allow surgical treatment via removal of abnormal testes, preventing typical presenting clinical signs in puberty (marked masculinization and hirsutism)	Endocrine; Genitourinary	2998649; 8075637; 8550739; 10599740; 21700882; 22212252; 22594312; 22445608; 22876557

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSD17B3 gene.

• not provided (20 variants)
• Testosterone 17-beta-dehydrogenase deficiency (10 variants)
• Pseudohermaphroditism (5 variants)
• Inborn genetic diseases (3 variants)
• HSD17B3-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSD17B3 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			1	62	1	64
missense	6	9	21	3	1	40
nonsense	6	2	1			9
start loss						0
frameshift	4	3	1			8
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	4	5				9
splice region	1		4	19	1	25
non coding			4	76	37	117
Total	20	20	29	141	39

Highest pathogenic variant AF is 0.000355

Variants in HSD17B3

This is a list of pathogenic ClinVar variants found in the HSD17B3 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-96235312-G-T		Testosterone 17-beta-dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
9-96235459-G-A		Testosterone 17-beta-dehydrogenase deficiency	Uncertain significance (Apr 28, 2017)
9-96235465-T-G		HSD17B3-related disorder	Likely benign (Jun 18, 2019)
9-96235470-T-G			Uncertain significance (Oct 31, 2022)
9-96235471-T-A			Uncertain significance (May 16, 2022)
9-96235499-G-A			Likely benign (Jan 22, 2024)
9-96235513-G-A		Testosterone 17-beta-dehydrogenase deficiency	Conflicting classifications of pathogenicity (Dec 11, 2023)
9-96235520-G-A			Likely benign (Feb 24, 2023)
9-96235528-C-T		not specified • Testosterone 17-beta-dehydrogenase deficiency	Benign/Likely benign (Feb 01, 2024)
9-96235529-G-A			Likely benign (Jan 17, 2024)
9-96235541-C-T			Likely pathogenic (May 23, 2023)
9-96235542-C-T			Likely pathogenic (May 30, 2023)
9-96235547-C-G			Likely benign (May 26, 2023)
9-96235547-C-T			Likely benign (Dec 29, 2023)
9-96235548-G-A		Pseudohermaphroditism • Testosterone 17-beta-dehydrogenase deficiency • Inborn genetic diseases	Pathogenic/Likely pathogenic (Jun 26, 2024)
9-96235553-C-T			Likely benign (Dec 09, 2023)
9-96235556-G-A			Likely benign (Jan 31, 2024)
9-96235562-A-G			Likely benign (Feb 21, 2023)
9-96235565-G-A			Likely benign (Jan 19, 2023)
9-96235569-G-A			Uncertain significance (Sep 24, 2021)
9-96235581-G-A			Likely benign (May 28, 2023)
9-96235582-A-G			Likely benign (Dec 30, 2022)
9-96235586-G-A			Likely benign (May 10, 2023)
9-96235628-ATCTTTGTGG-A			Benign (Aug 09, 2018)
9-96240473-C-G			Benign (Aug 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSD17B3	protein_coding	protein_coding	ENST00000375263	11	66847

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.49e-7	0.760	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.367	155	168	0.920	0.00000966	2001
Missense in Polyphen		49	53.89	0.90927		664
Synonymous	0.568	63	69.0	0.913	0.00000446	613
Loss of Function	1.28	12	17.8	0.673	7.76e-7	219

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000508	0.000508
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Favors the reduction of androstenedione to testosterone. Uses NADPH while the two other EDH17B enzymes use NADH. {ECO:0000269|PubMed:26545797}.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);17-Beta Hydroxysteroid Dehydrogenase III Deficiency;Androgen and Estrogen Metabolism;Aromatase deficiency;Androgen Receptor Network in Prostate Cancer;Steroid Biosynthesis;Metabolism of lipids;Fatty acyl-CoA biosynthesis;Metabolism;Fatty acid metabolism;Androgen biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;androgen biosynthesis;Synthesis of very long-chain fatty acyl-CoAs;superpathway of steroid hormone biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.219

Intolerance Scores

• loftool: 0.229
• rvis_EVS: -0.16
• rvis_percentile_EVS: 42.06

Haploinsufficiency Scores

• pHI: 0.122
• hipred: N
• hipred_score: 0.170
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0330

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hsd17b3

Gene ontology

• Biological process: steroid biosynthetic process;androgen biosynthetic process;male genitalia development;oxidation-reduction process;testosterone biosynthetic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;intracellular membrane-bounded organelle
• Molecular function: testosterone dehydrogenase [NAD(P)] activity;testosterone 17-beta-dehydrogenase (NADP+) activity