HSD17B6

hydroxysteroid 17-beta dehydrogenase 6, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 12:56752160-56787790

Links

ENSG00000025423 ∙ NCBI:8630 ∙ OMIM:606623 ∙ HGNC:23316 ∙ Uniprot:O14756 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSD17B6 gene.

• Inborn genetic diseases (12 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSD17B6 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	1	2
missense			11	1		12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	11	2	1

Variants in HSD17B6

This is a list of pathogenic ClinVar variants found in the HSD17B6 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-56752194-A-C			Likely pathogenic (Jul 01, 2022)
12-56752195-C-A		Microcephalic primordial dwarfism • Primordial dwarfism-immunodeficiency-lipodystrophy syndrome	Pathogenic (Aug 12, 2022)
12-56752201-C-T		not specified	Uncertain significance (Aug 15, 2023)
12-56752219-T-C		not specified	Uncertain significance (Jan 18, 2023)
12-56752228-G-C		not specified	Uncertain significance (Oct 14, 2023)
12-56752285-T-G			Benign (Apr 19, 2019)
12-56773869-C-T		not specified	Likely benign (Aug 17, 2021)
12-56773876-C-T			Likely benign (Apr 24, 2018)
12-56773914-G-A		not specified	Uncertain significance (Feb 16, 2023)
12-56773956-C-A		not specified	Uncertain significance (Sep 20, 2023)
12-56773958-G-A		not specified	Uncertain significance (Jan 30, 2024)
12-56773968-C-T		not specified	Uncertain significance (Oct 17, 2023)
12-56773994-C-G		not specified	Uncertain significance (Feb 11, 2022)
12-56774022-T-C		not specified	Uncertain significance (May 03, 2023)
12-56774024-G-A		not specified	Uncertain significance (Nov 03, 2023)
12-56774037-C-T		not specified	Uncertain significance (Jan 09, 2024)
12-56774044-G-C		not specified	Uncertain significance (Mar 22, 2023)
12-56774051-G-A		not specified	Uncertain significance (Jul 13, 2021)
12-56774089-G-A			Benign (Aug 04, 2017)
12-56781982-G-A		not specified	Uncertain significance (Sep 16, 2021)
12-56781985-C-G		not specified	Uncertain significance (Oct 14, 2021)
12-56782112-T-C		not specified	Uncertain significance (Mar 24, 2023)
12-56784855-G-A		not specified	Uncertain significance (Apr 07, 2022)
12-56784926-A-G		not specified	Uncertain significance (Sep 16, 2021)
12-56784969-C-A		not specified	Uncertain significance (Sep 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSD17B6	protein_coding	protein_coding	ENST00000554643	4	35630

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.348	0.649	125672	0	76	125748	0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.492	161	180	0.897	0.00000963	2045
Missense in Polyphen		58	57.114	1.0155		686
Synonymous	0.667	67	74.3	0.902	0.00000429	645
Loss of Function	2.59	3	13.1	0.229	8.37e-7	126

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00125	0.00125
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000306	0.000290
Middle Eastern	0.00	0.00
South Asian	0.0000990	0.0000980
Other	0.000531	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: NAD-dependent oxidoreductase with broad substrate specificity that shows both oxidative and reductive activity (in vitro). Has 17-beta-hydroxysteroid dehydrogenase activity towards various steroids (in vitro). Converts 5-alpha-androstan-3- alpha,17-beta-diol to androsterone and estradiol to estrone (in vitro). Has 3-alpha-hydroxysteroid dehydrogenase activity towards androsterone (in vitro). Has retinol dehydrogenase activity towards all-trans-retinol (in vitro). Can convert androsterone to epi-androsterone. Androsterone is first oxidized to 5-alpha- androstane-3,17-dione and then reduced to epi-andosterone. Can act on both C-19 and C-21 3-alpha-hydroxysteroids. {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992, ECO:0000269|PubMed:11513953}.
• Pathway: Retinol metabolism - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Signaling by GPCR;Signal Transduction;The canonical retinoid cycle in rods (twilight vision);G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.267

Intolerance Scores

• loftool: 0.373
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.66

Haploinsufficiency Scores

• pHI: 0.128
• hipred: N
• hipred_score: 0.273
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hsd17b6

Gene ontology

• Biological process: androgen biosynthetic process;androgen catabolic process;electron transport chain
• Cellular component: endoplasmic reticulum;early endosome membrane
• Molecular function: catalytic activity;estradiol 17-beta-dehydrogenase activity;retinol dehydrogenase activity;electron transfer activity;oxidoreductase activity;testosterone dehydrogenase (NAD+) activity