HSD17B1

protein-coding

hydroxysteroid 17-beta dehydrogenase 1, the group of Short chain dehydrogenase/reductase superfamily

Gene summary

This gene encodes a member of the 17beta-hydroxysteroid dehydrogenase family of short-chain dehydrogenases/reductases. It has a dual function in estrogen activation and androgen inactivation and plays a major role in establishing the estrogen E2 concentration gradient between serum and peripheral tissues. The encoded protein catalyzes the last step in estrogen activation, using NADPH to convert estrogens E1 and E2 and androgens like 4-androstenedione, to testosterone. It has an N-terminal short-chain dehydrogenase domain with a cofactor binding site, and a narrow, hydrophobic C-terminal domain with a steroid substrate binding site. This gene is expressed primarily in the placenta and ovarian granulosa cells, and to a lesser extent, in the endometrium, adipose tissue, and prostate. Polymorphisms in this gene have been linked to breast and prostate cancer. A pseudogene of this gene has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

Previous symbols:

EDHB17
EDH17B2

MANE transcript

NM_000413.4

Inheritance

—

ClinVar variants

U:74B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr17:42,552,922-42,555,214

External References & Databases

Ensembl (ENSG00000108786)

Transcript & Mutation Effects

hg38 • Region Span ~2.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSD17B1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 75

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000413.4. 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		1 clinvar	3
missense			70 clinvar	6 clinvar		76
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	74	6	1	81

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000413.4	RefSeq	NP_000404.2	6	MANE Select
ENST00000585807.6	Ensembl	ENSP00000466799.1	6	MANE Select
NM_001330219.3	RefSeq	NP_001317148.1	6	Standard
ENST00000225929.5	Ensembl	ENSP00000225929.5	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Steroid hormone biosynthesis - Homo sapiens (human)
Ovarian steroidogenesis - Homo sapiens (human)
Aromatase Inhibitor Pathway (Multiple Tissues), Pharmacodynamics
Estrogen Metabolism Pathway
Aromatase Inhibitor Pathway (Breast Cell), Pharmacodynamics

Biological Process

steroid biosynthetic process
estrogen biosynthetic process
estrogen metabolic process
oxidation-reduction process

Molecular Function

catalytic activity
estradiol 17-beta-dehydrogenase activity
steroid binding
NADP+ binding
estradiol binding

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000585807
Coding exons: 6
Length: 6000
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125746
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.351	236	221	1.07	0.0000143	2052
Missense (PolyPhen)		89	83.3	1.0684		790
Synonymous	-0.878	121	109	1.11	0.00000771	733
Loss of Function	0.805	7	9.70	0.721	4.10e-7	117

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.00023	0.00023	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.;

Recessive Scores

pRec: 0.285

Intolerance Scores

LoFtool: 0.196
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.738

Gene Damage Prediction

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