HSD17B7

Summary

HSD17B7 (hydroxysteroid 17-beta dehydrogenase 7, HGNC:5215) is a protein-coding gene on chromosome 1q23.3, encoding 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (P56937). Bifunctional enzyme involved in steroid-hormone metabolism and cholesterol biosynthesis.

HSD17B7 encodes an enzyme that functions both as a 17-beta-hydroxysteroid dehydrogenase (EC 1.1.1.62) in the biosynthesis of sex steroids and as a 3-ketosteroid reductase (EC 1.1.1.270) in the biosynthesis of cholesterol (Marijanovic et al., 2003 [PubMed 12829805]).

Source: NCBI Gene 51478 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• Druggable target: yes
• MANE Select transcript: NM_016371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5215
Approved symbol	HSD17B7
Name	hydroxysteroid 17-beta dehydrogenase 7
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	PRAP, SDR37C1
Ensembl gene	ENSG00000132196
Ensembl biotype	protein_coding
OMIM	606756
Entrez	51478

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000254521, ENST00000367915, ENST00000463037, ENST00000466176, ENST00000470195, ENST00000484251, ENST00000485405, ENST00000488656, ENST00000494450, ENST00000649629, ENST00000902166, ENST00000902167, ENST00000902168, ENST00000934358, ENST00000963897

RefSeq mRNA: 2 — MANE Select: NM_016371 NM_001304512, NM_016371

CCDS: CCDS1242

Canonical transcript exons

ENST00000254521 — 9 exons

Exon	Start	End
ENSE00001857070	162812298	162812823
ENSE00002309918	162790702	162790835
ENSE00003474367	162796585	162796677
ENSE00003487251	162797802	162797916
ENSE00003506847	162792659	162792862
ENSE00003550529	162804267	162804323
ENSE00003577847	162803431	162803535
ENSE00003608376	162799743	162799937
ENSE00003626427	162805394	162805492

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 94.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0358 / max 26.4748, expressed in 9 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6323	0.0261	9
201797	0.0097	1

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	94.67	gold quality
right lobe of liver	UBERON:0001114	94.26	gold quality
right adrenal gland	UBERON:0001233	92.12	gold quality
right adrenal gland cortex	UBERON:0035827	91.90	gold quality
left adrenal gland	UBERON:0001234	91.34	gold quality
left adrenal gland cortex	UBERON:0035825	91.14	gold quality
lower esophagus mucosa	UBERON:0035834	90.88	gold quality
adenohypophysis	UBERON:0002196	89.68	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.23	gold quality
adrenal gland	UBERON:0002369	88.69	gold quality
upper lobe of left lung	UBERON:0008952	88.49	gold quality
adrenal cortex	UBERON:0001235	87.76	gold quality
islet of Langerhans	UBERON:0000006	87.41	gold quality
ectocervix	UBERON:0012249	86.92	gold quality
right ovary	UBERON:0002118	86.85	gold quality
upper lobe of lung	UBERON:0008948	86.57	gold quality
left ovary	UBERON:0002119	86.25	gold quality
pituitary gland	UBERON:0000007	86.00	gold quality
skin of leg	UBERON:0001511	85.63	gold quality
mucosa of transverse colon	UBERON:0004991	85.63	gold quality
right lung	UBERON:0002167	85.61	gold quality
skin of abdomen	UBERON:0001416	85.58	gold quality
mucosa of stomach	UBERON:0001199	85.52	gold quality
spinal cord	UBERON:0002240	85.23	gold quality
esophagus mucosa	UBERON:0002469	85.12	gold quality
granulocyte	CL:0000094	85.01	gold quality
body of pancreas	UBERON:0001150	85.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.97	gold quality
left lobe of thyroid gland	UBERON:0001120	84.89	gold quality
minor salivary gland	UBERON:0001830	84.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-83139	no	2.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting HSD17B7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-6879-3P	93.93	64.00	759

Literature-anchored findings (GeneRIF, showing 20)

• HSD17B7 is a novel candidate for inborn errors of cholesterol metabolism (PMID:12829805)
• Comparison of the promoter region of the human and murine gene. (PMID:15862973)
• The identified proximal promoter regions of both human and murine HSD17B7 genes contain multiple transcription factor binding sites and show strong similarity to cholesterogenic genes. (PMID:16356630)
• Results provide unequivocal evidence for a role of 17beta-hydroxysteroid dehydrogenase type-7 in cholesterol biosynthesis. (PMID:16901934)
• 17beta-hydroxysteroid dehydrogenase type 7(17beta-HSD type 7)was significantly upregulated in ovarian tissue of patients with ovarian endometriosis. (PMID:17454161)
• 17-beta hydroxysteroid dehydrogenase type 7 (HSD17B7) -shRNA sequences were designed and tested for their effectiveness. (PMID:17498944)
• determined the activity and expression levels of known estrogenic 17beta-HSDs, namely types 1, 7 and 12 17beta-HSD in preadipocytes before and after differentiation into mature adipocytes (PMID:19429442)
• There is no difference in catalytic properties between variants of 17beta-HSD types 7 and 12 and wild-type enzymes, while variants p.Glu77Gly and p.Lys183Arg in 17beta-HSD type 5 showed a slightly decreased activity. (PMID:19460435)
• The transcriptional activity of the HSD17B7 gene containing the G allele is higher than that of the C allele. This difference in HSD17B7 expression may regulate the risk of peripheral edema as an adverse reaction induced by estramustine phosphate sodium (PMID:19735314)
• increased expression of HSD17B7 is associated with breast cancer. (PMID:20215536)
• Data show that apicidin significantly lowers HSD17B1 transcript and protein levels in endometrial adenocarcinoma cells, with no significant effect on HSD17B1 transcript stability. (PMID:21086175)
• estradiol stimulates HSD17B7 transcriptional activity in breast cancer cells through a novel mechanism requiring NF1 and strongly suggest a positive feedback mechanism, increasing estradiol synthesis causing growth of estrogen-dependent breast cancers (PMID:21372145)
• 17betaHSD7 is not the key enzyme responsible for androstenone and testosterone metabolism in porcine liver cells (PMID:23300627)
• 17beta-HSD1 and 17beta-HSD7 are principal reductive 17beta-hydroxysteroid dehydrogenases and major players in the viability of estrogen-dependent breast cancer cells. (PMID:25257817)
• the dual functional 17beta-HSD7 is proposed as a novel target for estrogen-dependent breast cancer by regulating the balance of estradiol and dihydrotestosterone. (PMID:25966904)
• Substrate inhibition of 17beta-HSD1 in tumor epithelial cells and regulation of 17beta-HSD7 by 17beta-HSD1 knockdown has been demonstrated. (PMID:28554725)
• Inhibition of 17beta-HSD 7 modulates breast cancer protein profile and enhances apoptosis by down-regulating GRP78. (PMID:28645527)
• Substrate affinity of 17beta-hydroxysteroid dehydrogenase type 7 toward estrone and 5alpha-dihydrotestosterone are similar. (PMID:30227243)
• Inhibition of 17beta-HSD7can provide a new basis for the design of combined endocrine therapy for breast cancer by controlling E2 and DHT, while up-regulating AR expression and stably controlling expression of ERalpha. (PMID:31207361)
• HSD17B7 gene in self-renewal and oncogenicity of keratinocytes from Black versus White populations. (PMID:34185380)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsd17b7	ENSDARG00000088140
mus_musculus	Hsd17b7	ENSMUSG00000026675
rattus_norvegicus	Hsd17b7	ENSRNOG00000002826

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSDL1 (ENSG00000103160), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B4 (ENSG00000133835), RDH5 (ENSG00000135437), RDH16 (ENSG00000139547), RDH12 (ENSG00000139988), HSD17B12 (ENSG00000149084), BDH1 (ENSG00000161267), DHRS3 (ENSG00000162496), SDR9C7 (ENSG00000170426), HSD17B13 (ENSG00000170509), SDR16C5 (ENSG00000170786), HSD11B2 (ENSG00000176387), WWOX (ENSG00000186153), HSD17B11 (ENSG00000198189), HSD17B8 (ENSG00000204228)

Protein

Protein identifiers

3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 — P56937 (reviewed: P56937)

Alternative names: 17-beta-hydroxysteroid dehydrogenase 7, 3-keto-steroid reductase, Dihydrotestosterone oxidoreductase, Estradiol 17-beta-dehydrogenase 7, Short chain dehydrogenase/reductase family 37C member 1

All UniProt accessions (4): P56937, F2Z2C2, Q5T249, V9GYN3

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme involved in steroid-hormone metabolism and cholesterol biosynthesis. Catalyzes the NADP(H)-dependent reduction of estrogens and androgens and regulates the biological potency of these steroids. Converts estrone (E1) to a more potent estrogen, 17beta-estradiol (E2). Converts dihydrotestosterone (DHT) to its inactive form 5a-androstane-3b,17b-diol. Converts moderately progesterone to 3beta-hydroxypregn-4-ene-20-one, leading to its inactivation. Additionally, participates in the post-squalene cholesterol biosynthesis, as a 3-ketosteroid reductase. Does not have enzymatic activities toward E1 and DHT.

Subunit / interactions. Binds to the short form of prolactin receptor.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in adrenal gland, liver, lung and thymus. Expressed in breast, ovaries, pituitary gland, pregnant uterus, prostate, kidney, lymph node, small intestine, spinal cord and trachea. Weakly expressed in all other tissues tested. Expressed in eye ciliary epithelial cells and neuroendocrine cells.

Post-translational modifications. Phosphorylated.

Activity regulation. Estradiol 17-beta-dehydrogenase and dihydrotestosterone oxidoreductase activities are selectively inhibited by 4-methyl-4-aza-5alpha-androstane derivatives, such as 17beta-[(N-Heptyl)methylamino]-4-aza-5r-androstan-3-one and 17beta-(N-Decylformamido)-4-aza-5r-androstan-3-one.

Pathway. Steroid biosynthesis; estrogen biosynthesis. Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 5/6.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family. ERG27 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P56937-1	1	yes
P56937-2	2
P56937-3	3

RefSeq proteins (2): NP_001291441, NP_057455* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR042829	HSD17B7/Erg27	Family
IPR052834	3KSR/17beta-HSD	Family

Pfam: PF00106

Enzyme classification (BRENDA):

• EC 1.1.1.270 — 3beta-hydroxysteroid 3-dehydrogenase (BRENDA: 11 organisms, 123 substrates, 36 inhibitors, 43 Km, 32 kcat entries)
• EC 1.1.1.62 — 17beta-estradiol 17-dehydrogenase (BRENDA: 20 organisms, 283 substrates, 790 inhibitors, 95 Km, 44 kcat entries)

Substrate kinetics (BRENDA)

52 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ESTRADIOL-17BETA	0.0008–0.025	14
ESTRONE	—	10
NADP+	0.0001–9	9
17BETA-ESTRADIOL	0.0006–0.082	7
NADPH	0.0003–0.16	7
ESTRADIOL	0.0036–0.118	6
5BETA-DIHYDROTESTOSTERONE	0.0035–0.039	5
5BETA-PREGNANE-21-OL-3,20-DIONE	0.0023–0.05	5
METHYLGLYOXAL	0.18–0.253	5
NADPH	0.0001–0.004	4
PYRIDINE-3-ALDEHYDE	0.011–0.048	4
TESTOSTERONE	0.0071–0.263	4
DEHYDROEPIANDROSTERONE	0.0037–0.0124	3
NAD+	0.0205–0.0341	3
DEHYDROEPIANDROSTERONE	0.0172–0.0598	3

Catalyzed reactions (Rhea), 9 shown:

• 5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADPH + H(+) (RHEA:16297)
• 4alpha-methyl-5alpha-cholest-7-en-3beta-ol + NADP(+) = 4alpha-methyl-5alpha-cholest-7-en-3-one + NADPH + H(+) (RHEA:18409)
• 17beta-estradiol + NADP(+) = estrone + NADPH + H(+) (RHEA:24616)
• zymosterone + NADPH + H(+) = zymosterol + NADP(+) (RHEA:33459)
• a 3beta-hydroxysteroid + NADP(+) = a 3-oxosteroid + NADPH + H(+) (RHEA:34787)
• 3-dehydro-4alpha-methylzymosterol + NADPH + H(+) = 4alpha-methylzymosterol + NADP(+) (RHEA:36379)
• progesterone + NADPH + H(+) = 3beta-hydroxypregn-4-ene-20-one + NADP(+) (RHEA:46216)
• 4alpha-methyl-5alpha-cholest-8-en-3-one + NADPH + H(+) = 4alpha-methyl-5alpha-cholest-8-en-3beta-ol + NADP(+) (RHEA:46832)
• 5alpha-cholest-8-en-3-one + NADPH + H(+) = 5alpha-cholest-8-en-3beta-ol + NADP(+) (RHEA:46852)

UniProt features (19 total): sequence conflict 7, glycosylation site 3, topological domain 2, splice variant 2, binding site 2, chain 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56937-F1	90.42	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 193 (proton acceptor)

Ligand- & substrate-binding residues (2): 8–15; 171

Glycosylation sites (3): 37, 178, 229

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807047	Cholesterol biosynthesis via desmosterol (Bloch pathway)
R-HSA-6807062	Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)
R-HSA-191273	Cholesterol biosynthesis

MSigDB gene sets: 185 (showing top): MODULE_93, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MODULE_205, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_HORMONE_BIOSYNTHETIC_PROCESS, GOBP_STEROID_BIOSYNTHETIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_ANDROGEN_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (11): cholesterol biosynthetic process (GO:0006695), estrogen biosynthetic process (GO:0006703), brain development (GO:0007420), androgen metabolic process (GO:0008209), cell differentiation (GO:0030154), obsolete cholesterol biosynthetic process via lathosterol (GO:0033490), embryonic organ development (GO:0048568), embryonic skeletal system development (GO:0048706), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), nervous system development (GO:0007399)

GO Molecular Function (4): 3-beta-hydroxysteroid 3-dehydrogenase (NADP+) activity (GO:0000253), estradiol 17-beta-dehydrogenase [NAD(P)+] activity (GO:0004303), 5-alpha-androstane-3-beta,17-beta-diol dehydrogenase (NADP+) activity (GO:0047024), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): mitochondrion (GO:0005739), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cholesterol biosynthesis	2
Metabolism of steroids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	3
animal organ development	2
steroid metabolic process	2
cytoplasm	2
intracellular membrane-bounded organelle	2
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
estrogen metabolic process	1
hormone biosynthetic process	1
steroid hormone biosynthetic process	1
central nervous system development	1
head development	1
hormone metabolic process	1
cellular developmental process	1
embryo development	1
skeletal system development	1
chordate embryonic development	1
primary metabolic process	1
lipid biosynthetic process	1
system development	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSD17B7	HSD17B1	P14061	918
HSD17B7	MSMO1	Q15800	905
HSD17B7	SC5D	O75845	897
HSD17B7	DHRS11	Q6UWP2	897
HSD17B7	CYP51A1	Q16850	853
HSD17B7	NSDHL	Q15738	852
HSD17B7	FDFT1	P37268	839
HSD17B7	HMGCR	P04035	828
HSD17B7	HMGCS1	Q01581	813
HSD17B7	SQLE	Q14534	775
HSD17B7	DHCR24	Q15392	772
HSD17B7	IDI1	Q13907	731
HSD17B7	ERG28	Q9UKR5	731
HSD17B7	HSD17B12	Q53GQ0	727
HSD17B7	FDPS	P14324	724

IntAct

38 interactions, top by confidence:

A	B	Type	Score
FAM174A	GAK	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
TFDP3	E2F3	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
ACOX1	HSD17B7	psi-mi:“MI:0915”(physical association)	0.400
CA1	HSD17B7	psi-mi:“MI:0915”(physical association)	0.370
DTYMK	HSD17B7	psi-mi:“MI:0915”(physical association)	0.370
HSD17B7	BRSK1	psi-mi:“MI:0915”(physical association)	0.370
GORAB	HSD17B7	psi-mi:“MI:0915”(physical association)	0.370
HSD17B7	GPAT4	psi-mi:“MI:0915”(physical association)	0.370
IGHM	ESYT2	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	TMEM223	psi-mi:“MI:0914”(association)	0.350
SV2A	ILVBL	psi-mi:“MI:0914”(association)	0.350
ORAI1	POTEF	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC18A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
LCN6	COCH	psi-mi:“MI:0914”(association)	0.350
HSD17B7	POLB	psi-mi:“MI:0914”(association)	0.350
P2RY10	TTI1	psi-mi:“MI:0914”(association)	0.350
ACVR1	NBAS	psi-mi:“MI:0914”(association)	0.350
C1QA	VWA8	psi-mi:“MI:0914”(association)	0.350
DUOXA2	CHRNB1	psi-mi:“MI:0914”(association)	0.350
GSDME	DDX39A	psi-mi:“MI:0914”(association)	0.350
HPN	DDX39A	psi-mi:“MI:0914”(association)	0.350
LCN6	HIGD1C	psi-mi:“MI:0914”(association)	0.350
LY86	MAP2K7	psi-mi:“MI:0914”(association)	0.350
MFAP4	PROS1	psi-mi:“MI:0914”(association)	0.350
P2RY8	CIT	psi-mi:“MI:0914”(association)	0.350
RAMP3	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): POLB (Affinity Capture-MS), SLAMF1 (Affinity Capture-MS), ACP5 (Affinity Capture-MS), ACP5 (Affinity Capture-MS), HSD17B7 (Affinity Capture-MS), POLB (Affinity Capture-MS), HSD17B7 (Affinity Capture-MS), HSD17B7 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), SLAMF1 (Affinity Capture-MS), HSD17B7 (Affinity Capture-MS), HSD17B7 (Co-fractionation), PCK2 (Co-fractionation), HSD17B7 (Affinity Capture-MS), ACOX1 (Proximity Label-MS)

ESM2 similar proteins: A0PJE2, A4FUZ6, A6QP05, D2WKD9, F1QWW8, O49213, O66148, O75884, O88736, O88851, P13653, P15904, P23591, P30043, P52556, P56658, P56937, Q06136, Q0IH28, Q0VCN1, Q0VFE7, Q13630, Q2KIJ5, Q3T0R4, Q41578, Q42850, Q566S6, Q59987, Q5R6U1, Q5RBE5, Q5RJY4, Q5ZID0, Q62904, Q66KC4, Q67WR2, Q6GV12, Q6IAN0, Q6P5L8, Q6PAY8, Q7XKF3

Diamond homologs: A0A084B9Z0, A0A097ZPD4, A0A1U8QP15, A6QP05, A7AZH2, E1ACR0, O88736, P56937, A0A0S2CGD3, A0A1V0QS34, A0A4P8GEE8, B8M9K8, G4MVZ5, G4N292, O74628, P19871, P39884, P48758, P59837, Q0CS96, Q0V6Q2, Q2TPA8, Q3SZD7, Q5R6U1, Q6IAN0, Q9P7B4, W6QCN3, A0A017SEY2, A0A078IS66, A0A078ISJ6, A0A0C6DRT7, A0A1B7YCL6, A0A1V6PAN1, A0A3Q8GLE8, A0A482ND39, A0A823A767, A2RVM0, C8VI80, D7UQ42, D7UTD0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

64 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2245 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:162799797:T:A	W168R	0.993
1:162799797:T:C	W168R	0.993
1:162805448:A:C	S287R	0.987
1:162805450:T:A	S287R	0.987
1:162805450:T:G	S287R	0.987
1:162799900:T:C	L202P	0.985
1:162799885:A:T	K197I	0.984
1:162799905:A:C	S204R	0.983
1:162799907:T:A	S204R	0.983
1:162799907:T:G	S204R	0.983
1:162799886:A:C	K197N	0.977
1:162799886:A:T	K197N	0.977
1:162799806:T:C	S171P	0.970
1:162799803:T:C	S170P	0.969
1:162797895:T:A	N142K	0.966
1:162797895:T:G	N142K	0.966
1:162797903:G:A	G145D	0.965
1:162799882:C:A	S196Y	0.965
1:162797884:T:C	F139L	0.964
1:162797886:T:A	F139L	0.964
1:162797886:T:G	F139L	0.964
1:162799882:C:T	S196F	0.964
1:162805441:A:C	K284N	0.964
1:162805441:A:T	K284N	0.964
1:162799885:A:C	K197T	0.963
1:162799881:T:C	S196P	0.962
1:162792730:G:T	R36M	0.961
1:162799890:G:C	A199P	0.959
1:162796615:T:A	N90K	0.958
1:162796615:T:G	N90K	0.958

dbSNP variants (sampled 300 via entrez): RS1000014964 (1:162802864 G>A), RS1000153960 (1:162796789 T>C), RS1000275827 (1:162790135 A>G), RS1000556097 (1:162803054 TC>T), RS1000860954 (1:162807723 A>G), RS1000917511 (1:162808009 T>C), RS1001153118 (1:162801700 A>G), RS1001530713 (1:162809897 C>A), RS1001583128 (1:162810187 C>T), RS1001834129 (1:162798566 A>G), RS1002010368 (1:162791664 T>C), RS1002359636 (1:162791436 T>C), RS1002470676 (1:162801176 A>C,G), RS1003214282 (1:162811549 A>G), RS1003366244 (1:162806000 G>T)

Disease associations

OMIM: gene MIM:606756 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5999 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.94	IC50	116	nM	CHEMBL1078003
6.72	IC50	189	nM	CHEMBL1080041
6.71	IC50	195	nM	CHEMBL1079512

PubChem BioAssay actives

3 with measured affinity, of 330 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1R,3aS,3bR,5aR,9aR,9bS,11aS)-3’,3’,6,9a,11a-pentamethylspiro[2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1,6’-oxane]-2’,7-dione	468990: Inhibition of human 17beta-HSD7 expressed in HEK293 cells assessed as inhibition of reduction of [14C]estrone into [14C]estradiol after 7 hrs	ic50	0.1160	uM
(1S,3aS,3bR,5aR,9aR,9bS,11aS)-1-[heptyl(methyl)amino]-6,9a,11a-trimethyl-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-7-one	468990: Inhibition of human 17beta-HSD7 expressed in HEK293 cells assessed as inhibition of reduction of [14C]estrone into [14C]estradiol after 7 hrs	ic50	0.1890	uM
N-[(3aS,3bR,5aR,9aR,9bS,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-N-decylformamide	468990: Inhibition of human 17beta-HSD7 expressed in HEK293 cells assessed as inhibition of reduction of [14C]estrone into [14C]estradiol after 7 hrs	ic50	0.1950	uM

CTD chemical–gene interactions

75 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, increases expression, affects expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
Cisplatin	affects cotreatment, increases expression	2
Estradiol	decreases expression, affects metabolic processing, increases chemical synthesis	2
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	2
afuresertib	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
FR900359	affects phosphorylation	1
bufotalin	decreases expression	1
methylmercuric chloride	affects reaction, increases expression	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	decreases expression	1
dodecyldimethylamine oxide	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases methylation, increases expression, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
fipronil	increases expression	1
tebuconazole	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
epoxiconazole	increases expression	1
K 7174	decreases expression	1
obeticholic acid	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1106724	Binding	Inhibition of human 17beta-HSD7 expressed in HEK293 cells assessed as inhibition of reduction of [14C]estrone into [14C]estradiol at 0.3 uM after 7 hrs	Potent and selective steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 7, an enzyme that catalyzes the reduction of the key hormones estrone and dihydrotestosterone. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.