HSD17B4

Summary

HSD17B4 (hydroxysteroid 17-beta dehydrogenase 4, HGNC:5213) is a protein-coding gene on chromosome 5q23.1, encoding Peroxisomal multifunctional enzyme type 2 (P51659). Bifunctional enzyme acting on the peroxisomal fatty acid beta-oxidation pathway.

The protein encoded by this gene is a bifunctional enzyme that is involved in the peroxisomal beta-oxidation pathway for fatty acids. It also acts as a catalyst for the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids. Defects in this gene that affect the peroxisomal fatty acid beta-oxidation activity are a cause of D-bifunctional protein deficiency (DBPD). An apparent pseudogene of this gene is present on chromosome 8. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 3295 — RefSeq curated summary.

At a glance

• Gene–disease (curated): d-bifunctional protein deficiency (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 27
• Clinical variants (ClinVar): 1,532 total — 73 pathogenic, 172 likely-pathogenic
• Phenotypes (HPO): 81
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000414

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5213
Approved symbol	HSD17B4
Name	hydroxysteroid 17-beta dehydrogenase 4
Location	5q23.1
Locus type	gene with protein product
Status	Approved
Aliases	MFE-2, DBP, SDR8C1
Ensembl gene	ENSG00000133835
Ensembl biotype	protein_coding
OMIM	601860
Entrez	3295

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 20 retained_intron, 17 nonsense_mediated_decay, 11 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000414835, ENST00000442060, ENST00000503168, ENST00000503310, ENST00000507353, ENST00000507695, ENST00000508750, ENST00000509514, ENST00000509606, ENST00000509951, ENST00000510025, ENST00000511186, ENST00000512029, ENST00000512644, ENST00000512841, ENST00000513628, ENST00000515235, ENST00000515320, ENST00000518349, ENST00000519184, ENST00000520216, ENST00000520244, ENST00000522415, ENST00000643250, ENST00000643897, ENST00000644146, ENST00000645099, ENST00000645702, ENST00000645832, ENST00000646058, ENST00000646355, ENST00000646554, ENST00000646590, ENST00000647335, ENST00000647342, ENST00000682445, ENST00000682531, ENST00000682626, ENST00000682996, ENST00000683265, ENST00000683335, ENST00000683371, ENST00000683372, ENST00000683390, ENST00000683476, ENST00000683549, ENST00000683936, ENST00000683974, ENST00000683996, ENST00000684131, ENST00000684160, ENST00000684214, ENST00000896450

RefSeq mRNA: 12 — MANE Select: NM_000414 NM_000414, NM_001199291, NM_001199292, NM_001292027, NM_001292028, NM_001374497, NM_001374498, NM_001374499, NM_001374500, NM_001374501, NM_001374502, NM_001374503

CCDS: CCDS4126, CCDS56378, CCDS56379, CCDS93762, CCDS93763, CCDS93764

Canonical transcript exons

ENST00000510025 — 24 exons

Exon	Start	End
ENSE00003460234	119531266	119531404
ENSE00003466335	119499317	119499553
ENSE00003514934	119493818	119493946
ENSE00003518313	119475706	119475727
ENSE00003524059	119525216	119525285
ENSE00003548867	119514981	119515046
ENSE00003552085	119477417	119477501
ENSE00003560761	119506818	119506889
ENSE00003561519	119492100	119492124
ENSE00003571451	119478834	119479021
ENSE00003574208	119525917	119526023
ENSE00003576557	119502041	119502092
ENSE00003610183	119536423	119536550
ENSE00003611081	119474401	119474460
ENSE00003612369	119489192	119489283
ENSE00003624601	119473908	119474015
ENSE00003629070	119475824	119475870
ENSE00003637583	119529894	119529980
ENSE00003642952	119527133	119527219
ENSE00003644557	119509141	119509244
ENSE00003663755	119496543	119496646
ENSE00003668263	119456315	119456368
ENSE00003899946	119452497	119452633
ENSE00003900400	119541905	119542332

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 96.7347 / max 1047.8138, expressed in 1826 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58147	89.9189	1826
58146	3.3337	1386
58149	1.0722	502
58148	0.8315	268
58154	0.6676	75
58150	0.5490	224
58155	0.2292	70
58153	0.1325	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.29	gold quality
right lobe of liver	UBERON:0001114	99.26	gold quality
left lobe of thyroid gland	UBERON:0001120	99.21	gold quality
thyroid gland	UBERON:0002046	99.14	gold quality
corpus callosum	UBERON:0002336	99.11	gold quality
liver	UBERON:0002107	98.91	gold quality
medial globus pallidus	UBERON:0002477	98.91	gold quality
right adrenal gland cortex	UBERON:0035827	98.89	gold quality
right adrenal gland	UBERON:0001233	98.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.88	gold quality
body of pancreas	UBERON:0001150	98.83	gold quality
left adrenal gland	UBERON:0001234	98.79	gold quality
left adrenal gland cortex	UBERON:0035825	98.77	gold quality
adrenal cortex	UBERON:0001235	98.75	gold quality
globus pallidus	UBERON:0001875	98.73	gold quality
seminal vesicle	UBERON:0000998	98.70	gold quality
calcaneal tendon	UBERON:0003701	98.67	gold quality
adrenal gland	UBERON:0002369	98.66	gold quality
spinal cord	UBERON:0002240	98.65	gold quality
mucosa of transverse colon	UBERON:0004991	98.62	gold quality
jejunal mucosa	UBERON:0000399	98.51	gold quality
substantia nigra	UBERON:0002038	98.39	gold quality
right lung	UBERON:0002167	98.39	gold quality
colonic epithelium	UBERON:0000397	98.38	gold quality
pancreas	UBERON:0001264	98.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.34	gold quality
ventricular zone	UBERON:0003053	98.34	gold quality
adenohypophysis	UBERON:0002196	98.31	gold quality
midbrain	UBERON:0001891	98.27	gold quality
lateral globus pallidus	UBERON:0002476	98.24	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	6.92
E-MTAB-6379	no	411.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, SP1

miRNA regulators (miRDB)

27 targeting HSD17B4, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 24)

• crystal structure of 2-enoyl-CoA hydratase 2 (PMID:15644212)
• Deficiency of this enzyme in man causes a severe developmental syndrome with abnormalities in several organs but in particular in the brain, leading to death within the first year of life. (PMID:16766224)
• HSD17B4 mRNA is expressed in human skin, at similar levels in men and women. HSD17B4 levels are not altered by topical 17-beta-estradiol treatment. (PMID:18794456)
• HSD17B4 is not only associated with the presence of prostate cancer, but is also a significant independent predictor of poor patient outcome. (PMID:19100308)
• rs11205 in HSD17B4 was associated with testicular germ cell tumor. Risk doubled per copy of the minor A allele. Homozygosity of this allele quadrupled the risk vs. homozygous major G allele. The risk was increased both for seminoma & nonseminoma. (PMID:19776291)
• MFE2 anchors its substrate around the region from Trp(249) to Arg(251) and positions the substrate along the hydrophobic cavity in the proper direction toward the catalytic center (PMID:20566640)
• Perrault syndrome and DBP deficiency overlap clinically and Perrault syndrome is genetically heterogeneous. (PMID:20673864)
• The diagnosis of a type III DBPD with a missense mutation (T15A) in the HSD17B4 gene, coding for D-bifunctional protein (DBP), could be established. (PMID:20949532)
• Epistasis between the HSD17B4 and thyroglobulin polymorphisms is associated with premature ovarian failure. A haplotype in the HSD17B4 gene was identified that was significantly associated with resistance to POF (PMID:22265031)
• Specific combination of compound heterozygous mutations in 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency. (PMID:23181892)
• Structural MFE-2 instability is the molecular basis of D-bifunctional protein deficiency type III. (PMID:23308274)
• Molecular models of domain structure of MFE-2 from human, C. elegans, and Drosophila melanogaster lend support to possible structural role of MFE-2 domains including SCP-2L (sterol carrier protein 2-like) domain in human and C. elegans proteins. (PMID:23313254)
• Results show that HSD17B4 is highly expressed in hepatocellular carcinoma (HCC) cells and activated NF-kappaB co-localized with the NF-kappaB-responsive element of HSD17B4 suggesting that HSD17B4 plays an important role in aggravated HCC progression. (PMID:25448063)
• ere we present eight families affected by Perrault syndrome. In five families we identified novel or previously reported variants in HSD17B4, LARS2, CLPP and C10orf2 (PMID:26970254)
• we identified that methylation of the promoter CpG island of HSD17B4 was associated with the pathological complete response of HER2-positive breast cancer to trastuzumab and chemotherapy with a specificity of 79% (PMID:28186977)
• This study reveals a crosstalk between acetylation and chaperone-mediated autophagy degradation in HSD17B4 regulation. (PMID:28296597)
• Our findings supported that HSD17B4 was one of the genes contributing to Perrault syndrome in this consanguineous Chinese Han family. (PMID:28830375)
• In HEK293 cells, the D-bifunctional protein (HSD17B4) and the peroxisomal ABC transporter ABCD3 are essential in peroxisomal oxidation of lauric and palmitic acid. (PMID:30540494)
• HSD17B4 overexpression increased STAT3 activation. (PMID:30747222)
• Acetylation-mediated degradation of HSD17B4 regulates the progression of prostate cancer. (PMID:32678070)
• Rapid whole-genome sequencing identifies a homozygous novel variant, His540Arg, in HSD17B4 resulting in D-bifunctional protein deficiency disorder diagnosis. (PMID:33115767)
• The Peroxisomal Localization of Hsd17b4 Is Regulated by Its Interaction with Phosphatidylserine. (PMID:33935042)
• HSD17B4 methylation enhances glucose dependence of BT-474 breast cancer cells and increases lapatinib sensitivity. (PMID:37378696)
• Exome sequencing reveals pathogenic mutations in the LARS2 and HSD17B4 genes associated with Perrault syndrome and D-bifunctional protein deficiency in Moroccan families. (PMID:39052101)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsd17b4	ENSDARG00000101239
mus_musculus	Hsd17b4	ENSMUSG00000024507
rattus_norvegicus	Hsd17b4	ENSRNOG00000015840
drosophila_melanogaster	Mfe2	FBGN0030731
caenorhabditis_elegans		WBGENE00000991

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSDL1 (ENSG00000103160), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B7 (ENSG00000132196), 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

Peroxisomal multifunctional enzyme type 2 — P51659 (reviewed: P51659)

Alternative names: 17-beta-hydroxysteroid dehydrogenase 4, D-bifunctional protein, Multifunctional protein 2, Short chain dehydrogenase/reductase family 8C member 1

All UniProt accessions (23): A0A0S2Z460, A0A0S2Z4J1, A0A2R8Y674, A0A2R8Y7L2, A0A2R8Y7W2, A0A2R8YCN2, A0A2R8YD50, A0A2R8YDT8, A0A2R8YEG2, A0A2R8YF39, A0A2R8YF45, A0A804HIG8, A0A804HIR1, A0A804HK65, A0A804HK88, A0A804HKB5, A0A804HKT2, P51659, A0A804HKU2, A0A804HLJ0, E7EPL9, E7ER27, E7ET17

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme acting on the peroxisomal fatty acid beta-oxidation pathway. Catalyzes two of the four reactions in fatty acid degradation: hydration of 2-enoyl-CoA (trans-2-enoyl-CoA) to produce (3R)-3-hydroxyacyl-CoA, and dehydrogenation of (3R)-3-hydroxyacyl-CoA to produce 3-ketoacyl-CoA (3-oxoacyl-CoA), which is further metabolized by SCPx. Can use straight-chain and branched-chain fatty acids, as well as bile acid intermediates as substrates.

Subunit / interactions. Homodimer.

Subcellular location. Peroxisome.

Tissue specificity. Present in many tissues with highest concentrations in liver, heart, prostate and testis.

Disease relevance. D-bifunctional protein deficiency (DBPD) [MIM:261515] Disorder of peroxisomal fatty acid beta-oxidation. The disease is caused by variants affecting the gene represented in this entry. Perrault syndrome 1 (PRLTS1) [MIM:233400] An autosomal recessive, sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild intellectual disability and cerebellar and peripheral nervous system involvement. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; fatty acid beta-oxidation.

Miscellaneous. The protein is found both as a full-length peptide and in a cleaved version.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P51659-1	1	yes
P51659-2	2
P51659-3	3

RefSeq proteins (12): NP_000405, NP_001186220, NP_001186221, NP_001278956, NP_001278957, NP_001361426, NP_001361427, NP_001361428, NP_001361429, NP_001361430, NP_001361431, NP_001361432 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR002539	MaoC-like_dom	Domain
IPR003033	SCP2_sterol-bd_dom	Domain
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR029069	HotDog_dom_sf	Homologous_superfamily
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR036527	SCP2_sterol-bd_dom_sf	Homologous_superfamily
IPR051687	Peroxisomal_Beta-Oxidation	Family
IPR054357	MFE-2_N	Domain
IPR057326	KR_dom	Domain

Pfam: PF00106, PF01575, PF02036, PF22622

Enzyme classification (BRENDA):

• EC 4.2.1.119 — enoyl-CoA hydratase 2 (BRENDA: 15 organisms, 79 substrates, 8 inhibitors, 40 Km, 13 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
CROTONYL-COA	0.024–60	6
(2E)-2-DECENOYL-COA	0.0081–0.0131	4
DEC-2-ENOYL-COA	0.007–0.042	4
DODEC-2-ENOYL-COA	0.005–0.043	4
(2E)-OCT-2-ENOYL-COA	0.021–0.076	3
HEXENOYL-COA	0.018–0.102	3
(2E)-DECENOYL-COA	0.0011–4.6	2
(2E)-HEXENOYL-COA	0.0667–8.7	2
HEX-2-ENOYL-COA	0.015–0.034	2
OCT-2-ENOYL-COA	0.009–0.05	2
(2E)-BUTENOYL-COA	0.0853	1
2-TRANS-BUTENOYL-COA	0.11	1
2-TRANS-DECENOYL-COA	0.0095	1
PENT-2-ENOYL-COA	0.036	1
TETRADEC-2-ENOYL-COA	0.005	1

Catalyzed reactions (Rhea), 12 shown:

• (24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-cholestan-26-oyl-CoA = (24E)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-en-26-oyl-CoA + H2O (RHEA:18933)
• a (3R)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O (RHEA:26526)
• a (3R)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + NADH + H(+) (RHEA:32711)
• (3R)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O (RHEA:39159)
• (2E)-octenoyl-CoA + H2O = (3R)-hydroxyoctanoyl-CoA (RHEA:40187)
• (3R)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + NADH + H(+) (RHEA:40191)
• (3R)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA + NADH + H(+) (RHEA:40243)
• (2E)-hexadecenedioyl-CoA + H2O = (3R)-hydroxyhexadecanedioyl-CoA (RHEA:40255)
• (3R)-hydroxyhexadecanedioyl-CoA + NAD(+) = 3-oxohexadecanedioyl-CoA + NADH + H(+) (RHEA:40263)
• (3R)-3-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + NADH + H(+) (RHEA:45832)
• (3R)-3-hydroxydecanoyl-CoA = (2E)-decenoyl-CoA + H2O (RHEA:45992)
• (24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-cholestan-26-oyl-CoA + NAD(+) = 3alpha,7alpha,12alpha-trihydroxy-24-oxo-5beta-cholestan-26-oyl-CoA + NADH + H(+) (RHEA:47088)

UniProt features (131 total): helix 34, strand 21, modified residue 18, binding site 15, sequence variant 15, mutagenesis site 12, turn 4, chain 3, domain 2, splice variant 2, region of interest 2, short sequence motif 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8AF3	X-RAY DIFFRACTION	1.52
1IKT	X-RAY DIFFRACTION	1.75
6Z1X	X-RAY DIFFRACTION	2.09
1ZBQ	X-RAY DIFFRACTION	2.19
6Z1W	X-RAY DIFFRACTION	2.48
8AF2	X-RAY DIFFRACTION	2.51
1S9C	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51659-F1	89.65	0.68

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): 164 (proton acceptor)

Ligand- & substrate-binding residues (15): 21; 40; 75–76; 99; 151; 164–168; 196–199; 406–407; 435; 510–515; 533; 563 …

Post-translational modifications (18): 46, 46, 52, 57, 68, 84, 265, 275, 304, 309, 356, 424, 565, 579, 663, 669, 707, 725

Mutagenesis-validated functional residues (12):

Position	Phenotype
347	no hydratase activity.
366	no hydratase activity.
370	no effect.
406	no effect.
408	no effect.
410	no effect.
490	no effect.
505	completely inactive.
510	no hydratase activity.
515	completely inactive.
517	no effect.
532	no effect.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-2046106	alpha-linolenic acid (ALA) metabolism
R-HSA-389887	Beta-oxidation of pristanoyl-CoA
R-HSA-390247	Beta-oxidation of very long chain fatty acids
R-HSA-9033241	Peroxisomal protein import
R-HSA-9033500	TYSND1 cleaves peroxisomal proteins

MSigDB gene sets: 716 (showing top): RNGTGGGC_UNKNOWN, GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, WANG_CLIM2_TARGETS_UP, MYOGENIN_Q6, GRUETZMANN_PANCREATIC_CANCER_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, RORA1_01, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_SERTOLI_CELL_DEVELOPMENT

GO Biological Process (15): very long-chain fatty acid metabolic process (GO:0000038), osteoblast differentiation (GO:0001649), fatty acid beta-oxidation (GO:0006635), unsaturated fatty acid biosynthetic process (GO:0006636), androgen metabolic process (GO:0008209), estrogen metabolic process (GO:0008210), fatty acid beta-oxidation using acyl-CoA oxidase (GO:0033540), alpha-linolenic acid metabolic process (GO:0036109), very long-chain fatty-acyl-CoA metabolic process (GO:0036111), medium-chain fatty-acyl-CoA metabolic process (GO:0036112), long-chain fatty acid biosynthetic process (GO:0042759), Sertoli cell development (GO:0060009), fatty acid derivative biosynthetic process (GO:1901570), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (11): (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity (GO:0003857), enoyl-CoA hydratase activity (GO:0004300), estradiol 17-beta-dehydrogenase [NAD(P)+] activity (GO:0004303), isomerase activity (GO:0016853), 3-hydroxyacyl-CoA dehydratase activity (GO:0018812), 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity (GO:0033989), protein homodimerization activity (GO:0042803), 17-beta-hydroxysteroid dehydrogenase (NAD+) activity (GO:0044594), (3R)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity (GO:0106386), oxidoreductase activity (GO:0016491), lyase activity (GO:0016829)

GO Cellular Component (6): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Peroxisomal lipid metabolism	2
Synthesis of bile acids and bile salts	1
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1
Protein localization	1
Peroxisomal protein import	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	3
cellular anatomical structure	3
fatty acid biosynthetic process	2
unsaturated fatty acid metabolic process	2
steroid metabolic process	2
hormone metabolic process	2
long-chain fatty acid metabolic process	2
fatty-acyl-CoA metabolic process	2
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
hydro-lyase activity	2
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
peroxisome	2
fatty acid metabolic process	1
ossification	1
cell differentiation	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
fatty acid beta-oxidation	1
olefinic compound metabolic process	1
epithelial cell development	1
developmental process involved in reproduction	1
Sertoli cell differentiation	1
lipid biosynthetic process	1
fatty acid derivative metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
enoyl-CoA hydratase activity	1
identical protein binding	1
protein dimerization activity	1
microbody	1
microbody membrane	1
microbody lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2071 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSD17B4	ACOX1	Q15067	969
HSD17B4	EHHADH	Q08426	966
HSD17B4	HSD17B3	P37058	953
HSD17B4	HSD17B2	P37059	928
HSD17B4	HSD17B1	P14061	928
HSD17B4	DHRS11	Q6UWP2	922
HSD17B4	ACAA1	P09110	920
HSD17B4	ECHS1	P30084	881
HSD17B4	ECH1	Q13011	868
HSD17B4	HADHB	P55084	862
HSD17B4	ACOX2	Q99424	845
HSD17B4	ACOX3	O15254	830
HSD17B4	HADH	Q16836	807
HSD17B4	GNPAT	O15228	780
HSD17B4	AIMP2	Q13155	742

IntAct

125 interactions, top by confidence:

A	B	Type	Score
FOS	JUN	psi-mi:“MI:0914”(association)	0.980
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PLEK	CAVIN2	psi-mi:“MI:0914”(association)	0.560
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	BIN1	psi-mi:“MI:0914”(association)	0.460
HSD17B4	HSD17B4	psi-mi:“MI:0407”(direct interaction)	0.440
CAT	NUDT19	psi-mi:“MI:0914”(association)	0.420
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
LTK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
HSD17B4	NDRG1	psi-mi:“MI:0915”(physical association)	0.400
DHX16	HSD17B4	psi-mi:“MI:0915”(physical association)	0.400
SCP2	HSD17B4	psi-mi:“MI:0915”(physical association)	0.400
COL6A1	HSD17B4	psi-mi:“MI:0915”(physical association)	0.400
TRIM59	HSD17B4	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
HSD17B4	CDK7	psi-mi:“MI:0915”(physical association)	0.370
HSD17B4	MAPK8	psi-mi:“MI:0915”(physical association)	0.370
BAK1	HSD17B4	psi-mi:“MI:0915”(physical association)	0.370
CASP9	HSD17B4	psi-mi:“MI:0915”(physical association)	0.370
Nedd1		psi-mi:“MI:0914”(association)	0.350
RACGAP1	STX18	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
Mtx2	NRDC	psi-mi:“MI:0914”(association)	0.350

BioGRID (275): HSD17B4 (Affinity Capture-MS), HSD17B4 (Affinity Capture-MS), HSD17B4 (Co-fractionation), HSD17B4 (Co-fractionation), HSD17B4 (Co-fractionation), HSD17B4 (Affinity Capture-MS), HSD17B4 (Affinity Capture-RNA), HSD17B4 (Proximity Label-MS), HSD17B4 (Affinity Capture-MS), HSD17B4 (Affinity Capture-MS), HSD17B4 (Affinity Capture-MS), HSD17B4 (Affinity Capture-MS), HSD17B4 (Affinity Capture-MS), HSD17B4 (Affinity Capture-MS), HSD17B4 (Affinity Capture-MS)

ESM2 similar proteins: A0A067XNI6, A0A0F7TN06, A0A0F7TN65, A0A0F7TRU0, A0A0S1RUN4, A0A0S2E7W7, A0A0S2E7Z1, A0A0U5CJU2, A0A0U5GHC1, A0A0U5GMR5, A0A0U5HAP0, A0A1L9WLD2, A0A1L9WLD7, A0A2I1C3W8, A0A2I1C3Y3, A0A2I2F2K6, A0A3B1EFQ2, A0A411PQL6, A0A411PQN4, A0A481WP37, A0A4P8DJH6, A0A4P8DJV0, A0A5B8YW48, B7STY1, C7ZC16, C8VQ92, E9F647, I1S6W0, I6NXV7, M1VWN3, M1W851, M1WG89, O52380, P0CU74, P51659, P51660, P51697, P56221, P59766, P59767

Diamond homologs: A0A0D1DNX1, A0A1C8AX29, A0A1U8QK63, B2KWH7, I1S489, M2XHU6, P07149, P34229, P34731, P51659, P51660, Q00706, Q2TXG3, Q5AV07, Q8TGA1, Q8VYI3, Q92215, Q9UUG0, A0A097ZPC9, A0A0F7U1Z1, A0A0H3KNE7, A0A0U5GHD4, A0A1E1FFP5, A0A1Y0BRF8, A0A2I1BSW8, A0A384JQF5, A0A3G9HAL8, A0A455R5K2, A0A6S6QNE4, A0A8D5M6H6, A0QYC2, A4IFA7, A6SSW9, A7IQF2, A7IQH5, B6H061, B6HV34, C1C4R8, C1DMX5, C8WGQ3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	24.5×	2e-04
Peroxisomal protein import	11	18.0×	2e-08
Downstream signal transduction	5	18.0×	1e-03
FCERI mediated MAPK activation	5	16.3×	1e-03
Signaling by SCF-KIT	5	11.7×	7e-03
Signaling by ALK fusions and activated point mutants	6	8.5×	7e-03
PKR-mediated signaling	6	8.0×	7e-03
PIP3 activates AKT signaling	8	5.0×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to reactive oxygen species	6	19.4×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1532 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	73
Likely pathogenic	172
Uncertain significance	385
Likely benign	675
Benign	84

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070670	NM_000414.4(HSD17B4):c.911C>G (p.Ser304Ter)	Pathogenic
1071247	NM_000414.4(HSD17B4):c.1499del (p.Asn500fs)	Pathogenic
1071457	NM_000414.4(HSD17B4):c.1921G>T (p.Glu641Ter)	Pathogenic
1074898	NM_000414.4(HSD17B4):c.1951G>T (p.Glu651Ter)	Pathogenic
1075507	NC_000005.9:g.(?118865579)(118867109_?)del	Pathogenic
1075802	NM_000414.4(HSD17B4):c.421C>T (p.Gln141Ter)	Pathogenic
1252039	NM_000414.4(HSD17B4):c.302+3delinsTGTTGTGATTTTTTAGTGAATTGTGTATTTTAGTGATGTGTGTATAATTTTTTTAAAAAGTATATACTTTCCTCCTTTTACCCTATACAACATTGATTT	Pathogenic
1333681	NM_000414.4(HSD17B4):c.1984del (p.Ala662fs)	Pathogenic
1353412	NM_000414.4(HSD17B4):c.1235_1236del (p.Glu412fs)	Pathogenic
1357638	NM_000414.4(HSD17B4):c.682G>T (p.Glu228Ter)	Pathogenic
1371276	NM_000414.4(HSD17B4):c.439del (p.Ile147fs)	Pathogenic
1404290	NM_000414.4(HSD17B4):c.590_597dup (p.Met200fs)	Pathogenic
1416308	NM_000414.4(HSD17B4):c.1708G>T (p.Gly570Ter)	Pathogenic
1423489	NM_000414.4(HSD17B4):c.1480_1481insGA (p.Thr494fs)	Pathogenic
1448621	NM_000414.4(HSD17B4):c.1954_1970del (p.Trp652fs)	Pathogenic
1452066	NM_000414.4(HSD17B4):c.1230C>G (p.Tyr410Ter)	Pathogenic
1453246	NM_000414.4(HSD17B4):c.657del (p.Pro220fs)	Pathogenic
1454962	NM_000414.4(HSD17B4):c.740T>G (p.Leu247Ter)	Pathogenic
1458501	NM_000414.4(HSD17B4):c.605dup (p.Thr203fs)	Pathogenic
1459060	NM_000414.4(HSD17B4):c.728G>A (p.Trp243Ter)	Pathogenic
1685886	NM_000414.4(HSD17B4):c.532C>T (p.Leu178Phe)	Pathogenic
1994245	NM_000414.4(HSD17B4):c.1986del (p.Lys663fs)	Pathogenic
2013219	NM_000414.4(HSD17B4):c.1956G>A (p.Trp652Ter)	Pathogenic
2032052	NM_000414.4(HSD17B4):c.857del (p.Gln286fs)	Pathogenic
2032538	NM_000414.4(HSD17B4):c.657dup (p.Pro220fs)	Pathogenic
2115984	NM_000414.4(HSD17B4):c.1426_1429del (p.Asp476fs)	Pathogenic
2134953	NM_000414.4(HSD17B4):c.561dup (p.His188fs)	Pathogenic
2228314	NM_000414.4(HSD17B4):c.707T>A (p.Leu236Ter)	Pathogenic
2423041	NC_000005.9:g.(?118837726)(118837797_?)del	Pathogenic
2423043	NC_000005.9:g.(?118827775)(118837807_?)del	Pathogenic

SpliceAI

4586 predictions. Top by Δscore:

Variant	Effect	Δscore
5:119471695:TTTC:T	donor_gain	1.0000
5:119471701:G:GG	donor_gain	1.0000
5:119471710:T:G	donor_gain	1.0000
5:119473898:T:TA	acceptor_gain	1.0000
5:119473901:A:AG	acceptor_gain	1.0000
5:119473902:T:G	acceptor_gain	1.0000
5:119473903:TACA:T	acceptor_loss	1.0000
5:119473906:A:AG	acceptor_gain	1.0000
5:119473906:AGT:A	acceptor_gain	1.0000
5:119473907:G:A	acceptor_loss	1.0000
5:119473907:G:GT	acceptor_gain	1.0000
5:119473907:GT:G	acceptor_gain	1.0000
5:119473907:GTG:G	acceptor_gain	1.0000
5:119473907:GTGA:G	acceptor_gain	1.0000
5:119473907:GTGAA:G	acceptor_gain	1.0000
5:119473993:TGGAA:T	donor_gain	1.0000
5:119474013:ATG:A	donor_loss	1.0000
5:119474016:G:GG	donor_gain	1.0000
5:119474016:GTATG:G	donor_loss	1.0000
5:119474017:T:C	donor_loss	1.0000
5:119474399:A:AG	acceptor_gain	1.0000
5:119474400:G:GG	acceptor_gain	1.0000
5:119474452:G:GT	donor_gain	1.0000
5:119474455:GAA:G	donor_gain	1.0000
5:119474457:A:AG	donor_gain	1.0000
5:119474522:T:G	donor_gain	1.0000
5:119475704:A:AG	acceptor_gain	1.0000
5:119475705:G:GG	acceptor_gain	1.0000
5:119477490:G:GT	donor_gain	1.0000
5:119477490:GAA:G	donor_gain	1.0000

AlphaMissense

4778 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:119475867:T:A	W116R	0.995
5:119475867:T:C	W116R	0.995
5:119478860:G:A	G154E	0.995
5:119525229:G:C	R506P	0.995
5:119525948:T:G	C535W	0.995
5:119527184:T:A	W578R	0.995
5:119527184:T:C	W578R	0.995
5:119478869:G:A	G157D	0.994
5:119478878:G:A	G160D	0.994
5:119478977:C:A	A193D	0.994
5:119493830:G:C	R251P	0.994
5:119478908:G:A	G170D	0.993
5:119531365:T:A	W652R	0.993
5:119531365:T:C	W652R	0.993
5:119473912:T:A	N39K	0.992
5:119473912:T:G	N39K	0.992
5:119475719:C:A	N98K	0.992
5:119475719:C:G	N98K	0.992
5:119475724:C:A	A100D	0.992
5:119477498:G:A	G144E	0.992
5:119478889:T:C	Y164H	0.992
5:119478917:G:A	G173D	0.992
5:119527186:G:C	W578C	0.992
5:119527186:G:T	W578C	0.992
5:119456321:G:A	G22D	0.991
5:119456363:T:A	V36D	0.991
5:119525240:G:C	D510H	0.991
5:119475715:T:A	V97D	0.990
5:119475722:T:A	N99K	0.990
5:119475722:T:G	N99K	0.990

dbSNP variants (sampled 300 via entrez): RS1000036445 (5:119479552 A>G,T), RS1000038498 (5:119510828 T>C), RS1000082445 (5:119520707 T>C), RS1000115027 (5:119520969 G>A), RS1000138735 (5:119472136 T>A,G), RS1000203152 (5:119457580 A>G,T), RS1000218176 (5:119458441 C>T), RS1000237410 (5:119531944 A>G), RS1000265696 (5:119489419 C>T), RS1000341121 (5:119538949 G>C), RS1000345657 (5:119500786 G>A,C), RS1000440303 (5:119532249 T>G), RS1000454043 (5:119453182 T>C,G), RS1000519596 (5:119457676 A>G,T), RS1000545859 (5:119500589 CT>C)

Disease associations

OMIM: gene MIM:601860 | disease phenotypes: MIM:261515, MIM:233400, MIM:213000

GenCC curated gene-disease

Disease	Classification	Inheritance
d-bifunctional protein deficiency	Definitive	Autosomal recessive
Perrault syndrome	Definitive	Autosomal recessive
Perrault syndrome 1	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
d-bifunctional protein deficiency	Definitive	AR
Perrault syndrome	Definitive	AR

Mondo (5): d-bifunctional protein deficiency (MONDO:0009855), Perrault syndrome (MONDO:0017312), Perrault syndrome 1 (MONDO:0009300), isolated cerebellar hypoplasia/agenesis (MONDO:0008939), congenital nervous system disorder (MONDO:0002320)

Orphanet (6): Perrault syndrome (Orphanet:2855), Bifunctional enzyme deficiency (Orphanet:300), Perrault syndrome type 1 (Orphanet:642945), Rare genetic deafness (Orphanet:96210), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246)

HPO phenotypes

81 total (30 of 81 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000107	Renal cyst
HP:0000133	Gonadal dysgenesis
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000270	Delayed cranial suture closure
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000550	Undetectable electroretinogram
HP:0000572	Visual loss
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000762	Decreased nerve conduction velocity
HP:0000767	Pectus excavatum
HP:0000786	Primary amenorrhea
HP:0000837	Increased circulating gonadotropin level
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001171	Split hand
HP:0001250	Seizure

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST002379_3	Pyoderma gangrenosum in inflammatory bowel disease	7.000000e-06
GCST002782_39	Waist-to-hip ratio adjusted for body mass index	7.000000e-12
GCST002782_40	Waist-to-hip ratio adjusted for body mass index	4.000000e-07
GCST002782_41	Waist-to-hip ratio adjusted for body mass index	4.000000e-12
GCST002782_42	Waist-to-hip ratio adjusted for body mass index	2.000000e-07
GCST004031_3	QT interval (sulfonylurea treatment interaction)	4.000000e-07
GCST004032_1	JT interval (sulfonylurea treatment interaction)	5.000000e-07
GCST004064_55	Waist-hip ratio	3.000000e-08
GCST004505_1	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-09
GCST005956_40	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005958_18	Waist-to-hip ratio adjusted for BMI (age >50)	9.000000e-07
GCST005962_27	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	9.000000e-09
GCST006195_84	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-09
GCST009798_70	Asthma	3.000000e-11
GCST90020025_1073	Waist-to-hip ratio adjusted for BMI	2.000000e-11
GCST90020025_1075	Waist-to-hip ratio adjusted for BMI	5.000000e-11
GCST90020025_676	Waist-to-hip ratio adjusted for BMI	6.000000e-11
GCST90020025_677	Waist-to-hip ratio adjusted for BMI	5.000000e-09
GCST90020026_341	Hip index	2.000000e-09
GCST90020026_343	Hip index	9.000000e-11
GCST90020026_344	Hip index	3.000000e-10
GCST90020027_904	Waist-hip index	5.000000e-11
GCST90020027_905	Waist-hip index	2.000000e-11
GCST90020027_906	Waist-hip index	6.000000e-11
GCST90020027_907	Waist-hip index	3.000000e-08
GCST90020028_1111	Hip circumference adjusted for BMI	1.000000e-09
GCST90020028_1112	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0006835	pyoderma gangrenosum
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004682	QT interval
EFO:0007922	response to sulfonylurea
EFO:0007885	JT interval
EFO:0004343	waist-hip ratio
EFO:0004318	smoking behavior
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562568	Cerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5814 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 11 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.07	Kd	849.6	nM	CHEMBL5653589
6.07	ED50	849.6	nM	CHEMBL5653589
5.87	Kd	1363	nM	CHEMBL3752910
5.87	ED50	1363	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 35 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148544: Binding affinity to human HSD17B4 incubated for 45 mins by Kinobead based pull down assay	kd	0.8496	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148544: Binding affinity to human HSD17B4 incubated for 45 mins by Kinobead based pull down assay	kd	1.3632	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Colforsin	affects reaction, decreases reaction, increases expression, affects expression, increases reaction	3
bisphenol A	decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	increases oxidation, affects expression, affects cotreatment, increases abundance, increases expression	2
Flame Retardants	increases expression, decreases expression	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance, affects expression	2
Valproic Acid	affects expression, affects reaction	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
4-nitro-3-cresol	affects cotreatment, increases expression	1
2,4-dibromophenol	increases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
bisphenol A diglycidyl ether	affects response to substance	1
perfluorooctanoic acid	increases expression	1
2,4,6-trichlorophenol	decreases expression	1
periodate-oxidized adenosine	affects expression	1
2-bromophenol	increases expression	1
3,3’,4,4’,5,5’-hexabromobiphenyl	increases expression	1
3,3’,4,4’-tetrabromobiphenyl	increases expression	1
2,6-dibromophenol	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
2,3,7,8-tetrabromodibenzo-4-dioxin	decreases expression	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

11 unique, capped per target: 10 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1919081	Binding	Inhibition of human 17beta-HSD4 expressed in Escherichia coli assessed as radiolabeled E1 formation using [6,7-3H]E2 as substrate at 1 uM by scintillation counting	Introduction of an electron withdrawing group on the hydroxyphenylnaphthol scaffold improves the potency of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors. — J Med Chem
CHEMBL3562041	Functional	PubChem BioAssay. Extended Characterization of HPGD Inhibitors: Counterscreen Against HSD17b4. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_BW65	GM13263	Finite cell line	Male
CVCL_BW66	GM13264	Finite cell line	Female
CVCL_D1N8	Abcam K-562 HSD17B4 KO	Cancer cell line	Female
CVCL_D2JT	Abcam Raji HSD17B4 KO	Cancer cell line	Male
CVCL_SR69	HAP1 HSD17B4 (-) 1	Cancer cell line	Male
CVCL_SR70	HAP1 HSD17B4 (-) 2	Cancer cell line	Male
CVCL_UQ74	Abcam Jurkat HSD17B4 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT00004442	Not specified	TERMINATED	Study of Bile Acids in Patients With Peroxisomal Disorders
NCT01668186	Not specified	RECRUITING	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)