HSD17B8

Summary

HSD17B8 (hydroxysteroid 17-beta dehydrogenase 8, HGNC:3554) is a protein-coding gene on chromosome 6p21.32, encoding (3R)-3-hydroxyacyl-CoA dehydrogenase (Q92506). Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS).

In mice, the Ke6 protein is a 17-beta-hydroxysteroid dehydrogenase that can regulate the concentration of biologically active estrogens and androgens. It is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. The protein encoded by this gene is similar to Ke6 and is a member of the short-chain dehydrogenase superfamily. An alternatively spliced transcript of this gene has been detected, but the full-length nature of this variant has not been determined.

Source: NCBI Gene 7923 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_014234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3554
Approved symbol	HSD17B8
Name	hydroxysteroid 17-beta dehydrogenase 8
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	HKE6, D6S2245E, RING2, KE6, H2-KE6, SDR30C1
Ensembl gene	ENSG00000204228
Ensembl biotype	protein_coding
OMIM	601417
Entrez	7923

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374662, ENST00000469186, ENST00000859229, ENST00000859230, ENST00000859231, ENST00000859232, ENST00000859233, ENST00000859234, ENST00000927257

RefSeq mRNA: 1 — MANE Select: NM_014234 NM_014234

CCDS: CCDS4769

Canonical transcript exons

ENST00000230236 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 95.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3420 / max 93.2164, expressed in 1753 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67251	7.6296	1542
67252	1.8037	839
67249	1.4817	896
67250	0.4270	238

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	95.61	gold quality
right lobe of liver	UBERON:0001114	94.21	gold quality
right uterine tube	UBERON:0001302	92.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.65	gold quality
liver	UBERON:0002107	92.53	gold quality
mucosa of transverse colon	UBERON:0004991	92.03	gold quality
right adrenal gland	UBERON:0001233	91.92	gold quality
adult mammalian kidney	UBERON:0000082	91.87	gold quality
right adrenal gland cortex	UBERON:0035827	91.66	gold quality
pancreas	UBERON:0001264	91.35	gold quality
left lobe of thyroid gland	UBERON:0001120	91.33	gold quality
right lobe of thyroid gland	UBERON:0001119	91.31	gold quality
thyroid gland	UBERON:0002046	90.99	gold quality
left adrenal gland cortex	UBERON:0035825	90.83	gold quality
left adrenal gland	UBERON:0001234	90.57	gold quality
skin of abdomen	UBERON:0001416	90.04	gold quality
esophagus mucosa	UBERON:0002469	89.55	gold quality
zone of skin	UBERON:0000014	89.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.27	gold quality
kidney	UBERON:0002113	89.13	gold quality
metanephros cortex	UBERON:0010533	89.09	gold quality
skin of leg	UBERON:0001511	89.08	gold quality
adrenal gland	UBERON:0002369	88.93	gold quality
apex of heart	UBERON:0002098	88.91	gold quality
cortex of kidney	UBERON:0001225	88.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.66	gold quality
saliva-secreting gland	UBERON:0001044	88.59	gold quality
minor salivary gland	UBERON:0001830	88.39	gold quality
duodenum	UBERON:0002114	88.15	gold quality
lower esophagus mucosa	UBERON:0035834	88.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AR, ARNT, CEBPB, ESR1, ESR2, STAT5B

miRNA regulators (miRDB)

32 targeting HSD17B8, 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-4692	100.00	67.32	2066
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-890	97.47	68.67	982
HSA-MIR-1292-5P	96.74	62.14	238
HSA-MIR-1178-5P	95.83	64.12	504
HSA-MIR-6891-3P	95.80	65.76	683

Literature-anchored findings (GeneRIF, showing 7)

• The results indicate that aromatase, 17beta-HSD type 7 and 17beta-HSD type 12, but not 17beta-HSD type 1, are commonly expressed in human breast cancer. (PMID:16930994)
• transcription in liver is regulated by C/EBPbeta (PMID:17583490)
• Expression of the human Ke 6 gene, 17beta-hydroxysteroid dehydrogenase type 8, in E. coli and the substrate specificity of the expressed protein were examined. The tissue distribution of mRNA expression of the human Ke 6 gene was also studied. (PMID:17978863)
• HSD17B8 mRNA is expressed in human skin, at lower levels in face vs arm or hip. HSD17B8 levels are not altered by topical 17-beta-estradiol treatment. (PMID:18794456)
• ERalpha is involved in the transcriptional regulation of HSD17B8 gene in response to E2 through its interaction with C/EBPbeta. (PMID:18852215)
• Hs17beta-HSD8 and HsCBR4 show a strong genetic interaction in vivo in yeast, where, only if they are expressed together, they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells. (PMID:19571038)
• The Obesity-Related Metabolic Gene HSD17B8 Protects Against Breast Cancer: High RNA/Protein Expression Means a Better Prognosis. (PMID:35184130)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsd17b8	ENSDARG00000001169
mus_musculus	Hsd17b8	ENSMUSG00000073422
rattus_norvegicus	Hsd17b8	ENSRNOG00000000466
drosophila_melanogaster	CG3603	FBGN0029648

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), 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)

Protein

Protein identifiers

(3R)-3-hydroxyacyl-CoA dehydrogenase — Q92506 (reviewed: Q92506)

Alternative names: 17-beta-hydroxysteroid dehydrogenase 8, 3-ketoacyl-[acyl-carrier-protein] reductase alpha subunit, 3-oxoacyl-[acyl-carrier-protein] reductase, Estradiol 17-beta-dehydrogenase 8, Protein Ke6, Short chain dehydrogenase/reductase family 30C member 1, Testosterone 17-beta-dehydrogenase 8

All UniProt accessions (2): A0A1U9X7U3, Q92506

UniProt curated annotations — full annotation on UniProt →

Function. Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex that acts as a scaffold protein required for the stability of carbonyl reductase type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-ACP reductase activity, thereby participating in mitochondrial fatty acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain length preference; this enzymatic activity is not needed for the KAR function. Prefers (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA and displays enzymatic activity only in the presence of NAD(+). Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they constitute an alternative route to the auxiliary enzyme pathways for the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters. NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol (17beta-estradiol or E2). Has very low activity towards testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one). Primarily an oxidative enzyme, it can switch to a reductive mode determined in the appropriate physiologic milieu and catalyze the reduction of estrone (E1) to form biologically active 17beta-estradiol.

Subunit / interactions. Heterotetramer with CBR4; contains two molecules of HSD17B8 and CBR4.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Widely expressed, particularly abundant in prostate, placenta and kidney. Expressed at protein level in various tissues like brain, cerebellum, heart, lung, kidney, ovary, testis, adrenals and prostate.

Induction. Up-regulated by estradiol.

Pathway. Steroid biosynthesis; estrogen biosynthesis. Lipid metabolism; fatty acid biosynthesis. Lipid metabolism; mitochondrial fatty acid beta-oxidation.

Miscellaneous. The fatty acyl-CoA dehydrogenase activity is several thousand times higher than the estradiol and testosterone 17beta-hydroxysteroid dehydrogenase conversion.

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

RefSeq proteins (1): NP_055049* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR057326	KR_dom	Domain

Pfam: PF13561

Enzyme classification (BRENDA):

• EC 1.1.1.100 — 3-oxoacyl-[acyl-carrier-protein] reductase (BRENDA: 52 organisms, 85 substrates, 53 inhibitors, 72 Km, 30 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ACETOACETYL-COA	0.0057–3.5	23
NADPH	0.0093–0.617	21
ACETOACETYL-[ACYL-CARRIER PROTEIN]	0.003–0.017	5
BETA-KETOBUTYRYL-COA	0.29–4.06	2
1,1,1-TRIFLUOROACETONE	89.2	1
2’,3’,4’,5’,6’-PENTAFLUOROACETOPHENONE	5.72	1
3’-FLUOROACETOPHENONE	7.38	1
3-OXODODECANOYL-[ACYL-CARRIER PROTEIN]	0.142	1
3-OXOOCTANOYL-COA	0.6	1
4’-CHLOROACETOPHENONE	14.34	1
4’-FLUOROACETOPHENONE	12.29	1
ACETOACETYL-N-ACETYLCYSTEAMINE	48	1
ACETOPHENONE	46.92	1
ALPHA-CHLOROACETOPHENONE	2.71	1
ETHYL 4-CHLOROACETOACETATE	8.31	1

Catalyzed reactions (Rhea), 4 shown:

• testosterone + NAD(+) = androst-4-ene-3,17-dione + NADH + H(+) (RHEA:14929)
• 17beta-estradiol + NAD(+) = estrone + NADH + H(+) (RHEA:24612)
• a (3R)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + NADH + H(+) (RHEA:32711)
• 17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha-androstan-3,17-dione + NADH + H(+) (RHEA:41992)

UniProt features (47 total): helix 13, strand 8, binding site 6, mutagenesis site 5, sequence conflict 4, turn 4, modified residue 3, sequence variant 2, chain 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2PD6	X-RAY DIFFRACTION	2
4CQM	X-RAY DIFFRACTION	2.34
4CQL	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92506-F1	93.80	0.89

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): 169 (proton acceptor)

Ligand- & substrate-binding residues (6): 15–23; 42–43; 74–76; 156; 169–173; 202–204

Post-translational modifications (3): 173, 60, 160

Mutagenesis-validated functional residues (5):

Position	Phenotype
42	reduced nadh-dependent reductase activity with acetoacetyl-coa. reduced nadh-dependent reductase activity with 9,10-phen
148	no effect on the ability to restore growth of an oar1-deficient yeast mutant.
169	strongly reduced nadh-dependent reductase activity with acetoacetyl-coa. strongly reduced nadh-dependent reductase activ
173	abolishes nadh-dependent reductase activity with acetoacetyl-coa. strongly reduced nadh-dependent reductase activity wit
189	no effect on the ability to restore growth of an oar1-deficient yeast mutant.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-75105	Fatty acyl-CoA biosynthesis

MSigDB gene sets: 185 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GCANCTGNY_MYOD_Q6, GOBP_REGULATION_OF_HORMONE_LEVELS, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, COUP_01, GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_HETEROTETRAMERIZATION, RAMALHO_STEMNESS_DN, GOBP_HORMONE_BIOSYNTHETIC_PROCESS, HNF4_DR1_Q3, GOBP_STEROID_BIOSYNTHETIC_PROCESS

GO Biological Process (8): fatty acid biosynthetic process (GO:0006633), estrogen biosynthetic process (GO:0006703), androgen metabolic process (GO:0008209), protein heterotetramerization (GO:0051290), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), steroid biosynthetic process (GO:0006694), estrogen metabolic process (GO:0008210)

GO Molecular Function (7): estradiol 17-beta-dehydrogenase [NAD(P)+] activity (GO:0004303), testosterone dehydrogenase (NAD+) activity (GO:0047035), quinone binding (GO:0048038), NADH binding (GO:0070404), (3R)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity (GO:0106386), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial envelope (GO:0005740), mitochondrial matrix (GO:0005759), plasma membrane (GO:0005886), oxidoreductase complex (GO:1990204), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Fatty acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	3
lipid biosynthetic process	2
hormone metabolic process	2
mitochondrion	2
fatty acid metabolic process	1
monocarboxylic acid biosynthetic process	1
estrogen metabolic process	1
hormone biosynthetic process	1
steroid hormone biosynthetic process	1
protein tetramerization	1
protein heterooligomerization	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
17-beta-hydroxysteroid dehydrogenase (NAD+) activity	1
small molecule binding	1
anion binding	1
NAD binding	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle envelope	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
catalytic complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3589 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSD17B8	SLC39A7	Q92504	918
HSD17B8	PFDN6	O15212	878
HSD17B8	RPS18	P25232	866
HSD17B8	RGL2	O15211	854
HSD17B8	KIFC1	Q9BW19	817
HSD17B8	COL11A2	P13942	798
HSD17B8	RXRB	P28702	795
HSD17B8	RING1	Q06587	784
HSD17B8	MCAT	Q8IVS2	706
HSD17B8	NEK8	Q86SG6	634
HSD17B8	OXSM	Q9NWU1	596
HSD17B8	HSD17B7	P56937	589
HSD17B8	MECR	Q9BV79	567
HSD17B8	HSD17B12	Q53GQ0	565
HSD17B8	PSMB9	P28065	547

IntAct

37 interactions, top by confidence:

A	B	Type	Score
SEPTIN3	SEPTIN6	psi-mi:“MI:0914”(association)	0.800
HSD17B8	CBR4	psi-mi:“MI:0915”(physical association)	0.670
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
ANGPTL7	TCP1	psi-mi:“MI:0914”(association)	0.530
HSD17B8	MTIF2	psi-mi:“MI:0914”(association)	0.530
BOLA3	FAAP100	psi-mi:“MI:0914”(association)	0.500
TCF4	OGT	psi-mi:“MI:0914”(association)	0.350
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
TAFA3	FUOM	psi-mi:“MI:0914”(association)	0.350
SUSD4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
OXLD1	NUDT19	psi-mi:“MI:0914”(association)	0.350
ZNF414	ANKHD1	psi-mi:“MI:0914”(association)	0.350
SEPTIN3	SEPTIN4	psi-mi:“MI:0914”(association)	0.350
	NUDT19	psi-mi:“MI:0914”(association)	0.350
C19orf25	NBAS	psi-mi:“MI:0914”(association)	0.350
ATXN7L1	USP27X	psi-mi:“MI:0914”(association)	0.350
	POLRMT	psi-mi:“MI:0914”(association)	0.350
RNF7	SOCS2	psi-mi:“MI:0914”(association)	0.350
ZNF414	CASK	psi-mi:“MI:0914”(association)	0.350
OXLD1	PRORP	psi-mi:“MI:0914”(association)	0.350
BEX4	KLHL41	psi-mi:“MI:0914”(association)	0.350
HSD17B8	TPP1	psi-mi:“MI:0914”(association)	0.350
ZNF414	KDM4B	psi-mi:“MI:0914”(association)	0.350

BioGRID (54): CBR4 (Affinity Capture-MS), MOCOS (Affinity Capture-MS), MRPS23 (Affinity Capture-MS), MTIF2 (Affinity Capture-MS), MRPS2 (Affinity Capture-MS), HSD17B8 (Affinity Capture-MS), HSD17B8 (Affinity Capture-MS), HSD17B8 (Affinity Capture-MS), HSD17B8 (Affinity Capture-MS), ARFIP1 (Co-fractionation), QDPR (Co-fractionation), HSD17B8 (Affinity Capture-MS), MOCOS (Affinity Capture-MS), HSD17B8 (Affinity Capture-MS), HNRNPF (Affinity Capture-MS)

ESM2 similar proteins: A0A2H3D8Y2, A0A3Q8GLE8, A0A3Q8GYY4, A0A8F5XX49, A0A8I6GJ95, A0AAT9JA24, A4IFA7, E9Q3D4, G4N290, K4N0V2, O54438, P0DKI3, P17611, P28643, P33207, P43713, P45375, P50163, P50171, P50204, P50205, P72332, P9WES5, Q08632, Q42182, Q5C9I9, Q5RCF8, Q5TJF5, Q6MGB5, Q6P0H7, Q7FAE1, Q7SHI4, Q8N4T8, Q8RX32, Q8SPU8, Q92506, Q93X67, Q93X68, Q949M2, Q949M3

Diamond homologs: A0A1A9TAK5, A0A1C9II22, A0A1L5BU05, A0QYC2, A3LZU7, A5W4G5, A7B3K3, A7DY56, C0KTJ6, C8WJW0, D4Z260, F4IKM1, G5EGA6, O31680, O34717, O49332, O67610, O93868, P0A2C9, P0A2D0, P0A2D1, P0A2D2, P0AET8, P0AET9, P0C622, P0DKI3, P37440, P38004, P39482, P39483, P39640, P40288, P46331, P50162, P50163, P50164, P50165, P50171, P50199, P50842

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1134 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33205358:G:GT	donor_gain	1.0000
6:33205536:A:T	donor_gain	1.0000
6:33205115:TGCAG:T	donor_loss	0.9900
6:33205116:GCAGG:G	donor_loss	0.9900
6:33205118:AGGT:A	donor_loss	0.9900
6:33205119:GGTGA:G	donor_loss	0.9900
6:33205120:G:GG	donor_loss	0.9900
6:33205121:T:A	donor_loss	0.9900
6:33205127:C:G	donor_gain	0.9900
6:33205385:G:GT	donor_gain	0.9900
6:33205714:G:GT	donor_gain	0.9900
6:33205722:G:GT	donor_gain	0.9900
6:33204727:G:GT	donor_gain	0.9800
6:33205115:TGC:T	donor_gain	0.9800
6:33205117:C:T	donor_gain	0.9800
6:33204715:TCAC:T	donor_gain	0.9700
6:33205302:G:GT	donor_gain	0.9700
6:33205360:C:G	donor_gain	0.9700
6:33205524:T:TA	donor_gain	0.9700
6:33205525:A:AA	donor_gain	0.9700
6:33205634:CTATA:C	acceptor_loss	0.9700
6:33205635:TATAG:T	acceptor_loss	0.9700
6:33205636:ATAGG:A	acceptor_loss	0.9700
6:33205637:TA:T	acceptor_loss	0.9700
6:33205735:A:G	donor_gain	0.9700
6:33206365:A:AG	acceptor_gain	0.9700
6:33206440:G:GT	donor_gain	0.9700
6:33204717:ACAG:A	donor_gain	0.9600
6:33204722:T:G	donor_gain	0.9600
6:33205025:G:GT	donor_gain	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000076425 (6:33204090 G>A,T), RS1000424042 (6:33204059 A>G), RS1002924466 (6:33206914 C>T), RS1003134062 (6:33206897 G>GA), RS1003429229 (6:33207193 C>T), RS1004647081 (6:33203314 A>G), RS1007115600 (6:33204141 C>G), RS1008263347 (6:33206204 G>A), RS1008591978 (6:33204509 G>T), RS1008954258 (6:33204364 C>A,T), RS1009893744 (6:33207232 C>A,G,T), RS1010439251 (6:33203422 T>C), RS1011449385 (6:33205590 A>C,G), RS1012459372 (6:33206865 C>G), RS1012786864 (6:33204817 C>A,T)

Disease associations

OMIM: gene MIM:601417 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002160_5	Wegener’s granulomatosis	2.000000e-50

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
mercuric bromide	decreases expression, affects cotreatment	2
Cisplatin	affects cotreatment, increases expression, affects response to substance	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
afuresertib	increases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
tris(2-butoxyethyl) phosphate	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
thifluzamide	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1

Clinical trials (associated diseases)

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