HACL1

Summary

HACL1 (2-hydroxyacyl-CoA lyase 1, HGNC:17856) is a protein-coding gene on chromosome 3p25.1, encoding 2-hydroxyacyl-CoA lyase 1 (Q9UJ83). Peroxisomal 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the fatty acid alpha-oxydation in a thiamine pyrophosphate (TPP)-dependent manner.

Enables several functions, including 2-hydroxyacyl-CoA lyase activity; ATP binding activity; and cation binding activity. Involved in fatty acid alpha-oxidation; phytanic acid metabolic process; and protein targeting to peroxisome. Located in nucleoplasm and peroxisome.

Source: NCBI Gene 26061 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 139 total — 1 pathogenic
• MANE Select transcript: NM_012260

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17856
Approved symbol	HACL1
Name	2-hydroxyacyl-CoA lyase 1
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Aliases	2-HPCL, PHYH2
Ensembl gene	ENSG00000131373
Ensembl biotype	protein_coding
OMIM	604300
Entrez	26061

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 29 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000321169, ENST00000383779, ENST00000414979, ENST00000421993, ENST00000422591, ENST00000435217, ENST00000451445, ENST00000456194, ENST00000457447, ENST00000460907, ENST00000469454, ENST00000472857, ENST00000628377, ENST00000900332, ENST00000900333, ENST00000900334, ENST00000900335, ENST00000900336, ENST00000900337, ENST00000900338, ENST00000900339, ENST00000900340, ENST00000936950, ENST00000936951, ENST00000936952, ENST00000936953, ENST00000936954, ENST00000936955, ENST00000947230, ENST00000947231, ENST00000947232, ENST00000947233, ENST00000947234, ENST00000947235

RefSeq mRNA: 4 — MANE Select: NM_012260 NM_001284413, NM_001284415, NM_001284416, NM_012260

CCDS: CCDS2627, CCDS68360, CCDS68361, CCDS68362

Canonical transcript exons

ENST00000321169 — 17 exons

Exon	Start	End
ENSE00000901344	15589540	15589612
ENSE00001222710	15591600	15591680
ENSE00001222717	15596384	15596424
ENSE00001809838	15560699	15560897
ENSE00003501135	15568432	15568586
ENSE00003503485	15574977	15575082
ENSE00003509194	15571668	15571769
ENSE00003530491	15601383	15601569
ENSE00003540992	15567844	15568002
ENSE00003556893	15586525	15586602
ENSE00003581748	15585248	15585342
ENSE00003590646	15573159	15573242
ENSE00003592635	15579910	15580045
ENSE00003637639	15564551	15564658
ENSE00003653660	15601090	15601194
ENSE00003666058	15582877	15582989
ENSE00003693947	15563358	15563544

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 97.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.6269 / max 302.4569, expressed in 1784 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41286	14.8086	1773
41285	3.7019	1458
41287	1.1164	743

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	97.08	gold quality
duodenum	UBERON:0002114	95.04	gold quality
right lobe of liver	UBERON:0001114	91.04	gold quality
secondary oocyte	CL:0000655	90.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.36	gold quality
liver	UBERON:0002107	90.36	gold quality
upper arm skin	UBERON:0004263	90.28	gold quality
kidney epithelium	UBERON:0004819	90.14	gold quality
ileal mucosa	UBERON:0000331	89.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.95	gold quality
oocyte	CL:0000023	88.39	gold quality
jejunum	UBERON:0002115	88.20	gold quality
right testis	UBERON:0004534	88.15	gold quality
upper leg skin	UBERON:0004262	88.06	gold quality
left testis	UBERON:0004533	87.87	gold quality
testis	UBERON:0000473	87.77	gold quality
calcaneal tendon	UBERON:0003701	87.71	gold quality
deltoid	UBERON:0001476	87.56	gold quality
islet of Langerhans	UBERON:0000006	87.40	gold quality
gastrocnemius	UBERON:0001388	87.19	gold quality
muscle of leg	UBERON:0001383	87.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.66	gold quality
adult organism	UBERON:0007023	86.47	gold quality
corpus epididymis	UBERON:0004359	86.29	gold quality
tendon	UBERON:0000043	86.23	gold quality
bronchial epithelial cell	CL:0002328	85.85	gold quality
adipose tissue	UBERON:0001013	85.65	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.48	gold quality
pancreas	UBERON:0001264	85.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting HACL1, 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-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-7114-5P	98.51	67.87	1349

Literature-anchored findings (GeneRIF, showing 4)

• peroxisomal thiamine-pyrophosphate depending enzyme required for the degradation of phytanic acid, catalyzing the cleavage of 2-hydroxyphytanoyl-CoA lyase into formyl-CoA and pristanal (PMID:10468558)
• 2-hydroxyphytanoyl-CoA lyase has a role in the breakdown of long chain 2-hydroxyfatty acids (PMID:15644336)
• Transport of thiamine pyrophosphate into peroxisomes is dependent on HACL1 import, without requirement of a specific solute transporter. (PMID:21708296)
• Data show that a easy assay for 2-hydroxyacyl-CoA lyase (HACL1) and sphingosine-1-phosphate lyase (SGPL1) activities was developed. (PMID:24323699)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hacl1	ENSDARG00000020529
mus_musculus	Hacl1	ENSMUSG00000021884
rattus_norvegicus	Hacl1	ENSRNOG00000019630
drosophila_melanogaster	Hacl	FBGN0034488
caenorhabditis_elegans		WBGENE00007143

Paralogs (1): ILVBL (ENSG00000105135)

Protein

Protein identifiers

2-hydroxyacyl-CoA lyase 1 — Q9UJ83 (reviewed: Q9UJ83)

Alternative names: 2-hydroxyphytanoyl-CoA lyase, Phytanoyl-CoA 2-hydroxylase 2

All UniProt accessions (6): B3KPX4, C9J306, C9JJM7, Q9UJ83, F8WCH9, Q7Z773

UniProt curated annotations — full annotation on UniProt →

Function. Peroxisomal 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the fatty acid alpha-oxydation in a thiamine pyrophosphate (TPP)-dependent manner. Involved in the degradation of 3-methyl-branched fatty acids like phytanic acid and the shortening of 2-hydroxy long-chain fatty acids. Plays a significant role in the biosynthesis of heptadecanal in the liver.

Subunit / interactions. Homotetramer.

Subcellular location. Peroxisome.

Tissue specificity. Widely expressed.

Cofactor. Binds 1 Mg(2+) ion per subunit. Binds 1 thiamine pyrophosphate per subunit.

Pathway. Lipid metabolism; fatty acid metabolism.

Similarity. Belongs to the TPP enzyme family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UJ83-1	1	yes
Q9UJ83-2	2
Q9UJ83-4	4
Q9UJ83-3	3

RefSeq proteins (4): NP_001271342, NP_001271344, NP_001271345, NP_036392* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011766	TPP_enzyme_TPP-bd	Domain
IPR012000	Thiamin_PyroP_enz_cen_dom	Domain
IPR012001	Thiamin_PyroP_enz_TPP-bd_dom	Domain
IPR029035	DHS-like_NAD/FAD-binding_dom	Homologous_superfamily
IPR029061	THDP-binding	Homologous_superfamily
IPR045025	HACL1-like	Family

Pfam: PF00205, PF02775, PF02776

Enzyme classification (BRENDA):

• EC 4.1.2.63 — 2-hydroxyacyl-CoA lyase (BRENDA: 6 organisms, 21 substrates, 1 inhibitors, 13 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FORMALDEHYDE	10–160	4
2-HYDROXYISOBUTYRYL-COA	0.021–0.079	2
FORMYL-COA	0.2	2
2-HYDROXY-3-METHYLHEXADECANOYL-COA	0.015	1
ACETONE	1600	1
PENTANAL	0.4	1
PROPANAL	16	1

Catalyzed reactions (Rhea), 5 shown:

• 2-hydroxyphytanoyl-CoA = 2,6,10,14-tetramethylpentadecanal + formyl-CoA (RHEA:25355)
• a 2-hydroxy-3-methyl fatty acyl-CoA = a 2-methyl-branched fatty aldehyde + formyl-CoA (RHEA:25375)
• 2-hydroxy-3-methylhexadecanoyl-CoA = 2-methylpentadecanal + formyl-CoA (RHEA:25379)
• 2-hydroxyoctadecanoyl-CoA = heptadecanal + formyl-CoA (RHEA:55196)
• an (R)-2-hydroxy-long-chain-fatty acyl-CoA = a long-chain fatty aldehyde + formyl-CoA (RHEA:67444)

UniProt features (18 total): splice variant 4, modified residue 4, binding site 3, mutagenesis site 2, sequence conflict 2, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJ83-F1	95.09	0.93

Functional residue map

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

Ligand- & substrate-binding residues (3): 60; 455; 482

Post-translational modifications (4): 4, 351, 358, 365

Mutagenesis-validated functional residues (2):

Position	Phenotype
455	does not affect subcellular localization. abolishes lyase activity. does not affect subcellular localization, abolishes
456	does not affect subcellular localization. abolishes lyase activity. does not affect subcellular localization, abolishes

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-389599	Alpha-oxidation of phytanate
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 122 (showing top): GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, HORIUCHI_WTAP_TARGETS_DN, GOBP_PROTEIN_TARGETING, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, WANG_LMO4_TARGETS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, AFFAR_YY1_TARGETS_UP, GOBP_MONOCARBOXYLIC_ACID_CATABOLIC_PROCESS

GO Biological Process (6): fatty acid alpha-oxidation (GO:0001561), protein targeting to peroxisome (GO:0006625), fatty acid metabolic process (GO:0006631), methyl-branched fatty acid metabolic process (GO:0097089), phytanic acid metabolic process (GO:1903512), lipid metabolic process (GO:0006629)

GO Molecular Function (11): magnesium ion binding (GO:0000287), ATP binding (GO:0005524), carbon-carbon lyase activity (GO:0016830), thiamine pyrophosphate binding (GO:0030976), identical protein binding (GO:0042802), 2-hydroxyacyl-CoA lyase activity (GO:0106359), 2-hydroxyphytanoyl-CoA lyase activity (GO:0106376), catalytic activity (GO:0003824), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peroxisomal lipid metabolism	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	2
cellular anatomical structure	2
fatty acid catabolic process	1
fatty acid oxidation	1
protein targeting	1
establishment of protein localization to peroxisome	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
long-chain fatty acid metabolic process	1
methyl-branched fatty acid metabolic process	1
primary metabolic process	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
lyase activity	1
vitamin binding	1
anion binding	1
quaternary ammonium group binding	1
heterocyclic compound binding	1
sulfur compound binding	1
protein binding	1
aldehyde-lyase activity	1
2-hydroxyacyl-CoA lyase activity	1
molecular_function	1
binding	1
catalytic activity	1
nuclear lumen	1
microbody	1
peroxisome	1
microbody lumen	1
cytoplasm	1

Protein interactions and networks

STRING

2172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HACL1	PHYH	O14832	678
HACL1	HAO2	Q9NYQ3	501
HACL1	FAR2	Q96K12	486
HACL1	SCP2	P22307	475
HACL1	TPK1	Q9H3S4	441
HACL1	AASDH	Q4L235	436
HACL1	BCKDHA	P12694	430
HACL1	AMACR	Q9UHK6	429
HACL1	AGPS	O00116	423
HACL1	PC	P11498	414
HACL1	AGXT	P21549	412
HACL1	HAO1	Q9UJM8	411
HACL1	TKT	P29401	407
HACL1	ECI1	P42126	400
HACL1	DECR2	Q9NUI1	398

IntAct

29 interactions, top by confidence:

A	B	Type	Score
HACL1	ZMYND19	psi-mi:“MI:0915”(physical association)	0.830
ZMYND19	HACL1	psi-mi:“MI:0915”(physical association)	0.830
ZMYND19	TNFAIP1	psi-mi:“MI:0914”(association)	0.670
HACL1	HACL1	psi-mi:“MI:0915”(physical association)	0.630
HACL1	MAGEB6	psi-mi:“MI:0915”(physical association)	0.560
RNA15	HACL1	psi-mi:“MI:0915”(physical association)	0.560
HACL1	RNA15	psi-mi:“MI:0915”(physical association)	0.560
HACL1	PLXDC2	psi-mi:“MI:0914”(association)	0.530
HACL1	SMARCB1	psi-mi:“MI:0915”(physical association)	0.370
HACL1	CFTR	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	HACL1	psi-mi:“MI:0915”(physical association)	0.370
ODF2L	GAPDHS	psi-mi:“MI:0914”(association)	0.350
PEX5	AGPS	psi-mi:“MI:0914”(association)	0.350
SLC15A1	MEN1	psi-mi:“MI:0914”(association)	0.350
CAT	VWA8	psi-mi:“MI:2364”(proximity)	0.270
ZMYND19	HACL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): HACL1 (Two-hybrid), ZMYND19 (Two-hybrid), MAGEB6 (Two-hybrid), HACL1 (Affinity Capture-MS), ZMYND19 (Two-hybrid), HACL1 (Two-hybrid), HACL1 (Affinity Capture-Western), PTPRF (Co-fractionation), WDFY1 (Co-fractionation), ASPSCR1 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), HACL1 (Affinity Capture-MS), HACL1 (Two-hybrid), HACL1 (Proximity Label-MS), HACL1 (Affinity Capture-MS)

ESM2 similar proteins: A0REB6, A3SR25, A4IPB6, A5YBJ6, A6L4N0, A7ZAH8, A9VGD1, B1HRX4, B2TJ86, B2V4K0, B7JPM3, C0ZC10, C1EVJ3, C3LHY1, C3PAZ3, O53182, O61856, P06169, P07003, P0AFI0, P0AFI1, P16467, P33149, P34734, P40149, P42415, Q0TUZ2, Q12629, Q2UKV4, Q4V1F5, Q5KYR0, Q5WIU9, Q5WKY8, Q63B73, Q65D03, Q6FJA3, Q6HIK2, Q723S8, Q81QB5, Q898E8

Diamond homologs: A0A2I2F2I5, A1L0T0, A4IPB6, A6QQT9, B2TJ86, O05031, O06335, O08353, O19929, O33112, O61856, O78518, O85293, P00893, P07342, P08142, P09114, P09342, P0A623, P0AEP7, P0AEP8, P0DP89, P0DP90, P14874, P17597, P27696, P27818, P27819, P27868, P36620, P37063, P37251, P39994, P40811, P42463, P45261, P57321, P69683, P69684, P96591

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	96
Likely benign	14
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4082123	NM_012260.4(HACL1):c.942T>G (p.Asn314Lys)	Pathogenic

SpliceAI

2676 predictions. Top by Δscore:

Variant	Effect	Δscore
3:15563540:GGACC:G	acceptor_gain	1.0000
3:15563541:GACC:G	acceptor_gain	1.0000
3:15563542:ACC:A	acceptor_gain	1.0000
3:15563542:ACCC:A	acceptor_loss	1.0000
3:15563543:CC:C	acceptor_gain	1.0000
3:15563543:CCC:C	acceptor_gain	1.0000
3:15563544:CC:C	acceptor_gain	1.0000
3:15563545:C:CA	acceptor_loss	1.0000
3:15563545:C:CC	acceptor_gain	1.0000
3:15563545:C:T	acceptor_gain	1.0000
3:15564544:TAC:T	donor_loss	1.0000
3:15564545:ACTT:A	donor_loss	1.0000
3:15564546:CTT:C	donor_loss	1.0000
3:15564548:TACAC:T	donor_loss	1.0000
3:15564549:A:AC	donor_gain	1.0000
3:15564550:C:CG	donor_gain	1.0000
3:15564550:CA:C	donor_gain	1.0000
3:15564550:CACT:C	donor_gain	1.0000
3:15564550:CACTG:C	donor_gain	1.0000
3:15564658:CCT:C	acceptor_loss	1.0000
3:15564659:C:CA	acceptor_loss	1.0000
3:15564660:T:G	acceptor_loss	1.0000
3:15564664:G:GC	acceptor_gain	1.0000
3:15568426:TCTTA:T	donor_loss	1.0000
3:15568427:CTTAC:C	donor_loss	1.0000
3:15568428:TTAC:T	donor_loss	1.0000
3:15568430:A:AC	donor_gain	1.0000
3:15568430:A:C	donor_loss	1.0000
3:15568431:C:CC	donor_gain	1.0000
3:15568431:C:CG	donor_loss	1.0000

AlphaMissense

3820 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:15575033:A:G	W285R	0.999
3:15575033:A:T	W285R	0.999
3:15575031:C:A	W285C	0.998
3:15575031:C:G	W285C	0.998
3:15575034:A:C	N284K	0.998
3:15575034:A:T	N284K	0.998
3:15591668:G:C	C80W	0.998
3:15585299:A:T	V168D	0.997
3:15589555:G:C	F122L	0.997
3:15589555:G:T	F122L	0.997
3:15589557:A:G	F122L	0.997
3:15567982:C:T	G424E	0.996
3:15575019:A:C	F289L	0.996
3:15575019:A:T	F289L	0.996
3:15575021:A:G	F289L	0.996
3:15579916:C:G	R266T	0.996
3:15582894:A:G	L217P	0.996
3:15585342:C:G	A154P	0.996
3:15591605:G:C	N101K	0.996
3:15591605:G:T	N101K	0.996
3:15601102:C:A	R58S	0.996
3:15601102:C:G	R58S	0.996
3:15601103:C:A	R58M	0.996
3:15575017:C:T	G290E	0.995
3:15579965:C:A	G250W	0.995
3:15589556:A:C	F122C	0.995
3:15591616:C:G	A98P	0.995
3:15591670:A:G	C80R	0.995
3:15601103:C:G	R58T	0.995
3:15601393:A:G	L24P	0.995

dbSNP variants (sampled 300 via entrez): RS1000066766 (3:15577191 A>G), RS1000154353 (3:15593844 C>A,T), RS1000318407 (3:15573451 T>G), RS1000346818 (3:15582073 C>T), RS1000376190 (3:15599740 C>A), RS1000379817 (3:15582298 C>A), RS1000434855 (3:15583636 CTCTTTTTTTTTTTTCTTT>C), RS1000481426 (3:15567130 G>C), RS1000512793 (3:15595591 T>C), RS1000556258 (3:15589352 C>A), RS1000678273 (3:15583612 G>A), RS1000710394 (3:15583756 C>G), RS1000730706 (3:15573733 G>C), RS1000731188 (3:15586443 C>T), RS1000769663 (3:15588620 A>C,G)

Disease associations

OMIM: gene MIM:604300 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): familial hypercholesterolemia (MONDO:0005439)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012480_11	C-reactive protein levels	1.000000e-31

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Cyclosporine	decreases expression, decreases methylation, increases expression	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
sodium arsenite	decreases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
bisphenol B	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Atazanavir Sulfate	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	affects cotreatment, decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Vehicle Emissions	decreases expression, decreases reaction	1
Benzo(a)pyrene	decreases expression	1
Carbamazepine	affects expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Deoxycholic Acid	decreases expression, affects cotreatment	1
Doxorubicin	increases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	PHASE3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	PHASE3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	PHASE3	ACTIVE_NOT_RECRUITING	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	PHASE3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT00079846	PHASE2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00079859	PHASE2	TERMINATED	Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00477594	PHASE2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00751608	PHASE2	WITHDRAWN	Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients
NCT02597127	PHASE2	COMPLETED	Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C)
NCT03060577	PHASE2	COMPLETED	An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
NCT04455581	PHASE2	UNKNOWN	A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia
NCT04941599	PHASE2	RECRUITING	2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)
NCT05261126	PHASE2	COMPLETED	A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)
NCT00004809	PHASE1	COMPLETED	Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia
NCT02709850	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia
NCT03747224	PHASE1	COMPLETED	Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients
NCT05043181	PHASE1	NOT_YET_RECRUITING	Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH
NCT05851066	PHASE1	COMPLETED	A VSA003 Phase 1 Study in Chinese Adult Healthy Volunteers
NCT02048410	PHASE1/PHASE2	COMPLETED	Efficacy of a New Symbiotic Formulation in Children With Familial Hypercholesterolemia
NCT02100839	PHASE1/PHASE2	COMPLETED	Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results