ANGPTL8

Summary

ANGPTL8 (angiopoietin like 8, HGNC:24933) is a protein-coding gene on chromosome 19p13.2, encoding Angiopoietin-like protein 8 (Q6UXH0). Hormone that acts as a blood lipid regulator by regulating serum triglyceride levels.

Predicted to enable hormone activity. Involved in regulation of lipid metabolic process and triglyceride homeostasis. Acts upstream of or within positive regulation of protein processing and regulation of lipoprotein metabolic process. Located in extracellular region.

Source: NCBI Gene 55908 — RefSeq curated summary.

At a glance

• Gene–disease (curated): coronary artery disorder (Limited, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 11 total — 3 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_018687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24933
Approved symbol	ANGPTL8
Name	angiopoietin like 8
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	TD26, RIFL
Ensembl gene	ENSG00000130173
Ensembl biotype	protein_coding
OMIM	616223
Entrez	55908

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000252453, ENST00000587543, ENST00000591200

RefSeq mRNA: 1 — MANE Select: NM_018687 NM_018687

CCDS: CCDS54220

Canonical transcript exons

ENST00000252453 — 4 exons

Exon	Start	End
ENSE00001311917	11241660	11241943
ENSE00001322319	11241445	11241554
ENSE00002223322	11239619	11239934
ENSE00003756367	11240135	11240296

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 97.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8635 / max 342.5933, expressed in 57 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173904	0.8635	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.40	gold quality
liver	UBERON:0002107	92.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.55	gold quality
subcutaneous adipose tissue	UBERON:0002190	77.42	gold quality
adipose tissue	UBERON:0001013	75.97	gold quality
connective tissue	UBERON:0002384	74.49	gold quality
tendon of biceps brachii	UBERON:0008188	73.98	gold quality
omental fat pad	UBERON:0010414	73.67	gold quality
peritoneum	UBERON:0002358	73.58	gold quality
adipose tissue of abdominal region	UBERON:0007808	73.35	gold quality
buccal mucosa cell	CL:0002336	72.38	gold quality
apex of heart	UBERON:0002098	67.48	gold quality
left coronary artery	UBERON:0001626	66.89	gold quality
colonic epithelium	UBERON:0000397	66.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	64.63	gold quality
coronary artery	UBERON:0001621	64.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	64.37	gold quality
tibial nerve	UBERON:0001323	64.17	gold quality
right adrenal gland cortex	UBERON:0035827	63.93	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.86	gold quality
lower esophagus	UBERON:0013473	63.85	gold quality
right atrium auricular region	UBERON:0006631	63.45	gold quality
stromal cell of endometrium	CL:0002255	63.34	gold quality
lower esophagus mucosa	UBERON:0035834	63.19	gold quality
body of uterus	UBERON:0009853	62.46	gold quality
adult mammalian kidney	UBERON:0000082	62.43	gold quality
cardiac atrium	UBERON:0002081	62.28	gold quality
mucosa of stomach	UBERON:0001199	61.88	gold quality
popliteal artery	UBERON:0002250	61.68	gold quality
tibial artery	UBERON:0007610	61.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting ANGPTL8, 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-4455	100.00	65.48	1587
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6806-5P	96.37	68.74	587
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-1914-3P	95.07	63.37	762

Literature-anchored findings (GeneRIF, showing 40)

• RIFL is an important new regulator of lipid metabolism. (PMID:22569073)
• Lipasin is highly enriched in the liver, where its expression is suppressed by fasting and induced by obesity. Adenovirus-mediated overexpression of Lipasin increases serum triglyceride levels in mice. Lipasin therefore is a nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. (PMID:22809513)
• Lipasin, ANGPTL3 and ANGPTL4 are within the same branch based on phylogenetic analysis of all ANGPTL members, and therefore Lipasin is a novel but atypical member of the ANGPTL family. Lipasin is abundant in brown fat, in which its expression is induced by cold exposure. Lipasin and ANGPTL4 expressions show opposite changes in response to fasting and cold exposure. (PMID:23261442)
• This review is about the current knowledge about Lipasin regarding its expression, regulation, function and mechanisms of action and discuss its potential roles in human physiology and pathology. [Review] (PMID:23415864)
• Circulating concentrations of betatrophin are increased in type 1 diabetes. (PMID:24078058)
• Thyroid hormone T3 regulates lipid metabolism through a C19orf80-activated autophagic process. (PMID:24262987)
• Elevated circulating lipasin is associated with type 2 diabetes and obesity. (PMID:24852694)
• Lipasin is a nutritionally-regulated hepatokine that is increased in human type 2 diabetes and obesity. (PMID:24852694)
• Betatrophin may play a role in the pathogenesis of type 2 diabetes mellitus. (PMID:25024395)
• Betatrophin levels are closely related to obesity-associated cardiometabolic risk factors, emerging as a potential biomarker of insulin resistance and type 2 diabetes. (PMID:25050901)
• Serum betatrophin levels were elevated in patients with T2DM compared with subjects with normal glucose tolerance, isolated impaired fasting glucose, or isolated impaired glucose tolerance (PMID:25303484)
• Circulating Angptl8 is positively and independently associated with type 2 diabetes mellitus and fasting glucose in vivo (PMID:25325797)
• results provide the first evidence that circulating betatrophin is significantly elevated in Japanese patients with diabetes (PMID:25753914)
• Women with gestational diabetes mellitus have significantly higher betatrophin levels as compared to healthy pregnant controls (PMID:25850828)
• Betatrophin levels are lower in youth onset type 2 diabetes and this association is likely mediated through insulin resistance. (PMID:25981323)
• These findings suggest that there may be an ethnic and genderspecific association of the ANGPTL8 rs2278426 polymorphism and serum lipid parameters. (PMID:26004022)
• Strong positive association has been found between betatrophin, plasma fibrinogen (FBG), and insulin resistance in non-diabetic subjects. Correlations with FBG and insulin resistance were diminished in type 2 diabetes subjects. (PMID:26077345)
• An increase in maternal and cord blood betatrophin might be a compensatory mechanism for enhanced insulin demand in Gestational diabetes mellitus. (PMID:26115519)
• Plasma betatrophin levels were elevated in anorexic patients, and reduced in morbidly obese women compared with normal-weight women. It correlated negatively with weight, BMI, body fat, glucose, insulin, and positively with high-density lipoprotein. (PMID:26171798)
• Increased betatrophin in T2D subject does not cause any increase in insulin production as indicated by C-peptide level. (PMID:26289721)
• in the gestational diabetes group, serum betatrophin levels were positively correlated with weight gain during pregnancy, systolic blood pressure, fasting insulin level, and insulin resistance (PMID:26291796)
• ANGPTL8/betatrophin might play an important role in glucose metabolism in the context of insulin resistance. (PMID:26387753)
• betatrophin levels are increased in patients with liver cirrhosis (PMID:26457026)
• ANGPTL8 is a stress-response protein that down-regulates expression of ATGL. (PMID:26569053)
• In patients with diabetes mellitus type 2, betatrophin levels did not correlate with beta-cell function-related variables or insulin resistance-related variables (PMID:26649318)
• Based on the findings of our meta-analysis, circulating betatrophin level of T2DM patients is higher than that of nondiabetic adults in the nonobese population, but not in the obese population. (PMID:26697500)
• ANGPTL8 levels were associated with baseline and future changes in triglyceride levels in Korean children. (PMID:26739706)
• Betatrophin is significantly increased in T2DM patients with different stages of albuminuria. Betatrophin may be a novel endocrine regulator involved in DN development. (PMID:26739836)
• Results demonstrate that ANGPTL8 was increased in obese patients. (PMID:26784326)
• Disruption of ANGPTL8 function in humans does not seem to have a large effect on measures of glucose tolerance. (PMID:26822414)
• Betatrophin levels were increased in women with PCOS and were associated with insulin resistance, c-reactive protein, and free-testosterone in these patients. (PMID:26832343)
• ANGPTL8 is increased in subjects with MetS and it was significantly associated with HsCRP levels in different subgroups. (PMID:26850725)
• Serum betatrophin concentrations are increased in type 2 diabetes patients under antidiabetic treatment and positively associated with diabetic retinopathy. (PMID:26863068)
• data shows for the first time that heterozygote form of ANGPTL8 Rs.2278426 variant was associated with higher FBG level in Arabs highlighting the importance of these variants in controlling the function of betatrophin. (PMID:26864934)
• circulating betatrophin is increased in mice and humans with NAFLD and its expression was induced by endoplasmic reticulum stress in hepatocytes (PMID:27045862)
• An ANGPTL3-4-8 model was proposed to explain the variations of lipoprotein lipase (LPL) activity during the fed-fast cycle. Feeding induces ANGPTL8, activating the ANGPTL8-ANGPTL3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating triglycerides (TG) to white adipose tissue; the reverse is true during fasting, which suppresses ANGPTL8 but induces ANGPTL4, thereby directing TG to muscles. (PMID:27053679)
• Circulating betatrophin concentration is negatively correlated with insulin resistance in obese children and adolescents. (PMID:27103367)
• These results confirm a role for ANGPTL8 in lipoprotein metabolism and provide novel support for functional consequences of the rs2278426 variant. (PMID:27117576)
• Betatrophin levels in patients with polycystic ovary syndrome (PCOS) are lower than those without PCOS and inversely related to insulin resistance. (PMID:27188865)
• Cord blood betatrophin may function as a potential biomarker of maternal intrauterine hyperglycemia and fetal insulin resistance, which may presage for long-term metabolic impact of gestational diabetes on offspring (PMID:27196053)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Angptl8	ENSMUSG00000047822
rattus_norvegicus	Angptl8	ENSRNOG00000011490

Protein

Protein identifiers

Angiopoietin-like protein 8 — Q6UXH0 (reviewed: Q6UXH0)

Alternative names: Betatrophin, Lipasin, Refeeding-induced fat and liver protein

All UniProt accessions (3): Q6UXH0, K7EIY2, K7EJY6

UniProt curated annotations — full annotation on UniProt →

Function. Hormone that acts as a blood lipid regulator by regulating serum triglyceride levels. May be involved in the metabolic transition between fasting and refeeding: required to direct fatty acids to adipose tissue for storage in the fed state.

Subunit / interactions. Interacts with ANGPTL3.

Subcellular location. Secreted.

Tissue specificity. Predominantly expressed in liver. Also expressed in adipose tissues.

Post-translational modifications. Proteolytically cleaved at the N-terminus.

Disease relevance. Type 1 diabetes mellitus (T1D) [MIM:222100] A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. The gene represented in this entry may be involved in disease pathogenesis. Increased protein levels are observed in the serum of patients. This result should however be reinvestigated in light of recent advances that suggest that this protein is not promoting pancreatic beta cell proliferation. Type 2 diabetes mellitus (T2D) [MIM:125853] A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. The gene represented in this entry may be involved in disease pathogenesis. Increased protein levels are observed in the serum of patients and are associated with insulin resistance. According to another report, protein levels are decreased in the serum of patients. Discrepancies between increased and decreased levels of proteins levels in T2D patients may be explained by the use of different kits developed on the market that either use antibodies recognizing the N-terminal or the C-terminal part of the protein. These results should however be reinvestigated in light of recent advances that suggest that this protein is not promoting pancreatic beta cell proliferation.

Induction. In response to food intake. Stimulated by insulin.

Similarity. Belongs to the ANGPTL8 family.

RefSeq proteins (1): NP_061157* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026614	ANGPTL8	Family

UniProt features (4 total): sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXH0-F1	85.15	0.65

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8963889	Assembly of active LPL and LIPC lipase complexes
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8963899	Plasma lipoprotein remodeling

MSigDB gene sets: 69 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GNF2_GSTM1, GNF2_HPN, TGACCTY_ERR1_Q2, GOBP_LIPID_HOMEOSTASIS, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_CELL_MATURATION, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GNF2_LCAT, HNF4_DR1_Q3, PPAR_DR1_Q2

GO Biological Process (8): lipid metabolic process (GO:0006629), positive regulation of protein processing (GO:0010954), regulation of lipid metabolic process (GO:0019216), fat cell differentiation (GO:0045444), cell maturation (GO:0048469), regulation of lipoprotein metabolic process (GO:0050746), triglyceride homeostasis (GO:0070328), signal transduction (GO:0007165)

GO Molecular Function (2): hormone activity (GO:0005179), protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Plasma lipoprotein remodeling	1
Transport of small molecules	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
protein processing	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
lipid metabolic process	1
regulation of primary metabolic process	1
cell differentiation	1
cell development	1
cellular developmental process	1
anatomical structure maturation	1
lipoprotein metabolic process	1
regulation of protein metabolic process	1
acylglycerol homeostasis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANGPTL8	ANGPTL3	Q9Y5C1	987
ANGPTL8	ANGPTL4	Q9BY76	805
ANGPTL8	GPIHBP1	Q8IV16	802
ANGPTL8	ANGPTL1	O95841	770
ANGPTL8	APOA5	Q6Q788	750
ANGPTL8	LPL	P06858	670
ANGPTL8	ANGPTL6	Q8NI99	660
ANGPTL8	LIPG	Q9Y5X9	637
ANGPTL8	FNDC5	Q8NAU1	595
ANGPTL8	INS	P01308	590
ANGPTL8	APOC3	P02656	518
ANGPTL8	DOCK6	Q96HP0	508
ANGPTL8	APOC2	P02655	505
ANGPTL8	MAGED2	Q9UNF1	479
ANGPTL8	ANGPTL5	Q86XS5	477

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RCHY1	ANGPTL8	psi-mi:“MI:0915”(physical association)	0.510
ANGPTL8	RCHY1	psi-mi:“MI:0915”(physical association)	0.510
ANGPTL3	ANGPTL8	psi-mi:“MI:0915”(physical association)	0.400
ANGPTL8	ACTA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): RIPK1 (Affinity Capture-Western), IKBKG (Affinity Capture-Western), IKBKB (Affinity Capture-Western), SQSTM1 (Affinity Capture-Western), C19orf80 (Affinity Capture-Western), C19orf80 (Affinity Capture-Western), C19orf80 (Reconstituted Complex), ACTA2 (Affinity Capture-MS), ACTA1 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), CHRDL2 (Affinity Capture-MS), RCHY1 (Two-hybrid)

ESM2 similar proteins: A1A5D9, A1L3T7, A4FV37, A6NC98, A6NJZ7, A6NNM3, O15049, P0C7N4, P0CW27, P58660, Q0P5D1, Q1HGE8, Q2NL23, Q3LUD3, Q3UPH7, Q494R4, Q4QRL3, Q5JYT7, Q5ND29, Q5XIS1, Q64697, Q6QZQ4, Q6UXH0, Q6ZS72, Q7Z6P3, Q8BLS7, Q8C2K5, Q8C7U1, Q8CB62, Q8CB87, Q8CHW5, Q8N137, Q8R1L8, Q8TE77, Q8TER5, Q91VJ2, Q969G5, Q96EN9, Q96FF7, Q96LX7

Diamond homologs: Q6UXH0, Q8R1L8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	5
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3242707	NC_000019.9:g.(?11346254)(11354578_?)del	Pathogenic
395688	GRCh37/hg19 19p13.2-13.12(chr19:9678768-14853426)	Pathogenic
983187	GRCh37/hg19 19p13.2(chr19:10957601-11672041)x1	Pathogenic

SpliceAI

1626 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11238043:A:AC	donor_gain	1.0000
19:11238044:C:CC	donor_gain	1.0000
19:11238302:TTC:T	acceptor_gain	1.0000
19:11238302:TTCCT:T	acceptor_loss	1.0000
19:11238303:TC:T	acceptor_gain	1.0000
19:11238304:CC:C	acceptor_gain	1.0000
19:11238305:C:CC	acceptor_gain	1.0000
19:11238305:C:CG	acceptor_loss	1.0000
19:11240295:AGGTA:A	donor_loss	1.0000
19:11241440:CACA:C	acceptor_loss	1.0000
19:11241442:CAG:C	acceptor_loss	1.0000
19:11241443:A:AC	acceptor_loss	1.0000
19:11241443:A:AG	acceptor_gain	1.0000
19:11241443:AG:A	acceptor_gain	1.0000
19:11241444:G:GA	acceptor_gain	1.0000
19:11241444:GG:G	acceptor_gain	1.0000
19:11241444:GGC:G	acceptor_gain	1.0000
19:11241444:GGCT:G	acceptor_gain	1.0000
19:11241444:GGCTC:G	acceptor_gain	1.0000
19:11241550:GAGAG:G	donor_gain	1.0000
19:11241551:A:T	donor_gain	1.0000
19:11241552:GAG:G	donor_gain	1.0000
19:11241555:G:GC	donor_loss	1.0000
19:11241555:G:GG	donor_gain	1.0000
19:11241556:T:G	donor_loss	1.0000
19:11237639:A:AC	donor_gain	0.9900
19:11237640:C:CC	donor_gain	0.9900
19:11238180:CACTG:C	donor_loss	0.9900
19:11238181:ACTGA:A	donor_loss	0.9900
19:11238182:C:CG	donor_loss	0.9900

AlphaMissense

1250 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11239758:G:T	G41W	0.920
19:11239779:G:C	A48P	0.911
19:11241545:T:C	I187T	0.910
19:11239765:T:C	L43P	0.906
19:11241451:G:C	A156P	0.905
19:11240296:G:C	K153N	0.901
19:11240296:G:T	K153N	0.901
19:11239771:T:C	L45P	0.898
19:11239783:T:A	L49H	0.898
19:11241482:T:C	L166P	0.898
19:11239758:G:A	G41R	0.894
19:11239758:G:C	G41R	0.894
19:11239750:T:A	L38H	0.893
19:11239759:G:A	G41E	0.889
19:11241536:T:C	L184P	0.886
19:11241477:G:C	W164C	0.881
19:11241477:G:T	W164C	0.881
19:11239783:T:C	L49P	0.876
19:11239909:T:C	L91P	0.870
19:11239750:T:C	L38P	0.864
19:11239752:T:C	F39L	0.863
19:11239754:C:A	F39L	0.863
19:11239754:C:G	F39L	0.863
19:11239824:G:C	A63P	0.856
19:11239759:G:T	G41V	0.848
19:11239816:T:C	L60P	0.844
19:11239921:T:C	L95P	0.841
19:11239750:T:G	L38R	0.837
19:11239747:T:C	L37P	0.833
19:11241545:T:G	I187S	0.831

dbSNP variants (sampled 300 via entrez): RS1000036199 (19:11241128 C>A), RS1000903662 (19:11241798 C>A,T), RS1001208423 (19:11240732 C>T), RS1002643598 (19:11239564 C>G,T), RS1002868063 (19:11239309 T>C), RS1003003216 (19:11239429 C>A), RS1003605654 (19:11238144 T>C), RS1004040125 (19:11239189 C>A,T), RS1004232260 (19:11238716 G>C), RS1004934989 (19:11240700 C>T), RS1006355953 (19:11242257 G>A,C), RS1007339147 (19:11241509 G>A), RS1007829749 (19:11239265 T>C), RS1008184889 (19:11238987 C>G), RS1010470904 (19:11239514 G>A)

Disease associations

OMIM: gene MIM:616223 | disease phenotypes: MIM:613325

GenCC curated gene-disease

Disease	Classification	Inheritance
coronary artery disorder	Limited	Autosomal dominant

Mondo (2): rhabdoid tumor predisposition syndrome 2 (MONDO:0013224), coronary artery disorder (MONDO:0005010)

Orphanet (2): Rhabdoid tumor predisposition syndrome (Orphanet:231108), Rhabdoid tumor (Orphanet:69077)

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002223_43	HDL cholesterol	5.000000e-17
GCST004232_19	HDL cholesterol levels	1.000000e-21
GCST004232_32	HDL cholesterol levels	9.000000e-11
GCST004234_9	HDL cholesterol levels	6.000000e-12
GCST006003_4	Triglyceride levels	2.000000e-13
GCST006611_155	HDL cholesterol	1.000000e-52
GCST006613_126	Triglycerides	3.000000e-14
GCST007441_4	Total cholesterol levels	1.000000e-08
GCST007850_7	HDL cholesterol	5.000000e-11
GCST009918_4	HDL cholesterol levels	3.000000e-07
GCST011345_34	Triglyceride levels	3.000000e-15
GCST012020_55	Serum metabolite levels	4.000000e-14
GCST012020_56	Serum metabolite levels	6.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0007805	HDL cholesterol change measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003324	Coronary Artery Disease	C14.280.647.250.260; C14.907.137.126.339; C14.907.585.250.260
C567643	Rhabdoid Tumor Predisposition Syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523352 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, increases methylation	5
Benzo(a)pyrene	decreases expression	3
Cyclosporine	increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
methyleugenol	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
benazol P	affects expression	1
pentanal	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Ammonium Chloride	decreases expression, decreases reaction	1
Chloroquine	decreases expression, decreases reaction	1
Diethylnitrosamine	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triiodothyronine	decreases expression, affects binding, increases reaction, increases expression, affects cotreatment (+1 more)	1
Urethane	decreases expression	1
Valproic Acid	decreases expression	1
Oxyquinoline	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4315654	Binding	Inhibition of human Angptl8 at 40 uM relative to control	Multigram scale synthesis of polycyclic lactones and evaluation of antitumor and other biological properties. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0TL	Ubigene Hep G2 ANGPTL8 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00025766	PHASE4	COMPLETED	Angioplasty and Heart Stents to Treat Individuals With an Occluded Artery Following a Heart Attack
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00111566	PHASE4	COMPLETED	BRIEF-PCI: Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention
NCT00129038	PHASE4	COMPLETED	Modified-release Dipyridamole/Aspirin (200mg/25mg bd) Versus Aspirin (75mg) in Aspirin-resistant Patients
NCT00133003	PHASE4	COMPLETED	Abciximab, Clopidogrel and Percutaneous Coronary Intervention in Acute Coronary Syndrome (ISAR-REACT-2)
NCT00133237	PHASE4	COMPLETED	Drug-eluting-stents for Unprotected Left Main Stem Disease (ISAR-LEFT-MAIN)
NCT00133692	PHASE4	COMPLETED	INVEST: INternational VErapamil SR Trandolapril STudy
NCT00139386	PHASE4	COMPLETED	Candesartan for Prevention of Cardiovascular Events After Cypher or Taxus Coronary Stenting (4C) Trial
NCT00140465	PHASE4	COMPLETED	75 or 150 mg Clopidogrel Maintenance Doses Following PCI (ISAR-CHOICE-2)
NCT00140530	PHASE4	COMPLETED	Nonpolymer- and Polymer-Based Drug-Eluting Stents for Restenosis (ISAR-TEST-1)
NCT00146575	PHASE4	COMPLETED	Sirolimus- and Paclitaxel-Eluting Stents for Small Vessels (ISAR-SMART-3)
NCT00152308	PHASE4	TERMINATED	Non-Polymer-Based, Rapamycin-Eluting Stents to Prevent Restenosis
NCT00155350	PHASE4	UNKNOWN	Treatment of Coronary Atherosclerosis by Insulin Sensitizers in Insulin-Resistant Patients
NCT00162370	PHASE4	COMPLETED	A Study of Stress Echocardiography in Post-Menopausal Women at Risk for Coronary Disease
NCT00163202	PHASE4	COMPLETED	Comparative Atorvastatin Pleiotropic Effects
NCT00169819	PHASE4	COMPLETED	EArly Discharge After Transradial Stenting of CoronarY Arteries: The EASY Study
NCT00171275	PHASE4	COMPLETED	Fluvastatin in the Therapy of Acute Coronary Syndrome
NCT00175240	PHASE4	COMPLETED	Enhancing the Secondary Prevention of Coronary Artery Disease
NCT00180388	PHASE4	TERMINATED	VENEK: Healing in Different Vein Harvesting Methods During Aortocoronary Coronary Artery Bypass Graft Surgery (CABG)
NCT00180583	PHASE4	COMPLETED	Vision II: Evaluation of GALILEO Intravascular Radiotherapy System
NCT00189215	PHASE4	COMPLETED	Long-Term Cognitive Decline After Coronary Artery Bypass Grafting: is Off-Pump Surgery Beneficial?
NCT00200629	PHASE4	TERMINATED	Both Exercise and Adenosine Stress Testing
NCT00202904	PHASE4	COMPLETED	Effectiveness and Safety of Ezetimibe Added to Atorvastatin in Patients With High Cholesterol and Coronary Heart Disease (Study P03740)
NCT00209404	PHASE4	COMPLETED	Iodixanol in Multidetector-Row Computed Tomography-Coronary Angiography (MDCT-CA)
NCT00209430	PHASE4	COMPLETED	Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Coronary Angiography
NCT00220558	PHASE4	UNKNOWN	GISSOC II: Sirolimus Eluting Stent Versus Bare Metal Stent in Chronic Total Coronary Occlusions
NCT00222261	PHASE4	COMPLETED	Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.
NCT00229528	PHASE4	COMPLETED	Effect of Paroxetine on COAT-Platelet Production in Normal Volunteers and Patients With Cardiovascular Disease
NCT00232804	PHASE4	COMPLETED	The BRIDGE Registry: Safety and Efficacy Registry of Bx Cypher Stent
NCT00232856	PHASE4	COMPLETED	A Study of the Cypher SES to Treat Restenotic Native Coronary Artery Lesions.
NCT00235066	PHASE4	COMPLETED	The CYPHER™ Stent Study in Patients With Small de Novo Coronary Artery Lesions.
NCT00235092	PHASE4	COMPLETED	The REALITY Study - Head-to-Head Comparison Between Cypher and Taxus
NCT00235950	PHASE4	COMPLETED	Assessment of the Lipid Lowering Effect of Rosuvastatin Compared to Atorvastatin in Subjects With Coronary Heart Disease
NCT00238004	PHASE4	UNKNOWN	The Low HDL On Six Weeks Statin Therapy (LOW) Study
NCT00241904	PHASE4	COMPLETED	Reducing Total Cardiovascular Risk in an Urban Community
NCT00242944	PHASE4	COMPLETED	Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS)
NCT00243477	PHASE4	COMPLETED	MOTIV Study- Effect of Antidepressive Treatment by Escitalopram in Patients Undergoing Coronary Artery Bypass Grafting
NCT00244530	PHASE4	COMPLETED	Prophylactic Effect of Nifedipine on Further Decline in Renal Function in Patients Undergoing Open-Heart Surgery
NCT00245401	PHASE4	COMPLETED	CYPHERTM Stent Post-Marketing Surveillance Registry (US-PMS)