ANGPTL1

Summary

ANGPTL1 (angiopoietin like 1, HGNC:489) is a protein-coding gene on chromosome 1q25.2, encoding Angiopoietin-related protein 1 (O95841).

Angiopoietins are members of the vascular endothelial growth factor family and the only known growth factors largely specific for vascular endothelium. Angiopoietin-1, angiopoietin-2, and angiopoietin-4 participate in the formation of blood vessels. The protein encoded by this gene is another member of the angiopoietin family that is widely expressed in adult tissues with mRNA levels highest in highly vascularized tissues. This protein was found to be a secretory protein that does not act as an endothelial cell mitogen in vitro.

Source: NCBI Gene 9068 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_004673

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:489
Approved symbol	ANGPTL1
Name	angiopoietin like 1
Location	1q25.2
Locus type	gene with protein product
Status	Approved
Aliases	ANG3, AngY, ARP1
Ensembl gene	ENSG00000116194
Ensembl biotype	protein_coding
OMIM	603874
Entrez	9068

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000234816, ENST00000367629, ENST00000444255, ENST00000853919, ENST00000853920, ENST00000853921, ENST00000853922, ENST00000963348, ENST00000963349

RefSeq mRNA: 2 — MANE Select: NM_004673 NM_001376763, NM_004673

CCDS: CCDS1327

Canonical transcript exons

ENST00000234816 — 6 exons

Exon	Start	End
ENSE00000790060	178852683	178852953
ENSE00000790061	178853594	178853787
ENSE00000790062	178864954	178865802
ENSE00001008125	178869114	178869223
ENSE00001345734	178870741	178871077
ENSE00001364446	178849535	178851316

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 96.99.

FANTOM5 (CAGE): breadth broad, TPM avg 4.9203 / max 175.1323, expressed in 523 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16063	1.5558	282
16062	1.2573	260
16057	0.9150	278
16060	0.7009	228
16059	0.3534	157
16061	0.0843	49
16058	0.0535	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	96.99	gold quality
smooth muscle tissue	UBERON:0001135	96.86	gold quality
calcaneal tendon	UBERON:0003701	96.55	gold quality
tendon of biceps brachii	UBERON:0008188	96.53	gold quality
popliteal artery	UBERON:0002250	96.33	gold quality
tibial artery	UBERON:0007610	96.32	gold quality
artery	UBERON:0001637	95.86	gold quality
tendon	UBERON:0000043	94.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.55	gold quality
lower esophagus	UBERON:0013473	94.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.11	gold quality
right ovary	UBERON:0002118	93.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.87	gold quality
left coronary artery	UBERON:0001626	93.45	gold quality
descending thoracic aorta	UBERON:0002345	93.44	gold quality
aorta	UBERON:0000947	93.40	gold quality
layer of synovial tissue	UBERON:0007616	93.39	gold quality
left ovary	UBERON:0002119	93.28	gold quality
synovial joint	UBERON:0002217	92.94	gold quality
body of uterus	UBERON:0009853	92.92	gold quality
coronary artery	UBERON:0001621	92.86	gold quality
epithelial cell of pancreas	CL:0000083	92.76	gold quality
mucosa of stomach	UBERON:0001199	92.75	gold quality
skin of hip	UBERON:0001554	92.72	gold quality
right coronary artery	UBERON:0001625	92.25	gold quality
vena cava	UBERON:0004087	92.12	gold quality
gall bladder	UBERON:0002110	91.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.38	gold quality
cauda epididymis	UBERON:0004360	91.34	gold quality
left adrenal gland	UBERON:0001234	91.32	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	36.17
E-ANND-3	yes	23.11
E-CURD-46	yes	20.73
E-CURD-112	yes	6.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting ANGPTL1, 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-3134	100.00	66.43	777
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-10527-5P	99.91	72.28	3754

Literature-anchored findings (GeneRIF, showing 12)

• Inhibits experimental melanoma growth when transfected into murine cells. (PMID:15940350)
• Immunohistochemical staining of Ang-1 was observed in smooth muscle cells, whereas Ang-2 was detected in endothelial cells, smooth muscle cells and macrophages. (PMID:18182823)
• Overexpression of angiopoietin 1 and metalloproteinases may be the characteristic feature of endometrium with greater potential to transform into endometriotic lesions in the peritoneal cavity. (PMID:18644593)
• ANGPTL1 represses lung cancer cell motility by abrogating the expression of the epithelial mesenchymal transformation mediator SLUG. (PMID:23434592)
• Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the regulation of human androgen biosynthesis (PMID:25970467)
• Aberrant expression of ANGPTL1 in cumulus cells is potentially associated with impaired oocyte developmental competence in polycystic ovary syndrome. (PMID:26829602)
• Low levels of ANGPTL1 is associated with colorectal cancer metastasis. (PMID:28606130)
• The findings demonstrate that lnc-ANGPTL1-3/miR-30a-3p/c-Maf axis plays a critical role in Multiple Myeloma bortezomib resistance. (PMID:31103265)
• Respiratory traits and coal workers’ pneumoconiosis: Mendelian randomisation and association analysis. (PMID:33097673)
• Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness. (PMID:33413536)
• ANGPTL1 attenuates cancer migration, invasion, and stemness through regulating FOXO3a-mediated SOX2 expression in colorectal cancer. (PMID:35475476)
• Exosome-transmitted ANGPTL1 suppresses angiogenesis in glioblastoma by inhibiting the VEGFA/VEGFR2/Akt/eNOS pathway. (PMID:38150891)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	angptl1a	ENSDARG00000012071
danio_rerio	angptl1b	ENSDARG00000100159
mus_musculus	Angptl1	ENSMUSG00000033544
rattus_norvegicus	Angptl1	ENSRNOG00000004712

Paralogs (25): TNC (ENSG00000041982), FCN1 (ENSG00000085265), ANGPT2 (ENSG00000091879), ANGPT4 (ENSG00000101280), FGL1 (ENSG00000104760), FN1 (ENSG00000115414), TNR (ENSG00000116147), TNN (ENSG00000120332), FGL2 (ENSG00000127951), FIBCD1 (ENSG00000130720), ANGPTL6 (ENSG00000130812), ANGPTL3 (ENSG00000132855), ANGPTL2 (ENSG00000136859), FCN3 (ENSG00000142748), FNDC7 (ENSG00000143107), ANGPT1 (ENSG00000154188), FCN2 (ENSG00000160339), MFAP4 (ENSG00000166482), ANGPTL4 (ENSG00000167772), TNXB (ENSG00000168477), FGG (ENSG00000171557), FGA (ENSG00000171560), FGB (ENSG00000171564), ANGPTL7 (ENSG00000171819), ANGPTL5 (ENSG00000187151)

Protein

Protein identifiers

Angiopoietin-related protein 1 — O95841 (reviewed: O95841)

Alternative names: Angiopoietin-3, Angiopoietin-like protein 1

All UniProt accessions (2): A0A0A0MSK1, O95841

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Highly expressed in adrenal gland, placenta, thyroid gland, heart, skeletal muscle and small intestine. Weakly expressed in testis, ovary, colon, pancreas, kidney and stomach.

RefSeq proteins (2): NP_001363692, NP_004664* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002181	Fibrinogen_a/b/g_C_dom	Domain
IPR014716	Fibrinogen_a/b/g_C_1	Homologous_superfamily
IPR020837	Fibrinogen_CS	Conserved_site
IPR036056	Fibrinogen-like_C	Homologous_superfamily
IPR037579	FIB_ANG-like	Family

Pfam: PF00147

UniProt features (8 total): glycosylation site 2, disulfide bond 2, signal peptide 1, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95841-F1	78.19	0.51

Functional residue map

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

Disulfide bonds (2): 280–309, 432–445

Glycosylation sites (2): 160, 188

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): RNGTGGGC_UNKNOWN, HNF3ALPHA_Q6, CCAWYNNGAAR_UNKNOWN, TAL1ALPHAE47_01, FOXD3_01, GOBP_WOUND_HEALING, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, MODULE_206, FOXJ2_01, HFH4_01, HFH1_01, HNF1_C, SABATES_COLORECTAL_ADENOMA_DN, GOBP_HEMOSTASIS, VECCHI_GASTRIC_CANCER_EARLY_DN

GO Biological Process (2): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), blood coagulation (GO:0007596)

GO Molecular Function (1): signaling receptor binding (GO:0005102)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
enzyme-linked receptor protein signaling pathway	1
hemostasis	1
wound healing	1
coagulation	1
protein binding	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANGPTL1	TEK	Q02763	847
ANGPTL1	LILRB2	Q8N423	804
ANGPTL1	ANGPTL8	Q6UXH0	770
ANGPTL1	TIE1	P35590	700
ANGPTL1	ANGPT4	Q9Y264	507
ANGPTL1	THBS1	P07996	466
ANGPTL1	EDNRB	P24530	462
ANGPTL1	FN1	P02751	451
ANGPTL1	EDNRA	P25101	439
ANGPTL1	HSPG2	P98160	436
ANGPTL1	FLT1	P16057	411
ANGPTL1	NID1	P14543	410
ANGPTL1	VASH1	Q7L8A9	377
ANGPTL1	LRRC47	Q8N1G4	372
ANGPTL1	FBN1	P35555	365

IntAct

0 interactions, top by confidence:

BioGRID (1): ANGPTL1 (Positive Genetic)

ESM2 similar proteins: A0A8J8, O08538, O15123, O18920, O35460, O35462, O35608, O43827, O77802, O95841, P02675, P02676, P02678, P02679, P02680, P04115, P12799, P12804, P14480, P17634, P21758, P30204, P86239, Q02020, Q08830, Q0P4P2, Q14314, Q15389, Q1RMR1, Q29RY7, Q3SZZ7, Q5EA66, Q5M8C6, Q5XK91, Q60FC1, Q640P2, Q6AX44, Q71KU9, Q86XS5, Q8K0E8

Diamond homologs: A0A8J8, A2AV25, D8VNS7, D8VNS8, D8VNS9, D8VNT0, E2IYB3, E9PV24, O00602, O08538, O15123, O18920, O35460, O35462, O35608, O43827, O70165, O70497, O75636, O77802, O93526, O95841, P02671, P02675, P02676, P02678, P02679, P02680, P04115, P06399, P10039, P12799, P12804, P14448, P14480, P17634, P19477, P21520, P22105, P24821

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ANGPTL1	up-regulates	TEK	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

823 predictions. Top by Δscore:

Variant	Effect	Δscore
1:178852950:CTTT:C	acceptor_gain	1.0000
1:178865819:CAG:C	acceptor_gain	1.0000
1:178865820:A:T	acceptor_gain	1.0000
1:178869137:G:C	donor_gain	1.0000
1:178869224:C:CC	acceptor_gain	1.0000
1:178870737:ATAC:A	donor_loss	1.0000
1:178870738:TACCT:T	donor_loss	1.0000
1:178870739:ACCTT:A	donor_loss	1.0000
1:178870740:C:CG	donor_loss	1.0000
1:178851316:CCTT:C	acceptor_gain	0.9900
1:178852679:TTAC:T	donor_loss	0.9900
1:178852680:TAC:T	donor_loss	0.9900
1:178852681:ACCT:A	donor_loss	0.9900
1:178852951:TTT:T	acceptor_gain	0.9900
1:178852951:TTTC:T	acceptor_loss	0.9900
1:178852952:TT:T	acceptor_gain	0.9900
1:178852952:TTC:T	acceptor_loss	0.9900
1:178852953:TCT:T	acceptor_loss	0.9900
1:178852954:C:CC	acceptor_gain	0.9900
1:178852960:A:AC	acceptor_gain	0.9900
1:178862578:G:GT	donor_gain	0.9900
1:178865814:C:CT	acceptor_gain	0.9900
1:178865821:G:C	acceptor_gain	0.9900
1:178865821:G:GC	acceptor_gain	0.9900
1:178869106:ATACT:A	donor_loss	0.9900
1:178869107:TACTT:T	donor_loss	0.9900
1:178869108:ACT:A	donor_loss	0.9900
1:178869109:CT:C	donor_loss	0.9900
1:178869110:TTACG:T	donor_loss	0.9900
1:178869111:TAC:T	donor_loss	0.9900

AlphaMissense

3276 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:178851195:C:A	W470C	1.000
1:178851195:C:G	W470C	1.000
1:178851197:A:G	W470R	1.000
1:178851197:A:T	W470R	1.000
1:178851250:C:T	G452E	1.000
1:178851270:A:C	C445W	1.000
1:178851271:C:G	C445S	1.000
1:178851271:C:T	C445Y	1.000
1:178851272:A:G	C445R	1.000
1:178851272:A:T	C445S	1.000
1:178851282:C:A	W441C	1.000
1:178851282:C:G	W441C	1.000
1:178851284:A:G	W441R	1.000
1:178851284:A:T	W441R	1.000
1:178851287:A:G	W440R	1.000
1:178851287:A:T	W440R	1.000
1:178851309:G:C	C432W	1.000
1:178851310:C:G	C432S	1.000
1:178851310:C:T	C432Y	1.000
1:178851311:A:G	C432R	1.000
1:178851311:A:T	C432S	1.000
1:178852717:G:C	F418L	1.000
1:178852717:G:T	F418L	1.000
1:178852718:A:C	F418C	1.000
1:178852718:A:G	F418S	1.000
1:178852719:A:G	F418L	1.000
1:178852923:A:G	W350R	1.000
1:178852923:A:T	W350R	1.000
1:178853606:C:A	W335C	1.000
1:178853606:C:G	W335C	1.000

dbSNP variants (sampled 300 via entrez): RS1000090913 (1:178851841 C>G,T), RS1000332602 (1:178872136 G>C), RS1000450296 (1:178871955 A>G), RS1000469920 (1:178872435 C>A), RS1000561357 (1:178853761 T>A,C), RS1000756119 (1:178872996 A>G), RS1000938748 (1:178866054 C>G), RS1001024633 (1:178860606 C>T), RS1001062308 (1:178860357 T>C), RS1001235214 (1:178866348 A>G), RS1001238073 (1:178859273 A>G), RS1001307337 (1:178865724 G>A), RS1001459651 (1:178872624 G>A), RS1001596857 (1:178873018 G>A), RS1001611105 (1:178863385 G>T)

Disease associations

OMIM: gene MIM:603874 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002223_41	HDL cholesterol	7.000000e-09
GCST004232_67	HDL cholesterol levels	2.000000e-09
GCST006585_255	Blood protein levels	3.000000e-14
GCST010697_44	Cortical surface area (min-P)	8.000000e-17
GCST010698_45	Subcortical volume (min-P)	1.000000e-11
GCST010699_30	Brain morphology (min-P)	3.000000e-09
GCST010700_47	Cortical thickness (MOSTest)	2.000000e-10
GCST010701_132	Cortical surface area (MOSTest)	3.000000e-10
GCST010702_9	Subcortical volume (MOSTest)	4.000000e-08
GCST010703_34	Brain morphology (MOSTest)	8.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	3
Dexamethasone	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
aminomethylphosphonic acid (AMPA)	increases expression	1
dicrotophos	decreases expression	1
geldanamycin	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects cotreatment, increases expression	1
trichostatin A	decreases expression	1
mancozeb	decreases expression	1
vanadyl sulfate	increases expression	1
rofecoxib	decreases expression	1
MRK 003	decreases expression	1
incobotulinumtoxinA	increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
2,4-Dichlorophenoxyacetic Acid	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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