ANGPTL7

Summary

ANGPTL7 (angiopoietin like 7, HGNC:24078) is a protein-coding gene on chromosome 1p36.22, encoding Angiopoietin-related protein 7 (O43827). Has a role in the formation and organization of the extracellular matrix.

Enables identical protein binding activity. Involved in negative regulation of vasculature development involved in avascular cornea development in camera-type eye and regulation of extracellular matrix organization. Located in extracellular region.

Source: NCBI Gene 10218 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 79 total — 1 likely-pathogenic
• MANE Select transcript: NM_021146

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24078
Approved symbol	ANGPTL7
Name	angiopoietin like 7
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	CDT6, AngX
Ensembl gene	ENSG00000171819
Ensembl biotype	protein_coding
OMIM	618517
Entrez	10218

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000376819, ENST00000476934

RefSeq mRNA: 1 — MANE Select: NM_021146 NM_021146

CCDS: CCDS128

Canonical transcript exons

ENST00000376819 — 5 exons

Exon	Start	End
ENSE00001168140	11194461	11194659
ENSE00001168146	11193580	11193774
ENSE00001168153	11192270	11192370
ENSE00001471787	11194854	11195981
ENSE00001471825	11189355	11189955

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 99.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.1968 / max 791.4313, expressed in 163 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
614	4.1968	163

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.94	gold quality
tibial nerve	UBERON:0001323	99.13	gold quality
tendon	UBERON:0000043	96.80	gold quality
sural nerve	UBERON:0015488	94.83	gold quality
tendon of biceps brachii	UBERON:0008188	93.73	gold quality
hair follicle	UBERON:0002073	92.09	gold quality
synovial joint	UBERON:0002217	91.99	gold quality
dorsal root ganglion	UBERON:0000044	89.50	gold quality
descending thoracic aorta	UBERON:0002345	83.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.25	gold quality
thoracic aorta	UBERON:0001515	81.68	gold quality
ascending aorta	UBERON:0001496	81.29	gold quality
aorta	UBERON:0000947	78.44	gold quality
left coronary artery	UBERON:0001626	77.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.72	gold quality
lower esophagus	UBERON:0013473	77.65	gold quality
trigeminal ganglion	UBERON:0001675	77.23	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	76.53	gold quality
popliteal artery	UBERON:0002250	76.34	gold quality
tibial artery	UBERON:0007610	76.30	gold quality
coronary artery	UBERON:0001621	75.88	gold quality
right atrium auricular region	UBERON:0006631	74.34	gold quality
cartilage tissue	UBERON:0002418	74.14	gold quality
olfactory bulb	UBERON:0002264	73.80	gold quality
gall bladder	UBERON:0002110	72.84	gold quality
cardiac atrium	UBERON:0002081	72.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.32	gold quality
layer of synovial tissue	UBERON:0007616	72.09	silver quality
hindlimb stylopod muscle	UBERON:0004252	71.41	gold quality
cerebellar hemisphere	UBERON:0002245	70.75	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9543	no	1011.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PAX6

miRNA regulators (miRDB)

55 targeting ANGPTL7, 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-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-150-3P	99.43	70.51	920

Literature-anchored findings (GeneRIF, showing 18)

• Induction of ANGPTL7 secretion by glaucoma stimuli and increased concentration of ANGPTL7 in glaucomatous AH suggest that ANGPTL7 is overexpressed in glaucoma. (PMID:18421092)
• Together with previous findings, these properties strengthen ANGPTL7’s candidacy for the regulation of intraocular pressure and glaucoma. (PMID:21199193)
• Angiopoietin-like 7 is a novel pro-angiogenetic factor over-expressed in cancer (PMID:24903490)
• ANGPTL7, which is abundantly expressed in keratocytes, plays a major role in maintaining corneal avascularity and transparency. (PMID:25622036)
• ANGPTL7 is markedly down regulated in metastatic liver cancer. (PMID:25854806)
• obesity increases the level of ANGPTL7 in both plasma and adipose tissue. Increased expression of ANGPTL7 might play a minor role in the regulation of TG level in obese subjects either directly or through interaction with other ANGPTL protein members. Physical exercise reduced the level of ANGPTL7 highlighting the potential for targeting this protein as a therapeutic target for regulating dyslipidemia. (PMID:28264047)
• Downregulation of ANGPTL7 reversed AngII-induced cell proliferation and cell inflammation and promoted apoptosis in AngII-induced VSMC cells. Therefore, ANGPTL7 can be a potential target in AngII-induced hypertension. (PMID:31302653)
• Angiopoietin-Like Protein 7 and Short-Term Mortality in Acute Heart Failure. (PMID:31962333)
• A rare missense variant in ANGPTL7 with glaucoma protective effect supports inhibition or down-regulation of ANGPTL7 as a therapeutic strategy for glaucoma. (PMID:32369491)
• Angiopoietin-like protein 7 mediates TNF-alpha-induced adhesion and oxidative stress in human umbilical vein epithelial cell. (PMID:32525822)
• Angptl7 promotes insulin resistance and type 2 diabetes mellitus by multiple mechanisms including SOCS3-mediated IRS1 degradation. (PMID:32786125)
• Cord Blood Levels of Angiopoietin-Like 7 (ANGPTL7) in Preterm Infants. (PMID:33313310)
• Increased plasma ANGPTL7 levels with increased obstructive sleep apnea severity. (PMID:36017324)
• ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma. (PMID:36192519)
• Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7. (PMID:36853945)
• Rare protective variants and glaucoma-relevant cell stressors modulate Angiopoietin-like 7 expression. (PMID:37220876)
• The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment. (PMID:37319434)
• ANGPTL7 and Its Role in IOP and Glaucoma. (PMID:38497513)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	angptl7	ENSDARG00000027582
mus_musculus	Angptl7	ENSMUSG00000028989
rattus_norvegicus	Angptl7	ENSRNOG00000009589

Paralogs (25): TNC (ENSG00000041982), FCN1 (ENSG00000085265), ANGPT2 (ENSG00000091879), ANGPT4 (ENSG00000101280), FGL1 (ENSG00000104760), FN1 (ENSG00000115414), TNR (ENSG00000116147), ANGPTL1 (ENSG00000116194), 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), ANGPTL5 (ENSG00000187151)

Protein

Protein identifiers

Angiopoietin-related protein 7 — O43827 (reviewed: O43827)

Alternative names: Angiopoietin-like factor, Angiopoietin-like protein 7, Cornea-derived transcript 6 protein

All UniProt accessions (1): O43827

UniProt curated annotations — full annotation on UniProt →

Function. Has a role in the formation and organization of the extracellular matrix. In the eye, it functions as a mediator of dexamethasone-induced matrix deposition in the trabecular meshwork, the tissue responsible for the outflow of the ocular aqueous humor and for the maintenance of intraocular pressure. Is a negative regulator of angiogenesis in the cornea, and plays a major role in maintaining corneal avascularity and transparency.

Subunit / interactions. Homotetramer; disulfide-linked.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in the cornea (at protein level). Expression is restricted to the stromal layer. Also detected at the junction between the corneal stromal layer and the conjuctiva. Not detected in the sclera.

Induction. Expression is up-regulated by dexamethasone.

RefSeq proteins (1): NP_066969* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00147

UniProt features (12 total): sequence variant 3, glycosylation site 3, 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-O43827-F1	86.45	0.69

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): 131–162, 285–298

Glycosylation sites (3): 58, 253, 267

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): GCANCTGNY_MYOD_Q6, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, MORF_ZNF10, GOBP_NEGATIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, MORF_EPHA7, MORF_RAB3A, MORF_BMPR2, LYF1_01, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_HEMOSTASIS, GOBP_SENSORY_ORGAN_DEVELOPMENT

GO Biological Process (4): response to oxidative stress (GO:0006979), blood coagulation (GO:0007596), negative regulation of vasculature development involved in avascular cornea development in camera-type eye (GO:1901346), regulation of extracellular matrix organization (GO:1903053)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	1
hemostasis	1
wound healing	1
coagulation	1
avascular cornea development in camera-type eye	1
negative regulation of vasculature development	1
extracellular matrix organization	1
regulation of cellular component organization	1
protein binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANGPTL7	MYOC	Q99972	611
ANGPTL7	TEK	Q02763	546
ANGPTL7	ANGPTL5	Q86XS5	465
ANGPTL7	ANGPTL8	Q6UXH0	435
ANGPTL7	CILP	O75339	415
ANGPTL7	VASH1	Q7L8A9	410
ANGPTL7	COL28A1	Q2UY09	403
ANGPTL7	TNFSF15	O95150	394
ANGPTL7	TIE1	P35590	383
ANGPTL7	ITGBL1	O95965	380
ANGPTL7	IL1R1	P14778	374
ANGPTL7	ZNF419	Q96HQ0	371
ANGPTL7	SCAND3	Q6R2W3	369
ANGPTL7	KRTAP5-1	Q6L8H4	368
ANGPTL7	NEURL1	O76050	361

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TFAP4	ANGPTL7	psi-mi:“MI:0914”(association)	0.640
ACTN2	ANGPTL7	psi-mi:“MI:0915”(physical association)	0.560
ANGPTL7	TCP1	psi-mi:“MI:0914”(association)	0.530
PURG	U2SURP	psi-mi:“MI:0914”(association)	0.530
ANGPTL7	IGLL5	psi-mi:“MI:0914”(association)	0.350
TFAP4	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): ANGPTL7 (Two-hybrid), ANGPTL7 (Affinity Capture-MS), HSD17B8 (Affinity Capture-MS), NMT1 (Affinity Capture-MS), EDEM3 (Affinity Capture-MS), EDEM2 (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT2 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TXNDC11 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), ANGPTL7 (Biochemical Activity), EDEM2 (Affinity Capture-MS)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	63
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
929342	GRCh37/hg19 1p36.22(chr1:11053101-11336968)x1	Likely pathogenic

SpliceAI

845 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11189952:GCAG:G	donor_gain	1.0000
1:11189953:CAGGT:C	donor_loss	1.0000
1:11189955:GGTA:G	donor_loss	1.0000
1:11189956:G:A	donor_loss	1.0000
1:11189957:T:A	donor_loss	1.0000
1:11192265:TGTA:T	acceptor_loss	1.0000
1:11192266:GTA:G	acceptor_loss	1.0000
1:11192267:TAGAT:T	acceptor_loss	1.0000
1:11192268:A:AG	acceptor_gain	1.0000
1:11192268:AGAT:A	acceptor_gain	1.0000
1:11192268:AGATG:A	acceptor_loss	1.0000
1:11192269:G:GA	acceptor_gain	1.0000
1:11192269:GA:G	acceptor_gain	1.0000
1:11192269:GAT:G	acceptor_gain	1.0000
1:11192269:GATG:G	acceptor_gain	1.0000
1:11192269:GATGC:G	acceptor_gain	1.0000
1:11192367:GGAG:G	donor_gain	1.0000
1:11192368:GAG:G	donor_gain	1.0000
1:11192368:GAGG:G	donor_gain	1.0000
1:11192369:AG:A	donor_loss	1.0000
1:11192370:GG:G	donor_loss	1.0000
1:11193572:T:TA	acceptor_gain	1.0000
1:11193576:TCA:T	acceptor_loss	1.0000
1:11193578:A:AG	acceptor_gain	1.0000
1:11193578:AG:A	acceptor_gain	1.0000
1:11193578:AGG:A	acceptor_loss	1.0000
1:11193578:AGGT:A	acceptor_gain	1.0000
1:11193579:G:GG	acceptor_gain	1.0000
1:11193579:GG:G	acceptor_gain	1.0000
1:11193579:GGT:G	acceptor_gain	1.0000

AlphaMissense

2310 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11193586:T:A	C162S	0.999
1:11193587:G:A	C162Y	0.999
1:11193587:G:C	C162S	0.999
1:11193588:T:G	C162W	0.999
1:11193632:G:C	R177P	0.999
1:11194641:T:A	C285S	0.999
1:11194641:T:C	C285R	0.999
1:11194642:G:C	C285S	0.999
1:11194864:G:C	W294C	0.999
1:11194864:G:T	W294C	0.999
1:11192285:G:A	C131Y	0.998
1:11192286:C:G	C131W	0.998
1:11193586:T:C	C162R	0.998
1:11193587:G:T	C162F	0.998
1:11193709:T:A	W203R	0.998
1:11193709:T:C	W203R	0.998
1:11193758:T:C	L219P	0.998
1:11194600:T:C	F271S	0.998
1:11194600:T:G	F271C	0.998
1:11194602:A:C	S272R	0.998
1:11194604:C:A	S272R	0.998
1:11194604:C:G	S272R	0.998
1:11194642:G:A	C285Y	0.998
1:11194642:G:T	C285F	0.998
1:11194643:T:G	C285W	0.998
1:11194862:T:A	W294R	0.998
1:11194862:T:C	W294R	0.998
1:11194874:T:A	C298S	0.998
1:11194874:T:C	C298R	0.998
1:11194875:G:A	C298Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000483893 (1:11187785 G>A,C), RS1000537759 (1:11187559 A>C), RS1000689007 (1:11193375 T>C,G), RS1000759509 (1:11191992 A>T), RS1001588851 (1:11191099 G>T), RS1001871518 (1:11192696 G>A,C), RS1002125206 (1:11191733 TG>T), RS1002282159 (1:11192013 C>T), RS1002540673 (1:11190116 T>C), RS1002690802 (1:11196131 A>G), RS1002788201 (1:11188926 A>G), RS1003123280 (1:11190318 A>C), RS1003153055 (1:11195808 C>A), RS1003232904 (1:11195101 G>A,C), RS1004711564 (1:11188215 T>C)

Disease associations

OMIM: gene MIM:618517 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003475_1	Beard thickness	4.000000e-07
GCST005580_217	Intraocular pressure	3.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Nickel	decreases expression	2
Aflatoxin B1	decreases expression, increases expression	2
deoxynivalenol	decreases expression	1
tricetin	decreases expression	1
Coal	increases abundance, increases expression	1
Smoke	increases abundance, increases expression	1
T-2 Toxin	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1
Raloxifene Hydrochloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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