ANGPTL5

Summary

ANGPTL5 (angiopoietin like 5, HGNC:19705) is a protein-coding gene on chromosome 11q22.1, encoding Angiopoietin-related protein 5 (Q86XS5).

Predicted to be located in extracellular region. Predicted to be active in collagen-containing extracellular matrix and extracellular space.

Source: NCBI Gene 253935 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 65 total — 2 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_178127

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19705
Approved symbol	ANGPTL5
Name	angiopoietin like 5
Location	11q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187151
Ensembl biotype	protein_coding
OMIM	607666
Entrez	253935

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000334289, ENST00000534527, ENST00000862061, ENST00000953417, ENST00000953418, ENST00000953419, ENST00000953420

RefSeq mRNA: 1 — MANE Select: NM_178127 NM_178127

CCDS: CCDS8312

Canonical transcript exons

ENST00000334289 — 9 exons

Exon	Start	End
ENSE00001338747	101894879	101895064
ENSE00001338749	101900430	101900550
ENSE00001338751	101902621	101902721
ENSE00001338753	101904814	101904907
ENSE00001338754	101905744	101905847
ENSE00001338757	101907103	101907247
ENSE00001338759	101890674	101891598
ENSE00001338761	101907814	101908001
ENSE00001357950	101916019	101916522

Expression profiles

Bgee: expression breadth ubiquitous, 104 present calls, max score 99.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2946 / max 108.5483, expressed in 73 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121950	0.2946	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.75	gold quality
left ovary	UBERON:0002119	78.72	gold quality
ovary	UBERON:0000992	78.69	gold quality
right ovary	UBERON:0002118	75.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	71.57	gold quality
popliteal artery	UBERON:0002250	68.02	gold quality
tibial artery	UBERON:0007610	68.02	gold quality
skin of leg	UBERON:0001511	67.47	gold quality
right coronary artery	UBERON:0001625	67.31	gold quality
right atrium auricular region	UBERON:0006631	67.19	gold quality
left coronary artery	UBERON:0001626	67.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	66.87	gold quality
adipose tissue	UBERON:0001013	65.37	gold quality
zone of skin	UBERON:0000014	65.06	gold quality
tibial nerve	UBERON:0001323	65.06	gold quality
apex of heart	UBERON:0002098	64.11	gold quality
heart	UBERON:0000948	62.58	gold quality
skin of abdomen	UBERON:0001416	61.50	gold quality
heart left ventricle	UBERON:0002084	59.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.87	gold quality
descending thoracic aorta	UBERON:0002345	57.93	gold quality
stromal cell of endometrium	CL:0002255	57.80	gold quality
omental fat pad	UBERON:0010414	57.67	gold quality
skeletal muscle tissue	UBERON:0001134	56.10	gold quality
thoracic aorta	UBERON:0001515	56.10	gold quality
ascending aorta	UBERON:0001496	55.61	gold quality
thoracic mammary gland	UBERON:0005200	55.21	gold quality
thyroid gland	UBERON:0002046	53.34	gold quality
left lobe of thyroid gland	UBERON:0001120	53.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	52.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting ANGPTL5, 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-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
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-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-142-5P	99.48	70.92	2416

Literature-anchored findings (GeneRIF, showing 4)

• Maps to 11q22, mainly expressed in adult human heart. (PMID:12624729)
• CD34+ CD133+ hematopoietic stem cells cultured with growth factors including Angptl5 efficiently engraft adult NOD-SCID Il2rgamma-/- (NSG) mice (PMID:21559522)
• Correlation of circulating ANGPTL5 levels with obesity, high sensitivity C-reactive protein and oxidized low-density lipoprotein in adolescents. (PMID:32286392)
• Elevated Plasma Angiopoietinlike Protein 5 (ANGPTL5) Is More Positively Associated with Glucose Metabolism Disorders in Patients with Metabolic Syndrome. (PMID:33486501)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	angptl5	ENSDARG00000056630

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), ANGPTL7 (ENSG00000171819)

Protein

Protein identifiers

Angiopoietin-related protein 5 — Q86XS5 (reviewed: Q86XS5)

Alternative names: Angiopoietin-like protein 5

All UniProt accessions (2): Q86XS5, E9PKF7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Mainly expressed in adult heart.

RefSeq proteins (1): NP_835228* (*=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
IPR050373	Fibrinogen_C-term_domain	Family

Pfam: PF00147

UniProt features (12 total): glycosylation site 3, sequence conflict 2, disulfide bond 2, signal peptide 1, chain 1, domain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XS5-F1	81.80	0.66

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): 310–314, 324–338

Glycosylation sites (3): 53, 238, 329

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): CMYB_01, TTTGTAG_MIR520D, chr11q22, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, YY1_Q6, WHN_B, GCCATNTTG_YY1_Q6, GOCC_EXTERNAL_ENCAPSULATING_STRUCTURE, MIR570_3P, MIR510_3P, MIR548L, MIR5590_3P, MIR142_5P, MIR548AV_5P_MIR548K, MIR8054

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANGPTL5	LILRB2	Q8N423	583
ANGPTL5	FGF1	P05230	555
ANGPTL5	CEP126	Q9P2H0	531
ANGPTL5	ANGPTL8	Q6UXH0	477
ANGPTL5	ANGPTL7	O43827	465
ANGPTL5	IGFBP2	P18065	420
ANGPTL5	FAM180A	Q6UWF9	420
ANGPTL5	TNFSF15	O95150	399
ANGPTL5	VASH1	Q7L8A9	389
ANGPTL5	TIE1	P35590	382
ANGPTL5	THPO	P40225	380
ANGPTL5	TRPC6	Q9Y210	380
ANGPTL5	CFAP300	Q9BRQ4	367
ANGPTL5	KITLG	P21583	365
ANGPTL5	THBS2	P35442	362

IntAct

8 interactions, top by confidence:

A	B	Type	Score
LILRB2	ANGPTL5	psi-mi:“MI:0915”(physical association)	0.710
ANGPTL5	LILRB2	psi-mi:“MI:0407”(direct interaction)	0.710
ANGPTL5	LILRB2	psi-mi:“MI:0915”(physical association)	0.710
ANGPTL5	Pirb	psi-mi:“MI:0915”(physical association)	0.400
ANGPTL5	HNRNPM	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): ANGPTL5 (Proximity Label-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

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	58
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
147379	GRCh38/hg38 11q22.1-22.3(chr11:98357901-106059146)x1	Pathogenic
147688	GRCh38/hg38 11q22.1-22.3(chr11:101452984-104044105)x3	Pathogenic
1807796	GRCh37/hg19 11q22.1-22.3(chr11:98770072-104602846)x1	Likely pathogenic
442680	GRCh37/hg19 11q22.1-22.3(chr11:98515900-104970876)x1	Likely pathogenic

SpliceAI

1798 predictions. Top by Δscore:

Variant	Effect	Δscore
11:101891595:TCACC:T	acceptor_loss	1.0000
11:101891597:ACC:A	acceptor_loss	1.0000
11:101891598:CCT:C	acceptor_loss	1.0000
11:101891599:C:CA	acceptor_loss	1.0000
11:101891600:T:A	acceptor_loss	1.0000
11:101900428:A:C	donor_gain	1.0000
11:101905815:T:C	acceptor_gain	1.0000
11:101905817:G:GC	acceptor_gain	1.0000
11:101905854:C:CT	acceptor_gain	1.0000
11:101907102:CTACA:C	donor_gain	1.0000
11:101907250:T:TC	acceptor_gain	1.0000
11:101907254:A:C	acceptor_gain	1.0000
11:101907255:T:C	acceptor_gain	1.0000
11:101907255:T:TC	acceptor_gain	1.0000
11:101891595:TCAC:T	acceptor_gain	0.9900
11:101891596:CAC:C	acceptor_gain	0.9900
11:101891596:CACC:C	acceptor_gain	0.9900
11:101891599:C:CC	acceptor_gain	0.9900
11:101894421:A:C	donor_gain	0.9900
11:101894872:ATCTT:A	donor_loss	0.9900
11:101894873:TCTTA:T	donor_loss	0.9900
11:101894874:CTTAC:C	donor_loss	0.9900
11:101894875:TTA:T	donor_loss	0.9900
11:101894876:T:TA	donor_loss	0.9900
11:101894877:A:C	donor_loss	0.9900
11:101894878:C:G	donor_loss	0.9900
11:101894878:CCAG:C	donor_gain	0.9900
11:101900433:G:C	donor_gain	0.9900
11:101900468:A:AT	donor_gain	0.9900
11:101901612:T:A	donor_gain	0.9900

AlphaMissense

2592 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:101891546:A:C	F300L	0.962
11:101891546:A:T	F300L	0.962
11:101891548:A:G	F300L	0.962
11:101900443:A:C	F216L	0.956
11:101900443:A:T	F216L	0.956
11:101900445:A:G	F216L	0.956
11:101891446:A:G	W334R	0.938
11:101891446:A:T	W334R	0.938
11:101891543:G:C	S301R	0.933
11:101891543:G:T	S301R	0.933
11:101891545:T:G	S301R	0.933
11:101900476:G:C	F205L	0.927
11:101900476:G:T	F205L	0.927
11:101900478:A:G	F205L	0.927
11:101891441:A:C	F335L	0.923
11:101891441:A:T	F335L	0.923
11:101891443:A:G	F335L	0.923
11:101891449:A:G	W333R	0.911
11:101891449:A:T	W333R	0.911
11:101891368:A:G	W360R	0.902
11:101891368:A:T	W360R	0.902
11:101891366:C:A	W360C	0.896
11:101891366:C:G	W360C	0.896
11:101895003:A:C	F241L	0.892
11:101895003:A:T	F241L	0.892
11:101895005:A:G	F241L	0.892
11:101895056:A:G	W224R	0.886
11:101895056:A:T	W224R	0.886
11:101891444:C:A	W334C	0.884
11:101891444:C:G	W334C	0.884

dbSNP variants (sampled 300 via entrez): RS1000039510 (11:101893580 G>A,C,T), RS1000225044 (11:101908457 A>T), RS1000327131 (11:101904668 C>T), RS1000414477 (11:101910528 G>A,C), RS1000719122 (11:101916836 T>A,C), RS1000928993 (11:101905967 T>C), RS1001201877 (11:101909503 T>C), RS1001331257 (11:101903113 CA>C), RS1001363307 (11:101906332 A>G), RS1001396863 (11:101903338 A>G), RS1001413400 (11:101911901 G>A,T), RS1001484983 (11:101912120 A>C,G), RS1001576247 (11:101890327 C>T), RS1001634710 (11:101909832 C>G), RS1001644314 (11:101915346 A>G)

Disease associations

OMIM: gene MIM:607666 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002408_13	Response to methotrexate in juvenile idiopathic arthritis	1.000000e-06
GCST005336_5	Systemic sclerosis	4.000000e-06
GCST011494_57	Daytime nap	4.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Fulvestrant	increases methylation	1
Endosulfan	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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