FBLN2

Summary

FBLN2 (fibulin 2, HGNC:3601) is a protein-coding gene on chromosome 3p25.1, encoding Fibulin-2 (P98095). Its binding to fibronectin and some other ligands is calcium dependent.

This gene encodes an extracellular matrix protein, which belongs to the fibulin family. This protein binds various extracellular ligands and calcium. It may play a role during organ development, in particular, during the differentiation of heart, skeletal and neuronal structures. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 2199 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 264 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 7 cancer types
• MANE Select transcript: NM_001004019

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3601
Approved symbol	FBLN2
Name	fibulin 2
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163520
Ensembl biotype	protein_coding
OMIM	135821
Entrez	2199

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 retained_intron

ENST00000295760, ENST00000295761, ENST00000404922, ENST00000421373, ENST00000465610, ENST00000477845, ENST00000492059, ENST00000859691, ENST00000859692, ENST00000939211, ENST00000939212, ENST00000939213, ENST00000952648, ENST00000952649, ENST00000952650, ENST00000952651, ENST00000952652, ENST00000952653

RefSeq mRNA: 3 — MANE Select: NM_001004019 NM_001004019, NM_001165035, NM_001998

CCDS: CCDS46761, CCDS46762

Canonical transcript exons

ENST00000404922 — 18 exons

Exon	Start	End
ENSE00001075620	13630699	13630815
ENSE00001075622	13636445	13636568
ENSE00001075627	13629820	13629945
ENSE00001075629	13626445	13626579
ENSE00001075631	13631329	13631457
ENSE00001075637	13627832	13627969
ENSE00001075639	13619730	13619831
ENSE00001075645	13621775	13621915
ENSE00001075648	13629164	13629292
ENSE00001075651	13628905	13629048
ENSE00001160811	13618904	13619017
ENSE00001301029	13549125	13549208
ENSE00001665137	13608062	13608173
ENSE00001678238	13609513	13609642
ENSE00001741030	13613984	13614164
ENSE00003480997	13618076	13618285
ENSE00003495580	13570315	13571661
ENSE00003842546	13637562	13638404

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.3184 / max 918.5274, expressed in 1119 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35408	25.1686	1047
35407	5.0169	859
35406	0.7562	425
35411	0.3390	63
35410	0.0307	18
35409	0.0070	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	98.61	gold quality
cardiac atrium	UBERON:0002081	98.17	gold quality
right coronary artery	UBERON:0001625	98.11	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.60	gold quality
adipose tissue	UBERON:0001013	96.77	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.59	gold quality
omental fat pad	UBERON:0010414	96.59	gold quality
peritoneum	UBERON:0002358	96.52	gold quality
coronary artery	UBERON:0001621	96.42	gold quality
left coronary artery	UBERON:0001626	96.32	gold quality
apex of heart	UBERON:0002098	96.19	gold quality
vena cava	UBERON:0004087	96.15	gold quality
connective tissue	UBERON:0002384	96.07	gold quality
saphenous vein	UBERON:0007318	95.74	gold quality
pericardium	UBERON:0002407	95.47	gold quality
peripheral nervous system	UBERON:0000010	95.29	gold quality
nerve	UBERON:0001021	95.29	gold quality
tibial nerve	UBERON:0001323	95.29	gold quality
skin of hip	UBERON:0001554	95.14	gold quality
stromal cell of endometrium	CL:0002255	95.10	gold quality
decidua	UBERON:0002450	95.09	gold quality
synovial joint	UBERON:0002217	94.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.44	gold quality
calcaneal tendon	UBERON:0003701	94.30	gold quality
right lobe of thyroid gland	UBERON:0001119	94.13	gold quality
skin of leg	UBERON:0001511	94.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.88	gold quality
endocervix	UBERON:0000458	93.85	gold quality
olfactory bulb	UBERON:0002264	93.36	gold quality
thoracic aorta	UBERON:0001515	93.31	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	961.22
E-MTAB-6701	yes	118.88
E-MTAB-8142	yes	103.76
E-HCAD-1	yes	78.01
E-GEOD-135922	yes	44.21
E-HCAD-10	yes	33.39
E-MTAB-6678	yes	27.15
E-HCAD-11	yes	21.94
E-MTAB-9543	yes	14.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ESR1, TP53

miRNA regulators (miRDB)

43 targeting FBLN2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
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-3681-3P	99.88	70.46	2254
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-497-3P	99.61	69.71	1990

Literature-anchored findings (GeneRIF, showing 17)

• fibulin-1 and -2 respond differentially to single and repeated damaging noxae, and their expression is differently present in liver cells (PMID:19609566)
• Data provide evidence that FBLN2 short isoform (FBLN2S) has an important tumor-suppressive and anti-angiogenic role in nasopharyngeal carcinoma (NPC). (PMID:21743496)
• Two variants in the fibulin2 gene are associated with lower systolic blood pressure and decreased risk of hypertension. (PMID:22912785)
• Study identified and validated a novel bona fide target of miR-1, Fibullin-2 (Fbln2), a secreted protein implicated in extracellular matrix remodeling. (PMID:23612897)
• levels of fibulin 2 dramatically increased in the retinal pigment epithelium following retinal detachment, suggesting a direct role for fibulin 2 in the re-attachment of the retina to the retinal pigment epithelium. (PMID:24692557)
• Using in vitro approaches and cultured breast cancer cell lines authors demonstrate that Fibulin-2 is a better substrate for ADAMTS-5 than it is for ADAMTS-4. Fibulin-2 degradation is associated to an enhancement of the invasive potential of T47D, MCF-7 and SK-BR-3 cells. (PMID:28099917)
• The enriched epithelial cells of peripheral blood lymphocytes of decreased FBLN2 expression was found to be correlated with metastasis. The fibulin-2 molecules might induce the metastatic potential through interaction with the other molecules in the microenvironment. (PMID:31069614)
• Identification of a Novel Candidate Gene for Serrated Polyposis Syndrome Germline Predisposition by Performing Linkage Analysis Combined With Whole-Exome Sequencing. (PMID:31663907)
• Gene-based tests indicated an association between intracranial aneurysms and FBLN2, a gene encoding an extracellular matrix protein implicated in vascular wall remodeling. (PMID:31732565)
• An Investigation of Fibulin-2 in Hypertrophic Cardiomyopathy. (PMID:33003281)
• Fibulin-2: A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas. (PMID:33429944)
• Fibulin-2 expression associates with vascular invasion and patient survival in breast cancer. (PMID:33836007)
• Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2. (PMID:33890711)
• Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH. (PMID:33971972)
• Knockdown of FBLN2 suppresses TGF-beta1-induced MRC-5 cell migration and fibrosis by downregulating VTN. (PMID:36608640)
• Fibulin-2 Facilitates Malignant Progression of Hepatocellular Carcinoma. (PMID:37162505)
• TMT-based quantitative proteomic analysis revealed that FBLN2 and NPR3 are involved in the early osteogenic differentiation of mesenchymal stem cells (MSCs). (PMID:37543430)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbln2	ENSDARG00000015156
mus_musculus	Fbln2	ENSMUSG00000064080
rattus_norvegicus	Fbln2	ENSRNOG00000007338

Paralogs (6): FBLN1 (ENSG00000077942), EFEMP1 (ENSG00000115380), FBLN5 (ENSG00000140092), VWDE (ENSG00000146530), EFEMP2 (ENSG00000172638), EYS (ENSG00000188107)

Protein

Protein identifiers

Fibulin-2 — P98095 (reviewed: P98095)

All UniProt accessions (4): C9JQS6, P98095, H7BXL0, H7C1A3

UniProt curated annotations — full annotation on UniProt →

Function. Its binding to fibronectin and some other ligands is calcium dependent. May act as an adapter that mediates the interaction between FBN1 and ELN.

Subunit / interactions. Homotrimer; disulfide-linked. Interacts with LAMA2. Interacts with FBN1 (via N-terminal domain). Forms a ternary complex with ELN and FBN1.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Component of both basement membranes and other connective tissues. Expressed in heart, placenta and ovary.

Post-translational modifications. O-glycosylated with core 1 or possibly core 8 glycans. It is unsure if the O-glycosylation is on Thr-347 or Ser-348.

Similarity. Belongs to the fibulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P98095-1	1	yes
P98095-2	2

RefSeq proteins (3): NP_001004019, NP_001158507, NP_001989 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000020	Anaphylatoxin/fibulin	Domain
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026823	cEGF	Domain
IPR049883	NOTCH1_EGF-like	Domain
IPR050751	ECM_structural_protein	Family
IPR055088	Fibulin_C	Domain
IPR056612	FIBL-2_dom	Domain

Pfam: PF01821, PF07645, PF12662, PF14670, PF22914, PF24532

UniProt features (76 total): disulfide bond 38, domain 13, region of interest 6, sequence variant 6, compositionally biased region 4, glycosylation site 3, sequence conflict 2, signal peptide 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98095-F1	67.85	0.12

Functional residue map

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

Post-translational modifications (1): 277

Disulfide bonds (38): 445–472, 446–479, 459–480, 489–518, 502–519, 521–545, 522–552, 535–553, 608–620, 616–629, 631–644, 683–693, 689–702, 704–717, 723–736, 730–745, 751–762, 768–781, 775–790, 796–808 …

Glycosylation sites (3): 180, 507, 1035

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2129379	Molecules associated with elastic fibres

MSigDB gene sets: 210 (showing top): KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO, LHX3_01, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, MARTINEZ_RB1_TARGETS_UP, SASAI_RESISTANCE_TO_NEOPLASTIC_TRANSFROMATION, CASTELLANO_NRAS_TARGETS_DN, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP, GOBP_REGULATION_OF_CELL_SUBSTRATE_ADHESION, NADLER_OBESITY_UP, AFP1_Q6, MODULE_88, GUO_HEX_TARGETS_UP

GO Biological Process (1): positive regulation of cell-substrate adhesion (GO:0010811)

GO Molecular Function (5): extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), extracellular matrix constituent conferring elasticity (GO:0030023), extracellular matrix binding (GO:0050840), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), extracellular matrix (GO:0031012), extracellular vesicle (GO:1903561)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Elastic fibre formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
structural molecule activity	1
extracellular matrix	1
metal ion binding	1
extracellular matrix structural constituent	1
structural molecule activity conferring elasticity	1
cellular anatomical structure	1
external encapsulating structure	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBLN2	FN1	P02751	985
FBLN2	HSPG2	P98160	985
FBLN2	ELN	P15502	960
FBLN2	FBN1	P35555	954
FBLN2	ACAN	P16112	898
FBLN2	NID1	P14543	819
FBLN2	CSPG5	O95196	790
FBLN2	LACRT	Q9GZZ8	785
FBLN2	NID2	Q14112	779
FBLN2	POSTN	Q15063	761
FBLN2	VTN	P01141	708
FBLN2	MFAP2	P55001	616
FBLN2	BGN	P13247	611
FBLN2	FBLN1	P23142	608
FBLN2	COL1A2	P02464	607

IntAct

46 interactions, top by confidence:

A	B	Type	Score
NEMP1	RGPD8	psi-mi:“MI:0914”(association)	0.640
FBLN2	FBXW5	psi-mi:“MI:0915”(physical association)	0.560
FBLN2	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	FBLN2	psi-mi:“MI:0915”(physical association)	0.560
FBLN2	HSD3B7	psi-mi:“MI:0915”(physical association)	0.560
FBLN2	JOSD1	psi-mi:“MI:0915”(physical association)	0.560
OTX1	FBLN2	psi-mi:“MI:0915”(physical association)	0.560
FBLN2	ZNF414	psi-mi:“MI:0915”(physical association)	0.560
FBLN2	NUFIP2	psi-mi:“MI:0915”(physical association)	0.550
FBLN2	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
TNKS2	FBLN2	psi-mi:“MI:0915”(physical association)	0.370
FBLN2	ZYX	psi-mi:“MI:0915”(physical association)	0.370
ZYX	FBLN2	psi-mi:“MI:0915”(physical association)	0.370
FBLN2		psi-mi:“MI:0915”(physical association)	0.370
	FBLN2	psi-mi:“MI:0915”(physical association)	0.370
FBLN2	TFAP2C	psi-mi:“MI:0915”(physical association)	0.370
FBLN2	ZNF316	psi-mi:“MI:0914”(association)	0.350
DEFB136	MANBA	psi-mi:“MI:0914”(association)	0.350
CXCL5	OLFM2	psi-mi:“MI:0914”(association)	0.350
FBLN2	PCBP3	psi-mi:“MI:0914”(association)	0.350
FBLN2	AURKA	psi-mi:“MI:0914”(association)	0.350
NTN5	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
RRP8	POLRMT	psi-mi:“MI:0914”(association)	0.350
UBAC1	ADCY9	psi-mi:“MI:0914”(association)	0.350
ATF3	ILVBL	psi-mi:“MI:0914”(association)	0.350
ATF1	ESYT2	psi-mi:“MI:0914”(association)	0.350
FBXW5	FBLN2	psi-mi:“MI:0915”(physical association)	0.000
LCE3D	FBLN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): FBLN2 (Two-hybrid), FBLN2 (Two-hybrid), FBLN2 (Two-hybrid), FBLN2 (Two-hybrid), FBLN2 (Two-hybrid), FBLN2 (Two-hybrid), FBLN2 (Two-hybrid), FBLN2 (Reconstituted Complex), FBLN2 (Reconstituted Complex), FBLN2 (Reconstituted Complex), FBLN2 (Reconstituted Complex), FBLN2 (Reconstituted Complex), FBLN2 (Reconstituted Complex), FBN1 (Reconstituted Complex), FBLN2 (Reconstituted Complex)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: A0A6I8RMG7, A2AJ76, B3EWY9, B5DFC9, O35568, O77469, O88322, P10493, P14543, P41413, P48960, P98095, Q04592, Q09165, Q14112, Q19267, Q2KIT5, Q2Q421, Q2Q426, Q4G063, Q4V7F2, Q4V7M2, Q5EA46, Q5RBP1, Q5XH36, Q60438, Q6UXH1, Q6UXI9, Q7SXF6, Q7ZXL5, Q86XX4, Q8BPB5, Q8K4G1, Q8R4U0, Q8R4Y4, Q91XD7, Q96HD1, Q96RW7, Q9CYA0, Q9JJS0

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 7 cancer types — BLCA, CHOL, HCC, HNSC, NBL, PAAD, PRAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	229
Likely benign	9
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

4138 predictions. Top by Δscore:

Variant	Effect	Δscore
3:13608057:CACA:C	acceptor_loss	1.0000
3:13608060:A:AG	acceptor_gain	1.0000
3:13608060:AG:A	acceptor_gain	1.0000
3:13608060:AGGC:A	acceptor_loss	1.0000
3:13608061:G:A	acceptor_loss	1.0000
3:13608061:G:GA	acceptor_gain	1.0000
3:13608061:GG:G	acceptor_gain	1.0000
3:13608061:GGC:G	acceptor_gain	1.0000
3:13608061:GGCT:G	acceptor_gain	1.0000
3:13608061:GGCTC:G	acceptor_gain	1.0000
3:13608172:AG:A	donor_loss	1.0000
3:13608173:GG:G	donor_loss	1.0000
3:13608174:G:A	donor_loss	1.0000
3:13619726:CCA:C	acceptor_loss	1.0000
3:13619727:CA:C	acceptor_loss	1.0000
3:13619728:A:AG	acceptor_gain	1.0000
3:13619729:G:GA	acceptor_gain	1.0000
3:13619729:GA:G	acceptor_gain	1.0000
3:13619729:GAC:G	acceptor_gain	1.0000
3:13619729:GACA:G	acceptor_gain	1.0000
3:13619829:AAGG:A	donor_loss	1.0000
3:13619830:AGGT:A	donor_loss	1.0000
3:13619831:GGTG:G	donor_loss	1.0000
3:13619833:T:A	donor_loss	1.0000
3:13621760:T:TA	acceptor_gain	1.0000
3:13621762:C:CA	acceptor_gain	1.0000
3:13621763:G:A	acceptor_gain	1.0000
3:13621905:G:GT	donor_gain	1.0000
3:13626440:TGCAG:T	acceptor_loss	1.0000
3:13626441:GCAGA:G	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010557 (3:13584391 C>T), RS1000017389 (3:13615351 G>A), RS1000084640 (3:13567586 G>T), RS1000112278 (3:13550878 C>G,T), RS1000245817 (3:13563095 G>A), RS1000288853 (3:13579242 G>A), RS1000379309 (3:13587009 GT>G), RS1000414508 (3:13593753 G>A,C), RS1000437340 (3:13573800 G>A), RS1000454005 (3:13612726 T>A), RS1000493603 (3:13565262 C>G), RS1000497919 (3:13572988 T>C), RS1000546464 (3:13600535 A>G), RS1000547801 (3:13550599 C>T), RS1000571384 (3:13572745 G>T)

Disease associations

OMIM: gene MIM:135821 | disease phenotypes: MIM:611783

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal dominant
pulmonary arterial hypertension	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Limited	AD
pulmonary arterial hypertension	Limited	AD

Mondo (3): pulmonary arterial hypertension (MONDO:0015924), erythrocytosis, familial, 4 (MONDO:0012729), congenital heart disease (MONDO:0005453)

Orphanet (3): Pulmonary arterial hypertension (Orphanet:182090), Autosomal dominant secondary polycythemia (Orphanet:247511), Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001715_5	Bipolar disorder with mood-incongruent psychosis	2.000000e-06
GCST003469_5	Response to cognitive-behavioural therapy in anxiety disorder	1.000000e-06
GCST005951_48	Body mass index	5.000000e-08
GCST012227_985	Hip circumference adjusted for BMI	1.000000e-09
GCST90000025_723	Appendicular lean mass	2.000000e-13
GCST90020028_1833	Hip circumference adjusted for BMI	2.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0004340	body mass index
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
C567086	Erythrocytosis, Familial, 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	3
Valproic Acid	affects expression, increases expression	3
entinostat	increases expression, affects cotreatment	2
bisphenol S	increases expression, increases methylation	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	increases methylation	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	increases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
pentanal	increases expression	1
paricalcitol	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
belinostat	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study