ADAMTS19

Summary

ADAMTS19 (ADAM metallopeptidase with thrombospondin type 1 motif 19, HGNC:17111) is a protein-coding gene on chromosome 5q23.3, encoding A disintegrin and metalloproteinase with thrombospondin motifs 19 (Q8TE59).

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The protein encoded by this gene has high sequence similarity to the protein encoded by ADAMTS16, another family member.

Source: NCBI Gene 171019 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiac valvular dysplasia 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 228 total — 10 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_133638

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17111
Approved symbol	ADAMTS19
Name	ADAM metallopeptidase with thrombospondin type 1 motif 19
Location	5q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145808
Ensembl biotype	protein_coding
OMIM	607513
Entrez	171019

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000274487, ENST00000502709, ENST00000505791, ENST00000509467, ENST00000913209, ENST00000913210, ENST00000913211, ENST00000913212, ENST00000913213, ENST00000913214, ENST00000913215, ENST00000913216

RefSeq mRNA: 1 — MANE Select: NM_133638 NM_133638

CCDS: CCDS4146

Canonical transcript exons

ENST00000274487 — 23 exons

Exon	Start	End
ENSE00001084115	129665499	129665579
ENSE00001172253	129734932	129735109
ENSE00001172271	129684120	129684273
ENSE00001172275	129679764	129679921
ENSE00001172284	129658617	129658737
ENSE00001172288	129654306	129654433
ENSE00001172291	129648798	129648970
ENSE00001172300	129647765	129647895
ENSE00001172309	129641859	129641960
ENSE00001172315	129622198	129622348
ENSE00001172322	129620618	129620758
ENSE00001231892	129596559	129596664
ENSE00001231905	129528520	129528677
ENSE00001231923	129526284	129526456
ENSE00001231943	129461102	129461757
ENSE00001386494	129737067	129738683
ENSE00002085506	129460298	129460482
ENSE00002445916	129551864	129551907
ENSE00003460114	129701388	129701592
ENSE00003475106	129694720	129694855
ENSE00003533621	129509077	129509242
ENSE00003551253	129527748	129527831
ENSE00003684629	129704239	129704391

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 84.88.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2105 / max 30.7434, expressed in 339 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58380	0.6513	227
58379	0.3809	214
58381	0.1783	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	84.88	gold quality
buccal mucosa cell	CL:0002336	82.57	silver quality
body of uterus	UBERON:0009853	77.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.84	gold quality
endocervix	UBERON:0000458	74.69	gold quality
smooth muscle tissue	UBERON:0001135	73.72	gold quality
myometrium	UBERON:0001296	73.47	gold quality
uterine cervix	UBERON:0000002	72.42	gold quality
placenta	UBERON:0001987	71.13	gold quality
uterus	UBERON:0000995	70.88	gold quality
ectocervix	UBERON:0012249	70.61	gold quality
left uterine tube	UBERON:0001303	69.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.77	gold quality
lower esophagus	UBERON:0013473	67.60	gold quality
endometrium	UBERON:0001295	66.95	gold quality
corpus callosum	UBERON:0002336	65.88	gold quality
prefrontal cortex	UBERON:0000451	63.97	gold quality
female reproductive system	UBERON:0000474	63.86	gold quality
pigmented layer of retina	UBERON:0001782	63.82	silver quality
caudate nucleus	UBERON:0001873	63.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.58	gold quality
putamen	UBERON:0001874	62.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.33	gold quality
nucleus accumbens	UBERON:0001882	60.99	gold quality
right ovary	UBERON:0002118	60.70	gold quality
decidua	UBERON:0002450	60.55	gold quality
lower lobe of lung	UBERON:0008949	59.35	silver quality
ovary	UBERON:0000992	59.27	gold quality
frontal cortex	UBERON:0001870	58.71	gold quality
right frontal lobe	UBERON:0002810	58.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	32.43
E-ANND-3	yes	5.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting ADAMTS19, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-380-3P	99.89	70.18	1978

Literature-anchored findings (GeneRIF, showing 7)

• Although limited by sample size, this proof-of-principle study’s findings reveal ADAMTS19 as a possible candidate gene for premature ovarian failure and thus a larger follow-up study is warranted. (PMID:19508998)
• Synergistic interactions were detected between SNPs, including a non-synonymous SNP, and diplotypes within IGF2R and ADAMTS19 which may contribute to POF. (PMID:24014609)
• We found that the AAAAA, AGGAG, and AGGGA haplotypes in ACVR2B were associated with susceptibility to Premature Ovarian Failure when they also had at least one CATAG haplotype in ADAMTS19. (PMID:25051287)
• The pregnancy loss rate does not appear to be affected by both ADAMTS-13 and ADAMTS-19. (PMID:28088271)
• Mutations in ADAMTS19 lead to progressive heart valve disease. (PMID:31844321)
• ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype. (PMID:32323311)
• ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-kappaB Pathway in Human Gastric Cancer. (PMID:33921267)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Adamts19	ENSMUSG00000053441
rattus_norvegicus	Adamts19	ENSRNOG00000019577

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS5 (ENSG00000154736), ADAMTS3 (ENSG00000156140), ADAMTSL3 (ENSG00000156218), ADAMTS4 (ENSG00000158859), ADAMTS13 (ENSG00000160323), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

A disintegrin and metalloproteinase with thrombospondin motifs 19 — Q8TE59 (reviewed: Q8TE59)

All UniProt accessions (4): A0A1X7SBR9, D6R9M2, Q8TE59, H0Y8Y0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in fetal lung, but not in any adult tissues examined. Expression was detected in an osteosarcoma cDNA library.

Post-translational modifications. The precursor is cleaved by a furin endopeptidase. Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion.

Disease relevance. Cardiac valvular dysplasia 2 (CVDP2) [MIM:620067] An autosomal recessive form of congenital heart defects, characterized primarily by congenital stenosis and insufficiency of the semilunar valves, although mild insufficiency of the atrioventricular valves has been observed as well. Other features include subaortic stenosis and dilation of the ascending aorta and/or pulmonary artery in some patients. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

RefSeq proteins (1): NP_598377* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001590	Peptidase_M12B	Domain
IPR006586	ADAM_Cys-rich	Domain
IPR010294	ADAMTS_spacer1	Domain
IPR010909	PLAC	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR041645	ADAMTS_CR_2	Domain
IPR050439	ADAMTS_ADAMTS-like	Family
IPR056270	ADAMTS17/19_C	Domain

Pfam: PF00090, PF01421, PF05986, PF17771, PF19030, PF23178

UniProt features (51 total): disulfide bond 14, domain 8, sequence variant 6, glycosylation site 5, compositionally biased region 4, binding site 4, region of interest 3, sequence conflict 2, signal peptide 1, propeptide 1, short sequence motif 1, active site 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TE59-F1	68.76	0.11

Functional residue map

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

Catalytic / active sites (1): 489

Ligand- & substrate-binding residues (4): 300 (in inhibited form); 488; 492; 498

Disulfide bonds (14): 407–472, 447–454, 466–546, 505–530, 575–599, 586–607, 594–626, 620–631, 651–686, 655–691, 666–676, 994–1037, 998–1042, 1009–1026

Glycosylation sites (5): 266, 803, 913, 955, 1015

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins

MSigDB gene sets: 168 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOZGIT_ESR1_TARGETS_DN, AREB6_01, TCF4_Q5, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, MYCMAX_01, GOBP_HEART_MORPHOGENESIS, WTGAAAT_UNKNOWN, ATTACAT_MIR3803P

GO Biological Process (8): aortic valve morphogenesis (GO:0003180), mitral valve morphogenesis (GO:0003183), pulmonary valve morphogenesis (GO:0003184), tricuspid valve morphogenesis (GO:0003186), proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), collagen fibril organization (GO:0030199), ventricular septum morphogenesis (GO:0060412)

GO Molecular Function (3): metalloendopeptidase activity (GO:0004222), metal ion binding (GO:0046872), metallopeptidase activity (GO:0008237)

GO Cellular Component (1): extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
heart valve morphogenesis	2
atrioventricular valve morphogenesis	2
aortic valve development	1
mitral valve development	1
pulmonary valve development	1
tricuspid valve development	1
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
extracellular matrix organization	1
ventricular septum development	1
cardiac septum morphogenesis	1
endopeptidase activity	1
metallopeptidase activity	1
cation binding	1
peptidase activity	1
external encapsulating structure	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS19	OR8A1	Q8NGG7	398
ADAMTS19	PRSS56	P0CW18	393
ADAMTS19	ISOC1	Q96CN7	391
ADAMTS19	MINAR2	P59773	380
ADAMTS19	SLC27A6	Q9Y2P4	378
ADAMTS19	OR5M9	Q8NGP3	367
ADAMTS19	LRRC71	Q8N4P6	361
ADAMTS19	ANHX	E9PGG2	355
ADAMTS19	OR9Q2	Q8NGE9	344
ADAMTS19	FRMD7	Q6ZUT3	338
ADAMTS19	THBS1	P07996	327
ADAMTS19	SH3BP1	Q9Y3L3	320
ADAMTS19	PRRT4	C9JH25	305
ADAMTS19	SPMIP10	Q6ZNM6	299
ADAMTS19	OR4X1	Q8NH49	299

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ADAMTS19	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): HIST1H2BH (Proximity Label-MS), ADAMTS19 (Affinity Capture-MS), SENP5 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0G2K1Q8, A0AAQ4VMX2, A2VE29, A6X935, O00534, O02668, O09126, O97827, P01029, P09172, P14046, P19823, P19827, P28665, P28666, P48831, P59509, P70505, P79263, P97278, P97279, Q00193, Q03626, Q0VCM5, Q14624, Q29052, Q3T052, Q3UV74, Q5RER0, Q60813, Q61702, Q61703, Q64237, Q68CI2, Q6IE52, Q75WE7, Q7Z3S7, Q86UX2, Q8BG22, Q8BJD1

Diamond homologs: A7MBS7, A8WGB1, B3EWY9, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, G5ECS8, O08721, O08722, O08747, O14514, O15072, O60241, O60242, O95185, O95450, P07996, P10643, P11680, P27590, P27918, P35440, P35441, P35442, P35446, P35447, P35448, P57110, P58397, P59384, P59509, P59510, P59511, P79331, Q03350, Q19204

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	4
Uncertain significance	181
Likely benign	15
Benign	4

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
155679	GRCh38/hg38 5q14.3-31.1(chr5:91411708-131319563)x1	Pathogenic
1706508	GRCh37/hg19 5q23.2-23.3(chr5:124997035-128900524)x1	Pathogenic
1707568	NM_133638.6(ADAMTS19):c.1984C>T (p.Arg662Ter)	Pathogenic
1707569	NM_133638.6(ADAMTS19):c.2003+1G>T	Pathogenic
1707571	NM_133638.6(ADAMTS19):c.1957C>T (p.Arg653Ter)	Pathogenic
2050921	NM_133638.6(ADAMTS19):c.270del (p.Ser91fs)	Pathogenic
2063500	NM_133638.6(ADAMTS19):c.237_238del (p.Gln81fs)	Pathogenic
2155981	NM_133638.6(ADAMTS19):c.1930G>T (p.Glu644Ter)	Pathogenic
4845660	NM_133638.6(ADAMTS19):c.2425+1G>A	Pathogenic
688598	GRCh37/hg19 5q14.3-23.3(chr5:89949118-129317455)x3	Pathogenic
3032008	NM_133638.6(ADAMTS19):c.2923C>T (p.Arg975Ter)	Likely pathogenic
3354014	NM_133638.6(ADAMTS19):c.3084del (p.Lys1030fs)	Likely pathogenic
3897987	NM_133638.6(ADAMTS19):c.1478+1G>A	Likely pathogenic
4849330	NM_133638.6(ADAMTS19):c.2922dup (p.Arg975fs)	Likely pathogenic

SpliceAI

4385 predictions. Top by Δscore:

Variant	Effect	Δscore
5:129460479:TCAGG:T	donor_loss	1.0000
5:129460480:CAGG:C	donor_loss	1.0000
5:129460481:AGGTA:A	donor_loss	1.0000
5:129460482:GGTA:G	donor_loss	1.0000
5:129460483:G:GG	donor_gain	1.0000
5:129460484:T:A	donor_loss	1.0000
5:129509230:G:GA	donor_gain	1.0000
5:129527832:G:GG	donor_gain	1.0000
5:129528517:CA:C	acceptor_loss	1.0000
5:129528518:A:AG	acceptor_gain	1.0000
5:129528518:AGCC:A	acceptor_loss	1.0000
5:129528519:G:GC	acceptor_gain	1.0000
5:129528519:GC:G	acceptor_gain	1.0000
5:129528519:GCC:G	acceptor_gain	1.0000
5:129528519:GCCA:G	acceptor_gain	1.0000
5:129528674:CAAGG:C	donor_loss	1.0000
5:129528675:AAGGT:A	donor_loss	1.0000
5:129528676:AGGT:A	donor_loss	1.0000
5:129528677:GGT:G	donor_loss	1.0000
5:129528678:G:GC	donor_loss	1.0000
5:129528679:T:A	donor_loss	1.0000
5:129551862:A:AG	acceptor_gain	1.0000
5:129551863:G:GG	acceptor_gain	1.0000
5:129596665:G:GG	donor_gain	1.0000
5:129620611:A:AG	acceptor_gain	1.0000
5:129620612:A:G	acceptor_gain	1.0000
5:129641857:A:AG	acceptor_gain	1.0000
5:129641857:AGCAT:A	acceptor_gain	1.0000
5:129641858:G:GG	acceptor_gain	1.0000
5:129641858:GC:G	acceptor_gain	1.0000

AlphaMissense

7948 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008939 (5:129477519 A>G), RS1000026617 (5:129735725 A>G), RS1000028984 (5:129707071 G>A,T), RS1000036421 (5:129614587 T>C), RS1000036937 (5:129650639 G>T), RS1000042785 (5:129585565 G>T), RS1000056854 (5:129533585 T>C), RS1000072071 (5:129707075 A>G), RS1000108171 (5:129495610 G>T), RS1000109288 (5:129584507 A>G), RS1000125916 (5:129566998 G>A), RS1000126172 (5:129588986 G>A,T), RS1000126440 (5:129700148 G>C), RS1000141337 (5:129579406 G>T), RS1000143346 (5:129658116 C>A,G,T)

Disease associations

OMIM: gene MIM:607513 | disease phenotypes: MIM:620067

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiac valvular dysplasia 2	Strong	Autosomal recessive
congenital heart disease	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AR

Mondo (2): cardiac valvular dysplasia 2 (MONDO:0859572), congenital heart disease (MONDO:0005453)

Orphanet (0):

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001642	Pulmonic stenosis
HP:0001647	Bicuspid aortic valve
HP:0001659	Aortic regurgitation
HP:0001682	Subvalvular aortic stenosis
HP:0001962	Palpitations
HP:0003577	Congenital onset
HP:0004927	Pulmonary artery dilatation
HP:0004970	Ascending tubular aorta aneurysm
HP:0005176	Dysplastic aortic valve
HP:0005180	Tricuspid regurgitation
HP:0010444	Pulmonic regurgitation
HP:0011463	Childhood onset
HP:0025168	Left ventricular diastolic dysfunction
HP:0030148	Heart murmur
HP:0031664	Systolic heart murmur
HP:0033755	Increased left ventricular end-diastolic volume
HP:0034032	Central cyanosis
HP:0100749	Chest pain

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001453_3	Sexual dysfunction (SSRI/SNRI-related)	1.000000e-06
GCST001762_781	Obesity-related traits	9.000000e-06
GCST009723_13	Vertical cup-disc ratio (adjusted for vertical disc diameter)	4.000000e-08
GCST010701_92	Cortical surface area (MOSTest)	9.000000e-14
GCST010702_112	Subcortical volume (MOSTest)	1.000000e-09
GCST010703_249	Brain morphology (MOSTest)	2.000000e-14
GCST011616_11	Cortical volume	4.000000e-18
GCST012292_11	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	8.000000e-06
GCST012297_6	Schizophrenia, bipolar disorder or major depressive disorder	3.000000e-06
GCST90000025_10	Appendicular lean mass	8.000000e-18
GCST90020028_1113	Hip circumference adjusted for BMI	8.000000e-10
GCST90020028_1114	Hip circumference adjusted for BMI	3.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004714	sexual dysfunction
EFO:0003939	energy intake
EFO:0006939	cup-to-disc ratio measurement
EFO:0004346	neuroimaging measurement
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M12: Astacin/Adamalysin

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	5
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
propionaldehyde	decreases expression	1
bisphenol A	increases methylation, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
tebuconazole	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression, affects cotreatment	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	decreases methylation	1
Tretinoin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

300 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
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE