ADAMTS2

Summary

ADAMTS2 (ADAM metallopeptidase with thrombospondin type 1 motif 2, HGNC:218) is a protein-coding gene on chromosome 5q35.3, encoding A disintegrin and metalloproteinase with thrombospondin motifs 2 (O95450). Cleaves the propeptides of type I and II collagen prior to fibril assembly.

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) 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 encoded preproprotein is proteolytically processed to generate the mature procollagen N-proteinase. This proteinase excises the N-propeptide of the fibrillar procollagens types I-III and type V. Mutations in this gene cause Ehlers-Danlos syndrome type VIIC, a recessively inherited connective-tissue disorder. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 9509 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Ehlers-Danlos syndrome, dermatosparaxis type (Definitive, GenCC)
• GWAS associations: 22
• Clinical variants (ClinVar): 2,154 total — 64 pathogenic, 70 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈1% of expected missense variation)
• GTEx eGene: eQTL in 19 tissues, sQTL in 13 (q < 0.05)
• Phenotypes (HPO): 71
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.57 (moderately constrained)
• MANE Select transcript: NM_014244

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:218
Approved symbol	ADAMTS2
Name	ADAM metallopeptidase with thrombospondin type 1 motif 2
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	ADAMTS-3, hPCPNI, PCINP, ADAM-TS2, NPI
Ensembl gene	ENSG00000087116
Ensembl biotype	protein_coding
OMIM	604539
Entrez	9509

Gene structure

Transcript identifiers

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

MANE Select: ENST00000251582

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 1

ENST00000251582, ENST00000274609, ENST00000518335, ENST00000522937, ENST00000523450, ENST00000698889, ENST00000957641, ENST00000981650, ENST00000981651, ENST00001010661, ENST00001112225, ENST00001132052

RefSeq mRNA: 2 — MANE Select: NM_014244 NM_014244, NM_021599

CCDS: CCDS34311, CCDS4444

Canonical transcript exons

ENST00000251582 — 22 exons

Exon	Start	End
ENSE00000387854	179139890	179140035
ENSE00000387859	179129932	179130098
ENSE00000770318	179127959	179128118
ENSE00000770319	179125998	179126130
ENSE00000770321	179124973	179125180
ENSE00000770323	179122644	179122773
ENSE00000853537	179272911	179273064
ENSE00000973031	179154049	179154192
ENSE00000973032	179153491	179153623
ENSE00000973036	179132230	179132310
ENSE00001055567	179343767	179344161
ENSE00001095829	179137769	179137944
ENSE00001095836	179135909	179136042
ENSE00001095839	179132777	179132900
ENSE00001194320	179110853	179114324
ENSE00001350993	179158723	179158879
ENSE00001350999	179207513	179207715
ENSE00002514040	179181072	179181155
ENSE00002518076	179152142	179152255
ENSE00002527178	179154814	179154919
ENSE00003641249	179121661	179121750
ENSE00003847948	179345190	179345461

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 92.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1803 / max 279.5366, expressed in 943 samples.

Highest expression (Bgee): stromal cell of endometrium, subcutaneous adipose tissue, adipose tissue, omental fat pad, lung.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ADAMTS2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 13 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	1.0e-30	-0.66	5:179269393:A:G
Brain Nucleus accumbens basal ganglia	eqtl	3.4e-22	+0.89	5:179166898:G:C
Brain Hippocampus	eqtl	4.7e-17	+0.93	5:179166898:G:C
Brain Cortex	sqtl	6.2e-16	-1.16	5:179166898:G:C
Brain Putamen basal ganglia	eqtl	2.9e-15	+0.89	5:179166898:G:C
Brain Hippocampus	sqtl	1.1e-14	-1.23	5:179166898:G:C
Brain Anterior cingulate cortex BA24	sqtl	2.0e-14	-1.31	5:179166898:G:C
Brain Frontal Cortex BA9	sqtl	2.6e-13	-1.12	5:179166898:G:C
Spleen	eqtl	7.6e-09	+0.36	5:179174084:A:G
Cells Cultured fibroblasts	eqtl	2.0e-08	+0.12	5:179259445:T:C
Artery Tibial	sqtl	2.7e-07	-1.81	5:179284959:C:T
Whole Blood	eqtl	7.0e-07	+0.11	5:179347859:A:G
Adrenal Gland	eqtl	1.5e-06	+0.29	5:179346202:C:T
Brain Anterior cingulate cortex BA24	eqtl	3.1e-06	+0.52	5:179166898:G:C
Brain Caudate basal ganglia	eqtl	3.9e-06	+0.54	5:179165301:C:T
Brain Putamen basal ganglia	sqtl	4.1e-06	-0.89	5:179166668:C:T
Adipose Visceral Omentum	eqtl	1.2e-05	+0.17	5:179337897:T:A
Lung	sqtl	2.6e-04	-0.41	5:179135237:G:A
Ovary	eqtl	7.1e-04	+2.48	5:178682394:C:T
Breast Mammary Tissue	sqtl	1.0e-03	-0.46	5:179150129:C:CCTGCTCCTGG

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
65198	9.9154	899
65197	2.4408	519
65199	0.2374	130
65196	0.2352	132
65195	0.2056	123
65194	0.1458	71

Top tissues by expression

showing 100 of 140 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	92.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.49	gold quality
adipose tissue	UBERON:0001013	91.29	gold quality
omental fat pad	UBERON:0010414	91.23	gold quality
right lung	UBERON:0002167	90.77	gold quality
right coronary artery	UBERON:0001625	90.10	gold quality
spleen	UBERON:0002106	88.67	gold quality
left coronary artery	UBERON:0001626	88.03	gold quality
upper lobe of left lung	UBERON:0008952	87.94	gold quality
mucosa of stomach	UBERON:0001199	87.79	gold quality
myometrium	UBERON:0001296	87.71	gold quality
right atrium auricular region	UBERON:0006631	87.22	gold quality
left uterine tube	UBERON:0001303	87.01	gold quality
placenta	UBERON:0001987	86.97	gold quality
endocervix	UBERON:0000458	86.54	gold quality
smooth muscle tissue	UBERON:0001135	86.41	gold quality
mammary gland	UBERON:0001911	85.83	gold quality
thoracic mammary gland	UBERON:0005200	85.83	gold quality
body of uterus	UBERON:0009853	85.80	gold quality
lung	UBERON:0002048	84.49	gold quality
ectocervix	UBERON:0012249	84.47	gold quality
uterus	UBERON:0000995	84.20	gold quality
ascending aorta	UBERON:0001496	84.05	gold quality
thoracic aorta	UBERON:0001515	83.98	gold quality
vagina	UBERON:0000996	83.74	gold quality
gall bladder	UBERON:0002110	83.68	gold quality
tibial nerve	UBERON:0001323	83.36	gold quality
tibial artery	UBERON:0007610	82.80	gold quality
popliteal artery	UBERON:0002250	82.79	gold quality
right ovary	UBERON:0002118	82.67	gold quality
right lobe of liver	UBERON:0001114	82.31	gold quality
metanephros cortex	UBERON:0010533	82.30	gold quality
sural nerve	UBERON:0015488	82.15	gold quality
uterine cervix	UBERON:0000002	81.92	gold quality
descending thoracic aorta	UBERON:0002345	81.91	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.66	gold quality
endometrium	UBERON:0001295	81.38	gold quality
urinary bladder	UBERON:0001255	81.35	gold quality
pituitary gland	UBERON:0000007	81.34	gold quality
heart	UBERON:0000948	81.27	gold quality
left adrenal gland	UBERON:0001234	81.14	gold quality
apex of heart	UBERON:0002098	80.93	gold quality
left adrenal gland cortex	UBERON:0035825	80.86	gold quality
right adrenal gland	UBERON:0001233	80.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.85	gold quality
lower esophagus	UBERON:0013473	80.80	gold quality
right adrenal gland cortex	UBERON:0035827	80.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.35	gold quality
islet of Langerhans	UBERON:0000006	80.20	gold quality
liver	UBERON:0002107	79.94	gold quality
left ovary	UBERON:0002119	79.87	gold quality
adrenal gland	UBERON:0002369	79.41	gold quality
ovary	UBERON:0000992	79.39	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.32	gold quality
calcaneal tendon	UBERON:0003701	78.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.40	gold quality
skin of leg	UBERON:0001511	78.22	gold quality
colon	UBERON:0001155	77.56	gold quality
small intestine	UBERON:0002108	77.52	gold quality
body of stomach	UBERON:0001161	77.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.25	silver quality
intestine	UBERON:0000160	77.24	gold quality
transverse colon	UBERON:0001157	77.08	gold quality
heart left ventricle	UBERON:0002084	77.01	gold quality
esophagus	UBERON:0001043	76.82	gold quality
zone of skin	UBERON:0000014	76.81	gold quality
prostate gland	UBERON:0002367	76.79	gold quality
stomach	UBERON:0000945	76.75	gold quality
adenohypophysis	UBERON:0002196	76.57	gold quality
cortex of kidney	UBERON:0001225	76.21	gold quality
fundus of stomach	UBERON:0001160	76.08	gold quality
right lobe of thyroid gland	UBERON:0001119	76.01	gold quality
vermiform appendix	UBERON:0001154	75.72	gold quality
material anatomical entity	UBERON:0000465	75.26	gold quality
multicellular organism	UBERON:0000468	75.26	gold quality
anatomical system	UBERON:0000467	75.25	gold quality
skin of abdomen	UBERON:0001416	75.19	gold quality
pancreas	UBERON:0001264	74.84	gold quality
left lobe of thyroid gland	UBERON:0001120	74.80	gold quality
fallopian tube	UBERON:0003889	74.61	gold quality
lower esophagus mucosa	UBERON:0035834	74.54	gold quality
thyroid gland	UBERON:0002046	74.45	gold quality
esophagus mucosa	UBERON:0002469	73.55	gold quality
colonic epithelium	UBERON:0000397	73.36	gold quality
minor salivary gland	UBERON:0001830	73.22	gold quality
saliva-secreting gland	UBERON:0001044	72.46	gold quality
lymph node	UBERON:0000029	72.39	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.34	gold quality
muscle tissue	UBERON:0002385	72.33	gold quality
body of pancreas	UBERON:0001150	71.82	gold quality
hypothalamus	UBERON:0001898	71.60	gold quality
rectum	UBERON:0001052	70.81	gold quality
gastrocnemius	UBERON:0001388	70.49	gold quality
muscle of leg	UBERON:0001383	70.42	gold quality
skeletal muscle organ	UBERON:0014892	70.33	gold quality
adrenal tissue	UBERON:0018303	70.00	gold quality
mucosa of transverse colon	UBERON:0004991	69.93	gold quality
duodenum	UBERON:0002114	69.92	gold quality
kidney	UBERON:0002113	69.78	gold quality
adult mammalian kidney	UBERON:0000082	69.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.66

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Vagina	tissue	13.8	medium
Pituitary gland	tissue	9.4
Placenta	tissue	9.0	medium
Smooth muscle	tissue	8.4	medium
Adipose tissue	tissue	7.6	low
Endometrium 1	tissue	6.6	medium
Ovary	tissue	6.0	medium
Locus coeruleus	tissue	6.0
Gallbladder	tissue	5.6	medium
Postcentral gyrus	tissue	5.6
Cervix	tissue	5.5	medium
Urinary bladder	tissue	5.1	medium
Spleen	tissue	4.8	low
Choroid plexus	tissue	3.6
Spinal cord	tissue	3.4
Liver	tissue	3.2	medium
Hypothalamus	tissue	3.0
Breast	tissue	2.9	low
Heart muscle	tissue	2.7	medium
Pons	tissue	2.6
Lung	tissue	2.4	medium
Frontal cortex	tissue	2.3
Caudate putamen	tissue	2.3
Appendix	tissue	2.2	medium
Hippocampus	tissue	2.1	medium
Medulla oblongata	tissue	2.0
Substantia nigra	tissue	2.0
Periaqueductal gray	tissue	1.9
Adrenal gland	tissue	1.8	medium
Skin 1	tissue	1.7	medium
Lymph node	tissue	1.7	medium
Seminal vesicle	tissue	1.7	medium
Nucleus accumbens	tissue	1.7
Hippocampal formation	tissue	1.7
Superior colliculi	tissue	1.5
Cerebellum	tissue	1.5	medium
Esophagus	tissue	1.4	medium
Pancreas	tissue	1.4	medium
Cerebral cortex	tissue	1.3	medium
Rectum	tissue	1.3	medium
Thalamus	tissue	1.3
Small intestine	tissue	1.3	medium
Duodenum	tissue	1.3	medium
Somatosensory cortex	tissue	1.3
Colon	tissue	1.2	medium
Amygdala	tissue	1.2
Midbrain	tissue	1.2
Prostate	tissue	1.2	low
Entorhinal cortex	tissue	1.2
Septum	tissue	1.2
Stomach 1	tissue	1.1	medium
Temporal cortex	tissue	1.1
Insular cortex	tissue	1.1
Retrosplenial and cingulate cortex	tissue	1.0
Testis	tissue	0.9	medium
Fallopian tube	tissue	0.9	medium
Motor cortex	tissue	0.8
Retrosplenial cortex	tissue	0.8
Occipital cortex	tissue	0.8
Prefrontal cortex	tissue	0.7

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (21.7), Nucleus raphe magnus (10.1), Nuclei of the trapezoid body (10.0), Medial periolivary nuclei (9.5), Ventral periolivary nuclei (9.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ADAMTS2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 81 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358

Functional genomics

gnomAD constraint: pLI 0.00101, LOEUF 0.568, missense Z 1.49 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000251582 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:179,113,870–179,154,181	953 / 1124.7	0.85	no
5:179,154,182–179,158,792	47 / 92.7	0.51	no
5:179,158,793–179,207,538	70 / 85.3	0.82	no
5:179,207,539–179,273,052	184 / 152.1	1.21	no
5:179,273,053–179,343,793	3 / 16.7	0.18	yes (p 7.9e-04)
5:179,343,794–179,345,328	237 / 233.7	1.01	no
ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 17)

• when conditioned media of TSP2-transfectants were added to cultures of bovine pulmonary microvascular endothelial cells (BPMEC), the BPMEC proliferation was significantly inhibited; suggesting that human TSP2 is a potential inhibitor of angiogenesis (PMID:11788898)
• Although exons 3-5 or 14-16 encode protein domains that have not been recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired, providing evidence for the requirement of these domains for proper enzyme function (PMID:15373769)
• Determination of the processing, activity and cleavage specificity of the bovine ADAMTS2 protein. (PMID:16046392)
• Data show that ADAMTS-2 is able to reduce proliferation of endothelial cells, and to induce their retraction and detachment from the substrate resulting in apoptosis. (PMID:20574651)
• ADAMTS-2, -3, and -13 expression, but not that of ADAMTS-14, are increased in plaques causing AMI compared those associated with stable angina. (PMID:22205175)
• Pathway inhibition studies revealed that ADAMTS-2 upregulation by IL-6 was mediated by JNK pathway. (PMID:24752352)
• ADAMTS2 was significantly overexpressed in Fibrous dysplasia (FD) tissues, but rarely expressed in normal bone tissues, suggesting that ADAMTS2 could be a potential biomarker for FD (PMID:25674217)
• Data indicate that ADAMTS2 and 3 cleave the amino-propeptide of fibrillar collagens and regulate blood vessels homeostasis and lymphangiogenesis. Also, ADAMTS2 deficiency leads to the dermatosparactic type of Ehlers-Danlos syndrome. [review] (PMID:25863161)
• IL-1a is a strong positive regulator of ADAMTS-2 and ADAMTS-3 expression. (PMID:26232334)
• We identified three novel homozygous loss-of-function mutations (c.2927_2928delCT, p.(Pro976Argfs*42); c.669_670dupG, p.(Pro224Argfs*24); and c.2751-2A>T) and one compound heterozygous mutation (c.2T>C, p.? and c.884_887delTGAA, p.(Met295Thrfs26*)) in ADAMTS2 in five patients from four unrelated families (PMID:26765342)
• ADAMTS-2, collagen type-1, TIMP-3 and papilin levels of the uterosacral ligament play essential roles in the etiopathogenesis of pelvic organ prolapse among postmenopausal women without stress urinary incontinence. (PMID:30388611)
• Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics. (PMID:31740729)
• Our research revealed that partial microduplication of ADAMTS2 (chr5:178728830-178997692) might be benign and not correlate with disorders. And there might exist phenotypic diversities of 5q35.3 duplications. (PMID:31804359)
• ADAMTS12, a new candidate gene for pediatric stroke. (PMID:32817637)
• Mutations in the TBX15-ADAMTS2 pathway associate with a novel soft palate dysplasia. (PMID:36124393)
• Genome-wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates ADAMTS2 and CDK18 and uncovers novel loci. (PMID:36602125)
• Opposing roles for ADAMTS2 and ADAMTS14 in myofibroblast differentiation and function. (PMID:37929635)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts2a	ENSDARG00000075930
danio_rerio	adamts2b	ENSDARG00000100772
danio_rerio		ENSDARG00000115504
mus_musculus	Adamts2	ENSMUSG00000036545
rattus_norvegicus	Adamts2	ENSRNOG00000061484

Paralogs (25): ADAMTS6 (ENSG00000049192), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1347356) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 35 distinct phenotype terms.

Mouse phenotype (MP)	Records
male infertility	2
abnormal cutaneous collagen fibril morphology	2
abnormal xiphoid process morphology	1
abnormal heart morphology	1
enlarged heart	1
abnormal hair follicle morphology	1
ruffled hair	1
short snout	1
abnormal spleen morphology	1
enlarged spleen	1
small spleen	1
abnormal thymus morphology	1
enlarged thymus	1
abnormal testis morphology	1
small testis	1
abnormal spermatogenesis	1
thin skin	1
abnormal homeostasis	1
female infertility	1
emphysema	1
abnormal skin morphology	1
abnormal tail morphology	1
abnormal epididymis morphology	1
oligozoospermia	1
abnormal molar morphology	1

+10 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	P61134	98.9%	Diamond
Pongo abelii	Q5RFQ8	98.7%	Diamond
Bos taurus	Q9TT92	98.1%	Diamond
Pongo pygmaeus	P61135	97.1%	Diamond
Xenopus laevis	C5IAW9	96.9%	Diamond
Gallus gallus	P35440	80.4%	Diamond
Cavia porcellus	Q64181	73.9%	Diamond
Oncorhynchus mykiss	Q90X85	70.2%	Diamond
Paralichthys olivaceus	Q9PVW7	70.2%	Diamond
Caenorhabditis elegans	O76840	58.8%	Diamond
Acropora millepora	B3EWZ3	58.7%	Diamond
Drosophila melanogaster	Q9VTT0	52.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ZNF354C	protein-coding	30832
ZNF879	protein-coding	345462
ZNF454	protein-coding	285676
GRM6	protein-coding	2916

Protein

Protein identifiers

A disintegrin and metalloproteinase with thrombospondin motifs 2 — O95450 (reviewed: O95450)

Alternative names: Procollagen I N-proteinase, Procollagen I/II amino propeptide-processing enzyme, Procollagen N-endopeptidase

All UniProt accessions (3): A0A1B0GTY3, A0A8V8TMU7, O95450

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves the propeptides of type I and II collagen prior to fibril assembly. Does not act on type III collagen. Cleaves lysyl oxidase LOX at a site downstream of its propeptide cleavage site to produce a short LOX form with reduced collagen-binding activity.

Subunit / interactions. May belong to a multimeric complex. Binds specifically to collagen type XIV.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed at high level in skin, bone, tendon and aorta and at low levels in thymus and brain.

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. Ehlers-Danlos syndrome, dermatosparaxis type (EDSDERMS) [MIM:225410] A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSDERMS is an autosomal recessive form characterized by extreme skin fragility and easy bruising, large fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia, and short fingers. Joint hypermobility becomes more important with age. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.

Miscellaneous. Has no significant N-procollagen peptidase activity.

Isoforms (2)

UniProt ID	Names	Canonical?
O95450-1	LpNPI	yes
O95450-2	SpNPI

RefSeq proteins (2): NP_055059, NP_067610 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001590	Peptidase_M12B	Domain
IPR002870	Peptidase_M12B_N	Domain
IPR010294	ADAMTS_spacer1	Domain
IPR010909	PLAC	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR013275	Pept_M12B_ADAM-TS2	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR041645	ADAMTS_CR_2	Domain
IPR045371	ADAMTS_CR_3	Domain
IPR050439	ADAMTS_ADAMTS-like	Family

Pfam: PF00090, PF01421, PF01562, PF05986, PF17771, PF19030, PF19236

Enzyme classification (BRENDA)

• EC 3.4.24.14 — procollagen N-endopeptidase (BRENDA: 10 organisms, 94 substrates, 74 inhibitors, 17 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PROCOLLAGEN I	—	12
PNCOLLAGEN, CARBOXYMETHYLATED	0.0028	1
PROCOLLAGEN II	0.0002	1
PROPEPTIDE OF COLLAGEN ALPHA-1 CHAIN	0.001	1
PROPEPTIDE OF COLLAGEN ALPHA-2 CHAIN	0.001	1

UniProt features (49 total): disulfide bond 13, glycosylation site 8, domain 7, sequence variant 7, binding site 3, region of interest 2, splice variant 2, sequence conflict 2, signal peptide 1, propeptide 1, short sequence motif 1, active site 1, chain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95450-F1	71.59	0.15

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted secreted proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of skin, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; vesicles

Antibody reliability (HPA): IH uncertain · IF approved

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)

Position	Role
409

Ligand- & substrate-binding residues (3)

Position	Role
408	Zn(2+)
412	Zn(2+)
418	Zn(2+)

Disulfide bonds (13)

Type	Positions
Disulfide bond	343–392, 386–465, 425–451, 492–517, 503–526, 512–545, 539–550, 573–610, 577–615, 588–600, 987–1023, 991–1028, 1002–1012

Glycosylation sites (8)

Type	Positions
N-linked (glcnac…) asparagine	112, 251, 949, 993, 1031, 1098, 1145, 1150

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 12; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

ID	Pathway	Evidence
R-HSA-5083635	Defective B3GALTL causes PpS ⚕	curated
R-HSA-1650814	Collagen biosynthesis and modifying enzymes	curated
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-3906995	Diseases associated with O-glycosylation of proteins ⚕	—
R-HSA-3781865	Diseases of glycosylation ⚕	—
R-HSA-5668914	Diseases of metabolism ⚕	—
R-HSA-1474290	Collagen formation	—
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-5173105	O-linked glycosylation	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 314 (showing top): RNGTGGGC_UNKNOWN, E2F_Q4, E2F_Q4_01, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, E2F4DP1_01, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_MALE_GAMETE_GENERATION, CAGCTG_AP4_Q5, BROWNE_HCMV_INFECTION_48HR_DN, E2F1DP1_01, GOBP_PROTEIN_MATURATION, E2F_Q3, E2F1DP2_01, WU_ALZHEIMER_DISEASE_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP

GO Biological Process (4): proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), collagen fibril organization (GO:0030199), collagen catabolic process (GO:0030574)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), extracellular matrix (GO:0031012)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Collagen formation	1
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Extracellular matrix organization	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

16 GO namespaces:

Category	Terms
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
extracellular matrix organization	1
catabolic process	1
collagen metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
peptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

showing 15 of 1,110 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS2	EFEMP2	O95967	803
ADAMTS2	COL1A2	P02464	801
ADAMTS2	FBLN5	Q9UBX5	774
ADAMTS2	ATP6V0A2	Q9Y487	770
ADAMTS2	COL1A1	P02452	763
ADAMTS2	CCBE1	Q6UXH8	714
ADAMTS2	COL5A2	P05997	664
ADAMTS2	COL3A1	P02461	662
ADAMTS2	LOX	P28300	652
ADAMTS2	PYCR1	P32322	643
ADAMTS2	PLOD1	Q02809	638
ADAMTS2	COL7A1	Q02388	577
ADAMTS2	COL5A1	P20908	570
ADAMTS2	BMP1	P13497	567
ADAMTS2	ZNF384	Q8TF68	551

IntAct

Human interaction partners of ADAMTS2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
H2BC9	physical association	0.400	1
ADAM2	association	0.350	1
UGT1A5	association	0.350	1
PIK3R5	physical association	0.000	1

BioGRID (72 interactions; top human partners by supporting records): CD1B (Affinity Capture-MS; 3 records), CLEC12A (Affinity Capture-MS; 3 records), IDS (Affinity Capture-MS; 3 records), PRG2 (Affinity Capture-MS; 3 records), SUSD4 (Affinity Capture-MS; 3 records), ADAM2 (Affinity Capture-MS; 2 records), ADAM30 (Affinity Capture-MS; 2 records), ADAMTS4 (Affinity Capture-MS; 2 records), B3GNT2 (Affinity Capture-MS; 2 records), DKKL1 (Affinity Capture-MS; 2 records), LYPD4 (Affinity Capture-MS; 2 records), ST8SIA4 (Affinity Capture-MS; 2 records), TCTN2 (Affinity Capture-MS; 2 records), TMPRSS11B (Affinity Capture-MS; 2 records), ADAM33 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for ADAMTS2: 2,154 ClinVar records (134 pathogenic / likely pathogenic); 22 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

2,154 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	64
Likely pathogenic	70
Uncertain significance	720
Likely benign	1019
Benign	110

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 134 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
5502	NM_014244.5(ADAMTS2):c.673C>T (p.Gln225Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
1481564	NM_014244.5(ADAMTS2):c.688+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
1503058	NM_014244.5(ADAMTS2):c.688+2T>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
847713	NM_014244.5(ADAMTS2):c.2085+1G>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1068382	NM_014244.5(ADAMTS2):c.689-9_695del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3592177	NM_014244.5(ADAMTS2):c.3088+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
4815611	NM_014244.5(ADAMTS2):c.1344G>A (p.Trp448Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
658082	NM_014244.5(ADAMTS2):c.32del (p.Leu11fs)	Pathogenic	criteria provided, single submitter	1
838442	NM_014244.5(ADAMTS2):c.2385G>A (p.Trp795Ter)	Pathogenic	criteria provided, single submitter	1
841489	NM_014244.5(ADAMTS2):c.1513dup (p.Ala505fs)	Pathogenic	criteria provided, single submitter	1
934514	NM_014244.5(ADAMTS2):c.2927del (p.Pro976fs)	Pathogenic	criteria provided, single submitter	1
945961	NM_014244.5(ADAMTS2):c.55del (p.Leu19fs)	Pathogenic	criteria provided, single submitter	1
952616	NM_014244.5(ADAMTS2):c.842dup (p.His282fs)	Pathogenic	criteria provided, single submitter	1
1070257	NM_014244.5(ADAMTS2):c.227C>A (p.Ser76Ter)	Pathogenic	criteria provided, single submitter	1
1369667	NM_014244.5(ADAMTS2):c.21del (p.Ala8fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ADAMTS2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 3,160):

Position(s)	Effect	Δscore	Sites
5:179125181	acceptor_loss	1.0000	2
5:179129930–179129931	donor_loss	1.0000	5
5:179132317	acceptor_gain	1.0000
5:179132901–179132902	acceptor_loss	1.0000	6
5:179150236	donor_gain	1.0000
5:179153489–179153490	donor_loss	1.0000	5
5:179153624–179153625	acceptor_loss	1.0000	4
5:179153626	acceptor_gain	1.0000
5:179154048	donor_loss	1.0000	3
5:179154812–179154813	donor_loss	1.0000	3

AlphaMissense

2,917 missense substitutions predicted likely pathogenic (of 7,949 scored), across 654 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M435	9	0.993	1.000
M376	9	0.971	0.998
M416	9	0.940	0.998
M385	9	0.840	0.996
H408	8	0.999	1.000
H412	8	0.999	1.000
H418	8	0.999	1.000
D419	8	0.997	0.999
D275	8	0.996	0.999
F404	8	0.993	1.000
F371	8	0.992	0.999
D361	8	0.990	0.997
F496	8	0.989	1.000
F443	8	0.986	0.998
H209	8	0.985	0.994
D495	8	0.982	0.996
D710	8	0.981	0.997
F400	8	0.978	0.999
S391	8	0.977	0.999
S452	8	0.977	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:604539 | disease phenotypes: MIM:225410

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Ehlers-Danlos syndrome, dermatosparaxis type	Definitive	Autosomal recessive	7

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Ehlers Danlos syndrome with a likely monogenic cause	green

Mondo (1): Ehlers-Danlos syndrome, dermatosparaxis type (MONDO:0009161)

Orphanet (1): Dermatosparaxis Ehlers-Danlos syndrome (Orphanet:1901)

HPO phenotypes

showing 60 of 71 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000164	Abnormality of the dentition
HP:0000212	Gingival overgrowth
HP:0000222	Gingival hyperkeratosis
HP:0000225	Gingival bleeding
HP:0000232	Everted lower lip vermilion
HP:0000239	Large fontanelles
HP:0000260	Wide anterior fontanel
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000520	Proptosis
HP:0000545	Myopia
HP:0000592	Blue sclerae
HP:0000668	Hypodontia
HP:0000678	Dental crowding
HP:0000776	Congenital diaphragmatic hernia
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000963	Thin skin
HP:0000974	Hyperextensible skin
HP:0000978	Bruising susceptibility
HP:0000998	Hypertrichosis
HP:0001007	Hirsutism
HP:0001027	Soft, doughy skin
HP:0001030	Fragile skin
HP:0001058	Poor wound healing
HP:0001075	Atrophic scars
HP:0001270	Motor delay
HP:0001373	Joint dislocation
HP:0001382	Joint hypermobility
HP:0001476	Delayed closure of the anterior fontanelle
HP:0001537	Umbilical hernia
HP:0001582	Redundant skin
HP:0001622	Premature birth
HP:0001773	Short foot
HP:0001788	Premature rupture of membranes
HP:0001831	Short toe
HP:0001933	Subcutaneous hemorrhage
HP:0002020	Gastroesophageal reflux
HP:0002035	Rectal prolapse
HP:0002036	Hiatus hernia
HP:0002650	Scoliosis
HP:0002757	Recurrent fractures
HP:0002761	Generalized joint hypermobility
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0004279	Short palm
HP:0004322	Short stature
HP:0004876	Spontaneous neonatal pneumothorax
HP:0005280	Depressed nasal bridge
HP:0005332	Recurrent mandibular subluxations
HP:0007392	Excessive wrinkled skin
HP:0007605	Excessive wrinkling of palmar skin

GWAS associations

22 associations:

Study	Trait	p-value
GCST007294_184	Body fat distribution (trunk fat ratio)	7e-18
GCST007294_144	Body fat distribution (trunk fat ratio)	1e-17
GCST007295_117	Body fat distribution (leg fat ratio)	2e-14
GCST007295_174	Body fat distribution (leg fat ratio)	3e-14
GCST90020029_1205	Waist circumference adjusted for body mass index	8e-14
GCST002647_166	Height	6e-11
GCST90013406_80	Liver enzyme levels (alkaline phosphatase)	6e-11
GCST90020029_1204	Waist circumference adjusted for body mass index	1e-9
GCST005580_177	Intraocular pressure	3e-9
GCST90020029_1231	Waist circumference adjusted for body mass index	8e-9
GCST005580_243	Intraocular pressure	1e-8
GCST005667_26	Central corneal thickness	4e-8
GCST003824_2	Depression in response to interferon-based therapy in chronic hepatitis C	8e-8
GCST009415_3	Intraocular pressure and central corneal thickness (multi-trait analysis)	1e-7
GCST012300_4	Schizophrenia, bipolar disorder or major depressive disorder	5e-7
GCST012297_10	Schizophrenia, bipolar disorder or major depressive disorder	2e-6
GCST007158_4	Refractive astigmatism	3e-6
GCST008759_52	Intake of total sugars	5e-6
GCST009413_14	Intraocular pressure	6e-6
GCST000280_11	Attention deficit hyperactivity disorder (time to onset)	8e-6
GCST001689_1	Stroke (pediatric)	8e-6
GCST001523_45	Visceral adipose tissue adjusted for BMI	9e-6

EFO canonical traits (from GWAS)

9 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007006	depressive symptom measurement
EFO:0007859	response to interferon
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0004341	body fat distribution
EFO:0010158	sugar consumption measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C567527	Ehlers-Danlos Syndrome, Type VII, Autosomal Recessive *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M12: Astacin/Adamalysin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression, affects cotreatment, increases abundance	3
Benzo(a)pyrene	increases methylation, affects methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
Cadmium Chloride	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
mercuric bromide	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	affects methylation	1
Paraquat	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Plant Oils	increases expression	1
Progesterone	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

52 trials:

NCT	Phase	Status	Title
NCT04890431	Phase 4	UNKNOWN	Impact of Oxygen Therapy on Fatigue in Patients With Hypermobile-type Ehlers-Danlos Syndrome
NCT05603741	Phase 4	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT05279937	Phase 3	NOT_YET_RECRUITING	The Ultrasound-Guided Dextrose Prolotherapy in Ehlers-Danlos Syndrome Patients
NCT07675135	Phase 3	RECRUITING	A Phase 3 Efficacy and Safety Study of HBS-301 in Participants With Narcolepsy
NCT00001966	Phase 2	COMPLETED	Mind-Body Therapy for Pain in Ehlers-Danlos Syndrome
NCT07688096	Phase 1/2	NOT_YET_RECRUITING	Regenerative Medicine for Joint Hypermobility and Instability
NCT03686748	Early Phase 1	ACTIVE_NOT_RECRUITING	Two Point Discrimination
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00270686	Not specified	COMPLETED	Studies of Heritable Disorders of Connective Tissue
NCT01322165	Not specified	COMPLETED	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
NCT01356134	Not specified	COMPLETED	Vascular Fundus Changes in Patients With High Probability of Chronic Cerebrospinal Venous Insufficiency (CCSVI)
NCT01367977	Not specified	COMPLETED	Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life
NCT02050113	Not specified	RECRUITING	Complex Aortic Aneurysm Repair Using Physician Modified Endografts and Custom Made Devices
NCT02435745	Not specified	COMPLETED	Obstructive Sleep Apnoea in Ehlers-Danlos Syndrome
NCT02721797	Not specified	UNKNOWN	Origins and Impact of EDS in Connective Tissues and Skin
NCT02985710	Not specified	COMPLETED	Assessment of Small Fiber Neuropathy in Rare Diseases Using Sudoscan
NCT03093493	Not specified	COMPLETED	Genetics of Ehlers-Danlos Syndrome
NCT03330977	Not specified	UNKNOWN	Efficiency Clinical Study of NOVATEX MEDICAL Compression Garments in Patients With Ehlers-Danlos Syndrome
NCT03575182	Not specified	UNKNOWN	Gait Retraining in Patients With Joint Hypermobility Syndrome/Hypermobile Ehlers Danlos Syndrome
NCT03596437	Not specified	UNKNOWN	Study of Arterial Properties by Ultra-high Frequency Ultrasound in Fibromuscular Dysplasia and Vascular Ehlers-Danlos Syndrome
NCT03602482	Not specified	COMPLETED	Standing Cognition and Co-morbidities of POTS Evaluation
NCT03681080	Not specified	COMPLETED	Concentration and Attentional Deficits in POTS and Other Autonomic Neuropathies
NCT03986229	Not specified	COMPLETED	Evaluation of the Effect of Custom Compression Garments on Standing Static Balance in Ehlers Danlos Syndrome
NCT04036305	Not specified	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT04133272	Not specified	RECRUITING	Registry of Ehlers-Danlos Syndrome
NCT04437589	Not specified	COMPLETED	Opioid-Free Anesthesia for Patients With Joint Hypermobility Syndrome Undergoing Craneo-Cervical Fixation: A Case-series
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NCT04742803	Not specified	COMPLETED	Straberi Epistamp Needling Treatment For Skin Rejuvenation
NCT04806620	Not specified	RECRUITING	Unhide® Project: A Digital Health Platform to Collect Lifestyle Data for Brain Inflammation Research
NCT05137379	Not specified	COMPLETED	Evaluation of a Cohort of Patients With Ehlers-Danlos Syndrome Treated With Orthopedic Surgery (SED-eval)
NCT05366114	Not specified	UNKNOWN	Vision-based Assessment of Joint Extensibility in Ehlers Danlos Syndrome
NCT05389865	Not specified	UNKNOWN	Proximal Aortopathy in Scotland - Epidemiology and Surgical Outcomes
NCT05429996	Not specified	UNKNOWN	Ultrastructural Collagen Markers in Ehlers Danlos Syndromes
NCT05434728	Not specified	UNKNOWN	Characterization of Bleeding Disorders in EDS
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NCT05561270	Not specified	UNKNOWN	Light Exposure on Pain in Hypermobile Ehlers-Danlos Syndrome
NCT05720923	Not specified	ACTIVE_NOT_RECRUITING	Analysis of Muscular Properties in Patients With MFS and EDS
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NCT06074276	Not specified	UNKNOWN	The Effects of Almond on Facial Skin Collagen and Wrinkles
NCT06105541	Not specified	COMPLETED	Hypermobile Ehlers-Danlos Syndrome - Transcutaneous Auricular Neuromodulation
NCT06325345	Not specified	UNKNOWN	RCT of Gut-directed Hypnotherapy in Ehlers-Danlos Syndromes and Generalized Hypermobility Spectrum Disorders
NCT06336473	Not specified	UNKNOWN	Evaluation of the Effects of Cross Linking on the Biomechanical Characteristics of Skin Samples From Patients With Classic or Hypermobile Ehlers-Danlos Syndrome
NCT06539169	Not specified	UNKNOWN	FLOWER: Following Longitudinal Outcomes With Epidemiology for Rare Diseases
NCT06571721	Not specified	UNKNOWN	The Effects of Topical Almond Oil and Tretinoin on Facial Wrinkles
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NCT07083713	Not specified	ENROLLING_BY_INVITATION	Group Coaching Study for Life Goals
NCT07151274	Not specified	RECRUITING	Impact of Ehlers-Danlos Syndrome on Gynaecological Health
NCT07169669	Not specified	NOT_YET_RECRUITING	Multicentre Longitudinal Study of Bone Mineralisation Characteristics in Marfan Syndrome and Ehlers-Danlos Syndrome
NCT07464093	Not specified	RECRUITING	STABLE Pilates for Hypermobility
NCT07743229	Not specified	NOT_YET_RECRUITING	COG+OT Telerehabilitation for Adults With Subjective Cognitive Complaints