ADAMTS8

Summary

ADAMTS8 (ADAM metallopeptidase with thrombospondin type 1 motif 8, HGNC:224) is a protein-coding gene on chromosome 11q24.3, encoding A disintegrin and metalloproteinase with thrombospondin motifs 8 (Q9UP79). Has anti-angiogenic properties.

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 enzyme. This enzyme contains two C-terminal TS motifs, and disrupts angiogenesis in vivo. A number of disorders have been mapped in the vicinity of this gene, most notably lung neoplasms. Reduced expression of this gene has been observed in multiple human cancers and this gene has been proposed as a potential tumor suppressor.

Source: NCBI Gene 11095 — RefSeq curated summary.

At a glance

• GWAS associations: 40
• Clinical variants (ClinVar): 173 total — 1 pathogenic
• MANE Select transcript: NM_007037

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:224
Approved symbol	ADAMTS8
Name	ADAM metallopeptidase with thrombospondin type 1 motif 8
Location	11q24.3
Locus type	gene with protein product
Status	Approved
Aliases	METH2, FLJ41712, ADAM-TS8
Ensembl gene	ENSG00000134917
Ensembl biotype	protein_coding
OMIM	605175
Entrez	11095

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000257359, ENST00000531752, ENST00000875535, ENST00000912959, ENST00000912960, ENST00000912961, ENST00000912962, ENST00000912963

RefSeq mRNA: 1 — MANE Select: NM_007037 NM_007037

CCDS: CCDS41732

Canonical transcript exons

ENST00000257359 — 9 exons

Exon	Start	End
ENSE00000749792	130416163	130416330
ENSE00000749793	130416940	130417075
ENSE00000990547	130419053	130419292
ENSE00000990549	130411417	130411600
ENSE00001001443	130427567	130428609
ENSE00001001447	130414531	130414832
ENSE00003475319	130408464	130408639
ENSE00003536668	130404923	130406128
ENSE00003545213	130408768	130408940

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 93.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1057 / max 14.3536, expressed in 52 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123172	0.0658	32
123173	0.0400	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	93.16	gold quality
upper lobe of left lung	UBERON:0008952	92.71	gold quality
upper lobe of lung	UBERON:0008948	91.91	gold quality
endothelial cell	CL:0000115	91.56	gold quality
lower lobe of lung	UBERON:0008949	90.91	gold quality
right lung	UBERON:0002167	88.79	gold quality
lung	UBERON:0002048	87.07	gold quality
lower esophagus mucosa	UBERON:0035834	85.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.70	gold quality
entorhinal cortex	UBERON:0002728	83.54	gold quality
lower esophagus	UBERON:0013473	83.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.22	gold quality
cauda epididymis	UBERON:0004360	82.95	gold quality
right coronary artery	UBERON:0001625	82.61	gold quality
visceral pleura	UBERON:0002401	82.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.33	gold quality
ascending aorta	UBERON:0001496	81.91	gold quality
superior frontal gyrus	UBERON:0002661	81.88	gold quality
thoracic aorta	UBERON:0001515	81.53	gold quality
prefrontal cortex	UBERON:0000451	80.99	gold quality
postcentral gyrus	UBERON:0002581	80.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.51	gold quality
vermiform appendix	UBERON:0001154	80.38	gold quality
frontal cortex	UBERON:0001870	79.70	gold quality
blood vessel layer	UBERON:0004797	79.61	gold quality
parietal lobe	UBERON:0001872	79.28	gold quality
caecum	UBERON:0001153	79.07	gold quality
caput epididymis	UBERON:0004358	78.76	gold quality
right frontal lobe	UBERON:0002810	78.48	gold quality
primary visual cortex	UBERON:0002436	78.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting ADAMTS8, 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-3134	100.00	66.43	777
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-143-5P	98.98	68.87	946

Literature-anchored findings (GeneRIF, showing 17)

• Ability of ADAMTS-8 to cleave aggrecan at aggrecanase-susceptible Glu373-Ala374 peptide bond. Presence of ADAMTS-8 mRNA transcripts in normal and osteoarthritic human cartilage. (ADAMTS-8) (PMID:15296936)
• Downdownregulation of METH-2 expression in primary NSCLC, often associated with promoter hypermethylation, is a frequent event, which may be related to the development of the disease. (PMID:15328519)
• ADAMTS8 and ADAMTS15 have emerged as novel predictors of survival in patients with breast carcinoma (PMID:16152618)
• Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% brain tumours. A role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis. (PMID:16570050)
• ADAMTS-4 and -8 are inflammatory regulated enzymes expressed in macrophage-rich areas of atherosclerotic plaques (PMID:17606262)
• Study uncovers the tumor suppressive function of ADAMTS8 and its frequent methylation in certain tumors could be developed as a potential biomarker. (PMID:24184540)
• ADAMTS 8, CCL23, and TNFSF15 are implicated in anti-angiogenic activities (PMID:24384427)
• ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer. (PMID:27493958)
• This study showed that ADAMTS1, 8, and 18 are highly expressed in GC and its nodal metastases, suggesting important roles of these proteases in carcinogenesis and lymphatic metastasis. The findings from the present study indicate that these proteases may be promising candidates for novel and alternative treatments in GC (gastric cancer) (PMID:28814085)
• Study revealed upregulation of ADAMTS8 and downregulation of FRAS1 and SOSTDC1 in primary fibroblasts from linear morphoea (LM) lesions. SOSTDC1 knock-down recapitulated the reduced TGF -beta1 responsiveness and LM fibroblast migration, while overexpression of ADAMTS 8 induced myofibroblast markers. (PMID:30367460)
• The expression level of ADAMTS8 mRNA increased 3.5 fold in Hip Degenerative Arthritis group when compared with Femoral neck fractures group. (PMID:30655094)
• ADAMTS8 is frequently down-regulated in colorectal cancer and functions as a tumor suppressor. (PMID:32033751)
• Post-translational regulation and proteolytic activity of the metalloproteinase ADAMTS8. (PMID:34687701)
• ADAMTS8 inhibited lung cancer progression through suppressing VEGFA. (PMID:35149432)
• The Prognostic Value of ADAMTS8 and Its Role as a Tumor Suppressor in Breast Cancer. (PMID:36346393)
• ADAMTS8 inhibits glioma development in vitro and in vivo. (PMID:37587889)
• HSFAS mediates fibroblast proliferation, migration, trans-differentiation and apoptosis in hypertrophic scars via interacting with ADAMTS8. (PMID:38006215)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts8a	ENSDARG00000007709
danio_rerio	ADAMTS8	ENSDARG00000058252
mus_musculus	Adamts8	ENSMUSG00000031994
rattus_norvegicus	Adamts8	ENSRNOG00000005574

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), 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)

Protein

Protein identifiers

A disintegrin and metalloproteinase with thrombospondin motifs 8 — Q9UP79 (reviewed: Q9UP79)

Alternative names: METH-2, METH-8

All UniProt accessions (1): Q9UP79

UniProt curated annotations — full annotation on UniProt →

Function. Has anti-angiogenic properties.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Highly expressed in adult and fetal lung, lower expression in brain, placenta, heart, stomach and fetal brain and kidney.

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.

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.

RefSeq proteins (1): NP_008968* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001590	Peptidase_M12B	Domain
IPR002870	Peptidase_M12B_N	Domain
IPR006586	ADAM_Cys-rich	Domain
IPR010294	ADAMTS_spacer1	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR013277	Pept_M12B_ADAM-TS8	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

UniProt features (37 total): disulfide bond 11, sequence conflict 6, glycosylation site 5, domain 4, binding site 3, compositionally biased region 2, region of interest 2, signal peptide 1, propeptide 1, active site 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UP79-F1	80.22	0.48

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): 364

Ligand- & substrate-binding residues (3): 363; 367; 373

Disulfide bonds (11): 294–347, 323–329, 341–424, 379–408, 452–477, 463–486, 472–507, 501–512, 538–575, 542–580, 553–565

Glycosylation sites (5): 344, 400, 465, 490, 599

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
R-HSA-1474244	Extracellular matrix organization
R-HSA-1643685	Disease
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 124 (showing top): MYOGENIN_Q6, GOMF_METALLOPEPTIDASE_ACTIVITY, GCANCTGNY_MYOD_Q6, RACCACAR_AML_Q6, CAGCTG_AP4_Q5, INAMURA_LUNG_CANCER_SCC_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOMF_GLYCOSAMINOGLYCAN_BINDING, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, AML1_01, GOMF_SIGNALING_RECEPTOR_BINDING, GOMF_HEPARIN_BINDING, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_PROTEOLYSIS, OSF2_Q6

GO Biological Process (4): proteolysis (GO:0006508), negative regulation of cell population proliferation (GO:0008285), extracellular matrix organization (GO:0030198), inorganic anion transport (GO:0015698)

GO Molecular Function (9): metalloendopeptidase activity (GO:0004222), integrin binding (GO:0005178), heparin binding (GO:0008201), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), low-affinity phosphate transmembrane transporter activity (GO:0009673), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): extracellular matrix (GO:0031012), extracellular region (GO:0005576), obsolete collagen-containing extracellular matrix (GO:0062023)

Reactome top-level categories

Rollup of top-8 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
extracellular structure organization	1
external encapsulating structure organization	1
transport	1
endopeptidase activity	1
metallopeptidase activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
peptidase activity	1
transition metal ion binding	1
phosphate transmembrane transporter activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS8	COL18A1	P39060	789
ADAMTS8	BCAN	Q96GW7	614
ADAMTS8	ADAMTS2	O95450	553
ADAMTS8	HAPLN4	Q86UW8	495
ADAMTS8	ACAN	P16112	477
ADAMTS8	ADAMTS4	O75173	465
ADAMTS8	SCARB2	Q14108	441
ADAMTS8	SCARB1	Q8WTV0	439
ADAMTS8	CD36	P16671	433
ADAMTS8	COMP	P49747	403
ADAMTS8	MMP15	P51511	401
ADAMTS8	THBS1	P07996	394
ADAMTS8	MMP16	P51512	394
ADAMTS8	TIMP3	P35625	383
ADAMTS8	FMOD	Q06828	383

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DSCR9	ADAMTS8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): ADAMTS8 (Proximity Label-MS), ADAMTS8 (Negative Genetic), ADAMTS8 (Two-hybrid)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A2A5I3, O19010, O19011, O42596, P01137, P04202, P04629, P07200, P09533, P16562, P17246, P18341, P35739, P50414, P54108, P54831, P57110, Q01974, Q38HS2, Q3KPV7, Q3UFB7, Q505J3, Q5R7Y0, Q5T4F7, Q60477, Q658N2, Q6UWX4, Q7T141, Q7TSQ1, Q80XH4, Q8BG58, Q91009, Q99JR5, Q9CXM0, Q9D2G9, Q9EQT5, Q9GZM7, Q9H3Y0

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	158
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625560	GRCh37/hg19 11q24.2-24.3(chr11:126809705-130289168)	Pathogenic

SpliceAI

1156 predictions. Top by Δscore:

Variant	Effect	Δscore
11:130406124:CATAA:C	acceptor_gain	1.0000
11:130406126:TAA:T	acceptor_gain	1.0000
11:130406127:AA:A	acceptor_gain	1.0000
11:130406127:AACT:A	acceptor_loss	1.0000
11:130406128:AC:A	acceptor_loss	1.0000
11:130406129:C:CC	acceptor_gain	1.0000
11:130406131:G:C	acceptor_gain	1.0000
11:130408462:A:AC	donor_gain	1.0000
11:130408463:C:CC	donor_gain	1.0000
11:130408463:CTTG:C	donor_gain	1.0000
11:130408492:T:A	donor_gain	1.0000
11:130408540:T:TA	donor_gain	1.0000
11:130408635:ATCAC:A	acceptor_gain	1.0000
11:130408636:TCAC:T	acceptor_gain	1.0000
11:130408637:CAC:C	acceptor_gain	1.0000
11:130408637:CACC:C	acceptor_gain	1.0000
11:130408638:AC:A	acceptor_gain	1.0000
11:130408639:CC:C	acceptor_gain	1.0000
11:130408640:C:CA	acceptor_loss	1.0000
11:130408640:C:CC	acceptor_gain	1.0000
11:130408641:T:C	acceptor_loss	1.0000
11:130408763:CTCA:C	donor_loss	1.0000
11:130408764:TCA:T	donor_loss	1.0000
11:130408765:CA:C	donor_loss	1.0000
11:130408766:A:C	donor_loss	1.0000
11:130408936:TTTCC:T	acceptor_gain	1.0000
11:130408937:TTCC:T	acceptor_gain	1.0000
11:130408938:TCC:T	acceptor_gain	1.0000
11:130408938:TCCC:T	acceptor_loss	1.0000
11:130408939:CC:C	acceptor_gain	1.0000

AlphaMissense

5770 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:130408823:C:G	C623S	0.999
11:130408824:A:T	C623S	0.999
11:130408916:C:G	C592S	0.999
11:130408917:A:T	C592S	0.999
11:130408581:C:G	C661S	0.998
11:130408582:A:T	C661S	0.998
11:130408595:A:C	C656W	0.998
11:130408596:C:G	C656S	0.998
11:130408596:C:T	C656Y	0.998
11:130408597:A:G	C656R	0.998
11:130408597:A:T	C656S	0.998
11:130408810:G:C	C627W	0.998
11:130408811:C:G	C627S	0.998
11:130408811:C:T	C627Y	0.998
11:130408812:A:T	C627S	0.998
11:130408824:A:G	C623R	0.998
11:130408861:C:A	W610C	0.998
11:130408861:C:G	W610C	0.998
11:130408917:A:G	C592R	0.998
11:130411580:C:A	W529C	0.998
11:130411580:C:G	W529C	0.998
11:130408566:C:G	C666S	0.997
11:130408567:A:T	C666S	0.997
11:130408620:C:G	C648S	0.997
11:130408621:A:T	C648S	0.997
11:130408812:A:G	C627R	0.997
11:130408823:C:T	C623Y	0.997
11:130408863:A:G	W610R	0.997
11:130408863:A:T	W610R	0.997
11:130408916:C:T	C592Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000073917 (11:130425887 C>A,T), RS1000090539 (11:130420850 A>G), RS1000135900 (11:130429381 C>G,T), RS1000211417 (11:130428989 C>G), RS1000233449 (11:130422789 A>G,T), RS1000388374 (11:130417673 T>G), RS1000467722 (11:130427297 A>T), RS1000499992 (11:130404428 T>C), RS1000540887 (11:130427038 A>G), RS1000565767 (11:130405687 G>A,C), RS1000566258 (11:130425978 A>C), RS1000974285 (11:130421703 C>A,T), RS1001211215 (11:130430438 C>T), RS1001435757 (11:130424363 G>A), RS1001569956 (11:130423376 C>T)

Disease associations

OMIM: gene MIM:605175 | disease phenotypes: MIM:157900, MIM:147791

GenCC curated gene-disease

Mondo (2): Mobius syndrome (MONDO:0008006), Jacobsen syndrome (MONDO:0007838)

Orphanet (2): Moebius syndrome (Orphanet:570), Jacobsen syndrome (Orphanet:2308)

HPO phenotypes

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

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST002626_9	Vertical cup-disc ratio	5.000000e-09
GCST003274_8	Pulse pressure	4.000000e-06
GCST004074_5	Intraocular pressure	4.000000e-06
GCST004074_6	Intraocular pressure	2.000000e-08
GCST004075_44	Vertical cup-disc ratio	3.000000e-09
GCST004075_45	Vertical cup-disc ratio	7.000000e-09
GCST004137_12	Optic cup area	5.000000e-08
GCST004137_4	Optic cup area	1.000000e-07
GCST004278_70	Pulse pressure	2.000000e-07
GCST004278_72	Pulse pressure	2.000000e-07
GCST004775_31	Pulse pressure	2.000000e-12
GCST005170_35	Intraocular pressure	4.000000e-06
GCST005580_206	Intraocular pressure	4.000000e-25
GCST005580_233	Intraocular pressure	4.000000e-17
GCST005667_27	Central corneal thickness	1.000000e-26
GCST006168_13	Pulse pressure x alcohol consumption interaction (2df test)	1.000000e-52
GCST006168_37	Pulse pressure x alcohol consumption interaction (2df test)	7.000000e-48
GCST007094_139	Diastolic blood pressure	1.000000e-12
GCST007096_197	Pulse pressure	8.000000e-69
GCST007097_21	Pulse pressure	3.000000e-21
GCST007097_22	Pulse pressure	3.000000e-17
GCST007097_23	Pulse pressure	2.000000e-06
GCST007099_69	Systolic blood pressure	6.000000e-15
GCST007159_30	Corneal astigmatism	1.000000e-06
GCST008276_3	Corneal resistance factor	3.000000e-09
GCST008277_2	Corneal hysteresis	4.000000e-09
GCST009391_1097	Metabolite levels	9.000000e-06
GCST009412_11	Vertical cup-disc ratio	1.000000e-11
GCST009414_3	Central corneal thickness	2.000000e-09
GCST009723_74	Vertical cup-disc ratio (adjusted for vertical disc diameter)	1.000000e-21

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004695	intraocular pressure measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0005213	central corneal thickness
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:1002040	Corneal astigmatism
EFO:0010067	corneal resistance factor
EFO:0010066	corneal hysteresis
EFO:0010446	2-hydroxyglutaric acid measurement
EFO:0004346	neuroimaging measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595

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

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression	3
Progesterone	affects cotreatment, increases expression, decreases expression	3
Acetaminophen	decreases expression, increases expression	2
Doxorubicin	increases expression	2
Nickel	increases expression	2
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
sodium arsenite	affects methylation	1
butyraldehyde	increases expression	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
rofecoxib	affects expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects expression	1
Ibuprofen	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes