ADAMTS20

Summary

ADAMTS20 (ADAM metallopeptidase with thrombospondin type 1 motif 20, HGNC:17178) is a protein-coding gene on chromosome 12q12, encoding A disintegrin and metalloproteinase with thrombospondin motifs 20 (P59510). May play a role in tissue-remodeling process occurring in both normal and pathological conditions.

The protein encoded by this gene is a member of the ADAMTS family of zinc-dependent proteases. The encoded protein has a signal peptide that is cleaved to release the mature peptide, which is secreted and found in the extracellular matrix. This protein may be involved in tissue remodeling.

Source: NCBI Gene 80070 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 302 total — 1 pathogenic
• MANE Select transcript: NM_025003

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17178
Approved symbol	ADAMTS20
Name	ADAM metallopeptidase with thrombospondin type 1 motif 20
Location	12q12
Locus type	gene with protein product
Status	Approved
Aliases	GON-1
Ensembl gene	ENSG00000173157
Ensembl biotype	protein_coding
OMIM	611681
Entrez	80070

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000389420, ENST00000549670, ENST00000553158, ENST00000935091

RefSeq mRNA: 1 — MANE Select: NM_025003 NM_025003

CCDS: CCDS31778

Canonical transcript exons

ENST00000389420 — 39 exons

Exon	Start	End
ENSE00001182374	43425514	43425690
ENSE00001182378	43427308	43427469
ENSE00001182387	43428241	43428531
ENSE00001182395	43428635	43428799
ENSE00001182404	43430352	43430471
ENSE00001182411	43431332	43431496
ENSE00001182418	43432304	43432468
ENSE00001182424	43432601	43432811
ENSE00001182432	43434245	43434371
ENSE00001215605	43376524	43376653
ENSE00001215612	43377365	43377562
ENSE00001215623	43383558	43383728
ENSE00001215629	43383804	43383977
ENSE00001215646	43399066	43399233
ENSE00001292061	43369290	43369381
ENSE00001301522	43375379	43375512
ENSE00001312903	43356484	43356588
ENSE00001313964	43376236	43376330
ENSE00001317665	43429617	43429724
ENSE00001322356	43376057	43376148
ENSE00001522072	43353866	43354298
ENSE00001608485	43490395	43490435
ENSE00001614273	43492505	43492629
ENSE00001617800	43452274	43452410
ENSE00001623637	43452514	43452695
ENSE00001671990	43439622	43439751
ENSE00001674296	43439897	43440069
ENSE00001707132	43446595	43446712
ENSE00001720838	43468600	43468705
ENSE00001728974	43502152	43502405
ENSE00001730776	43550909	43551270
ENSE00001741222	43462895	43462999
ENSE00001759316	43493170	43493253
ENSE00001765638	43443791	43443883
ENSE00001768016	43532036	43532195
ENSE00001777776	43466652	43466795
ENSE00001787036	43464591	43464732
ENSE00001789433	43453907	43454052
ENSE00003890561	43551831	43552203

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 77.58.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9982 / max 98.5168, expressed in 186 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130502	0.9982	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.55	gold quality
cranial nerve II	UBERON:0000941	61.34	silver quality
buccal mucosa cell	CL:0002336	61.16	gold quality
tibialis anterior	UBERON:0001385	51.08	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
epithelial cell of pancreas	CL:0000083	49.07	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
quadriceps femoris	UBERON:0001377	48.88	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
ileal mucosa	UBERON:0000331	47.76	silver quality
pancreatic ductal cell	CL:0002079	47.73	silver quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality
thymus	UBERON:0002370	47.42	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.52

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• ADAMTS-9 and ADAMTS-20 have an identical modular structure, are distinct in possessing 15 thrombospondin type I repeats and a unique C-terminal domain, and have a similar gene structure (PMID:12514189)
• This protein is identified and characterized and its relation to other disintegrins and thrombospondin 1 repeats is examined. (PMID:12562771)
• In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans. (PMID:25798845)
• CRISPR-Cas9 inactivation of ADAMTS9 impaired ciliogenesis in RPE-1 cells, which was restored by catalytically active ADAMTS9 or ADAMTS20 acting in trans, but not by their proteolytically inactive mutants. (PMID:30814516)
• Degradomic Identification of Membrane Type 1-Matrix Metalloproteinase as an ADAMTS9 and ADAMTS20 Substrate. (PMID:37169079)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Adamts20	ENSMUSG00000022449
rattus_norvegicus	Adamts20	ENSRNOG00000033397

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), 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), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

A disintegrin and metalloproteinase with thrombospondin motifs 20 — P59510 (reviewed: P59510)

All UniProt accessions (3): P59510, G3V1X8, H0YHN3

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in tissue-remodeling process occurring in both normal and pathological conditions. May have a protease-independent function in the transport from the endoplasmic reticulum to the Golgi apparatus of secretory cargos, mediated by the GON domain.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Very sparingly expressed, although is detected at low levels in testis, prostate, ovary, heart, placenta, lung and pancreas. Overexpressed in several brain, colon and breast carcinomas.

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.

Isoforms (3)

UniProt ID	Names	Canonical?
P59510-1	1	yes
P59510-2	2
P59510-3	3

RefSeq proteins (1): NP_079279* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001590	Peptidase_M12B	Domain
IPR002870	Peptidase_M12B_N	Domain
IPR010294	ADAMTS_spacer1	Domain
IPR012314	Pept_M12B_GON-ADAMTSs	Domain
IPR013273	ADAMTS/ADAMTS-like	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, PF08685, PF17771, PF19030, PF19236

UniProt features (70 total): domain 18, glycosylation site 15, disulfide bond 11, sequence conflict 11, splice variant 4, binding site 3, sequence variant 3, signal peptide 1, propeptide 1, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59510-F1	69.35	0.07

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): 404

Ligand- & substrate-binding residues (3): 403; 407; 413

Disulfide bonds (11): 334–387, 363–369, 381–462, 419–446, 489–511, 500–521, 506–540, 534–545, 568–605, 572–610, 583–595

Glycosylation sites (15): 92, 191, 445, 702, 717, 728, 809, 870, 1061, 1456, 1542, 1572, 1763, 1781, 1852

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
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: 79 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, chr12q12, GOBP_PIGMENTATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, WTGAAAT_UNKNOWN, GOBP_PIGMENT_CELL_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PIGMENTATION, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_MELANOCYTE_DIFFERENTIATION, CUI_TCF21_TARGETS_2_UP, GOBP_PROTEOLYSIS, WILCOX_RESPONSE_TO_PROGESTERONE_UP, GOMF_PEPTIDASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (9): proteolysis (GO:0006508), apoptotic process (GO:0006915), signal transduction (GO:0007165), positive regulation of signal transduction (GO:0009967), extracellular matrix organization (GO:0030198), melanocyte differentiation (GO:0030318), negative regulation of apoptotic process (GO:0043066), positive regulation of melanocyte differentiation (GO:0045636), regulation of developmental pigmentation (GO:0048070)

GO Molecular Function (7): metalloendopeptidase activity (GO:0004222), zinc ion binding (GO:0008270), endopeptidase activity (GO:0004175), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
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
peptidase activity	2
protein metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
extracellular structure organization	1
external encapsulating structure organization	1
pigment cell differentiation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
melanocyte differentiation	1
regulation of melanocyte differentiation	1
positive regulation of pigment cell differentiation	1
developmental pigmentation	1
regulation of pigmentation	1
endopeptidase activity	1
metallopeptidase activity	1
transition metal ion binding	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

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS20	FURIN	P09958	660
ADAMTS20	SCARB2	Q14108	648
ADAMTS20	CD36	P16671	643
ADAMTS20	ACAN	P16112	572
ADAMTS20	SCARB1	Q8WTV0	557
ADAMTS20	SSBP2	P81877	466
ADAMTS20	B3GLCT	Q6Y288	454
ADAMTS20	SLC45A2	Q9UMX9	450
ADAMTS20	KITLG	P21583	441
ADAMTS20	TSR3	Q9UJK0	436
ADAMTS20	TPCN2	Q8NHX9	434
ADAMTS20	DCT	P40126	418
ADAMTS20	ACP4	Q9BZG2	398
ADAMTS20	TBX22	Q9Y458	398
ADAMTS20	ADAMTS9	Q9P2N4	398

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): ADAMTS20 (Affinity Capture-MS), ADAMTS20 (Affinity Capture-RNA), QARS (Cross-Linking-MS (XL-MS)), ADAMTS20 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A5A6L1, B3F211, D3Z5L9, O00622, O15072, O54775, O95388, O95450, P08833, P18406, P19336, P24593, P24594, P47876, P51609, P59384, P59510, P59511, P79331, P97857, Q05717, Q07079, Q1EHB3, Q28985, Q4VC17, Q5XHC5, Q64299, Q68SA9, Q69Z28, Q7T3Q2, Q8AWW5, Q8C9W3, Q8CJ69, Q8N8U9, Q8TE57, Q8TE58, Q8TE60, Q8WXS8, Q90WV8, Q91713

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	246
Likely benign	37
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
149635	GRCh38/hg38 12q12-13.11(chr12:40713887-46551900)x1	Pathogenic

SpliceAI

6789 predictions. Top by Δscore:

Variant	Effect	Δscore
12:43369285:AATAC:A	donor_loss	1.0000
12:43369286:ATAC:A	donor_loss	1.0000
12:43369287:TA:T	donor_loss	1.0000
12:43369288:AC:A	donor_loss	1.0000
12:43369289:CCTG:C	donor_loss	1.0000
12:43369377:CGTAG:C	acceptor_gain	1.0000
12:43369378:GTAG:G	acceptor_gain	1.0000
12:43369378:GTAGC:G	acceptor_loss	1.0000
12:43369379:TAG:T	acceptor_gain	1.0000
12:43369380:AGCTA:A	acceptor_loss	1.0000
12:43369381:GCTAG:G	acceptor_loss	1.0000
12:43369382:C:CC	acceptor_gain	1.0000
12:43369382:C:CG	acceptor_loss	1.0000
12:43369383:T:G	acceptor_loss	1.0000
12:43375372:CACT:C	donor_loss	1.0000
12:43375373:ACTT:A	donor_loss	1.0000
12:43375374:CTT:C	donor_loss	1.0000
12:43375375:TTACT:T	donor_loss	1.0000
12:43375376:TACT:T	donor_loss	1.0000
12:43375377:A:AC	donor_gain	1.0000
12:43375377:A:C	donor_loss	1.0000
12:43375378:C:CG	donor_gain	1.0000
12:43375378:CT:C	donor_gain	1.0000
12:43375481:CAT:C	acceptor_gain	1.0000
12:43375508:TTAGT:T	acceptor_gain	1.0000
12:43375509:TAGT:T	acceptor_gain	1.0000
12:43375511:GT:G	acceptor_gain	1.0000
12:43375513:C:CC	acceptor_gain	1.0000
12:43376230:TAATA:T	donor_loss	1.0000
12:43376232:ATACC:A	donor_loss	1.0000

AlphaMissense

12644 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006846 (12:43394515 C>A,G,T), RS1000016945 (12:43358655 G>A), RS1000034026 (12:43477837 G>A,T), RS1000034831 (12:43537247 G>C,T), RS1000041689 (12:43446544 C>A,G), RS1000043295 (12:43352878 T>A,C), RS1000045890 (12:43506364 T>C), RS1000071584 (12:43529333 T>C), RS1000092023 (12:43499794 C>A,T), RS1000094887 (12:43411810 A>G), RS1000123379 (12:43499422 C>A,T), RS1000126853 (12:43365557 C>A), RS1000151595 (12:43494801 C>T), RS1000152627 (12:43401088 T>C), RS1000153902 (12:43386784 T>G)

Disease associations

OMIM: gene MIM:611681 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001431_2	Adverse response to lamotrigine and phenytoin	1.000000e-06
GCST001762_560	Obesity-related traits	5.000000e-06
GCST002245_28	Alzheimer’s disease (late onset)	3.000000e-07
GCST002806_9	Type 2 diabetes	9.000000e-06
GCST003984_16	Parkinson’s disease	5.000000e-09
GCST005170_19	Intraocular pressure	3.000000e-08
GCST007511_7	Alzheimer’s disease (late onset)	4.000000e-07
GCST007629_3	Impulsivity (non-planning)	4.000000e-07
GCST010002_215	Refractive error	3.000000e-11
GCST011358_8	Academic attainment (English)	9.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004695	intraocular pressure measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0006946	behavioural disinhibition measurement
EFO:0011015	educational attainment

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
Valproic Acid	decreases expression, affects cotreatment	3
arsenite	increases methylation, affects binding, decreases reaction	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	decreases methylation	1
methylmercuric chloride	decreases expression	1
trichostatin A	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
mercuric bromide	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Glucosamine	decreases cleavage	1
Lipopolysaccharides	affects response to substance, increases expression	1
Malathion	decreases expression	1
Methapyrilene	decreases methylation	1
Oxygen	increases expression	1
Progesterone	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
p-Chloromercuribenzoic Acid	decreases expression	1

Clinical trials (associated diseases)

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