ADAMTS17

Summary

ADAMTS17 (ADAM metallopeptidase with thrombospondin type 1 motif 17, HGNC:17109) is a protein-coding gene on chromosome 15q26.3, encoding A disintegrin and metalloproteinase with thrombospondin motifs 17 (Q8TE56).

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members 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 protein, which may promote breast cancer cell growth and survival. Mutations in this gene are associated with a Weill-Marchesani-like syndrome, which is characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature.

Source: NCBI Gene 170691 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Weill-Marchesani 4 syndrome, recessive (Definitive, GenCC)
• GWAS associations: 88
• Clinical variants (ClinVar): 1,588 total — 99 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 27
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_139057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17109
Approved symbol	ADAMTS17
Name	ADAM metallopeptidase with thrombospondin type 1 motif 17
Location	15q26.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32769, FLJ16363
Ensembl gene	ENSG00000140470
Ensembl biotype	protein_coding
OMIM	607511
Entrez	170691

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000268070, ENST00000378898, ENST00000557896, ENST00000558930, ENST00000558960, ENST00000559976, ENST00000560486, ENST00000561355, ENST00000568565, ENST00000961098

RefSeq mRNA: 1 — MANE Select: NM_139057 NM_139057

CCDS: CCDS10383

Canonical transcript exons

ENST00000268070 — 22 exons

Exon	Start	End
ENSE00001106614	100051572	100051731
ENSE00001124065	99997385	99997589
ENSE00001124074	100048857	100048992
ENSE00001124086	100053897	100054054
ENSE00001124112	99993048	99993200
ENSE00001276757	99976045	99976222
ENSE00001301933	99971437	99974562
ENSE00001635114	100341039	100341409
ENSE00003466971	100132007	100132152
ENSE00003472381	100152612	100152762
ENSE00003480527	100096356	100096476
ENSE00003501185	100199318	100199423
ENSE00003506532	100254136	100254179
ENSE00003543027	100108989	100109116
ENSE00003557817	100155180	100155320
ENSE00003562470	100133214	100133315
ENSE00003568657	100262352	100262435
ENSE00003572700	100281229	100281401
ENSE00003596046	100261479	100261636
ENSE00003662605	100330889	100331054
ENSE00003672322	100116847	100117013
ENSE00003843698	100341821	100341975

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 84.31.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5716 / max 123.3577, expressed in 515 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151783	0.7908	309
151784	0.5492	305
151782	0.1304	34
151781	0.0521	13
151779	0.0232	5
151770	0.0160	4
151780	0.0100	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	84.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.98	gold quality
right lobe of liver	UBERON:0001114	80.17	gold quality
tibia	UBERON:0000979	79.28	gold quality
lower esophagus mucosa	UBERON:0035834	78.24	gold quality
gastrocnemius	UBERON:0001388	77.86	gold quality
body of pancreas	UBERON:0001150	76.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.47	gold quality
muscle of leg	UBERON:0001383	75.80	gold quality
right testis	UBERON:0004534	72.86	gold quality
liver	UBERON:0002107	72.27	gold quality
left testis	UBERON:0004533	72.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.01	gold quality
pancreas	UBERON:0001264	71.82	gold quality
ventricular zone	UBERON:0003053	71.52	gold quality
testis	UBERON:0000473	71.11	gold quality
amniotic fluid	UBERON:0000173	70.95	silver quality
esophagus mucosa	UBERON:0002469	70.54	gold quality
skin of leg	UBERON:0001511	70.33	gold quality
minor salivary gland	UBERON:0001830	70.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.15	gold quality
esophagus	UBERON:0001043	69.38	gold quality
germinal epithelium of ovary	UBERON:0001304	68.84	silver quality
skin of abdomen	UBERON:0001416	68.47	gold quality
lower esophagus	UBERON:0013473	68.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	68.22	gold quality
mucosa of stomach	UBERON:0001199	68.20	gold quality
calcaneal tendon	UBERON:0003701	68.10	gold quality
right adrenal gland cortex	UBERON:0035827	67.75	gold quality
zone of skin	UBERON:0000014	67.72	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	50.01
E-ANND-3	no	5.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

163 targeting ADAMTS17, 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-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-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• Homozygous mutation in ADAMTS17 causes lenticular myopia, ectopia lentis, glaucoma, spheropakia, and short stature. (PMID:19836009)
• ADAMTS17 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• Recessive ADAMTS17 mutations are a recurrent cause of isolated spherophakia with short stature. (PMID:22486325)
• Endothelial protease nexin-1 is a novel regulator of A disintegrin and metalloproteinase 17 maturation and endothelial protein C receptor shedding via furin inhibition. (PMID:23661674)
• higher Adamts17 expression is found in several human cancer cell subtypes, especially in breast ductal carcinoma and there is an inverse correlation between higher Adamts17 expression and patients’ survival. (PMID:24906090)
• A mutation in WMS-like gene ADAMTS17 also causes WMS. (PMID:24940034)
• The mutation in the Weill-Marchesani syndrome (WMS)- gene ADAMTS17 also causes WMS in an Indian family. (PMID:24940034)
• Secretion of ADAMTS17 requires O-fucosylation. ADAMTS17 binds fibrillin-2 but not fibrillin-1 and does not cleave either. ADAMTS17 regulates fibrillin isoform composition of microfibrils in the eye. (PMID:28176809)
• A novel nonsense mutation c.1051 A > T in ADAMTS17 had been identified caused autosomal recessive WMS in the Chinese family. (PMID:31019231)
• A novel ADAMTS17 variant that causes Weill-Marchesani syndrome 4 alters fibrillin-1 and collagen type I deposition in the extracellular matrix. (PMID:31726086)
• A novel pathogenic missense ADAMTS17 variant that impairs secretion causes Weill-Marchesani Syndrome with variably dysmorphic hand features. (PMID:32616716)
• The role of ADAMTS6 and ADAMTS17 polymorphisms in susceptibility to lumbar disc herniation in Chinese Han population. (PMID:36810712)
• A common variant rs2054564 in ADAMST17 is associated with susceptibility to lumbar spondylosis. (PMID:36966180)
• Characteristics and genotype-phenotype correlations in ADAMTS17 mutation-related Weill-Marchesani syndrome. (PMID:37506754)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts17	ENSDARG00000075555
mus_musculus	Adamts17	ENSMUSG00000058145
rattus_norvegicus	Adamts17	ENSRNOG00000037080

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), 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 17 — Q8TE56 (reviewed: Q8TE56)

All UniProt accessions (4): Q8TE56, H0YMH1, H3BRA9, H3BV94

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Isoform 1 and isoform 2 are expressed at high levels in the lung, brain, whole eye and retina. Isoform 1 shows a weaker expression in the heart, kidney and skeletal muscle. Isoform 2 shows a weaker expression in the kidney, bone marrow and skeletal muscle. Isoform 1 and isoform 2 are expressed at high levels in the fetal heart, kidney, and whole eye, whereas a weak expression is seen in the fetal liver.

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. Weill-Marchesani syndrome 4 (WMS4) [MIM:613195] An autosomal recessive syndrome characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia and short stature. Brachydactyly and decreased joint flexibility are present in some patients. The disease is caused by variants affecting the gene represented in this entry.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TE56-1	1, a	yes
Q8TE56-2	2, b

RefSeq proteins (1): NP_620688* (*=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
IPR010909	PLAC	Domain
IPR013087	Znf_C2H2_type	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
IPR056270	ADAMTS17/19_C	Domain

Pfam: PF00090, PF01421, PF01562, PF05986, PF17771, PF19030, PF19236, PF23178

UniProt features (48 total): disulfide bond 14, domain 8, glycosylation site 7, binding site 4, sequence variant 4, splice variant 3, region of interest 2, signal peptide 1, propeptide 1, short sequence motif 1, active site 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TE56-F1	70.06	0.05

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): 390

Ligand- & substrate-binding residues (4): 201 (in inhibited form); 389; 393; 399

Disulfide bonds (14): 308–373, 348–355, 367–447, 406–431, 476–500, 487–508, 495–527, 521–532, 555–592, 559–597, 570–582, 873–916, 877–921, 888–905

Glycosylation sites (7): 167, 483, 785, 790, 832, 839, 894

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: 159 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOMF_METALLOPEPTIDASE_ACTIVITY, LHX3_01, CHX10_01, USF_C, NKX62_Q2, MYCMAX_01, NIKOLSKY_BREAST_CANCER_15Q26_AMPLICON, HOXA4_Q2, NKX3A_01, TGGAAA_NFAT_Q4_01, TAATTA_CHX10_01, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, MAX_01

GO Biological Process (2): proteolysis (GO:0006508), extracellular matrix organization (GO:0030198)

GO Molecular Function (5): metalloendopeptidase activity (GO:0004222), metal ion binding (GO:0046872), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (2): 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
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
endopeptidase activity	1
metallopeptidase activity	1
cation binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS17	FBN2	P35556	902
ADAMTS17	FBN1	P35555	858
ADAMTS17	LTBP2	Q14767	576
ADAMTS17	LTBP1	P22064	530
ADAMTS17	LTBP3	Q9NS15	483
ADAMTS17	B3GLCT	Q6Y288	475
ADAMTS17	MFAP4	P55083	443
ADAMTS17	CERS3	Q8IU89	437
ADAMTS17	LOX	P28300	422
ADAMTS17	POFUT2	Q9Y2G5	410
ADAMTS17	ANKS1B	Q7Z6G8	394
ADAMTS17	TBRG1	Q3YBR2	368
ADAMTS17	LYSMD4	Q5XG99	366
ADAMTS17	CHSY1	Q86X52	357
ADAMTS17	ACAN	P16112	355

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CEP164	TTBK2	psi-mi:“MI:0914”(association)	0.680
ADAMTS17	ATL3	psi-mi:“MI:0915”(physical association)	0.400
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
OS9	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF7	AGRN	psi-mi:“MI:0914”(association)	0.350
ADAMTS17	GAS6	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): ADAMTS17 (Proximity Label-MS), GPR98 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), ADAMTS17 (Affinity Capture-MS), N4BP2L2 (Affinity Capture-MS), LIPK (Affinity Capture-MS), ADAMTS17 (Affinity Capture-MS), ADAMTS17 (Affinity Capture-MS), ADAMTS17 (Affinity Capture-MS), FREM2 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), ADAMTS17 (Affinity Capture-MS)

ESM2 similar proteins: A0JNK3, A2RT60, A4IHA1, A6YFB5, A9JRB3, D3ZA76, D3ZKF5, E1BJW1, F1N152, O08644, O09127, O15197, O35453, O43464, P00743, P05981, P09958, P0C0K6, P0C0K7, P21709, P22457, P23188, P23377, P26011, P29122, P29322, P35590, P51840, P52785, P54754, P54760, P54761, P58459, P83105, P83110, P98139, Q02846, Q05511, Q06805, Q5JZY3

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

1588 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	99
Likely pathogenic	29
Uncertain significance	623
Likely benign	529
Benign	217

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1180505	GRCh37/hg19 15q26.1-26.3(chr15:92335751-102399741)x1	Pathogenic
1421924	NM_139057.4(ADAMTS17):c.313C>T (p.Arg105Ter)	Pathogenic
1451922	NC_000015.9:g.(?100657032)(100801861_?)del	Pathogenic
145641	GRCh38/hg38 15q26.3(chr15:99155987-101843270)x1	Pathogenic
1457096	NM_139057.4(ADAMTS17):c.2671C>T (p.Gln891Ter)	Pathogenic
1458329	NC_000015.9:g.(?100516230)(100516447_?)del	Pathogenic
146071	GRCh38/hg38 15q26.2-26.3(chr15:97014065-101843270)x1	Pathogenic
147708	GRCh38/hg38 15q26.2-26.3(chr15:95770627-101810992)x1	Pathogenic
1526470	GRCh37/hg19 15q26.2-26.3(chr15:94836128-101302111)	Pathogenic
1526471	GRCh37/hg19 15q26.2-26.3(chr15:97026327-102429112)	Pathogenic
1526472	GRCh37/hg19 15q26.2-26.3(chr15:97223728-102429112)	Pathogenic
152750	GRCh38/hg38 15q26.2-26.3(chr15:97172754-101920998)x1	Pathogenic
152930	GRCh38/hg38 15q26.1-26.3(chr15:93041524-101941326)x3	Pathogenic
154512	GRCh38/hg38 15q26.3(chr15:99338283-101843270)x3	Pathogenic
154661	GRCh38/hg38 15q26.3(chr15:98467297-101843270)x1	Pathogenic
155021	GRCh38/hg38 15q26.2-26.3(chr15:96024127-101920998)x1	Pathogenic
155459	GRCh38/hg38 15q26.3(chr15:98280297-101888909)x3	Pathogenic
155620	GRCh38/hg38 15q26.2-26.3(chr15:93805032-101326876)x1	Pathogenic
1687282	NM_139057.4(ADAMTS17):c.662_665del (p.Glu221fs)	Pathogenic
2013405	NM_139057.4(ADAMTS17):c.2710del (p.Tyr904fs)	Pathogenic
2024713	NM_139057.4(ADAMTS17):c.171del (p.Arg60fs)	Pathogenic
2032271	NM_139057.4(ADAMTS17):c.2635_2638del (p.Lys879fs)	Pathogenic
2079701	NM_139057.4(ADAMTS17):c.1114_1115del (p.Lys372fs)	Pathogenic
2079967	NM_139057.4(ADAMTS17):c.2992C>T (p.Gln998Ter)	Pathogenic
2126569	NM_139057.4(ADAMTS17):c.805C>T (p.Gln269Ter)	Pathogenic
2130471	NM_139057.4(ADAMTS17):c.783del (p.Met261fs)	Pathogenic
2159984	NM_139057.4(ADAMTS17):c.2712C>A (p.Tyr904Ter)	Pathogenic
2427275	NC_000015.9:g.(?100739503)(100739648_?)del	Pathogenic
2427276	NC_000015.9:g.(?100794321)(100801861_?)del	Pathogenic
253671	GRCh37/hg19 15q26.1-26.3(chr15:92197136-102354857)x1	Pathogenic

SpliceAI

6703 predictions. Top by Δscore:

Variant	Effect	Δscore
15:100051742:C:CT	acceptor_gain	1.0000
15:100117009:CAGGG:C	acceptor_gain	1.0000
15:100117014:C:CC	acceptor_gain	1.0000
15:100199316:A:AC	donor_gain	1.0000
15:100199317:C:CG	donor_gain	1.0000
15:100261474:CTTA:C	donor_loss	1.0000
15:100261475:TTA:T	donor_loss	1.0000
15:100261476:TA:T	donor_loss	1.0000
15:100261477:A:AG	donor_loss	1.0000
15:100261478:CCTGG:C	donor_gain	1.0000
15:100261632:TTAGC:T	acceptor_gain	1.0000
15:100261633:TAGC:T	acceptor_gain	1.0000
15:100261633:TAGCC:T	acceptor_gain	1.0000
15:100261634:AGC:A	acceptor_gain	1.0000
15:100261634:AGCC:A	acceptor_loss	1.0000
15:100261634:AGCCT:A	acceptor_gain	1.0000
15:100261635:GC:G	acceptor_gain	1.0000
15:100261636:CC:C	acceptor_gain	1.0000
15:100261637:C:CC	acceptor_gain	1.0000
15:100261637:CT:C	acceptor_loss	1.0000
15:100261638:T:A	acceptor_loss	1.0000
15:100262350:A:AC	donor_gain	1.0000
15:100262351:C:CC	donor_gain	1.0000
15:100262351:CGGGA:C	donor_gain	1.0000
15:100281225:TCA:T	donor_loss	1.0000
15:100281226:CA:C	donor_loss	1.0000
15:100281227:A:AC	donor_gain	1.0000
15:100281227:A:AT	donor_loss	1.0000
15:100281227:AC:A	donor_gain	1.0000
15:100281228:C:CC	donor_gain	1.0000

AlphaMissense

7120 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:100132148:C:G	C527S	1.000
15:100132149:A:T	C527S	1.000
15:100133227:C:G	C521S	1.000
15:100133228:A:T	C521S	1.000
15:100133289:G:C	C500W	1.000
15:100133290:C:G	C500S	1.000
15:100133291:A:G	C500R	1.000
15:100133291:A:T	C500S	1.000
15:100133292:C:A	W499C	1.000
15:100133292:C:G	W499C	1.000
15:100133304:A:C	C495W	1.000
15:100152657:G:C	C476W	1.000
15:100152658:C:G	C476S	1.000
15:100152659:A:G	C476R	1.000
15:100152659:A:T	C476S	1.000
15:100155218:C:A	W428C	1.000
15:100155218:C:G	W428C	1.000
15:100155220:A:G	W428R	1.000
15:100155220:A:T	W428R	1.000
15:100155251:C:A	W417C	1.000
15:100155251:C:G	W417C	1.000
15:99974516:G:C	C1058W	1.000
15:100048881:C:G	C856S	0.999
15:100048882:A:T	C856S	0.999
15:100048967:A:C	C827W	0.999
15:100048968:C:G	C827S	0.999
15:100048968:C:T	C827Y	0.999
15:100048969:A:T	C827S	0.999
15:100051600:C:A	W809C	0.999
15:100051600:C:G	W809C	0.999

dbSNP variants (sampled 300 via entrez): RS1000007500 (15:100223998 G>A), RS1000019016 (15:100047475 G>A), RS1000019358 (15:100037711 G>A,C), RS1000034094 (15:100133909 T>C), RS1000038118 (15:100136137 A>G,T), RS1000040838 (15:100221680 G>A), RS1000048128 (15:100193783 G>A,C), RS1000053151 (15:100250792 G>T), RS1000070366 (15:100083701 T>C), RS1000073571 (15:100052638 A>G), RS1000078060 (15:100237610 G>A,C), RS1000081010 (15:100252556 C>T), RS1000081295 (15:100162911 T>C), RS1000101896 (15:100224217 G>A), RS1000111020 (15:100125359 GCA>G)

Disease associations

OMIM: gene MIM:607511 | disease phenotypes: MIM:612626, MIM:613195, MIM:107250

GenCC curated gene-disease

Disease	Classification	Inheritance
Weill-Marchesani 4 syndrome, recessive	Definitive	Autosomal recessive

Mondo (3): chromosome 15q26-qter deletion syndrome (MONDO:0012964), Weill-Marchesani 4 syndrome, recessive (MONDO:0013176), anterior segment dysgenesis (MONDO:0019503)

Orphanet (3): Distal deletion 15q syndrome (Orphanet:1596), Ichthyosis-short stature-brachydactyly-microspherophakia syndrome (Orphanet:363992), Anterior segment developmental anomaly (Orphanet:88632)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000572	Visual loss
HP:0000594	Shallow anterior chamber
HP:0001072	Thickened skin
HP:0001083	Ectopia lentis
HP:0001156	Brachydactyly
HP:0001256	Mild intellectual disability
HP:0001376	Limitation of joint mobility
HP:0001387	Joint stiffness
HP:0001629	Ventricular septal defect
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001650	Aortic valve stenosis
HP:0001653	Mitral regurgitation
HP:0002750	Delayed skeletal maturation
HP:0004322	Short stature
HP:0005184	Prolonged QTc interval
HP:0007906	Ocular hypertension
HP:0009778	Short thumb
HP:0011003	High myopia
HP:0011484	Posterior synechiae of the anterior chamber
HP:0012629	Phakodonesis
HP:0030680	Abnormal cardiovascular system morphology
HP:0030961	Microspherophakia
HP:0100693	Iridodonesis

GWAS associations

88 associations (top):

Study	Trait	p-value
GCST000175_16	Height	3.000000e-08
GCST000817_155	Height	4.000000e-13
GCST001956_35	Height	7.000000e-10
GCST002056_4	Osteosarcoma	1.000000e-06
GCST002647_116	Height	6.000000e-20
GCST002702_75	Height	1.000000e-13
GCST002830_17	Urate levels in lean individuals	9.000000e-06
GCST003488_1	Response to fenofibrate (triglyceride levels)	6.000000e-06
GCST003631_6	Gastroesophageal reflux disease	6.000000e-06
GCST004063_145	Waist circumference adjusted for body mass index	3.000000e-07
GCST004063_161	Waist circumference adjusted for body mass index	6.000000e-09
GCST004067_180	Hip circumference adjusted for BMI	1.000000e-06
GCST004067_86	Hip circumference adjusted for BMI	4.000000e-08
GCST004500_117	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	5.000000e-06
GCST005170_8	Intraocular pressure	1.000000e-21
GCST005173_52	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	5.000000e-06
GCST005580_118	Intraocular pressure	3.000000e-45
GCST007293_10	Body fat distribution (arm fat ratio)	1.000000e-17
GCST007293_11	Body fat distribution (arm fat ratio)	7.000000e-06
GCST007293_114	Body fat distribution (arm fat ratio)	4.000000e-14
GCST007293_39	Body fat distribution (arm fat ratio)	5.000000e-18
GCST007294_117	Body fat distribution (trunk fat ratio)	2.000000e-15
GCST007294_127	Body fat distribution (trunk fat ratio)	2.000000e-40
GCST007294_76	Body fat distribution (trunk fat ratio)	5.000000e-53
GCST007294_77	Body fat distribution (trunk fat ratio)	7.000000e-21
GCST007295_173	Body fat distribution (leg fat ratio)	8.000000e-26
GCST007295_40	Body fat distribution (leg fat ratio)	2.000000e-36
GCST007295_41	Body fat distribution (leg fat ratio)	9.000000e-14
GCST007295_74	Body fat distribution (leg fat ratio)	7.000000e-12
GCST007581_15	Carpal tunnel syndrome	2.000000e-15

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007681	triglyceride change measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0004695	intraocular pressure measurement
EFO:0004723	coronary artery calcification
EFO:0004341	body fat distribution
EFO:0010067	corneal resistance factor
EFO:0004530	triglyceride measurement
EFO:0005213	central corneal thickness
EFO:0009819	comparative body size at age 10, self-reported
EFO:0010749	motor function measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567232	Chromosome 15q26-Qter Deletion Syndrome (supp.)
C567710	Weill-Marchesani-Like Syndrome (supp.)

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	increases expression, affects expression, increases methylation, affects cotreatment	8
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Aflatoxin B1	decreases expression, decreases methylation, affects expression, affects methylation	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	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
Fulvestrant	affects cotreatment, decreases methylation	1
Panobinostat	affects cotreatment, increases expression	1
Atrazine	increases expression	1
Doxorubicin	increases expression	1
Methapyrilene	increases methylation	1
Niclosamide	decreases expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05641103	Not specified	COMPLETED	PREDIGA 2: Spanish Acronym of Educational and Diagnostic Project for Gaucher and ASMD