ADAMTS10

Summary

ADAMTS10 (ADAM metallopeptidase with thrombospondin type 1 motif 10, HGNC:13201) is a protein-coding gene on chromosome 19p13.2, encoding A disintegrin and metalloproteinase with thrombospondin motifs 10 (Q9H324). Metalloprotease that participate in microfibrils assembly.

This gene belongs to the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin type-1 motifs) family of zinc-dependent proteases. ADAMTS proteases are complex secreted enzymes containing a prometalloprotease domain of the reprolysin type attached to an ancillary domain with a highly conserved structure that includes at least one thrombospondin type 1 repeat. They have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis and cell migration. The product of this gene plays a major role in growth and in skin, lens, and heart development. It is also a candidate gene for autosomal recessive Weill-Marchesani syndrome.

Source: NCBI Gene 81794 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Weill-Marchesani syndrome 1 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 59
• Clinical variants (ClinVar): 1,101 total — 25 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 42
• MANE Select transcript: NM_030957

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13201
Approved symbol	ADAMTS10
Name	ADAM metallopeptidase with thrombospondin type 1 motif 10
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	ADAM-TS10
Ensembl gene	ENSG00000142303
Ensembl biotype	protein_coding
OMIM	608990
Entrez	81794

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 6 retained_intron, 4 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000270328, ENST00000593534, ENST00000593826, ENST00000593913, ENST00000595838, ENST00000596236, ENST00000596466, ENST00000596709, ENST00000596851, ENST00000596911, ENST00000597188, ENST00000601163, ENST00000601872, ENST00000603221, ENST00000906412

RefSeq mRNA: 2 — MANE Select: NM_030957 NM_001282352, NM_030957

CCDS: CCDS12206, CCDS62529

Canonical transcript exons

ENST00000597188 — 26 exons

Exon	Start	End
ENSE00000953329	8597234	8597317
ENSE00002727768	8605623	8605809
ENSE00002976031	8608134	8608248
ENSE00003109980	8580240	8581002
ENSE00003459061	8591800	8591863
ENSE00003465473	8589452	8589585
ENSE00003483362	8605012	8605358
ENSE00003499041	8585456	8585660
ENSE00003515336	8585132	8585308
ENSE00003537473	8596307	8596412
ENSE00003552126	8596987	8597132
ENSE00003559080	8592763	8592870
ENSE00003560582	8586122	8586251
ENSE00003597227	8589242	8589365
ENSE00003613111	8595762	8595903
ENSE00003617565	8589889	8589991
ENSE00003621981	8596073	8596219
ENSE00003632445	8596542	8596585
ENSE00003640808	8584895	8585054
ENSE00003642256	8586558	8586721
ENSE00003673671	8603728	8603884
ENSE00003679958	8586816	8586896
ENSE00003682536	8591958	8592103
ENSE00003688295	8600928	8601145
ENSE00003693258	8586344	8586470
ENSE00003850845	8610644	8610715

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 96.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.0454 / max 77.9198, expressed in 1025 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178969	3.9510	1020
178970	0.0944	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	96.98	gold quality
right coronary artery	UBERON:0001625	96.93	gold quality
kidney epithelium	UBERON:0004819	96.78	gold quality
upper arm skin	UBERON:0004263	96.68	gold quality
thoracic aorta	UBERON:0001515	96.30	gold quality
ascending aorta	UBERON:0001496	96.29	gold quality
nasal cavity epithelium	UBERON:0005384	96.20	silver quality
left ventricle myocardium	UBERON:0006566	95.76	silver quality
granulocyte	CL:0000094	95.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.68	silver quality
aorta	UBERON:0000947	95.26	gold quality
cerebellar vermis	UBERON:0004720	94.75	gold quality
cortical plate	UBERON:0005343	94.75	gold quality
parotid gland	UBERON:0001831	94.59	gold quality
vena cava	UBERON:0004087	94.59	gold quality
popliteal artery	UBERON:0002250	94.58	gold quality
tibial artery	UBERON:0007610	94.58	gold quality
left coronary artery	UBERON:0001626	94.48	gold quality
artery	UBERON:0001637	94.48	gold quality
coronary artery	UBERON:0001621	94.41	gold quality
left uterine tube	UBERON:0001303	93.83	gold quality
endocervix	UBERON:0000458	93.82	gold quality
body of tongue	UBERON:0011876	93.45	gold quality
body of uterus	UBERON:0009853	93.24	gold quality
mucosa of stomach	UBERON:0001199	92.98	gold quality
pancreatic ductal cell	CL:0002079	92.93	silver quality
right ovary	UBERON:0002118	92.84	gold quality
myocardium	UBERON:0002349	92.54	silver quality
lateral nuclear group of thalamus	UBERON:0002736	92.50	gold quality
lateral globus pallidus	UBERON:0002476	92.46	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting ADAMTS10, 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-6870-5P	99.99	68.55	2115
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-608	98.93	67.83	2013

Literature-anchored findings (GeneRIF, showing 11)

• ADAMTS10 is a functional metalloprotease as demonstrated by cleavage of alpha2-macroglobulin (PMID:15355968)
• Expression in human colonic cell lines. (PMID:15358598)
• ADAMTS10 plays a major role in growth and in skin, lens, and heart development in humans. (PMID:15368195)
• infer that folding of the complex C-terminal ancillary domain is the rate-limiting step in biosynthesis of ADAMTS10, and that it (but not catalytic domain) is sensitive to subtle changes in efficiency of signal peptide cleavage. (PMID:18567016)
• Mutations in ADAMTS10 gene is not responsible for microspherophakia. (PMID:19696795)
• Homozygous mutation in ADAMTS10 causes lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. (PMID:19836009)
• ADAMTS10 participates in microfibril biogenesis rather than in fibrillin-1 turnover (PMID:21402694)
• These findings support the Gly661Arg mutation of ADAMTS10 as the likely cause of POAG in beagles. (PMID:23422823)
• Using siRNA, over-expression and mutagenesis, it was found ADAMTS6 inhibits and ADAMTS10 is required for focal adhesions, epithelial cell-cell junction formation, and microfibril deposition. (PMID:27779234)
• ADAMTS10 inhibits aggressiveness via JAK/STAT/c-MYC pathway and reprograms macrophage to create an anti-malignant microenvironment in gastric cancer. (PMID:35925524)
• A Novel Mutation in the ADAMTS10 Associated with Weil-Marchesani Syndrome with a Unique Presentation of Developed Membranes Causing Severe Stenosis of the Supra Pulmonic, Supramitral, and Subaortic Areas in the Heart. (PMID:37240210)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts10	ENSDARG00000075188
mus_musculus	Adamts10	ENSMUSG00000024299
rattus_norvegicus	Adamts10	ENSRNOG00000008857

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), 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 10 — Q9H324 (reviewed: Q9H324)

All UniProt accessions (4): Q9H324, A0A0A0MQW6, M0QY12, M0QY36

UniProt curated annotations — full annotation on UniProt →

Function. Metalloprotease that participate in microfibrils assembly. Microfibrils are extracellular matrix components occurring independently or along with elastin in the formation of elastic tissues.

Subunit / interactions. Interacts with FBN1; this interaction promotes microfibrils assembly.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Widely expressed in adult tissues.

Post-translational modifications. 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 1 (WMS1) [MIM:277600] A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma. 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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H324-1	1	yes
Q9H324-2	2

RefSeq proteins (2): NP_001269281, NP_112219* (*=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
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, PF08686, PF17771, PF19030, PF19236

UniProt features (42 total): disulfide bond 11, domain 8, glycosylation site 6, sequence conflict 4, binding site 3, sequence variant 3, region of interest 2, signal peptide 1, propeptide 1, active site 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H324-F1	73.88	0.09

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): 393

Ligand- & substrate-binding residues (3): 392; 396; 402

Disulfide bonds (11): 315–376, 351–358, 370–452, 409–436, 479–501, 490–508, 496–531, 521–536, 559–596, 563–601, 574–586

Glycosylation sites (6): 90, 222, 323, 740, 795, 892

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: 225 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, CHO_NR4A1_TARGETS, MODULE_48, MODULE_95, TAATTA_CHX10_01, GOBP_PROTEOLYSIS, chr19p13, GOMF_PEPTIDASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MARTENS_BOUND_BY_PML_RARA_FUSION, RP58_01, KATSANOU_ELAVL1_TARGETS_UP, GOCC_MICROFIBRIL

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

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (3): microfibril (GO:0001527), 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
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
elastic fiber	1
supramolecular fiber	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS10	FBN1	P35555	995
ADAMTS10	LTBP1	P22064	876
ADAMTS10	LTBP2	Q14767	787
ADAMTS10	FBN2	P35556	761
ADAMTS10	LTBP3	Q9NS15	749
ADAMTS10	ADAMTSL2	Q86TH1	630
ADAMTS10	COL8A2	P25067	554
ADAMTS10	COL16A1	Q07092	520
ADAMTS10	RECK	O95980	517
ADAMTS10	LOX	P28300	507
ADAMTS10	TBRG1	Q3YBR2	506
ADAMTS10	SLC8A2	Q9UPR5	502
ADAMTS10	COL6A1	P12109	493
ADAMTS10	ABHD17A	Q96GS6	467
ADAMTS10	THSD4	Q6ZMP0	451

IntAct

16 interactions, top by confidence:

A	B	Type	Score
Lox	ADAMTS10	psi-mi:“MI:2364”(proximity)	0.470
Lox	ADAMTS10	psi-mi:“MI:0915”(physical association)	0.470
ADAMTS10	H2BC20P	psi-mi:“MI:0915”(physical association)	0.400
ADAMTS10	YTHDC1	psi-mi:“MI:0915”(physical association)	0.400
LOXL2	ADAMTS10	psi-mi:“MI:0915”(physical association)	0.400
ANXA7	ADAMTS10	psi-mi:“MI:0915”(physical association)	0.370
ADAMTS10	CDKN1A	psi-mi:“MI:0915”(physical association)	0.370
ADAMTS10	HMGCL	psi-mi:“MI:0915”(physical association)	0.370
ADAMTS10	LAMTOR3	psi-mi:“MI:0915”(physical association)	0.370
ADAMTS10	PCYT2	psi-mi:“MI:0915”(physical association)	0.370
ADAMTS10	SMN1	psi-mi:“MI:0915”(physical association)	0.370
ADAMTS10	TK1	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): ADAMTS10 (Affinity Capture-RNA), ADAMTS10 (Proximity Label-MS), ADAMTS10 (Proximity Label-MS), ADAMTS10 (Affinity Capture-RNA), ADAMTS10 (Negative Genetic), ADAMTS12 (Negative Genetic), ADAMTS10 (Affinity Capture-RNA), ADAMTS10 (Two-hybrid), ADAMTS10 (Two-hybrid), ADAMTS10 (Two-hybrid), ADAMTS10 (Two-hybrid), ADAMTS10 (Two-hybrid), ADAMTS10 (Two-hybrid), ADAMTS10 (Two-hybrid)

ESM2 similar proteins: A0JNK3, A2RT60, A4IHA1, A6YFB5, A9JRB3, B3LVG7, D3ZA76, D3ZKF5, E1BJW1, F1N152, O09127, O13146, O19045, O43464, O88917, O94910, O97831, P00743, P05981, P09958, P23188, P23377, P29122, P29317, P29322, P54753, P54754, P54760, P54761, P56677, P83105, P83110, P98139, Q03145, Q05511, Q06805, Q0IIH7, Q1KL86, Q28193, Q28661

Diamond homologs: A2VEC9, B3EWY9, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, G5ECS8, O08721, O08722, O08747, O14514, O15072, O60241, O60242, O75173, O95185, O95450, P07358, P07996, P10643, P11680, P27918, P35440, P35441, P35442, P35446, P35447, P35448, P55314, P57110, P58397, P59384, P79331, P82987, P98137, P98167, Q03350

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1101 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	15
Uncertain significance	393
Likely benign	527
Benign	60

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1414363	NM_030957.4(ADAMTS10):c.623_633del (p.Trp208fs)	Pathogenic
1430013	NM_030957.4(ADAMTS10):c.280_305del (p.Ser94fs)	Pathogenic
1430522	NM_030957.4(ADAMTS10):c.954_961dup (p.Ile321fs)	Pathogenic
1434770	NM_030957.4(ADAMTS10):c.2293dup (p.Gln765fs)	Pathogenic
1455640	NM_030957.4(ADAMTS10):c.1499G>A (p.Trp500Ter)	Pathogenic
1459344	NC_000019.9:g.(?8656664)(8670595_?)del	Pathogenic
1944	NM_030957.4(ADAMTS10):c.709C>T (p.Arg237Ter)	Pathogenic
1945	NM_030957.4(ADAMTS10):c.1190+1G>A	Pathogenic
1948	NM_030957.4(ADAMTS10):c.952C>T (p.Gln318Ter)	Pathogenic
1949	NM_030957.4(ADAMTS10):c.1553G>A (p.Gly518Asp)	Pathogenic
1949579	NM_030957.4(ADAMTS10):c.621G>A (p.Trp207Ter)	Pathogenic
1950	NM_030957.4(ADAMTS10):c.2098G>T (p.Gly700Cys)	Pathogenic
1995812	NM_030957.4(ADAMTS10):c.1919C>A (p.Ser640Ter)	Pathogenic
2036670	NM_030957.4(ADAMTS10):c.1569_1581del (p.His524fs)	Pathogenic
2096377	NM_030957.4(ADAMTS10):c.2611A>T (p.Lys871Ter)	Pathogenic
2164100	NM_030957.4(ADAMTS10):c.2050C>T (p.Arg684Ter)	Pathogenic
2708871	NM_030957.4(ADAMTS10):c.2046C>A (p.Cys682Ter)	Pathogenic
2862729	NM_030957.4(ADAMTS10):c.3154C>T (p.Gln1052Ter)	Pathogenic
3242715	NC_000019.9:g.(?8654106)(8654895_?)del	Pathogenic
3242716	NC_000019.9:g.(?8654106)(8662221_?)del	Pathogenic
3642189	NM_030957.4(ADAMTS10):c.2708_2717dup (p.Ser906fs)	Pathogenic
3655544	NM_030957.4(ADAMTS10):c.2107del (p.Ser703fs)	Pathogenic
3776263	NM_030957.4(ADAMTS10):c.174_213del (p.Pro60fs)	Pathogenic
4722122	NM_030957.4(ADAMTS10):c.2513C>A (p.Ser838Ter)	Pathogenic
4761177	NM_030957.4(ADAMTS10):c.2859G>A (p.Trp953Ter)	Pathogenic
1946	NM_030957.4(ADAMTS10):c.810+1G>A	Likely pathogenic
2570574	NM_030957.4(ADAMTS10):c.1179G>C (p.Glu393Asp)	Likely pathogenic
2570575	NM_030957.4(ADAMTS10):c.1219A>G (p.Asn407Asp)	Likely pathogenic
2570582	NM_030957.4(ADAMTS10):c.2720G>A (p.Arg907His)	Likely pathogenic
2570585	NM_030957.4(ADAMTS10):c.1462C>A (p.Arg488Ser)	Likely pathogenic

SpliceAI

3663 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8581001:CT:C	acceptor_gain	1.0000
19:8581003:C:CC	acceptor_gain	1.0000
19:8584891:ATAC:A	donor_loss	1.0000
19:8584892:TA:T	donor_loss	1.0000
19:8584894:C:CT	donor_loss	1.0000
19:8585050:GAGCA:G	acceptor_gain	1.0000
19:8585051:AGCA:A	acceptor_gain	1.0000
19:8585052:GCA:G	acceptor_gain	1.0000
19:8585053:CA:C	acceptor_gain	1.0000
19:8585053:CAC:C	acceptor_gain	1.0000
19:8585055:C:CC	acceptor_gain	1.0000
19:8585055:CTGCG:C	acceptor_loss	1.0000
19:8585656:CCCAG:C	acceptor_gain	1.0000
19:8585657:CCAG:C	acceptor_gain	1.0000
19:8585657:CCAGC:C	acceptor_gain	1.0000
19:8585658:CAG:C	acceptor_gain	1.0000
19:8585658:CAGC:C	acceptor_gain	1.0000
19:8585659:AG:A	acceptor_gain	1.0000
19:8586081:T:A	donor_gain	1.0000
19:8586115:CACT:C	donor_loss	1.0000
19:8586119:CA:C	donor_loss	1.0000
19:8586120:A:AC	donor_gain	1.0000
19:8586120:ACT:A	donor_gain	1.0000
19:8586121:C:CT	donor_gain	1.0000
19:8586121:CT:C	donor_gain	1.0000
19:8586121:CTC:C	donor_gain	1.0000
19:8586121:CTCT:C	donor_gain	1.0000
19:8586248:CTAC:C	acceptor_gain	1.0000
19:8586250:ACC:A	acceptor_loss	1.0000
19:8586252:C:CC	acceptor_gain	1.0000

AlphaMissense

7180 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8580917:G:C	C1096W	1.000
19:8580918:C:G	C1096S	1.000
19:8580919:A:T	C1096S	1.000
19:8580930:A:C	F1092C	1.000
19:8580972:C:G	C1078S	1.000
19:8580973:A:G	C1078R	1.000
19:8580973:A:T	C1078S	1.000
19:8585462:C:A	W953C	1.000
19:8585462:C:G	W953C	1.000
19:8585477:C:A	W948C	1.000
19:8585477:C:G	W948C	1.000
19:8589537:A:C	F650C	1.000
19:8589557:G:C	C643W	1.000
19:8589559:A:G	C643R	1.000
19:8589905:C:A	W628C	1.000
19:8589905:C:G	W628C	1.000
19:8589907:A:G	W628R	1.000
19:8589907:A:T	W628R	1.000
19:8589951:C:G	C613S	1.000
19:8589952:A:T	C613S	1.000
19:8591840:C:G	C586S	1.000
19:8591841:A:T	C586S	1.000
19:8592032:C:A	W553C	1.000
19:8592032:C:G	W553C	1.000
19:8592041:C:A	W550C	1.000
19:8592041:C:G	W550C	1.000
19:8592083:A:C	C536W	1.000
19:8592084:C:A	C536F	1.000
19:8592084:C:G	C536S	1.000
19:8592084:C:T	C536Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000282786 (19:8584340 C>T), RS1000634220 (19:8607020 G>A,C), RS1000749690 (19:8590107 G>A,T), RS1000784492 (19:8585820 T>C), RS1001259088 (19:8603263 C>G,T), RS1001344312 (19:8591537 G>A), RS1001444122 (19:8597781 T>C), RS1001454274 (19:8598107 C>A,T), RS1001645823 (19:8608025 G>A,T), RS1001788138 (19:8587655 G>A,C), RS1001839077 (19:8587992 T>C), RS1002229132 (19:8598918 G>A,C), RS1002309771 (19:8604508 G>T), RS1002552550 (19:8580438 C>A,G,T), RS1002647127 (19:8609396 C>T)

Disease associations

OMIM: gene MIM:608990 | disease phenotypes: MIM:277600, MIM:252650

GenCC curated gene-disease

Disease	Classification	Inheritance
Weill-Marchesani syndrome 1	Definitive	Autosomal recessive
Weill-Marchesani syndrome	Supportive	Autosomal dominant

Mondo (3): Weill-Marchesani syndrome 1 (MONDO:0010194), Weill-Marchesani syndrome (MONDO:0018096), mucolipidosis type IV (MONDO:0009653)

Orphanet (2): Weill-Marchesani syndrome (Orphanet:3449), Mucolipidosis type IV (Orphanet:578)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000189	Narrow palate
HP:0000248	Brachycephaly
HP:0000327	Hypoplasia of the maxilla
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000572	Visual loss
HP:0000586	Shallow orbits
HP:0000594	Shallow anterior chamber
HP:0000618	Blindness
HP:0000692	Tooth malposition
HP:0000885	Broad ribs
HP:0001072	Thickened skin
HP:0001083	Ectopia lentis
HP:0001156	Brachydactyly
HP:0001169	Broad palm
HP:0001230	Broad metacarpals
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:0001783	Broad metatarsal
HP:0002650	Scoliosis
HP:0002682	Broad skull
HP:0002750	Delayed skeletal maturation
HP:0002753	Thin bony cortex

GWAS associations

59 associations (top):

Study	Trait	p-value
GCST000175_8	Height	1.000000e-06
GCST000817_90	Height	4.000000e-13
GCST002647_161	Height	1.000000e-18
GCST003184_36	Atopic dermatitis	5.000000e-12
GCST003995_23	Tonsillectomy	1.000000e-09
GCST004063_31	Waist circumference adjusted for body mass index	2.000000e-08
GCST004063_53	Waist circumference adjusted for body mass index	3.000000e-06
GCST004500_136	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-08
GCST004500_58	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	6.000000e-07
GCST004501_1	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	4.000000e-07
GCST004501_38	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-08
GCST004504_21	Waist circumference adjusted for BMI in non-smokers	4.000000e-06
GCST004523_10	Resting metabolic rate	9.000000e-06
GCST004861_23	Itch intensity from mosquito bite	4.000000e-15
GCST004862_161	Itch intensity from mosquito bite adjusted by bite size	8.000000e-12
GCST004862_207	Itch intensity from mosquito bite adjusted by bite size	5.000000e-09
GCST004865_20	Itch intensity from mosquito bite adjusted by bite size	1.000000e-09
GCST005014_21	Tonsillectomy	1.000000e-09
GCST007293_113	Body fat distribution (arm fat ratio)	3.000000e-06
GCST007293_38	Body fat distribution (arm fat ratio)	5.000000e-07
GCST007293_9	Body fat distribution (arm fat ratio)	7.000000e-10
GCST007294_125	Body fat distribution (trunk fat ratio)	1.000000e-36
GCST007294_4	Body fat distribution (trunk fat ratio)	8.000000e-46
GCST007295_172	Body fat distribution (leg fat ratio)	2.000000e-28
GCST007295_38	Body fat distribution (leg fat ratio)	2.000000e-33
GCST007485_12	Anthropometric traits	5.000000e-121
GCST007490_2	Anthropometric traits (multi-trait analysis)	1.000000e-70
GCST007581_16	Carpal tunnel syndrome	8.000000e-14
GCST007798_108	Asthma	9.000000e-07
GCST007800_61	Asthma (childhood onset)	5.000000e-10

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0007924	tonsillectomy risk measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0008004	resting metabolic rate measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004341	body fat distribution
EFO:0004324	body weights and measures
EFO:0004847	age at onset
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D056846	Weill-Marchesani Syndrome	C05.116.099.343.957; C11.270.921; C16.131.077.941; C16.320.290.842; C17.300.899

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7255721	ADAMTS10		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M12: Astacin/Adamalysin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
afuresertib	increases expression	1
bufotalin	decreases expression	1
propionaldehyde	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	decreases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases expression, affects response to substance	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1
Aflatoxin B1	decreases methylation	1
Gold Compounds	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07398872	PHASE1	ENROLLING_BY_INVITATION	Safety and Efficacy of AAV9. hMCOLN1co For Patients With Mucolipidosis Type IV
NCT00015782	Not specified	COMPLETED	The Natural History and Pathogenesis of Mucolipidosis Type IV
NCT01067742	Not specified	TERMINATED	The Natural History of Mucolipidosis Type IV
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05782387	Not specified	ACTIVE_NOT_RECRUITING	Mucolipidosis Type IV Natural History Study