ADAMTS16

Summary

ADAMTS16 (ADAM metallopeptidase with thrombospondin type 1 motif 16, HGNC:17108) is a protein-coding gene on chromosome 5p15.32, encoding A disintegrin and metalloproteinase with thrombospondin motifs 16 (Q8TE57).

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 inhibit chondrosarcoma cell proliferation and migration. This gene may regulate blood pressure.

Source: NCBI Gene 170690 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 298 total — 75 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_139056

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17108
Approved symbol	ADAMTS16
Name	ADAM metallopeptidase with thrombospondin type 1 motif 16
Location	5p15.32
Locus type	gene with protein product
Status	Approved
Aliases	ADAMTS16s
Ensembl gene	ENSG00000145536
Ensembl biotype	protein_coding
OMIM	607510
Entrez	170690

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000274181, ENST00000433402, ENST00000511368, ENST00000513709, ENST00000918351

RefSeq mRNA: 1 — MANE Select: NM_139056 NM_139056

CCDS: CCDS43299

Canonical transcript exons

ENST00000274181 — 23 exons

Exon	Start	End
ENSE00001294092	5318134	5318281
ENSE00001312496	5319023	5320304
ENSE00001312646	5306504	5306728
ENSE00001318062	5303572	5303766
ENSE00001323050	5140330	5140539
ENSE00003471090	5235014	5235186
ENSE00003477606	5200132	5200269
ENSE00003481776	5209093	5209246
ENSE00003488712	5236969	5237099
ENSE00003492486	5186052	5186251
ENSE00003521373	5146130	5146455
ENSE00003531079	5232368	5232516
ENSE00003544155	5242053	5242191
ENSE00003558544	5182044	5182305
ENSE00003570783	5140664	5140766
ENSE00003577780	5189971	5190130
ENSE00003594991	5262657	5262783
ENSE00003608723	5187725	5187808
ENSE00003617759	5222789	5222884
ENSE00003620608	5239151	5239274
ENSE00003629544	5303268	5303469
ENSE00003647713	5239681	5239925
ENSE00003655982	5191685	5191790

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 89.19.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3585 / max 78.9514, expressed in 414 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55620	0.4390	147
55616	0.3969	171
55617	0.3213	137
55615	0.1440	68
55619	0.0288	13
55618	0.0284	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	89.19	silver quality
tendon of biceps brachii	UBERON:0008188	84.09	gold quality
left ovary	UBERON:0002119	77.98	gold quality
gall bladder	UBERON:0002110	77.95	gold quality
cerebellar hemisphere	UBERON:0002245	77.44	gold quality
cerebellar cortex	UBERON:0002129	77.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.96	gold quality
kidney epithelium	UBERON:0004819	76.91	gold quality
cerebellum	UBERON:0002037	76.84	gold quality
right ovary	UBERON:0002118	75.32	gold quality
ovary	UBERON:0000992	75.17	gold quality
cerebellar vermis	UBERON:0004720	73.02	silver quality
adult mammalian kidney	UBERON:0000082	69.43	gold quality
kidney	UBERON:0002113	68.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	68.06	gold quality
heart right ventricle	UBERON:0002080	67.63	gold quality
parotid gland	UBERON:0001831	66.02	gold quality
vena cava	UBERON:0004087	65.97	gold quality
metanephros	UBERON:0000081	65.85	gold quality
smooth muscle tissue	UBERON:0001135	65.29	gold quality
layer of synovial tissue	UBERON:0007616	65.21	silver quality
myocardium	UBERON:0002349	63.05	gold quality
metanephros cortex	UBERON:0010533	62.77	gold quality
nasal cavity epithelium	UBERON:0005384	62.27	gold quality
peritoneum	UBERON:0002358	62.04	gold quality
omental fat pad	UBERON:0010414	62.04	gold quality
sural nerve	UBERON:0015488	61.94	silver quality
deltoid	UBERON:0001476	61.87	gold quality
body of pancreas	UBERON:0001150	61.42	gold quality
cortex of kidney	UBERON:0001225	61.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	38.84
E-ANND-3	yes	5.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, SP1, WT1

miRNA regulators (miRDB)

48 targeting ADAMTS16, 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-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6165	99.44	67.12	1389

Literature-anchored findings (GeneRIF, showing 10)

• comparison of the effects of C-terminal truncation on the GAG-binding properties and aggrecanase activity of ADAMTS-5 relative to three other ADAMTS family members, ADAMTS-9, ADAMTS-16 and ADAMTS-18 (PMID:16507336)
• These studies provide the first evidence that ADAMTS-16 is an active protease and suggest a physiological role of ADAMTS-16 in ovarian follicles, at least during the pre-ovulatory phase. (PMID:17519324)
• Blood pressure is associated with SNPs of ADAMTS16 in human. (PMID:19423552)
• Results describe the distribution, regulation and function of human ADAMTS-16. (PMID:19635554)
• Data show that the expression of ADAMTS4, 9, 16 and was up-regulated during chondrogenesis, ADAMTS1 and 5 were down-regulated. (PMID:22562232)
• Epistasis between single nucleotide polymorphisms within the TSHB and ADAMTS16 genes may increase the risk of premature ovarian failure in Korean women. (PMID:24366283)
• The pregnancy loss rate seems to be affected by both ADAMTS-3 and ADAMTS-16. (PMID:28088271)
• Through a combination of sequencing studies on eighteen North Carolina macular dystrophy families, two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16, have been reported. (PMID:28790370)
• ADAMTS16 is novel gene with cancer-specific promoter hypermethylation in colorectal cancer, lung cancer and oral squamous cell carcinoma patients implicating ADAMTS16 as potential biomarker for these tumors. (PMID:30081852)
• Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation. (PMID:38018454)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts16	ENSDARG00000074646
mus_musculus	Adamts16	ENSMUSG00000049538
rattus_norvegicus	Adamts16	ENSRNOG00000016812

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), 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 16 — Q8TE57 (reviewed: Q8TE57)

All UniProt accessions (2): Q8TE57, Q2XQZ0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in fetal lung and kidney and in adult prostate and ovary.

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. 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?
Q8TE57-1	1	yes
Q8TE57-2	2

RefSeq proteins (1): NP_620687* (*=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 (52 total): disulfide bond 14, domain 9, glycosylation site 7, sequence variant 5, binding site 4, sequence conflict 3, region of interest 2, splice variant 2, signal peptide 1, propeptide 1, short sequence motif 1, compositionally biased region 1, active site 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TE57-F1	72.07	0.11

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): 434

Ligand- & substrate-binding residues (4): 249 (in inhibited form); 433; 437; 443

Disulfide bonds (14): 366–417, 392–399, 411–490, 450–474, 518–543, 529–550, 538–569, 563–574, 598–635, 602–640, 613–625, 939–981, 943–986, 954–970

Glycosylation sites (7): 156, 310, 741, 780, 835, 905, 935

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: 98 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_MALE_GAMETE_GENERATION, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_NEPHRON_EPITHELIUM_DEVELOPMENT, GOBP_CILIUM_ORGANIZATION, GOBP_RENAL_TUBULE_DEVELOPMENT

GO Biological Process (6): branching involved in ureteric bud morphogenesis (GO:0001658), regulation of systemic arterial blood pressure (GO:0003073), proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), male gamete generation (GO:0048232), regulation of cilium assembly (GO:1902017)

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-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
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
regulation of blood pressure	1
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
gamete generation	1
cilium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of organelle assembly	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

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS16	IRX3	P78415	444
ADAMTS16	NID1	P14543	426
ADAMTS16	PI15	O43692	404
ADAMTS16	ISLR	O14498	398
ADAMTS16	GPC2	Q8N158	398
ADAMTS16	CUBN	O60494	393
ADAMTS16	ZNF541	Q9H0D2	381
ADAMTS16	PCDH7	O60245	379
ADAMTS16	FGFR2	P18443	373
ADAMTS16	CREB3L1	Q96BA8	371
ADAMTS16	WIF1	Q9Y5W5	371
ADAMTS16	ACAN	P16112	370
ADAMTS16	CREB3	O43889	366
ADAMTS16	PTGS2	P35354	366
ADAMTS16	DNASE1	P24855	365

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ADAMTS16	SERPINH1	psi-mi:“MI:0915”(physical association)	0.400
ADAMTS16	TOP1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): ADAMTS16 (Proximity Label-MS), ADAMTS16 (Proximity Label-MS), ADAMTS16 (Proximity Label-MS), ADAMTS16 (Cross-Linking-MS (XL-MS)), ADAMTS16 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1A5Y0, A1KZ92, A2AJ76, B0S5N4, D3YXG0, D3ZPX4, F1MMS9, O00187, O55005, O60500, O75093, O88279, O88280, P11627, P17852, P26006, P32004, P51805, P57110, P59511, P70208, P85171, Q05695, Q0PMG2, Q13219, Q3UH53, Q4KMG0, Q62470, Q62918, Q7Z5N4, Q80TR4, Q8AV58, Q8AXZ4, Q8CIY2, Q8HZK2, Q8HZK3, Q8NDA2, Q8R4K8, Q8TE57, Q91WP0

Diamond homologs: A7MBS7, B3EWY9, B3EWZ8, Q1RMU1, Q2MKA7, Q3UPR9, Q5R328, Q5R7Y0, Q69Z28, Q69ZU6, Q6P4U0, Q8BMS2, Q8IVN8, Q8TE57, Q9BUD6, Q9C0I4, Q9UPZ6, Q9WV75, Q9Z132, A8WGB1, B3EWZ3, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, G5ECS8, O08721, O08722, O08747, O14514, O15072, O60241, O60242, O95185, O95450, P07996, P10643, P11680, P27590

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	1
Uncertain significance	184
Likely benign	17
Benign	1

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012369	GRCh37/hg19 5p15.33-13.3(chr5:22149-29048823)x1	Pathogenic
1340533	GRCh37/hg19 5p15.33-15.1(chr5:113577-16952167)x1	Pathogenic
145514	GRCh38/hg38 5p15.33-14.1(chr5:22149-27788616)x1	Pathogenic
146365	GRCh38/hg38 5p15.33-13.3(chr5:22149-32248010)x1	Pathogenic
147356	GRCh38/hg38 5p15.33-15.1(chr5:22149-16584575)x1	Pathogenic
147751	GRCh38/hg38 5p15.33-15.31(chr5:1544285-8681441)x3	Pathogenic
148081	GRCh38/hg38 5p15.33-14.1(chr5:22149-28429241)x1	Pathogenic
148505	GRCh38/hg38 5p15.33-15.31(chr5:2886163-7108295)x1	Pathogenic
148612	GRCh38/hg38 5p15.33-14.1(chr5:22149-28075106)x3	Pathogenic
148819	GRCh38/hg38 5p15.33-15.2(chr5:22149-11429258)x1	Pathogenic
149039	GRCh38/hg38 5p15.33-14.1(chr5:22149-27187950)x1	Pathogenic
149159	GRCh38/hg38 5p15.33-15.32(chr5:22149-6060102)x1	Pathogenic
149556	GRCh38/hg38 5p15.33-14.3(chr5:22149-21217120)x1	Pathogenic
152423	GRCh38/hg38 5p15.33-15.1(chr5:22149-16930016)x1	Pathogenic
152692	GRCh38/hg38 5p15.33-14.1(chr5:22149-28589192)x1	Pathogenic
153385	GRCh38/hg38 5p15.32-14.3(chr5:4932707-18465361)x1	Pathogenic
153553	GRCh38/hg38 5p15.33-15.32(chr5:113461-6243977)x1	Pathogenic
153600	GRCh38/hg38 5p15.33-15.31(chr5:113461-8875933)x1	Pathogenic
154630	GRCh38/hg38 5p15.33-15.32(chr5:95128-5834551)x1	Pathogenic
154867	GRCh38/hg38 5p15.33-14.1(chr5:22149-27611163)x1	Pathogenic
154955	GRCh38/hg38 5p15.33-14.3(chr5:22149-21726360)x1	Pathogenic
161034	GRCh38/hg38 5p15.33-15.1(chr5:49978-15678451)x1	Pathogenic
1703686	GRCh37/hg19 5p15.33-15.2(chr5:113576-12601027)	Pathogenic
1706484	GRCh37/hg19 5p15.33-13.3(chr5:113576-30712376)x1	Pathogenic
1707436	GRCh37/hg19 5p15.33-15.31(chr5:113576-8007018)x1	Pathogenic
1807906	GRCh37/hg19 5p15.33-13.3(chr5:1-32091038)x1	Pathogenic
1808602	GRCh37/hg19 5p15.33-15.1(chr5:113577-17654787)x1	Pathogenic
1809293	GRCh37/hg19 5p15.33-13.3(chr5:113577-31448527)x1	Pathogenic
242852	GRCh37/hg19 5p15.33-14.3(chr5:25328-19661628)x3	Pathogenic
253478	GRCh37/hg19 5p15.33-15.1(chr5:79146-15509107)x1	Pathogenic

SpliceAI

4830 predictions. Top by Δscore:

Variant	Effect	Δscore
5:5140762:GGGCG:G	donor_gain	1.0000
5:5140763:GGCGG:G	donor_gain	1.0000
5:5146124:TTTCA:T	acceptor_loss	1.0000
5:5146125:TTCA:T	acceptor_loss	1.0000
5:5146127:CAGA:C	acceptor_loss	1.0000
5:5146128:A:AG	acceptor_gain	1.0000
5:5146128:AGAA:A	acceptor_loss	1.0000
5:5146129:G:A	acceptor_loss	1.0000
5:5146129:G:GC	acceptor_gain	1.0000
5:5146129:GAAT:G	acceptor_gain	1.0000
5:5182043:GTC:G	acceptor_gain	1.0000
5:5182043:GTCA:G	acceptor_gain	1.0000
5:5182301:GAAAT:G	donor_gain	1.0000
5:5186050:A:AG	acceptor_gain	1.0000
5:5186051:G:GG	acceptor_gain	1.0000
5:5186051:GAC:G	acceptor_gain	1.0000
5:5186051:GACAT:G	acceptor_gain	1.0000
5:5186270:T:G	donor_gain	1.0000
5:5187720:TTCA:T	acceptor_loss	1.0000
5:5187721:TCA:T	acceptor_loss	1.0000
5:5187722:CA:C	acceptor_loss	1.0000
5:5187723:A:AG	acceptor_gain	1.0000
5:5187724:G:GG	acceptor_gain	1.0000
5:5187724:GGT:G	acceptor_gain	1.0000
5:5187724:GGTAT:G	acceptor_gain	1.0000
5:5187805:ACAG:A	donor_loss	1.0000
5:5187807:AGGTA:A	donor_loss	1.0000
5:5187808:GG:G	donor_loss	1.0000
5:5187810:T:G	donor_loss	1.0000
5:5191787:ACAAG:A	donor_loss	1.0000

AlphaMissense

8008 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:5200229:T:A	W471R	1.000
5:5200229:T:C	W471R	1.000
5:5200231:G:C	W471C	1.000
5:5200231:G:T	W471C	1.000
5:5209193:T:A	C518S	1.000
5:5209194:G:C	C518S	1.000
5:5190027:G:C	W368C	0.999
5:5190027:G:T	W368C	0.999
5:5190097:T:A	C392S	0.999
5:5190097:T:C	C392R	0.999
5:5190098:G:A	C392Y	0.999
5:5190098:G:C	C392S	0.999
5:5190099:T:G	C392W	0.999
5:5190118:T:A	C399S	0.999
5:5190119:G:A	C399Y	0.999
5:5190119:G:C	C399S	0.999
5:5190120:T:G	C399W	0.999
5:5190130:G:A	G403R	0.999
5:5190130:G:C	G403R	0.999
5:5191685:G:A	G403E	0.999
5:5191728:C:G	C417W	0.999
5:5191774:C:G	H433D	0.999
5:5191786:C:G	H437D	0.999
5:5200241:A:C	S475R	0.999
5:5200243:C:A	S475R	0.999
5:5200243:C:G	S475R	0.999
5:5209193:T:C	C518R	0.999
5:5209194:G:A	C518Y	0.999
5:5209194:G:T	C518F	0.999
5:5209195:C:G	C518W	0.999

dbSNP variants (sampled 300 via entrez): RS1000007273 (5:5177066 C>T), RS1000019463 (5:5264177 C>A,T), RS1000031313 (5:5220747 A>G), RS1000038571 (5:5259203 G>T), RS1000041117 (5:5214630 C>T), RS1000057856 (5:5220485 T>C), RS1000059166 (5:5299465 T>G), RS1000087147 (5:5143775 T>C), RS1000095140 (5:5226537 A>G), RS1000107840 (5:5285152 TA>T,TAA), RS1000110553 (5:5256512 C>G,T), RS1000116843 (5:5304867 T>C), RS1000124447 (5:5262006 A>C,T), RS1000137148 (5:5269495 C>G), RS1000150750 (5:5160895 A>G,T)

Disease associations

OMIM: gene MIM:607510 | disease phenotypes: MIM:123450, MIM:617061

GenCC curated gene-disease

Mondo (3): Cri-du-chat syndrome (MONDO:0007404), 46 XY differences of sex development (MONDO:0020040), micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome (MONDO:0014892)

Orphanet (3): Monosomy 5p syndrome (Orphanet:281), 46,XY difference of sex development (Orphanet:98085), Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome (Orphanet:476126)

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002188_4	Functional impairment in major depressive disorder, bipolar disorder and schizophrenia	6.000000e-08
GCST002723_2	Urgency urinary incontinence	2.000000e-07
GCST003542_116	Night sleep phenotypes	6.000000e-06
GCST006144_1	Heparin-induced thrombocytopenia	3.000000e-08
GCST006144_3	Heparin-induced thrombocytopenia	5.000000e-06
GCST006903_12	Hip shape (DXA scan)	6.000000e-09
GCST007002_3	Cerebrospinal fluid t-tau levels in normal cognition	9.000000e-07
GCST007239_7	Ovarian cancer	9.000000e-07
GCST007639_1	Femoral neck length	2.000000e-08
GCST009702_2	Body mass index	8.000000e-06
GCST011039_5	Parkinson’s disease progression (composite)	3.000000e-06
GCST012490_393	Femur bone mineral density x serum urate levels interaction	4.000000e-08
GCST90000015_16	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	6.000000e-06
GCST90006987_4	Gut microbiota relative abundance (Bifidobacterium)	8.000000e-07

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005412	functional impairment measurement
EFO:0006865	urgency urinary incontinence
EFO:0004685	hip geometry
EFO:0004760	t-tau measurement
EFO:0004511	femoral neck bone geometry
EFO:0004340	body mass index
EFO:0008336	disease progression measurement
EFO:0004531	urate measurement
EFO:0600011	Parkinson’s disease symptom measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003410	Cri-du-Chat Syndrome	C10.597.606.360.180; C16.131.077.262; C16.131.260.190; C16.320.180.190
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096

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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases mutagenesis	4
Phenylmercuric Acetate	affects cotreatment, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	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
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Testosterone	increases expression	1
Triclosan	increases expression	1
Vanadates	increases expression	1
Aflatoxin B1	increases methylation	1
Magnetite Nanoparticles	decreases expression, increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT06740162	Not specified	RECRUITING	Physical Activity and Community EmPOWERment Project
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT06723938	Not specified	RECRUITING	Phenotypic and Genotypic Characterisation of a Large, Multicentre Italian Cohort of 46, XY DSD Patients