ADAMTS14

Summary

ADAMTS14 (ADAM metallopeptidase with thrombospondin type 1 motif 14, HGNC:14899) is a protein-coding gene on chromosome 10q22.1, encoding A disintegrin and metalloproteinase with thrombospondin motifs 14 (Q8WXS8). Has aminoprocollagen type I processing activity in the absence of ADAMTS2.

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients.

Source: NCBI Gene 140766 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 288 total — 3 pathogenic
• MANE Select transcript: NM_080722

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14899
Approved symbol	ADAMTS14
Name	ADAM metallopeptidase with thrombospondin type 1 motif 14
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138316
Ensembl biotype	protein_coding
OMIM	607506
Entrez	140766

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000373207, ENST00000373208, ENST00000886732, ENST00000915987, ENST00000955383

RefSeq mRNA: 2 — MANE Select: NM_080722 NM_080722, NM_139155

CCDS: CCDS7306, CCDS7307

Canonical transcript exons

ENST00000373207 — 22 exons

Exon	Start	End
ENSE00001100998	70751478	70751646
ENSE00001101003	70732254	70732359
ENSE00001101013	70757962	70758091
ENSE00001101018	70735169	70735301
ENSE00001101051	70744066	70744189
ENSE00001101058	70758175	70758285
ENSE00001101061	70749822	70749985
ENSE00001101063	70738842	70738990
ENSE00001101077	70729294	70729377
ENSE00001101080	70743548	70743681
ENSE00001101085	70702312	70702468
ENSE00001101094	70752095	70752227
ENSE00001101097	70708588	70708778
ENSE00001101109	70733885	70734028
ENSE00001154427	70674556	70674995
ENSE00001185896	70745226	70745306
ENSE00001185909	70740987	70741162
ENSE00001307196	70753800	70754007
ENSE00001371874	70730102	70730249
ENSE00001459769	70760360	70762441
ENSE00002467590	70736680	70736793
ENSE00003844968	70672506	70672884

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 75.77.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7392 / max 198.8709, expressed in 767 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105397	3.1277	685
105398	0.4398	270
105396	0.0865	41
105399	0.0852	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	75.77	gold quality
vena cava	UBERON:0004087	74.46	silver quality
mucosa of transverse colon	UBERON:0004991	73.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.72	gold quality
epithelial cell of pancreas	CL:0000083	71.96	gold quality
cerebellar vermis	UBERON:0004720	71.60	gold quality
putamen	UBERON:0001874	70.88	gold quality
vermiform appendix	UBERON:0001154	70.29	gold quality
caecum	UBERON:0001153	70.25	gold quality
tibial nerve	UBERON:0001323	70.15	gold quality
sperm	CL:0000019	69.94	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	68.94	gold quality
pancreatic ductal cell	CL:0002079	68.90	silver quality
cartilage tissue	UBERON:0002418	68.57	gold quality
sural nerve	UBERON:0015488	68.55	silver quality
nipple	UBERON:0002030	68.52	gold quality
lateral nuclear group of thalamus	UBERON:0002736	68.47	silver quality
inferior vagus X ganglion	UBERON:0005363	68.30	silver quality
substantia nigra pars compacta	UBERON:0001965	68.24	silver quality
layer of synovial tissue	UBERON:0007616	68.20	gold quality
vastus lateralis	UBERON:0001379	67.91	gold quality
biceps brachii	UBERON:0001507	67.66	gold quality
quadriceps femoris	UBERON:0001377	67.60	gold quality
placenta	UBERON:0001987	67.57	gold quality
trachea	UBERON:0003126	67.37	gold quality
saphenous vein	UBERON:0007318	67.15	gold quality
parotid gland	UBERON:0001831	67.10	gold quality
pericardium	UBERON:0002407	67.01	gold quality
stromal cell of endometrium	CL:0002255	66.93	gold quality
upper arm skin	UBERON:0004263	66.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting ADAMTS14, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662

Literature-anchored findings (GeneRIF, showing 20)

• This study suggest potentially important role for the ADAMTS14 gene in predisposition to MS. (PMID:15913795)
• findings implicate ADAMTS14 in osteoarthritis (PMID:18790654)
• ADAMTS-2, -3, and -13 expression, but not that of ADAMTS-14, are increased in plaques causing AMI compared those associated with stable angina. (PMID:22205175)
• Carriage of the ADAMTS14 rs4747096 GG variant appears to delay onset of the injury in Achilles tendon pathology. (PMID:23491141)
• No significant associations were observed in males. In conclusion, the nsSNP rs4747096 in ADAMTS14 was associated with knee OA in female Thai patients; therefore, the role of ADAMTS14 in OA seems to be gender-dependent. (PMID:24301791)
• Suggest the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for colorectal cancer in African Americans. (PMID:25638164)
• Data indicate that ADAMTS2, 3 and 14 cleave the amino-propeptide of fibrillar collagens. [review] (PMID:25863161)
• ADAMTS14 SNPs and environmental mutagens are a risk factor of oral tumorigenesis. (PMID:27463966)
• These results suggest an involvement of ADAMTS14 single-nucleotide polymorphisms rs12774070 and rs61573157 in the liver tumorigenesis and implicate the ADAMTS14 gene polymorphism as a predict factor during the progression of hepatocellular carcinoma. (PMID:28231306)
• ADAMTS14 gene polymorphism was associated with KOA, and the GG genotype increased the risk of KOA in Chinese Han population. The ADAMTS14 may be a diagnostic marker and therapeutic target for KOA treatment. (PMID:30266746)
• Our results demonstrated that circADAMTS14 might suppress hepatocellular carcinoma (HCC) progression through regulating miR-572/ RCAN1 as the competing endogenous RNA. (PMID:30317540)
• Inflammasome components and ADAMTS4 in premature rupture of membranes. (PMID:33300067)
• Identification of crucial noncoding RNAs and mRNAs in hypertrophic scars via RNA sequencing. (PMID:33932142)
• Lack of association between MMP13 (rs3819089), ADAM12 (rs3740199-rs1871054) and ADAMTS14 (rs4747096) genotypes and advanced-stage knee osteoarthritis. (PMID:34145804)
• The expression of ADAMTS14 is regulated by promoter DNA methylation and is associated with poor prognosis in colorectal cancer. (PMID:34856162)
• Survival Prognosis, Tumor Immune Landscape, and Immune Responses of ADAMTS14 in Clear Cell Renal Cell Carcinoma and Its Potential Mechanisms. (PMID:35572505)
• Large scale phenotype imputation and in vivo functional validation implicate ADAMTS14 as an adiposity gene. (PMID:36658113)
• Correlation investigation between a single nucleotide polymorphism in ADAMTS14 (rs4747096) and osteoarthritis: a meta-analysis. (PMID:37550675)
• Association between ADAMTS14_rs4747096 gene polymorphism and bone mineral density of Chinese Han population residing in fluorine exposed areas in ShanXi Province, China. (PMID:37725302)
• Opposing roles for ADAMTS2 and ADAMTS14 in myofibroblast differentiation and function. (PMID:37929635)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts14	ENSDARG00000078494
mus_musculus	Adamts14	ENSMUSG00000059901
rattus_norvegicus	Adamts14	ENSRNOG00000000563

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS5 (ENSG00000154736), ADAMTS3 (ENSG00000156140), ADAMTSL3 (ENSG00000156218), ADAMTS4 (ENSG00000158859), ADAMTS13 (ENSG00000160323), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

A disintegrin and metalloproteinase with thrombospondin motifs 14 — Q8WXS8 (reviewed: Q8WXS8)

All UniProt accessions (1): Q8WXS8

UniProt curated annotations — full annotation on UniProt →

Function. Has aminoprocollagen type I processing activity in the absence of ADAMTS2. Seems to be synthesized as a latent enzyme that requires activation to display aminoprocollagen peptidase activity. Cleaves lysyl oxidase LOX at a site downstream of its propeptide cleavage site to produce a short LOX form.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in retina and at low levels in brain, lung and placenta. High expression in fetal tissues.

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.

Domain organisation. The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.

Miscellaneous. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative splicing of isoform B. Produced by alternative splicing of isoform A.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8WXS8-1	A	yes
Q8WXS8-2	B
Q8WXS8-3	C
Q8WXS8-4	D

RefSeq proteins (2): NP_542453, NP_631894 (=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
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, PF17771, PF19030, PF19236

Enzyme classification (BRENDA):

• EC 3.4.24.14 — procollagen N-endopeptidase (BRENDA: 10 organisms, 94 substrates, 74 inhibitors, 17 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PROCOLLAGEN I	—	12
PNCOLLAGEN, CARBOXYMETHYLATED	0.0028	1
PROCOLLAGEN II	0.0002	1
PROPEPTIDE OF COLLAGEN ALPHA-1 CHAIN	0.001	1
PROPEPTIDE OF COLLAGEN ALPHA-2 CHAIN	0.001	1

UniProt features (47 total): disulfide bond 13, domain 7, sequence variant 5, sequence conflict 5, glycosylation site 4, binding site 3, region of interest 2, compositionally biased region 2, splice variant 2, signal peptide 1, propeptide 1, active site 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXS8-F1	70.22	0.16

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): 399

Ligand- & substrate-binding residues (3): 398; 402; 408

Disulfide bonds (13): 336–382, 376–455, 415–441, 482–507, 493–516, 502–535, 529–540, 564–601, 568–606, 579–591, 980–1016, 984–1021, 995–1005

Glycosylation sites (4): 109, 475, 941, 1027

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
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-1474290	Collagen formation
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): RNGTGGGC_UNKNOWN, HNF3ALPHA_Q6, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOMF_METALLOPEPTIDASE_ACTIVITY, TGACCTY_ERR1_Q2, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, HFH4_01, HFH3_01, TGANTCA_AP1_C, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, FOX_Q2, TGGAAA_NFAT_Q4_01, GRYDER_PAX3FOXO1_TOP_ENHANCERS, HNF3_Q6, GOBP_PROTEOLYSIS

GO Biological Process (4): proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), collagen fibril organization (GO:0030199), collagen catabolic process (GO:0030574)

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 region (GO:0005576), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Collagen formation	1
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Extracellular matrix organization	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
extracellular matrix organization	1
catabolic process	1
collagen metabolic process	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
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS14	SGPL1	O95470	836
ADAMTS14	FURIN	P09958	589
ADAMTS14	CNIH1	O95406	586
ADAMTS14	CNIH3	Q8TBE1	552
ADAMTS14	SEC16B	Q96JE7	525
ADAMTS14	PALD1	Q9ULE6	482
ADAMTS14	CCBE1	Q6UXH8	468
ADAMTS14	ZNF646	O15015	457
ADAMTS14	BMP1	P13497	435
ADAMTS14	COL4A6	Q14031	423
ADAMTS14	COL21A1	Q96P44	405
ADAMTS14	TLL1	O43897	374
ADAMTS14	CRTAP	O75718	372
ADAMTS14	SPINK8	P0C7L1	368
ADAMTS14	COL19A1	Q14993	364

IntAct

4 interactions, top by confidence:

A	B	Type	Score
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): ADAMTS14 (Affinity Capture-MS), ADAMTS14 (Affinity Capture-MS), HNRNPA2B1 (Cross-Linking-MS (XL-MS)), HIST1H3A (Cross-Linking-MS (XL-MS)), ADAMTS14 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9PFP2, A2A863, A2VE29, A6X935, O02668, P01029, P01030, P08649, P0C0L4, P0C0L5, P16144, P19069, P19823, P19827, P56652, P58459, P59384, P79263, P97278, P97279, P97280, P97857, Q06033, Q06274, Q0VCM5, Q14624, Q1EHB3, Q29052, Q3T052, Q5RB37, Q5RER0, Q60750, Q61702, Q61703, Q61704, Q63416, Q64632, Q68SA9, Q86UX2, Q8BG22

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

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	244
Likely benign	21
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
146115	GRCh38/hg38 10q21.3-22.3(chr10:67196567-79422057)x3	Pathogenic
1527589	GRCh37/hg19 10q21.3-22.3(chr10:68735254-78885714)	Pathogenic
58726	GRCh38/hg38 10q21.1-22.2(chr10:58436466-74415216)x1	Pathogenic

SpliceAI

5048 predictions. Top by Δscore:

Variant	Effect	Δscore
10:70692486:G:T	donor_gain	1.0000
10:70702288:C:CA	acceptor_gain	1.0000
10:70702291:T:A	acceptor_gain	1.0000
10:70702295:T:TA	acceptor_gain	1.0000
10:70702298:C:A	acceptor_gain	1.0000
10:70702304:T:A	acceptor_gain	1.0000
10:70702310:A:G	acceptor_loss	1.0000
10:70702311:GGC:G	acceptor_gain	1.0000
10:70702466:AAG:A	donor_loss	1.0000
10:70702467:AG:A	donor_loss	1.0000
10:70702468:GG:G	donor_loss	1.0000
10:70702469:G:GA	donor_loss	1.0000
10:70702470:T:G	donor_loss	1.0000
10:70708579:T:TA	acceptor_gain	1.0000
10:70708580:G:A	acceptor_gain	1.0000
10:70708585:CAGCC:C	acceptor_loss	1.0000
10:70708586:A:AG	acceptor_gain	1.0000
10:70708587:G:GG	acceptor_gain	1.0000
10:70708587:GCC:G	acceptor_gain	1.0000
10:70708587:GCCT:G	acceptor_gain	1.0000
10:70708774:ATATC:A	donor_gain	1.0000
10:70708775:TATC:T	donor_gain	1.0000
10:70708776:ATC:A	donor_gain	1.0000
10:70708777:TC:T	donor_gain	1.0000
10:70708779:G:GG	donor_gain	1.0000
10:70729289:TGCA:T	acceptor_loss	1.0000
10:70729291:CA:C	acceptor_loss	1.0000
10:70729292:A:AG	acceptor_gain	1.0000
10:70729292:A:C	acceptor_loss	1.0000
10:70729293:G:GG	acceptor_gain	1.0000

AlphaMissense

7969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:70733990:G:C	W438C	1.000
10:70733990:G:T	W438C	1.000
10:70733988:T:A	W438R	0.999
10:70733988:T:C	W438R	0.999
10:70735260:T:A	C482S	0.999
10:70735261:G:C	C482S	0.999
10:70736740:T:A	C516S	0.999
10:70736741:G:C	C516S	0.999
10:70741090:T:A	C618S	0.999
10:70741091:G:C	C618S	0.999
10:70741138:T:A	W634R	0.999
10:70741138:T:C	W634R	0.999
10:70741140:G:C	W634C	0.999
10:70741140:G:T	W634C	0.999
10:70743571:T:A	C650S	0.999
10:70743571:T:C	C650R	0.999
10:70743572:G:C	C650S	0.999
10:70743573:C:G	C650W	0.999
10:70744114:T:A	C703S	0.999
10:70744115:G:C	C703S	0.999
10:70744144:T:A	C713S	0.999
10:70744145:G:C	C713S	0.999
10:70751603:G:C	W851C	0.999
10:70751603:G:T	W851C	0.999
10:70751618:G:C	W856C	0.999
10:70751618:G:T	W856C	0.999
10:70753818:G:C	W916C	0.999
10:70753818:G:T	W916C	0.999
10:70730138:A:C	S331R	0.998
10:70730140:C:A	S331R	0.998

dbSNP variants (sampled 300 via entrez): RS1000007435 (10:70679952 G>A,T), RS1000015177 (10:70738785 C>T), RS1000067655 (10:70738484 T>A), RS1000117015 (10:70673901 C>A,G), RS1000155369 (10:70715276 C>A), RS1000207462 (10:70690793 A>G), RS1000242877 (10:70758896 G>A,T), RS1000254613 (10:70700845 G>A), RS1000260676 (10:70694547 C>T), RS1000268744 (10:70759252 A>G), RS1000277591 (10:70720935 C>A,T), RS1000314261 (10:70694853 G>T), RS1000354898 (10:70732726 G>A), RS1000366532 (10:70695129 T>C), RS1000393057 (10:70727242 C>G)

Disease associations

OMIM: gene MIM:607506 | disease phenotypes: MIM:617667

GenCC curated gene-disease

Mondo (1): Fraser syndrome 3 (MONDO:0054739)

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002053_6	Sleep duration	5.000000e-06
GCST002969_2	Suicide behavior	2.000000e-06
GCST006979_590	Heel bone mineral density	4.000000e-11
GCST007294_126	Body fat distribution (trunk fat ratio)	1.000000e-10
GCST007294_5	Body fat distribution (trunk fat ratio)	3.000000e-14
GCST007295_39	Body fat distribution (leg fat ratio)	9.000000e-14
GCST007295_73	Body fat distribution (leg fat ratio)	3.000000e-08
GCST008179_17	Moderate-to-late spontaneous preterm birth	4.000000e-06
GCST008180_1	Spontaneous preterm birth with premature rupture of membranes	5.000000e-06
GCST009462_106	Optic disc size	1.000000e-08
GCST90000025_438	Appendicular lean mass	3.000000e-34

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007623	suicide behaviour
EFO:0009270	heel bone mineral density
EFO:0004341	body fat distribution
EFO:0006917	spontaneous preterm birth
EFO:0004980	appendicular lean mass

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
rs2791188	ADAMTS14		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M12: Astacin/Adamalysin

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	decreases methylation	2
propionaldehyde	increases expression	1
bisphenol A	increases methylation, affects cotreatment	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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