ADAMTSL3

Summary

ADAMTSL3 (ADAMTS like 3, HGNC:14633) is a protein-coding gene on chromosome 15q25.2, encoding ADAMTS-like protein 3 (P82987).

Predicted to be involved in extracellular matrix organization. Located in intracellular membrane-bounded organelle.

Source: NCBI Gene 57188 — RefSeq curated summary.

At a glance

• GWAS associations: 253
• Clinical variants (ClinVar): 393 total — 2 pathogenic, 5 likely-pathogenic
• MANE Select transcript: NM_207517

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14633
Approved symbol	ADAMTSL3
Name	ADAMTS like 3
Location	15q25.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1233, punctin-2
Ensembl gene	ENSG00000156218
Ensembl biotype	protein_coding
OMIM	609199
Entrez	57188

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding_CDS_not_defined, 3 protein_coding, 2 retained_intron

ENST00000286744, ENST00000561483, ENST00000562296, ENST00000565653, ENST00000567476, ENST00000567663, ENST00000567716, ENST00000569510, ENST00000963409

RefSeq mRNA: 2 — MANE Select: NM_207517 NM_001301110, NM_207517

CCDS: CCDS10326, CCDS73773

Canonical transcript exons

ENST00000286744 — 30 exons

Exon	Start	End
ENSE00001025226	84031335	84031432
ENSE00001158400	84036773	84036987
ENSE00001158409	84025238	84025436
ENSE00001158698	84037700	84039842
ENSE00001416211	83654123	83654276
ENSE00003466898	83885101	83885212
ENSE00003495970	83838089	83838215
ENSE00003508786	83899647	83899731
ENSE00003512437	83913092	83913378
ENSE00003526989	83991086	83991214
ENSE00003532146	83858766	83858840
ENSE00003532156	83982273	83983344
ENSE00003536183	83891329	83891379
ENSE00003536980	84021410	84021593
ENSE00003542459	83942903	83943082
ENSE00003547770	83970484	83970637
ENSE00003574865	83892684	83892888
ENSE00003575379	83942596	83942788
ENSE00003590176	83655729	83655830
ENSE00003617761	84016383	84016499
ENSE00003618081	83704389	83704508
ENSE00003622534	83870802	83870959
ENSE00003626438	83988691	83988818
ENSE00003628155	83890109	83890247
ENSE00003628438	83819811	83820047
ENSE00003648421	83923904	83924033
ENSE00003660934	83897858	83898005
ENSE00003661003	83804650	83804695
ENSE00003681860	83773523	83773650
ENSE00003685004	84014542	84014724

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 92.77.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8701 / max 87.5901, expressed in 440 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148126	0.9669	258
148125	0.4760	201
148124	0.4273	216

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.77	gold quality
descending thoracic aorta	UBERON:0002345	88.11	gold quality
thoracic aorta	UBERON:0001515	87.61	gold quality
ascending aorta	UBERON:0001496	87.50	gold quality
tendon	UBERON:0000043	86.58	gold quality
pigmented layer of retina	UBERON:0001782	86.56	gold quality
aorta	UBERON:0000947	85.69	gold quality
sural nerve	UBERON:0015488	85.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.79	gold quality
lower lobe of lung	UBERON:0008949	84.72	gold quality
popliteal artery	UBERON:0002250	84.28	gold quality
tibial artery	UBERON:0007610	84.23	gold quality
right atrium auricular region	UBERON:0006631	83.74	gold quality
cardiac atrium	UBERON:0002081	83.64	gold quality
mucosa of stomach	UBERON:0001199	82.16	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.96	gold quality
secondary oocyte	CL:0000655	81.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.81	gold quality
right lung	UBERON:0002167	81.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.44	gold quality
tendon of biceps brachii	UBERON:0008188	81.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.95	gold quality
buccal mucosa cell	CL:0002336	80.45	silver quality
lower esophagus muscularis layer	UBERON:0035833	80.24	gold quality
lower esophagus	UBERON:0013473	80.16	gold quality
synovial joint	UBERON:0002217	79.48	gold quality
colonic epithelium	UBERON:0000397	79.01	gold quality
visceral pleura	UBERON:0002401	78.50	gold quality
right coronary artery	UBERON:0001625	78.14	gold quality
lung	UBERON:0002048	78.10	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	3046.89
E-MTAB-7052	yes	148.97
E-CURD-119	yes	25.79
E-MTAB-5061	yes	14.10
E-ANND-3	yes	13.11
E-ENAD-20	no	81.76
E-MTAB-6142	no	3.40
E-HCAD-31	no	2.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

136 targeting ADAMTSL3, 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-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-196A-1-3P	99.99	72.15	2772
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-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434

Literature-anchored findings (GeneRIF, showing 6)

• Highest expression of ADAMTSL3 was found in liver, kidney, heart and skeletal muscle. (PMID:14667842)
• ADAMTSL3 is expressed in numerous tissues, suggesting a broader regulatory role than in colorectal epithelium alone, and that colorectal cancer has both structural mutations as well as decreased expression of ADAMTSL3. (PMID:17597111)
• The results of this study suggested that the ADAMTSL3 as a candidate gene for schizophrenia. (PMID:21239144)
• Compared with the George-Abraham’ study [2012], ADAMTSL3 might be more related to the cardiac disorders in tetrasomy 15q patients (PMID:24793337)
• A137T in ADAMTSL3 may be a susceptibility mutation for diabetes. (PMID:29162515)
• knocking out either the ADAMTSL3 or PTEN genes promoted either the proliferation or metastasis of hepatocellular carcinoma cells, respectively (PMID:32266537)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamtsl3	ENSDARG00000027903
mus_musculus	Adamtsl3	ENSMUSG00000070469
rattus_norvegicus	Adamtsl3	ENSRNOG00000010840

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS5 (ENSG00000154736), ADAMTS3 (ENSG00000156140), ADAMTS4 (ENSG00000158859), ADAMTS13 (ENSG00000160323), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

ADAMTS-like protein 3 — P82987 (reviewed: P82987)

Alternative names: Punctin-2

All UniProt accessions (1): P82987

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in epithelial cells of the colon, fallopian tube, skin, breast, prostate, epididymis, liver, pancreatic islets and bile ducts, as well as by vascular endothelial cells, smooth muscle cells, fibroblasts, cortical and ganglionic neurons and cardiac myocytes. Also expressed by malignant epithelial cells in colon cancer, as well as breast, prostate, renal and skin tumors. Expression is significantly reduced in colon cancer compared to normal colon.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
P82987-1	1	yes
P82987-2	2

RefSeq proteins (2): NP_001288039, NP_997400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR010909	PLAC	Domain
IPR013098	Ig_I-set	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR045371	ADAMTS_CR_3	Domain
IPR050439	ADAMTS_ADAMTS-like	Family

Pfam: PF00090, PF07679, PF08686, PF13927, PF19030, PF19236

UniProt features (65 total): glycosylation site 17, domain 14, sequence variant 14, disulfide bond 12, sequence conflict 3, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P82987-F1	65.99	0.04

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (12): 87–118, 91–123, 102–108, 576–620, 580–625, 591–609, 831–875, 835–880, 846–863, 934–982, 1215–1263, 1321–1367

Glycosylation sites (17): 293, 681, 797, 915, 927, 1102, 1191, 1292, 1316, 1330, 1343, 1349, 1356, 1432, 1516, 1574, 1591

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: 178 (showing top): MORF_ITGA2, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGACCTY_ERR1_Q2, CACCAGC_MIR138, MORF_RAD51L3, INAMURA_LUNG_CANCER_SCC_DN, MORF_CTSB, MORF_IL4, MORF_PRKCA, AAAGACA_MIR511, MORF_THPO, AACTTT_UNKNOWN, RYTTCCTG_ETS2_B, MORF_ATF2, CTTTGTA_MIR524

GO Biological Process (1): extracellular matrix organization (GO:0030198)

GO Molecular Function (1): protein binding (GO:0005515)

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
extracellular structure organization	1
external encapsulating structure organization	1
binding	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTSL3	HSD17B11	Q8NBQ5	543
ADAMTSL3	LTBP1	P22064	498
ADAMTSL3	LCORL	Q8N3X6	417
ADAMTSL3	ADAM32	Q8TC27	373
ADAMTSL3	EFEMP1	Q12805	371
ADAMTSL3	EGR2	P11161	366
ADAMTSL3	GOLGA6L4	A6NEF3	366
ADAMTSL3	ZBTB38	Q8NAP3	365
ADAMTSL3	ATXN2L	Q8WWM7	355
ADAMTSL3	FTO	Q9C0B1	349
ADAMTSL3	ADAM11	O75078	344
ADAMTSL3	SH3GL3	Q99963	339
ADAMTSL3	CDCP2	Q5VXM1	337
ADAMTSL3	SCMH1	Q96GD3	333
ADAMTSL3	ADAMTS1	Q9UHI8	330

IntAct

65 interactions, top by confidence:

A	B	Type	Score
KRTAP10-8	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.720
MDFI	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL3	MDFI	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL3	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
FPR2	ARL6IP5	psi-mi:“MI:0914”(association)	0.640
	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP2-3	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.560
KRT40	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL3	KRT40	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL3	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL3	KRTAP2-3	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL3	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL3	KRTAP5-7	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL3	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	ADAMTSL3	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL3	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530

BioGRID (19): ADAMTSL3 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), ADAMTSL3 (Two-hybrid), ADAMTSL3 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-6 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP2-3 (Two-hybrid), KRTAP3-2 (Two-hybrid)

ESM2 similar proteins: A7MBS7, D3YXF5, F1LW30, O89103, P10643, P11680, P27918, P35446, P82987, P90884, Q29RQ1, Q2I0M5, Q2MKA7, Q3UPR9, Q3UTY6, Q4R7Z5, Q5M7L6, Q5RAD0, Q5RBP1, Q5RBP8, Q5UE90, Q64181, Q66PY1, Q69ZU6, Q6NZL8, Q6P4U0, Q6UXX9, Q6ZMP0, Q7T3Q2, Q7TSK7, Q80YN4, Q86TH1, Q8BFU0, Q8BJ73, Q8BLI0, Q8IUX8, Q8IWY4, Q8IX30, Q8N6G6, Q8VCC9

Diamond homologs: A1KZ92, A2AJ76, A2ASS6, A4IGL7, A4IIW9, A8WGA3, B0BNK7, B4JEF2, D2HFT7, D3YXG0, D4A1J9, D4ABX8, F1NY98, G5EG78, O01761, O42414, O55005, O88280, O89026, P0C192, P0C5E3, P0C6S8, P0C7J6, P0CC10, P11799, P12960, P14781, P20241, P32004, P82987, P97685, Q03696, Q0E9H9, Q12860, Q149C3, Q15746, Q1RMS4, Q28106, Q2WF71, Q3KNY0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	9	15.7×	4e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	5
Uncertain significance	254
Likely benign	20
Benign	89

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
687860	GRCh37/hg19 15q25.2(chr15:82688216-84796779)x1	Pathogenic
980540	GRCh37/hg19 15q25.2-25.3(chr15:83201955-85786847)x1	Pathogenic
147948	GRCh38/hg38 15q25.2-25.3(chr15:82560915-85185613)x1	Likely pathogenic
155058	GRCh38/hg38 15q25.2-25.3(chr15:82627214-85243616)x1	Likely pathogenic
221753	GRCh37/hg19 15q25.2(chr15:83213963-84811815)x1	Likely pathogenic
441679	GRCh37/hg19 15q25.2(chr15:83169558-84847653)x1	Likely pathogenic
549640	NC_000015.9:g.83214012_84812693del1598682	Likely pathogenic

SpliceAI

6620 predictions. Top by Δscore:

Variant	Effect	Δscore
15:83654273:CAAGG:C	donor_loss	1.0000
15:83654274:AAGGT:A	donor_loss	1.0000
15:83654278:T:A	donor_loss	1.0000
15:83655828:CAGG:C	donor_loss	1.0000
15:83655829:AG:A	donor_loss	1.0000
15:83655831:GTA:G	donor_loss	1.0000
15:83655832:T:A	donor_loss	1.0000
15:83704385:TCAG:T	acceptor_loss	1.0000
15:83704387:A:AG	acceptor_gain	1.0000
15:83704387:A:C	acceptor_loss	1.0000
15:83704388:G:GG	acceptor_gain	1.0000
15:83704505:CCAGG:C	donor_loss	1.0000
15:83704507:AGG:A	donor_loss	1.0000
15:83704508:GGT:G	donor_loss	1.0000
15:83704510:T:A	donor_loss	1.0000
15:83773514:A:AG	acceptor_gain	1.0000
15:83773647:GAAGG:G	donor_loss	1.0000
15:83773648:AAGGT:A	donor_loss	1.0000
15:83773649:AGGTT:A	donor_loss	1.0000
15:83773650:GGTT:G	donor_loss	1.0000
15:83773651:G:GC	donor_loss	1.0000
15:83773652:T:A	donor_loss	1.0000
15:83804645:TTTAG:T	acceptor_loss	1.0000
15:83804646:TTA:T	acceptor_loss	1.0000
15:83804647:TAGG:T	acceptor_loss	1.0000
15:83804648:A:AT	acceptor_loss	1.0000
15:83804648:AG:A	acceptor_gain	1.0000
15:83804649:GG:G	acceptor_gain	1.0000
15:83804649:GGA:G	acceptor_gain	1.0000
15:83804691:ATCAT:A	donor_gain	1.0000

AlphaMissense

11113 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:83892687:G:C	W422C	1.000
15:83892687:G:T	W422C	1.000
15:83892882:G:C	W487C	1.000
15:83892882:G:T	W487C	1.000
15:83773576:G:C	W81C	0.999
15:83773576:G:T	W81C	0.999
15:83773585:G:C	W84C	0.999
15:83773585:G:T	W84C	0.999
15:83819836:T:G	F130C	0.999
15:83819850:T:A	C135S	0.999
15:83819850:T:C	C135R	0.999
15:83819851:G:C	C135S	0.999
15:83819895:T:A	W150R	0.999
15:83819895:T:C	W150R	0.999
15:83819897:G:C	W150C	0.999
15:83819897:G:T	W150C	0.999
15:83819940:T:A	C165S	0.999
15:83819941:G:C	C165S	0.999
15:83820003:T:A	C186S	0.999
15:83820004:G:C	C186S	0.999
15:83820027:T:A	C194S	0.999
15:83820028:G:C	C194S	0.999
15:83885167:T:A	W343R	0.999
15:83885167:T:C	W343R	0.999
15:83885169:G:C	W343C	0.999
15:83885169:G:T	W343C	0.999
15:83890132:T:A	C366S	0.999
15:83890132:T:C	C366R	0.999
15:83890133:G:C	C366S	0.999
15:83890176:T:G	C380W	0.999

dbSNP variants (sampled 300 via entrez): RS1000009228 (15:83730712 C>T), RS1000018478 (15:83853642 G>C), RS1000035251 (15:83909813 A>C), RS1000045260 (15:83789931 T>A), RS1000051144 (15:83880427 A>G), RS1000059668 (15:83682864 G>A,T), RS1000068263 (15:83953246 A>G), RS1000072968 (15:83960510 GA>G,GAA), RS1000075443 (15:83974874 G>C,T), RS1000077948 (15:83789625 C>G), RS1000080941 (15:83724496 C>T), RS1000084493 (15:83835023 A>C), RS1000085165 (15:83679676 G>C,T), RS1000110515 (15:83916458 A>G), RS1000118100 (15:83705133 A>G)

Disease associations

OMIM: gene MIM:609199 | disease phenotypes:

GenCC curated gene-disease

Mondo (4): primary ovarian failure (MONDO:0005387), squamous cell carcinoma (MONDO:0005096), lung adenocarcinoma (MONDO:0005061), primary amenorrhea (MONDO:1060208)

Orphanet (2): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

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

GWAS associations

253 associations (top):

Study	Trait	p-value
GCST000174_4	Height	2.000000e-08
GCST000175_10	Height	9.000000e-07
GCST000176_14	Height	6.000000e-08
GCST000372_12	Height	3.000000e-08
GCST000611_6	Height	1.000000e-07
GCST000644_2	Height	4.000000e-07
GCST000644_4	Height	5.000000e-07
GCST000817_109	Height	2.000000e-35
GCST001263_13	Height	9.000000e-07
GCST001956_13	Height	1.000000e-19
GCST002337_39	Amyotrophic lateral sclerosis (sporadic)	6.000000e-06
GCST002539_78	Schizophrenia	2.000000e-11
GCST002647_113	Height	8.000000e-55
GCST002702_72	Height	4.000000e-21
GCST003335_4	Waist circumference	1.000000e-06
GCST003336_2	Waist circumference adjusted for body mass index	9.000000e-27
GCST003336_5	Waist circumference adjusted for body mass index	6.000000e-06
GCST003336_7	Waist circumference adjusted for body mass index	2.000000e-09
GCST004063_132	Waist circumference adjusted for body mass index	3.000000e-16
GCST004063_133	Waist circumference adjusted for body mass index	1.000000e-28
GCST004063_134	Waist circumference adjusted for body mass index	1.000000e-17
GCST004066_123	Hip circumference	5.000000e-08
GCST004067_105	Hip circumference adjusted for BMI	2.000000e-30
GCST004067_144	Hip circumference adjusted for BMI	5.000000e-14
GCST004067_37	Hip circumference adjusted for BMI	1.000000e-20
GCST004500_26	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-23
GCST004500_76	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-14
GCST004500_90	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-12
GCST004501_4	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	5.000000e-25
GCST004501_5	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-16

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004995	lean body mass
EFO:0004980	appendicular lean mass
EFO:0005763	pulse pressure measurement
EFO:0004341	body fat distribution
EFO:0004508	spine bone size
EFO:0007874	gut microbiome measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004340	body mass index

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	3
Tobacco Smoke Pollution	decreases expression, increases methylation	2
testosterone enanthate	affects expression	1
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Copper	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Phthalic Acids	increases methylation	1
Theophylline	affects cotreatment, increases expression	1
Toluene	decreases expression, increases methylation	1
Triclosan	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00868088	PHASE4	COMPLETED	Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip
NCT02088515	PHASE4	COMPLETED	Nedaplatin (Jiebaishu®) Combined With Docetaxel for Advanced Lung Squamous Cell Carcinoma
NCT02151149	PHASE4	COMPLETED	Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly
NCT03388931	PHASE4	WITHDRAWN	Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00101582	PHASE3	COMPLETED	Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
NCT00201279	PHASE3	COMPLETED	Chemoprevention Study of Oral Cavity Squamous Cell Carcinoma
NCT00201383	PHASE3	COMPLETED	Post-Operative Adjuvant Concurrent Chemoradiotherapy For High Risk Oral Cavity Squamous Cell Carcinoma Patients
NCT00382031	PHASE3	COMPLETED	Zalutumumab in Patients With Non-curable Head and Neck Cancer
NCT00472459	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer
NCT00559351	PHASE3	TERMINATED	RCT on the Combined Modality Treatment of Squamous Cell Carcinoma of the Esophagus
NCT01161498	PHASE3	TERMINATED	Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer
NCT01363466	PHASE3	TERMINATED	Evaluation of Hysterectomy After Chemoradiation Therapy for Stage IB2/II Cervical Cancer
NCT01532453	PHASE3	TERMINATED	Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients
NCT01706939	PHASE3	ACTIVE_NOT_RECRUITING	The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
NCT03115476	PHASE3	TERMINATED	A Trial to Compare the Incidence of Squamous Cell Carcinoma (SCC) and Other Skin Neoplasia on Skin Areas Treated With Ingenol Disoxate Gel or Vehicle Gel for Actinic Keratosis on Face and Chest or Scalp
NCT03257267	PHASE3	COMPLETED	Study of Cemiplimab in Adults With Cervical Cancer
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT00139230	PHASE2	COMPLETED	Combination Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck
NCT00176254	PHASE2	COMPLETED	Paclitaxel, Carboplatin and Radiotherapy as Induction Therapy in Locally Advanced Head and Neck Cancer
NCT00176267	PHASE2	COMPLETED	Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer
NCT00197444	PHASE2	COMPLETED	Low-Dose Nedaplatin (CDGP:Cis-Diammine-Glycolatoplatinum)/5-FU Combined With Radiation for Esophageal Cancer
NCT00255476	PHASE2	COMPLETED	The IRESSA Novel Head and Neck Chemotherapy Evaluation Study
NCT00400205	PHASE2	TERMINATED	Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil
NCT00409565	PHASE2	COMPLETED	A Phase II Trial of Cetuximab and Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer
NCT00446446	PHASE2	COMPLETED	PRISM (Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer)
NCT00476476	PHASE2	COMPLETED	Erlotinib in Women With Squamous Cell Carcinoma of the Vulvar
NCT00485485	PHASE2	COMPLETED	Imatinib Mesylate (Gleevec) and Docetaxel in Patients With Head and Neck Squamous Cell Cancer
NCT00500760	PHASE2	COMPLETED	Study of Addition of Panitumumab to Chemoradiation Therapy in Patients With Locally Advanced Head and Neck Cancer