ADAMDEC1

Summary

ADAMDEC1 (ADAM like decysin 1, HGNC:16299) is a protein-coding gene on chromosome 8p21.2, encoding ADAM DEC1 (O15204). May play an important role in the control of the immune response and during pregnancy.

This encoded protein is thought to be a secreted protein belonging to the disintegrin metalloproteinase family. Its expression is upregulated during dendritic cells maturation. This protein may play an important role in dendritic cell function and their interactions with germinal center T cells.

Source: NCBI Gene 27299 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 3 total — 1 pathogenic
• MANE Select transcript: NM_014479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16299
Approved symbol	ADAMDEC1
Name	ADAM like decysin 1
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	M12.219
Ensembl gene	ENSG00000134028
Ensembl biotype	protein_coding
OMIM	606393
Entrez	27299

Gene structure

Transcript identifiers

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

ENST00000256412, ENST00000519953, ENST00000520193, ENST00000522298, ENST00000893450

RefSeq mRNA: 3 — MANE Select: NM_014479 NM_001145271, NM_001145272, NM_014479

CCDS: CCDS55212, CCDS6044

Canonical transcript exons

ENST00000256412 — 14 exons

Exon	Start	End
ENSE00001109019	24405292	24406013
ENSE00003464062	24398480	24398551
ENSE00003471944	24400170	24400300
ENSE00003483493	24398874	24399040
ENSE00003558628	24392262	24392380
ENSE00003565516	24394069	24394147
ENSE00003619911	24401915	24402092
ENSE00003638726	24395720	24395796
ENSE00003641573	24393262	24393338
ENSE00003649521	24384285	24384592
ENSE00003655799	24399393	24399474
ENSE00003656449	24404003	24404088
ENSE00003678880	24397270	24397456
ENSE00003689747	24397683	24397745

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.80.

FANTOM5 (CAGE): breadth broad, TPM avg 14.8088 / max 2442.9530, expressed in 251 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87951	7.2228	205
87950	5.3166	198
87949	1.1225	147
87962	0.6345	128
87959	0.1308	55
87960	0.1238	59
87961	0.0907	35
87958	0.0874	40
87948	0.0796	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.74	gold quality
rectum	UBERON:0001052	99.31	gold quality
ileal mucosa	UBERON:0000331	99.25	gold quality
ileum	UBERON:0002116	99.14	silver quality
colonic mucosa	UBERON:0000317	98.74	gold quality
mucosa of transverse colon	UBERON:0004991	98.69	gold quality
duodenum	UBERON:0002114	97.88	gold quality
caecum	UBERON:0001153	95.46	gold quality
vermiform appendix	UBERON:0001154	94.51	gold quality
colonic epithelium	UBERON:0000397	93.24	gold quality
small intestine	UBERON:0002108	92.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.21	gold quality
lymph node	UBERON:0000029	90.29	gold quality
transverse colon	UBERON:0001157	89.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.79	gold quality
intestine	UBERON:0000160	82.95	gold quality
epithelium of nasopharynx	UBERON:0001951	82.52	gold quality
nasopharynx	UBERON:0001728	82.51	gold quality
jejunum	UBERON:0002115	82.33	gold quality
large intestine	UBERON:0000059	79.76	gold quality
palpebral conjunctiva	UBERON:0001812	79.76	gold quality
colon	UBERON:0001155	78.85	gold quality
buccal mucosa cell	CL:0002336	77.20	gold quality
superficial temporal artery	UBERON:0001614	76.34	gold quality
spleen	UBERON:0002106	75.18	gold quality
gall bladder	UBERON:0002110	72.68	gold quality
right coronary artery	UBERON:0001625	70.72	gold quality
tonsil	UBERON:0002372	67.87	gold quality
smooth muscle tissue	UBERON:0001135	66.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	17057.80
E-HCAD-11	yes	15084.76
E-CURD-46	yes	14354.02
E-MTAB-8410	yes	13440.93
E-ANND-3	yes	4.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting ADAMDEC1, 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-3646	100.00	73.56	5283
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 14)

• molecular evolution by duplication in a metalloprotease gene cluster on chromosome 8p12 (PMID:12037602)
• The ADAMDEC 1 haplotype may indicate an underlying mechanism for high FVIII levels in venous thromboembolism. (PMID:18449420)
• Gene expression profiling performed on tissues obtained from pulmonary sarcoidosis patients identified ADAMDEC1 as a potential pathogenic mediator of lung damage and/or remodeling and may serve as a marker for this disease. (PMID:19218196)
• ADAMDEC1 functions as an active metalloprotease. (PMID:23754285)
• We hypothesize that these unique features of ADAMDEC1 may have evolved to escape from inhibition by endogenous metalloprotease inhibitors (PMID:25564618)
• Data suggest that activated platelets release ADAMDEC1, which hydrolyzes pro-EGF (epidermal growth factor) to soluble, active HMW-EGF; proteolytic cleavage of pro-EGF first occurs at the C-terminal arginyl residue of the EGF domain; proteolysis is the regulated, rate-limiting step in generating soluble EGF from activated platelets. (PMID:28455445)
• ADAMDEC1 is a positive regulator of Epithelial Defense Against Cancer (EDAC) that promotes apical extrusion of RasV12-transformed cells (PMID:29941981)
• Data show the critical pathways regulating the expression of ADAMDEC1 and the roles of enhancer RNAs and mechanistically links E1A binding protein p300 (p300) and enhancer RNAs, which is dependent on NF-kappa B (NFkappaB). (PMID:30352365)
• ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells. (PMID:31434712)
• The ADAMDEC1 plays a pro-inflammatory role in rosacea via modulating the M1 polarization of macrophages. (PMID:31627897)
• Knockdown of ADAMDEC1 inhibits the progression of glioma in vitro. (PMID:32378728)
• Upregulation of ADAMDEC1 correlates with tumor progression and predicts poor prognosis in non-small cell lung cancer (NSCLC) via the PI3K/AKT pathway. (PMID:35178875)
• ADAMDEC1 induces EMT and promotes colorectal cancer cells metastasis by enhancing Wnt/beta-catenin signaling via negative modulation of GSK-3beta. (PMID:37187249)
• Knockdown of ADAMDEC1 ameliorates ox-LDL-induced endothelial cell injury and atherosclerosis progression. (PMID:38063920)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	adam10b	ENSDARG00000015502
danio_rerio	adam10a	ENSDARG00000053468
danio_rerio	adam9b	ENSDARG00000057138
mus_musculus	Adamdec1	ENSMUSG00000022057
rattus_norvegicus	Adamdec1	ENSRNOG00000030724
drosophila_melanogaster	mmd	FBGN0259110
drosophila_melanogaster	kuz	FBGN0259984
caenorhabditis_elegans	sup-17	WBGENE00006324
caenorhabditis_elegans		WBGENE00006804

Paralogs (20): ADAM22 (ENSG00000008277), ADAM28 (ENSG00000042980), ADAM7 (ENSG00000069206), ADAM11 (ENSG00000073670), ADAM2 (ENSG00000104755), ADAM23 (ENSG00000114948), ADAM20 (ENSG00000134007), ADAM30 (ENSG00000134249), ADAM19 (ENSG00000135074), ADAM10 (ENSG00000137845), ADAM21 (ENSG00000139985), ADAM15 (ENSG00000143537), ADAM12 (ENSG00000148848), ADAM33 (ENSG00000149451), ADAM8 (ENSG00000151651), ADAM17 (ENSG00000151694), ADAM29 (ENSG00000168594), ADAM9 (ENSG00000168615), ADAM18 (ENSG00000168619), ADAM32 (ENSG00000197140)

Protein

Protein identifiers

ADAM DEC1 — O15204 (reviewed: O15204)

Alternative names: A disintegrin and metalloproteinase domain-like protein decysin-1

All UniProt accessions (2): O15204, E5RK05

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in the control of the immune response and during pregnancy.

Subcellular location. Secreted.

Tissue specificity. Expressed highly in the small intestine and appendix, moderately in lymph node, mucosal lining of the colon, thymus, spleen and very weakly in the bone marrow. Predominantly expressed in dendritic cells (DC) of the germinal center. Weakly expressed in monocyte and highly expressed in macrophage. Absent in immature DC.

Cofactor. Binds 1 zinc ion per subunit.

Induction. Induced during DC maturation and up-regulated in response to T-cell signals. In macrophage up-regulated by bacterial lipopolysaccharides (LPS). Up-regulated by 1-alpha,25-dihydroxyvitamin D3 during differentiation of primary monocyte into macrophage.

Isoforms (2)

UniProt ID	Names	Canonical?
O15204-1	1	yes
O15204-2	2

RefSeq proteins (3): NP_001138743, NP_001138744, NP_055294* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001590	Peptidase_M12B	Domain
IPR001762	Disintegrin_dom	Domain
IPR002870	Peptidase_M12B_N	Domain
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR034027	Reprolysin_adamalysin	Domain
IPR036436	Disintegrin_dom_sf	Homologous_superfamily

Pfam: PF01421, PF01562

UniProt features (19 total): glycosylation site 4, binding site 3, disulfide bond 2, sequence variant 2, domain 2, signal peptide 1, propeptide 1, splice variant 1, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15204-F1	80.32	0.50

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): 353

Ligand- & substrate-binding residues (3): 352; 356; 362

Disulfide bonds (2): 328–407, 369–374

Glycosylation sites (4): 61, 184, 237, 466

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 182 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, MCLACHLAN_DENTAL_CARIES_UP, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, MODULE_64, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, GOBP_WOUND_HEALING, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, ONKEN_UVEAL_MELANOMA_UP, chr8p21, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, BLALOCK_ALZHEIMERS_DISEASE_UP, SU_THYMUS

GO Biological Process (3): proteolysis (GO:0006508), immune response (GO:0006955), negative regulation of cell adhesion (GO:0007162)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), zinc ion binding (GO:0008270), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
immune system process	1
response to stimulus	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
endopeptidase activity	1
metallopeptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMDEC1	ZNF511	Q8NB15	474
ADAMDEC1	FURIN	P09958	470
ADAMDEC1	DPEP1	P16444	411
ADAMDEC1	IL18	Q14116	405
ADAMDEC1	ADAMTSL5	Q6ZMM2	386
ADAMDEC1	PNMA2	Q9UL42	374
ADAMDEC1	CD34	P28906	371
ADAMDEC1	CD40	P25942	367
ADAMDEC1	HCST	Q9UBK5	362
ADAMDEC1	H7BY64	H7BY64	353
ADAMDEC1	PI16	Q6UXB8	349
ADAMDEC1	DEFA5	Q01523	311
ADAMDEC1	IL21R	Q9HBE5	307
ADAMDEC1	MEP1A	Q16819	303
ADAMDEC1	PCOLCE2	Q9UKZ9	299

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ADAMDEC1	yapH	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): HSP90AA1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: F8VQ03, O15072, O15204, O35227, O77780, P58397, P59509, P59510, P70505, P97776, P97857, Q1EHB3, Q28475, Q28478, Q28483, Q28660, Q3TTE0, Q5BK84, Q60411, Q60472, Q60718, Q60813, Q63180, Q63202, Q68SA9, Q811B3, Q811Q4, Q8C9W3, Q8K410, Q8N2E2, Q8R534, Q8TC27, Q8TE59, Q99965, Q9H2U9, Q9JI76, Q9JLN6, Q9R0X2, Q9R157, Q9R158

Diamond homologs: A0A0B4U9L8, A3R0T9, A4PBQ9, A8QL48, A8QL49, A8QL59, B8K1W0, C0L2T8, C9E1R7, C9E1R8, C9E1R9, C9E1S0, C9E1S1, D3TTC1, D3TTC2, D5LMJ3, D6PXE8, D8VNS0, E9NW26, E9NW27, F8RKV9, F8RKW0, F8RKW1, F8S108, J3S829, J3S830, J3SBP9, J3SDW6, J3SDW8, J9Z332, O15204, O35227, O42138, O57413, O73795, O93523, P0C6B6, P0C6E4, P0C7B0, P0DM87

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2685301	GRCh37/hg19 8p23.1-21.1(chr8:12490999-28150620)x1	Pathogenic

SpliceAI

2019 predictions. Top by Δscore:

Variant	Effect	Δscore
8:24393339:G:GG	donor_gain	1.0000
8:24397676:T:TA	acceptor_gain	1.0000
8:24397679:A:AG	acceptor_gain	1.0000
8:24397680:A:G	acceptor_gain	1.0000
8:24398474:TTACA:T	acceptor_loss	1.0000
8:24398476:ACAG:A	acceptor_loss	1.0000
8:24398477:CA:C	acceptor_loss	1.0000
8:24398478:A:AG	acceptor_gain	1.0000
8:24398479:G:GT	acceptor_gain	1.0000
8:24398479:GT:G	acceptor_gain	1.0000
8:24398479:GTAT:G	acceptor_gain	1.0000
8:24398479:GTATA:G	acceptor_gain	1.0000
8:24402983:G:A	acceptor_gain	1.0000
8:24403849:A:AG	acceptor_gain	1.0000
8:24384589:CAAGG:C	donor_loss	0.9900
8:24384591:AGGTA:A	donor_loss	0.9900
8:24384592:GGTA:G	donor_loss	0.9900
8:24395792:TTGAG:T	donor_loss	0.9900
8:24395793:TGAGG:T	donor_loss	0.9900
8:24395794:GAGG:G	donor_loss	0.9900
8:24395795:AG:A	donor_loss	0.9900
8:24395796:GG:G	donor_loss	0.9900
8:24395797:G:C	donor_loss	0.9900
8:24395798:T:G	donor_loss	0.9900
8:24396081:T:G	donor_gain	0.9900
8:24397268:AGAG:A	acceptor_gain	0.9900
8:24397269:GA:G	acceptor_gain	0.9900
8:24397269:GAGG:G	acceptor_gain	0.9900
8:24397454:GAG:G	donor_gain	0.9900
8:24397681:A:AG	acceptor_gain	0.9900

AlphaMissense

3115 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:24401934:T:C	F388L	0.990
8:24401936:C:A	F388L	0.990
8:24401936:C:G	F388L	0.990
8:24400263:T:C	C369R	0.988
8:24398924:G:C	W271C	0.987
8:24398924:G:T	W271C	0.987
8:24400278:T:A	C374S	0.986
8:24400279:G:C	C374S	0.986
8:24400286:G:A	M376I	0.986
8:24400286:G:C	M376I	0.986
8:24400286:G:T	M376I	0.986
8:24398922:T:A	W271R	0.985
8:24398922:T:C	W271R	0.985
8:24400263:T:A	C369S	0.985
8:24400264:G:C	C369S	0.985
8:24401935:T:G	F388C	0.985
8:24400278:T:C	C374R	0.983
8:24399034:T:C	L308P	0.980
8:24399039:A:C	S310R	0.980
8:24399393:C:A	S310R	0.980
8:24399393:C:G	S310R	0.980
8:24401935:T:C	F388S	0.980
8:24400280:T:G	C374W	0.979
8:24401937:A:C	S389R	0.979
8:24401939:T:A	S389R	0.979
8:24401939:T:G	S389R	0.979
8:24400219:T:C	L354P	0.978
8:24400237:T:C	M360T	0.977
8:24400279:G:A	C374Y	0.977
8:24399463:G:C	A334P	0.976

dbSNP variants (sampled 300 via entrez): RS1000889333 (8:24385279 T>A), RS1000978217 (8:24390470 C>A,T), RS1001249271 (8:24403412 G>C), RS1001274703 (8:24396632 T>G), RS1001378716 (8:24396937 T>G), RS1001524559 (8:24403636 A>G), RS1001557978 (8:24384754 A>C), RS1001567740 (8:24391381 T>C), RS1002258127 (8:24401985 C>A,G,T), RS1002280598 (8:24385234 T>A), RS1002342205 (8:24386010 C>T), RS1002477184 (8:24405305 A>G), RS1002910803 (8:24382662 G>A), RS1002920941 (8:24382458 A>T), RS1003013507 (8:24388281 TC>T)

Disease associations

OMIM: gene MIM:606393 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003478_5	Hair greying	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
bisphenol A	decreases methylation	1
Decitabine	increases expression	1
Arsenic Trioxide	increases expression	1
Dust	increases expression	1
Formaldehyde	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Antirheumatic Agents	decreases expression	1
beta-Naphthoflavone	increases expression	1

Clinical trials (associated diseases)

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