ADAM8

Summary

ADAM8 (ADAM metallopeptidase domain 8, HGNC:215) is a protein-coding gene on chromosome 10q26.3, encoding Disintegrin and metalloproteinase domain-containing protein 8 (P78325). Possible involvement in extravasation of leukocytes.

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene may be involved in cell adhesion during neurodegeneration, and it is thought to be a target for allergic respiratory diseases, including asthma. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 101 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 250 total — 22 pathogenic, 3 likely-pathogenic
• GTEx eGene: eQTL in 29 tissues, sQTL in 26 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.42 (unconstrained)
• MANE Select transcript: NM_001109
• Notable: 250 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:215
Approved symbol	ADAM8
Name	ADAM metallopeptidase domain 8
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	CD156, MS2, CD156A
Ensembl gene	ENSG00000151651
Ensembl biotype	protein_coding
OMIM	602267
Entrez	101

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000445355

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 1, TSL 5: 4

ENST00000445355, ENST00000415217, ENST00000463298, ENST00000468964, ENST00000485491, ENST00000486609, ENST00000537099, ENST00000559018, ENST00000559180, ENST00000560135, ENST00000561175, ENST00000897045, ENST00000897046, ENST00000897047, ENST00000897048, ENST00000916032, ENST00001004525, ENST00001141226

RefSeq mRNA: 3 — MANE Select: NM_001109 NM_001109, NM_001164489, NM_001164490

CCDS: CCDS31319, CCDS58102, CCDS58103

Canonical transcript exons

ENST00000445355 — 23 exons

Exon	Start	End
ENSE00001893770	133262423	133263233
ENSE00002431587	133271806	133271954
ENSE00002466382	133270881	133271070
ENSE00002475412	133271528	133271705
ENSE00002490565	133268748	133268862
ENSE00002499610	133269897	133269974
ENSE00002501184	133269445	133269529
ENSE00002519127	133270736	133270805
ENSE00002521112	133267929	133268118
ENSE00002524787	133270360	133270510
ENSE00002535778	133271200	133271289
ENSE00003460874	133276772	133276868
ENSE00003470045	133273762	133273838
ENSE00003476925	133263688	133263765
ENSE00003489193	133274159	133274235
ENSE00003531507	133273951	133274029
ENSE00003543916	133267352	133267417
ENSE00003550483	133272798	133272866
ENSE00003552823	133272193	133272274
ENSE00003561471	133272957	133273019
ENSE00003579082	133272416	133272585
ENSE00003653215	133273254	133273443
ENSE00003691035	133275484	133275587

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 98.66.

FANTOM5 (CAGE): breadth broad, TPM avg 13.6373 / max 1419.5952, expressed in 608 samples.

Highest expression (Bgee): granulocyte, blood, leukocyte, spleen, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ADAM8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 26 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 55 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	2.2e-74	+0.88	10:133269660:C:T
Cells EBV-transformed lymphocytes	sqtl	6.2e-34	+2.23	10:133263761:A:G
Lung	sqtl	2.7e-32	+0.76	10:133269306:C:T
Spleen	sqtl	5.2e-17	+1.92	10:133261897:C:T
Skin Not Sun Exposed Suprapubic	sqtl	3.1e-15	+1.41	10:133263761:A:G
Adipose Subcutaneous	sqtl	4.8e-15	+1.39	10:133263761:A:G
Breast Mammary Tissue	sqtl	2.0e-12	+1.84	10:133263761:A:G
Thyroid	sqtl	8.5e-12	+1.33	10:133263761:A:G
Esophagus Mucosa	sqtl	3.0e-10	+1.21	10:133263761:A:G
Cells EBV-transformed lymphocytes	eqtl	1.2e-09	-0.32	10:133263399:A:G
Artery Tibial	sqtl	1.5e-09	+1.20	10:133263761:A:G
Adipose Visceral Omentum	sqtl	1.1e-08	+0.67	10:133266358:T:C
Skin Sun Exposed Lower leg	sqtl	2.4e-08	+1.10	10:133263761:A:G
Heart Atrial Appendage	sqtl	3.1e-08	+1.41	10:133261897:C:T
Colon Transverse	sqtl	6.8e-08	+1.27	10:133261897:C:T
Nerve Tibial	sqtl	7.9e-08	+1.06	10:133263761:A:G
Stomach	sqtl	8.5e-08	+1.30	10:133265777:G:A
Artery Aorta	sqtl	1.3e-07	+0.59	10:133263254:T:C
Pituitary	sqtl	8.2e-06	+0.70	10:133271817:C:T
Brain Cerebellum	sqtl	9.7e-06	+1.38	10:133263761:A:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
112102	10.7951	576
112101	2.6388	375
112100	0.2034	71

Top tissues by expression

showing 100 of 278 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.66	gold quality
blood	UBERON:0000178	97.17	gold quality
leukocyte	CL:0000738	93.12	gold quality
spleen	UBERON:0002106	93.00	gold quality
monocyte	CL:0000576	92.87	gold quality
mononuclear cell	CL:0000842	92.75	gold quality
bone marrow cell	CL:0002092	92.63	gold quality
pancreatic ductal cell	CL:0002079	92.52	silver quality
periodontal ligament	UBERON:0008266	91.46	silver quality
vermiform appendix	UBERON:0001154	89.62	gold quality
bone marrow	UBERON:0002371	88.84	gold quality
upper lobe of left lung	UBERON:0008952	87.91	gold quality
right lung	UBERON:0002167	87.69	gold quality
upper lobe of lung	UBERON:0008948	86.81	gold quality
oocyte	CL:0000023	86.52	gold quality
caecum	UBERON:0001153	85.33	gold quality
secondary oocyte	CL:0000655	85.08	gold quality
trabecular bone tissue	UBERON:0002483	84.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.86	gold quality
right lobe of liver	UBERON:0001114	84.31	gold quality
amniotic fluid	UBERON:0000173	83.23	silver quality
lymph node	UBERON:0000029	83.21	gold quality
epithelium of nasopharynx	UBERON:0001951	82.91	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.59	gold quality
left uterine tube	UBERON:0001303	82.54	gold quality
gall bladder	UBERON:0002110	81.77	gold quality
endometrium epithelium	UBERON:0004811	81.66	silver quality
cervix squamous epithelium	UBERON:0006922	81.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.75	gold quality
mucosa of urinary bladder	UBERON:0001259	80.61	gold quality
mucosa of transverse colon	UBERON:0004991	80.50	gold quality
tendon of biceps brachii	UBERON:0008188	80.04	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	79.70	gold quality
palpebral conjunctiva	UBERON:0001812	78.97	gold quality
right uterine tube	UBERON:0001302	78.90	gold quality
small intestine	UBERON:0002108	78.90	gold quality
lung	UBERON:0002048	78.54	gold quality
stromal cell of endometrium	CL:0002255	78.43	gold quality
tongue squamous epithelium	UBERON:0006919	78.40	gold quality
lower esophagus mucosa	UBERON:0035834	78.15	gold quality
omental fat pad	UBERON:0010414	78.09	gold quality
peritoneum	UBERON:0002358	78.05	gold quality
adipose tissue of abdominal region	UBERON:0007808	77.82	gold quality
gingival epithelium	UBERON:0001949	77.45	gold quality
epithelial cell of pancreas	CL:0000083	77.26	silver quality
endocervix	UBERON:0000458	77.04	gold quality
tonsil	UBERON:0002372	77.01	gold quality
body of stomach	UBERON:0001161	76.95	gold quality
body of pancreas	UBERON:0001150	76.91	gold quality
urinary bladder	UBERON:0001255	76.57	gold quality
descending thoracic aorta	UBERON:0002345	76.57	gold quality
metanephros cortex	UBERON:0010533	76.46	gold quality
right coronary artery	UBERON:0001625	76.45	gold quality
right ovary	UBERON:0002118	76.37	gold quality
colonic epithelium	UBERON:0000397	76.15	gold quality
nasal cavity mucosa	UBERON:0001826	76.14	gold quality
ileal mucosa	UBERON:0000331	76.09	silver quality
minor salivary gland	UBERON:0001830	75.54	gold quality
gingiva	UBERON:0001828	75.40	silver quality
squamous epithelium	UBERON:0006914	75.33	gold quality
liver	UBERON:0002107	74.89	gold quality
mouth mucosa	UBERON:0003729	74.84	gold quality
saliva-secreting gland	UBERON:0001044	74.81	gold quality
mucosa of stomach	UBERON:0001199	74.77	gold quality
stomach	UBERON:0000945	74.65	gold quality
triceps brachii	UBERON:0001509	74.54	gold quality
left lobe of thyroid gland	UBERON:0001120	74.45	gold quality
right lobe of thyroid gland	UBERON:0001119	74.42	gold quality
esophagus mucosa	UBERON:0002469	74.33	gold quality
skin of abdomen	UBERON:0001416	74.23	gold quality
subcutaneous adipose tissue	UBERON:0002190	74.22	gold quality
adenohypophysis	UBERON:0002196	74.22	gold quality
skin of leg	UBERON:0001511	74.20	gold quality
left coronary artery	UBERON:0001626	74.15	gold quality
ascending aorta	UBERON:0001496	74.10	gold quality
left adrenal gland cortex	UBERON:0035825	74.09	gold quality
thoracic aorta	UBERON:0001515	74.08	gold quality
thyroid gland	UBERON:0002046	74.07	gold quality
pituitary gland	UBERON:0000007	74.01	gold quality
transverse colon	UBERON:0001157	73.90	gold quality
coronary artery	UBERON:0001621	73.75	gold quality
right frontal lobe	UBERON:0002810	73.49	gold quality
uterine cervix	UBERON:0000002	73.36	gold quality
fundus of stomach	UBERON:0001160	73.31	gold quality
adipose tissue	UBERON:0001013	73.29	gold quality
duodenum	UBERON:0002114	73.29	gold quality
left ovary	UBERON:0002119	73.13	gold quality
prostate gland	UBERON:0002367	73.12	gold quality
anatomical system	UBERON:0000467	73.10	gold quality
intestine	UBERON:0000160	73.09	gold quality
connective tissue	UBERON:0002384	73.04	gold quality
medial globus pallidus	UBERON:0002477	73.03	silver quality
multicellular organism	UBERON:0000468	72.97	gold quality
material anatomical entity	UBERON:0000465	72.96	gold quality
adrenal cortex	UBERON:0001235	72.82	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.69	gold quality
vagina	UBERON:0000996	72.64	gold quality
body of uterus	UBERON:0009853	72.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.62	gold quality
zone of skin	UBERON:0000014	72.60	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	79.91
E-MTAB-9067	yes	15.75
E-CURD-112	yes	11.42
E-ANND-3	yes	9.70

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	64.8	medium
Spleen	tissue	22.9	low
Appendix	tissue	20.8	medium
Urinary bladder	tissue	11.1	low
Lymph node	tissue	10.9	medium
Stomach 1	tissue	10.9	medium
Tonsil	tissue	7.7	low
Small intestine	tissue	6.5	medium
Lung	tissue	6.0	medium
Duodenum	tissue	5.5	medium
Gallbladder	tissue	4.8	medium
Nucleus accumbens	tissue	4.1
Thymus	tissue	3.8
Adipose tissue	tissue	3.7	low
Choroid plexus	tissue	3.7
Pituitary gland	tissue	3.5
Cervix	tissue	3.3	low
Vagina	tissue	3.2	not detected
Locus coeruleus	tissue	3.2
Skin 1	tissue	3.1	not detected
Pancreas	tissue	3.1	medium
Hippocampus	tissue	3.0	low
Placenta	tissue	2.9	medium
Salivary gland	tissue	2.7	low
Postcentral gyrus	tissue	2.3
Esophagus	tissue	2.1	not detected
Colon	tissue	2.1	low
Epididymis	tissue	2.0	medium
Smooth muscle	tissue	1.9	not detected
Liver	tissue	1.8	not detected
Prostate	tissue	1.7	not detected
Tongue	tissue	1.6
Rectum	tissue	1.5	low
Adrenal gland	tissue	1.5	medium
Retina	tissue	1.4
Fallopian tube	tissue	1.4	low
Endometrium 1	tissue	1.3	medium
Seminal vesicle	tissue	1.1	medium
Skeletal muscle	tissue	1.1	not detected
Testis	tissue	1.0	medium
Breast	tissue	0.9	low
Ovary	tissue	0.8	low
Heart muscle	tissue	0.7	not detected
Kidney	tissue	0.7	medium
Thyroid gland	tissue	0.5	medium
Spinal cord	tissue	0.4
Cerebral cortex	tissue	0.2	medium
Parathyroid gland	tissue	0.2	not detected
Motor cortex	tissue	0.2
Basal ganglia	tissue	0.2	low
Putamen	tissue	0.2
Midbrain	tissue	0.2
Medulla oblongata	tissue	0.2
Thalamus	tissue	0.2
Hypothalamus	tissue	0.2
Superior colliculi	tissue	0.2
Cerebellum	tissue	0.2	not detected
Olfactory bulb	tissue	0.2
Occipital cortex	tissue	0.2
Prefrontal cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Area parastriata, superior (44.4), Anterior thalamic nucleus, ventral (13.0), Ventrolateral tegmental area, A5 NE cell group (9.4), Posterior thalamic nucleus (7.1), Nucleus ambiguus (7.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ADAM8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 32 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-596	97.48	63.13	469
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-4484	96.35	64.08	382
HSA-MIR-10396B-5P	94.99	63.57	358

Functional genomics

gnomAD constraint: pLI 2.84e-40, LOEUF 1.42, missense Z -1.4 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000445355 — one region, missense o/e 0.98.

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of ADAM8 is associated with lung cancer progression (PMID:15623614)
• ADAM8 may contribute to the airway remodeling process that occurs with asthma progression. (PMID:17339047)
• All these data support a potential relevant role for ADAM-8 in the function of neutrophils during inflammatory response. (PMID:17548643)
• ADAM8 is overexpressed in pancreatic ductal adenocarcinoma, influences cancer cell invasiveness and correlates with reduced survival. (PMID:17979891)
• ADAM8 may have a role as a hypoxia-dependent protein in the pathogenesis and evolution of pancreatic cancer (PMID:18566576)
• ADAM8 might be a therapeutic target for allergic respiratory diseases. (PMID:18691140)
• ADAM8 and EGFR are overexpressed in non-small cell lung cancer. (PMID:18710625)
• Autoactivation of ADAM8: a novel pre-processing step is required for catalytic activity. (PMID:18811590)
• ADAM8 is up-regulated upon formation of multinuclear giant cells after HPIV2 induction. (PMID:19284887)
• The structure, function & expression of ADAM8 and its role in asthma are reviewed. Review. (PMID:19397475)
• Increasing trend for ADAM8 expression is associated with early to advanced stages of myelodysplastic syndrome. (PMID:19469654)
• ADAM8 is a promising candidate to be involved in atherosclerosis, and its 2662 T/G allelic variant significantly associates with advanced atherosclerotic lesion areas and myocardial infarction. (PMID:19575316)
• ADAM-8 as a fibronectinase in human osteoarthritis chondrocytes. (PMID:19714641)
• the effects of pH on substrate cleavage by ADAM8 beyond autocatalysis (PMID:19766586)
• expression of truncated forms of ADAM8 by the lung cancer cells may result in the specific upregulation of their invasive and osteoclastogenic activities in the bone microenvironment (PMID:20453887)
• It regulates onset of blood circulation. (review) (PMID:21077325)
• variation in the ADAM8 gene may affect serum sADAM8 concentrations and the risk of myocardial infarction (PMID:21640993)
• increased expression in allergic rhinitis (PMID:21679521)
• gene expressions for ADAM8 and ADAM15 were notably lower in ascending aorta as compared with aortic dissection (PMID:21728902)
• These findings suggest for the first time that ADAM8 is frequently overexpressed in human gliomas and is closely associated with poor clinical outcome. (PMID:21983884)
• Upregulation of a disintegrin and metalloprotease 8 influences tumor metastasis with osteosarcoma. (PMID:22215309)
• ADAM8 is both associated with PSGL-1 through the ezrin-radixin-moesin actin-binding proteins and able to cause the proteolytic cleavage of this adhesion receptor. (PMID:22229154)
• ADAM8 was highly expressed in 54.3% of hepatocellular carcinoma patients. ADAM8 expression was closely associated with tumor size, histological differentiation, recurrence, metastasis, and stage. High levels of ADAM8 resulted in poor prognosis. (PMID:22878099)
• High expression of ADAM8 is associated with hepatocellular carcinoma. (PMID:22941466)
• ADAM8 mRNA & protein were highly expressed in medulloblastoma tissues when compared with normal cerebellum. This correlated with advanced stage, aggressive type, undifferentiated tumor & decreased survival. (PMID:22959284)
• We used immunohistochemistry to compare ADAM8 protein expression in HCC and normal liver tissues and further analyze the ADAM8 protein expression in 105 HCC cases. Studied knocked down expression of ADAM8 in HepG2 cells. (PMID:22965687)
• ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients (PMID:23670189)
• ADAM8 expression is increased in both severe asthma and COPD and associated with sputum total cell count and neutrophils. ADAM8 may facilitate neutrophil migration to the airways in severe asthma and COPD. (PMID:24147597)
• Data show that Cu2+-generated reactive oxygen species (ROS), human ADAM8, ADAM10, and ADAM17 are all capable of cleaving mouse PrP (MoPrP). (PMID:24247244)
• ADAM8 is abundantly expressed in breast tumors and derived metastases compared to normal tissue. (PMID:24375628)
• High ADAM8 expression is associated with pancreatic adenocarcinoma. (PMID:24526468)
• Data indicate that fibronectin fragments (FN-fs) are present in adult ntervertebral disc (IVD) from adult subjects, and ADAM-8, known to cleave FN, is present at the pericellular matrix of disc cells. (PMID:25010013)
• Results show that ADAM8 is overexpressed in colorectal cancer and promotes cell growth. (PMID:25098630)
• N-glycosylation is essential for processing, localization, stability, and activity of ADAM8. (PMID:25336660)
• ADAM8 and endostatin play a role in osteosarcoma progression. (PMID:25481287)
• ADAM8 expression is associated with increased migration and invasiveness of pancreatic ductal adenocarcinoma cells. (PMID:25629724)
• ADAM8 causes temozolomide resistance in glioblastoma cells by enhancing pAkt/PI3K, pERK1/2, and cleavage of CD44 and HGF R/c-met (PMID:25825051)
• ADAM8 promotes GC cell proliferation and invasion, and its expression is positively correlated with poor survival, indicating that it might be a promising target in GC therapy (PMID:26024798)
• miR-720 is elevated in serum of patients with ADAM8-high TNBC and, in a group with other miRNAs downstream of ADAM8, holds promise as a biomarker for early detection of or treatment response of ADAM8-positive triple-negative breast cancer (PMID:27039296)
• ADAM8 on leukocytes holds a proinflammatory function in acute lung inflammation by promoting alveolar leukocyte recruitment. (PMID:28596294)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adam8a	ENSDARG00000001452
danio_rerio	adam8b	ENSDARG00000057644
mus_musculus	Adam8	ENSMUSG00000025473
rattus_norvegicus	Adam8	ENSRNOG00000017897

Paralogs (20): ADAM22 (ENSG00000008277), ADAM28 (ENSG00000042980), ADAM7 (ENSG00000069206), ADAM11 (ENSG00000073670), ADAM2 (ENSG00000104755), ADAM23 (ENSG00000114948), ADAM20 (ENSG00000134007), ADAMDEC1 (ENSG00000134028), ADAM30 (ENSG00000134249), ADAM19 (ENSG00000135074), ADAM10 (ENSG00000137845), ADAM21 (ENSG00000139985), ADAM15 (ENSG00000143537), ADAM12 (ENSG00000148848), ADAM33 (ENSG00000149451), ADAM17 (ENSG00000151694), ADAM29 (ENSG00000168594), ADAM9 (ENSG00000168615), ADAM18 (ENSG00000168619), ADAM32 (ENSG00000197140)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:107825) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
abnormal trabecular bone morphology	1
decreased susceptibility to induced arthritis	1
abnormal response/metabolism to endogenous compounds	1
abnormal osteoclast morphology	1
increased osteoclast cell number	1
increased bone resorption	1
abnormal osteoclast differentiation	1
decreased bone volume	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bothrops atrox	C5H5D3	99.5%	Diamond
Lachesis muta rhombeata	C5H5D6	99.5%	Diamond
Gloydius halys	Q90Y44	98.6%	Diamond
Crotalus durissus terrificus	Q076D1	98.1%	Diamond
Gloydius brevicauda	O93517	97.1%	Diamond
Naja kaouthia	P82942	91.3%	Diamond
Macaca fascicularis	Q28475	91.1%	Diamond
Bothrops alternatus	P0C6R9	91.0%	Diamond
Bothrops jararaca	Q0NZY0	89.8%	Diamond
Crotalus ruber ruber	Q9PSN7	87.0%	Diamond
Macrovipera lebetina transmediterranea	C0LZJ5	77.8%	Diamond
Xenopus laevis	Q9PSZ3	77.8%	Diamond
Cavia porcellus	Q60411	56.5%	Diamond
Micropechis ikaheca	P0DJ43	52.8%	Diamond
Schizosaccharomyces pombe 972h-	O13766	48.7%	Diamond
Caenorhabditis elegans	G5EDW5	38.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TUBGCP2	protein-coding	10844
VENTX	protein-coding	27287
MIR202	ncRNA	574448
UTF1	protein-coding	8433
MIR3944	ncRNA	100500911
PRAP1	protein-coding	118471
ZNF511	protein-coding	118472
ECHS1	protein-coding	1892
FUOM	protein-coding	282969
CALY	protein-coding	50632
MIR202HG	ncRNA	101927671
ZNF511-PRAP1	protein-coding	104326056
KNDC1	protein-coding	85442

Protein

Protein identifiers

Disintegrin and metalloproteinase domain-containing protein 8 — P78325 (reviewed: P78325)

Alternative names: Cell surface antigen MS2

All UniProt accessions (3): P78325, H0YKZ1, H0YMT6

UniProt curated annotations — full annotation on UniProt →

Function. Possible involvement in extravasation of leukocytes.

Subunit / interactions. Interacts with FST3.

Subcellular location. Membrane.

Tissue specificity. Expressed on neutrophils and monocytes.

Cofactor. Binds 1 zinc ion per subunit.

Isoforms (3)

UniProt ID	Names	Canonical?
P78325-1	1	yes
P78325-2	2
P78325-3	3

RefSeq proteins (3): NP_001100, NP_001157961, NP_001157962 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR001590	Peptidase_M12B	Domain
IPR001762	Disintegrin_dom	Domain
IPR002870	Peptidase_M12B_N	Domain
IPR006586	ADAM_Cys-rich	Domain
IPR018358	Disintegrin_CS	Conserved_site
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR034027	Reprolysin_adamalysin	Domain
IPR036436	Disintegrin_dom_sf	Homologous_superfamily

Pfam: PF00200, PF01421, PF01562, PF08516

Enzyme classification (BRENDA)

• EC 3.4.24.46 — adamalysin (BRENDA: 4 organisms, 34 substrates, 24 inhibitors, 0 Km, 0 kcat entries)

UniProt features (63 total): disulfide bond 12, helix 8, splice variant 6, sequence variant 6, sequence conflict 5, strand 5, glycosylation site 4, binding site 3, domain 3, compositionally biased region 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, active site 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
4DD8	ADAM-8 metalloproteinase domain with bound batimastat	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78325-F1	74.28	0.34

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

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)

Position	Role
335

Ligand- & substrate-binding residues (3)

Position	Role
334	Zn(2+)
338	Zn(2+)
344	Zn(2+)

Disulfide bonds (12)

Type	Positions
Disulfide bond	310–395, 351–379, 353–362, 435–457, 448–454, 466–486, 473–503, 498–508, 566–613, 613–623, 617–629, 631–640

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	67, 91, 436, 612

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-1474228	Degradation of the extracellular matrix	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—

MSigDB gene sets: 496 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION

GO Biological Process (29): cell morphogenesis (GO:0000902), angiogenesis (GO:0001525), leukocyte migration involved in inflammatory response (GO:0002523), positive regulation of acute inflammatory response (GO:0002675), positive regulation of cellular extravasation (GO:0002693), proteolysis (GO:0006508), inflammatory response (GO:0006954), canonical NF-kappaB signal transduction (GO:0007249), positive regulation of epithelial to mesenchymal transition (GO:0010718), positive regulation of protein processing (GO:0010954), regulation of cell-cell adhesion (GO:0022407), extracellular matrix disassembly (GO:0022617), signal release (GO:0023061), positive regulation of T cell differentiation in thymus (GO:0033089), positive regulation of MAPK cascade (GO:0043410), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of innate immune response (GO:0045089), positive regulation of bone resorption (GO:0045780), positive regulation of cell adhesion (GO:0045785), lymphocyte chemotaxis (GO:0048247), positive regulation of protein secretion (GO:0050714), positive regulation of membrane protein ectodomain proteolysis (GO:0051044), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of thymocyte apoptotic process (GO:0070245), cellular response to hypoxia (GO:0071456), positive regulation of tumor necrosis factor (ligand) superfamily member 11 production (GO:2000309), positive regulation of neutrophil extravasation (GO:2000391), positive regulation of fibronectin-dependent thymocyte migration (GO:2000415), positive regulation of eosinophil migration (GO:2000418)

GO Molecular Function (12): metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), tumor necrosis factor receptor superfamily binding (GO:0032813), immunoglobulin receptor binding (GO:0034987), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (13): podosome (GO:0002102), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), phagolysosome (GO:0032010), dense core granule membrane (GO:0032127), specific granule membrane (GO:0035579), specific granule (GO:0042581), tertiary granule (GO:0070820), tertiary granule membrane (GO:0070821), alpha9-beta1 integrin-ADAM8 complex (GO:0071133), ficolin-1-rich granule membrane (GO:0101003), membrane (GO:0016020)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Extracellular matrix organization	1
Innate Immune System	1
Immune System	1

GO top-level categories

showing 60 of 77 GO namespaces:

Category	Terms
secretory granule membrane	4
cellular anatomical structure	3
positive regulation of multicellular organismal process	2
regulation of cell adhesion	2
endopeptidase activity	2
secretory granule	2
tertiary granule	2
anatomical structure morphogenesis	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
inflammatory response	1
leukocyte migration	1
acute inflammatory response	1
regulation of acute inflammatory response	1
positive regulation of inflammatory response	1
positive regulation of leukocyte migration	1
regulation of cellular extravasation	1
cellular extravasation	1
protein metabolic process	1
defense response	1
intracellular signaling cassette	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
protein processing	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
cell-cell adhesion	1
cellular component disassembly	1
extracellular matrix organization	1
cell-cell signaling	1
secretion by cell	1
T cell differentiation in thymus	1
regulation of T cell differentiation in thymus	1
positive regulation of T cell differentiation	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
positive regulation of response to biotic stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
positive regulation of immune response	1
regulation of bone resorption	1
bone resorption	1
cell adhesion	1
positive regulation of cellular process	1
leukocyte chemotaxis	1
lymphocyte migration	1
metallopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
peptidase activity	1
transition metal ion binding	1
cytokine receptor binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 54 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to hypoxia	BP	direct assay
inflammatory response	BP	direct assay
positive regulation of membrane protein ectodomain proteolysis	BP	direct assay
positive regulation of neutrophil extravasation	BP	direct assay
regulation of cell-cell adhesion	BP	direct assay
signal release	BP	direct assay
cell surface	CC	direct assay
cytoplasm	CC	direct assay
dense core granule membrane	CC	direct assay
phagolysosome	CC	direct assay
plasma membrane	CC	direct assay
podosome	CC	direct assay
specific granule	CC	direct assay
tertiary granule	CC	direct assay
immunoglobulin receptor binding	MF	physical interaction
metallopeptidase activity	MF	direct assay
tumor necrosis factor receptor superfamily binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,200 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAM8	MRPL13	Q9BYD1	827
ADAM8	ASB17	Q8WXJ9	719
ADAM8	CP	P00450	711
ADAM8	ASB2	Q96Q27	520
ADAM8	EIF3J	O75822	514
ADAM8	TGM6	O95932	499
ADAM8	MMP24	Q9Y5R2	487
ADAM8	SRC	P12931	424
ADAM8	MMP28	Q9H239	405
ADAM8	MMP12	P39900	399
ADAM8	MMP25	Q9NPA2	398
ADAM8	MMP9	P14780	390
ADAM8	ADAM10	O14672	387
ADAM8	PLEC	Q15149	370
ADAM8	DOCK8	Q8NF50	370

IntAct

Human interaction partners of ADAM8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
FNBP1L	direct interaction	0.560	2
NCF1	direct interaction	0.560	2
TEC	direct interaction	0.560	2
TRIP10	direct interaction	0.560	2
FNBP1	direct interaction	0.440	1
FST	direct interaction	0.440	1
FSTL3	direct interaction	0.440	1
OSTF1	direct interaction	0.440	1
SNX18	direct interaction	0.440	1
SNX33	direct interaction	0.440	1
SNX9	direct interaction	0.440	1
SRC	direct interaction	0.440	1

BioGRID (5 interactions; top human partners by supporting records): ANXA6 (Cross-Linking-MS (XL-MS)), APEX1 (Affinity Capture-RNA), CA9 (Proximity Label-MS), MIR150 (Protein-RNA), TPP2 (Co-fractionation)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ ITGA9-ITGB1-ADAM8 complex	3	ADAM8, ITGA9, ITGB1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 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
Clathrin-mediated endocytosis	5	38.7×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
endocytosis	5	39.7×	5e-06

Disease & clinical

Genetic variants

Variant evidence for ADAM8: 250 ClinVar records (25 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	3
Uncertain significance	160
Likely benign	47
Benign	5

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 25 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
57314	GRCh38/hg38 10q26.3(chr10:131457361-133620674)x1	Pathogenic	criteria provided, single submitter	1
58825	GRCh38/hg38 10q26.3(chr10:129673966-133613938)x1	Pathogenic	criteria provided, single submitter	1
58853	GRCh38/hg38 10q26.3(chr10:131914873-133613938)x1	Pathogenic	criteria provided, single submitter	1
58854	GRCh38/hg38 10q26.3(chr10:132475849-133620674)x1	Pathogenic	criteria provided, single submitter	1
815387	GRCh37/hg19 10q26.2-26.3(chr10:129381095-135427143)x1	Pathogenic	criteria provided, single submitter	1
1456992	NC_000010.10:g.(?134916201)(135439108_?)del	Pathogenic	criteria provided, single submitter	1
1527616	GRCh37/hg19 10q26.2-26.3(chr10:128465436-135427143)x1	Pathogenic	criteria provided, single submitter	1
1527622	GRCh37/hg19 10q26.2-26.3(chr10:129914228-135427143)x1	Pathogenic	criteria provided, single submitter	1
1808640	GRCh37/hg19 10q26.2-26.3(chr10:130043370-135345340)x1	Pathogenic	criteria provided, single submitter	1
2685391	GRCh37/hg19 10q26.2-26.3(chr10:128925940-135427143)x1	Pathogenic	criteria provided, single submitter	1
3063154	GRCh37/hg19 10q26.3(chr10:131398569-135427143)x1	Pathogenic	criteria provided, single submitter	1
4682767	GRCh37/hg19 10q26.2-26.3(chr10:128423873-135126133)x1	Pathogenic	criteria provided, single submitter	1
4682769	GRCh37/hg19 10q26.3(chr10:131515269-135427143)x1	Pathogenic	criteria provided, single submitter	1
144558	GRCh38/hg38 10q26.2-26.3(chr10:126730896-133620609)x1	Pathogenic	no assertion criteria provided	1
146073	GRCh38/hg38 10q26.3(chr10:132178475-133620674)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ADAM8’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 2,065):

Position(s)	Effect	Δscore	Sites
10:133268119–133268120	acceptor_loss	1.0000	5
10:133268746–133268747	donor_loss	1.0000	4
10:133268863–133268864	acceptor_loss	1.0000	6
10:133270358–133270359	donor_loss	1.0000	5
10:133270511–133270512	acceptor_loss	1.0000	6
10:133270806–133270807	acceptor_loss	1.0000	5
10:133270967	donor_gain	1.0000
10:133271848	donor_gain	1.0000
10:133272414	donor_loss	1.0000
10:133272867–133272868	acceptor_loss	1.0000	6

AlphaMissense

1,128 missense substitutions predicted likely pathogenic (of 5,353 scored), across 283 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M364	9	0.916	0.992
H338	8	0.979	0.993
H334	8	0.970	0.991
H344	8	0.961	0.987
F376	8	0.957	0.997
D423	8	0.948	0.969
F296	8	0.943	0.990
D209	8	0.938	0.986
D320	8	0.927	0.970
D345	8	0.925	0.963
D234	8	0.923	0.987
S380	8	0.910	0.995
N413	8	0.907	0.984
S377	8	0.901	0.992
D474	8	0.900	0.949
D286	8	0.876	0.950
N75	8	0.865	0.939
H152	8	0.845	0.932
C479	7	0.977	0.989
C435	7	0.974	0.993

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	3.37e-08

Disease associations

OMIM: gene MIM:602267 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST007250_1	Nonunion in individuals with fractures	2e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009707	fractures, ununited

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5665 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M12: Astacin/Adamalysin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
INCB3619	Inhibition	6.0	pIC50

Binding affinities (BindingDB)

20 measured of 24 human assays (24 total across all organisms); most potent 20 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate	IC50	35 nM
CHEMBL3828456	IC50	142 nM
CHEMBL3828497	IC50	157 nM
CHEMBL3827850	IC50	182 nM
CHEMBL3827732	IC50	192 nM
CHEMBL3827980	IC50	220 nM
CHEMBL3827893	IC50	240 nM
CHEMBL2431028	IC50	240 nM
CHEMBL3827446	IC50	256 nM
CHEMBL3827091	IC50	368 nM
CHEMBL3827647	IC50	378 nM
CHEMBL3828432	IC50	420 nM
CHEMBL3827027	IC50	452 nM
CHEMBL3827271	IC50	890 nM
CHEMBL5276957	IC50	900 nM
CHEMBL3828603	IC50	1240 nM
CHEMBL3827625	IC50	1640 nM
CHEMBL3827487	IC50	2340 nM
CHEMBL5283335	IC50	3000 nM
CHEMBL5267938	IC50	4660 nM

ChEMBL bioactivities

24 potent at pChembl≥5 of 24 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.92	IC50	12	nM	CHEMBL2431028
7.39	IC50	41	nM	CHEMBL5267938
7.14	IC50	73	nM	CHEMBL5283335
6.92	IC50	120	nM	CHEMBL2431028
6.85	IC50	142	nM	CHEMBL3828456
6.80	IC50	157	nM	CHEMBL3828497
6.74	IC50	182	nM	CHEMBL3827850
6.72	IC50	192	nM	CHEMBL3827732
6.66	IC50	220	nM	CHEMBL3827980
6.62	IC50	240	nM	CHEMBL3827893
6.59	IC50	256	nM	CHEMBL3827446
6.46	IC50	350	nM	CHEMBL5283335
6.43	IC50	368	nM	CHEMBL3827091
6.42	IC50	378	nM	CHEMBL3827647
6.38	IC50	420	nM	CHEMBL3828432
6.34	IC50	452	nM	CHEMBL3827027
6.25	IC50	567	nM	CHEMBL5276957
6.10	IC50	800	nM	CHEMBL5276957
6.05	IC50	890	nM	CHEMBL3827271
6.00	IC50	1000	nM	CHEMBL434567
5.91	IC50	1245	nM	CHEMBL3828603
5.78	IC50	1645	nM	CHEMBL3827625
5.65	IC50	2250	nM	CHEMBL5575976
5.63	IC50	2345	nM	CHEMBL3827487

PubChem BioAssay actives

23 with measured affinity, of 37 total; 20 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R)-5-(carbamoylamino)-2-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-N-hydroxypentanamide	1926173: Inhibition of human recombinant ADAM8 using PepDAB13 as substrate preincubated with enzyme for 45 mins followed by substrate addition and measured for 6 hrs by fluorometric assay	ic50	0.0120	uM
1-N,3-N-bis[4-[[(4R)-4-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]amino]-4-oxobutyl]benzene-1,3-dicarboxamide	1926173: Inhibition of human recombinant ADAM8 using PepDAB13 as substrate preincubated with enzyme for 45 mins followed by substrate addition and measured for 6 hrs by fluorometric assay	ic50	0.0410	uM
1-N,3-N-bis[(4R)-4-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]benzene-1,3-dicarboxamide	1926173: Inhibition of human recombinant ADAM8 using PepDAB13 as substrate preincubated with enzyme for 45 mins followed by substrate addition and measured for 6 hrs by fluorometric assay	ic50	0.0730	uM
2-[(2S,5S,8S,11S,14S,17R)-2,8-bis(4-aminobutyl)-11-[3-(diaminomethylideneamino)propyl]-17-(hydroxymethyl)-14-(3-methylbutyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.1420	uM
2-[(2S,5S,8S,11S,14S,17R)-2,8-bis(4-aminobutyl)-11-[3-(diaminomethylideneamino)propyl]-17-(hydroxymethyl)-14-(2-methylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.1570	uM
2-[(2S,5S,8S,11S,14R,17S)-5,17-bis(4-aminobutyl)-8-[3-(diaminomethylideneamino)propyl]-14-(hydroxymethyl)-11-(2-methylpropyl)-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]acetic acid	1314102: Inhibition of recombinant ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 24 hrs by ELISA	ic50	0.1820	uM
2-[(2S,5S,8S,11S,14S,17R)-2,8-bis(4-aminobutyl)-11-[3-(carbamoylamino)propyl]-17-(hydroxymethyl)-14-(2-methylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.1920	uM
2-[(2S,5S,8S,11S,14S)-2,8-bis(4-aminobutyl)-11-[3-(diaminomethylideneamino)propyl]-14-(3-methylbutyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.2200	uM
2-[(2S,5S,8S,11S,14S,17S)-5,17-bis(4-aminobutyl)-8-[3-(diaminomethylideneamino)propyl]-14-(hydroxymethyl)-11-(2-methylpropyl)-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.2400	uM
2-[(2S,5S,8S,11S,14S)-2,8-bis(4-aminobutyl)-11-[3-(diaminomethylideneamino)propyl]-14-(2,2-dimethylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.2560	uM
2-[(2S,5S,8S,11S,14S,17R)-2,8-bis(4-aminobutyl)-11-[4-(diaminomethylideneamino)butyl]-17-(hydroxymethyl)-14-(2-methylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.3680	uM
2-[(2S,5S,8S,11S,14S)-2,8-bis(4-aminobutyl)-14-butyl-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.3780	uM
(2S,5S,8S,11S,14S,17S)-2,8-bis(4-aminobutyl)-5-(carboxymethyl)-11-[3-(diaminomethylideneamino)propyl]-14-(2-methylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadecane-17-carboxylic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.4200	uM
2-[(2S,5S,8S,11S,14S)-2,8-bis(4-aminobutyl)-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15,19-hexaoxo-14-propyl-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.4520	uM
(2R)-2-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-5-[[(4R)-4-[[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]carbamoylamino]-N-hydroxypentanamide	1926173: Inhibition of human recombinant ADAM8 using PepDAB13 as substrate preincubated with enzyme for 45 mins followed by substrate addition and measured for 6 hrs by fluorometric assay	ic50	0.5670	uM
2-[(2S,5S,8S,11S,14S)-2,8-bis(4-aminobutyl)-11-[3-(carbamoylamino)propyl]-14-(2-methylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	0.8900	uM
methyl (6S,7S)-7-(hydroxycarbamoyl)-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate	344631: Inhibition of ADAM8	ic50	1.0000	uM
2-[(2S,5S,8S,11S,14S,17R)-2,8-bis(4-aminobutyl)-11-[3-[[amino(nitramido)methylidene]amino]propyl]-17-(hydroxymethyl)-14-(2-methylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	1.2450	uM
2-[(2S,5S,8S,11S,14S)-2,8-bis(4-aminobutyl)-11-[3-(diaminomethylideneamino)propyl]-14-(2-methylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	1.6450	uM
2-[(2S,5S,8S,11S,14S)-2,8-bis(4-aminobutyl)-11-[3-[[amino(nitramido)methylidene]amino]propyl]-14-(2-methylpropyl)-3,6,9,12,15,19-hexaoxo-1,4,7,10,13,16-hexazacyclononadec-5-yl]acetic acid	1314103: Inhibition of ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 6 hrs by ELISA	ic50	2.3450	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, increases expression	4
Ozone	affects expression, increases abundance, increases expression	3
Silicon Dioxide	increases expression	3
sodium arsenite	increases expression, decreases expression	2
Rotenone	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
peficitinib	increases phosphorylation, decreases reaction, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
entinostat	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	decreases expression	1
Endosulfan	increases expression	1
Estradiol	decreases expression, affects cotreatment	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Phenytoin	decreases expression	1
Smoke	decreases expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3829986	Binding	Inhibition of recombinant ADAM8 (unknown origin) expressed in African green monkey COS7 cells co-expressing CD23 assessed as inhibition of CD23 shedding after 24 hrs by ELISA	Synthesis and biological evaluation of analogues of the potent ADAM8 inhibitor cyclo(RLsKDK) for the treatment of inflammatory diseases and cancer metastasis. — *Bioorg Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F4I1	HyCyte U2OS KO-hADAM8	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ADAM8 across ~30M SureChEMBL compounds — explore on Sugi Predict.