ADAM10

Summary

ADAM10 (ADAM metallopeptidase domain 10, HGNC:188) is a protein-coding gene on chromosome 15q21.3, encoding Disintegrin and metalloproteinase domain-containing protein 10 (O14672). Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins, including adhesion proteins, growth factor precursors and cytokines being essential for development and tissue homeostasis.

Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing.

Source: NCBI Gene 102 — RefSeq curated summary.

At a glance

• Gene–disease (curated): reticulate acropigmentation of Kitamura (Strong, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 146 total — 12 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 38 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 5
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.28 (highly constrained)
• MANE Select transcript: NM_001110
• Interaction hub: 2,827 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:188
Approved symbol	ADAM10
Name	ADAM metallopeptidase domain 10
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	kuz, MADM, HsT18717, CD156C
Ensembl gene	ENSG00000137845
Ensembl biotype	protein_coding
OMIM	602192
Entrez	102

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 22 protein_coding, 9 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 4 retained_intron

MANE Select: ENST00000260408

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

ENST00000260408, ENST00000396136, ENST00000402627, ENST00000439637, ENST00000461408, ENST00000462061, ENST00000470269, ENST00000475898, ENST00000481164, ENST00000482945, ENST00000497846, ENST00000558004, ENST00000558733, ENST00000559053, ENST00000560608, ENST00000561149, ENST00000561288, ENST00000861945, ENST00000933846, ENST00000933847, ENST00000933848, ENST00000944911, ENST00000944912, ENST00000944913, ENST00000944914, ENST00001005744, ENST00001005745, ENST00001005746, ENST00001005747, ENST00001036446, ENST00001036447, ENST00001036448, ENST00001036449, ENST00001065209, ENST00001065211, ENST00001065213, ENST00001109696, ENST00001109697, ENST00001109698, ENST00001132661

RefSeq mRNA: 2 — MANE Select: NM_001110 NM_001110, NM_001320570

CCDS: CCDS10167

Canonical transcript exons

ENST00000260408 — 16 exons

Exon	Start	End
ENSE00001809760	58588809	58597641
ENSE00002542201	58749480	58749707
ENSE00003462446	58643886	58643978
ENSE00003477324	58633196	58633359
ENSE00003490982	58621471	58621621
ENSE00003503014	58599598	58599724
ENSE00003559202	58679124	58679282
ENSE00003581776	58640777	58640960
ENSE00003582465	58646055	58646204
ENSE00003591868	58627700	58627883
ENSE00003615258	58717577	58717727
ENSE00003632357	58682196	58682314
ENSE00003637170	58610999	58611107
ENSE00003638942	58610297	58610517
ENSE00003661775	58665097	58665197
ENSE00003681481	58611808	58611991

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.6480 / max 371.7705, expressed in 1816 samples.

Highest expression (Bgee): stromal cell of endometrium, amniotic fluid, trigeminal ganglion, visceral pleura, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ADAM10 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 38 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 45 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	9.1e-33	-0.43	15:58473365:G:A
Skin Sun Exposed Lower leg	eqtl	2.2e-27	+0.38	15:58625762:T:C
Thyroid	eqtl	2.0e-19	+0.25	15:58378979:C:A
Whole Blood	eqtl	4.2e-19	+0.19	15:58478324:C:T
Skin Not Sun Exposed Suprapubic	eqtl	2.7e-18	+0.35	15:58610884:A:G
Esophagus Mucosa	eqtl	3.4e-18	+0.23	15:58749813:T:C
Muscle Skeletal	eqtl	2.4e-11	+0.20	15:58707169:G:A
Artery Tibial	eqtl	5.3e-11	+0.27	15:58690650:A:C
Pancreas	eqtl	1.7e-10	+0.31	15:58606485:C:T
Colon Transverse	eqtl	4.9e-10	+0.19	15:58603307:C:T
Esophagus Muscularis	eqtl	1.1e-09	+0.21	15:58562970:G:T
Brain Spinal cord cervical c-1	eqtl	3.6e-09	-0.34	15:58667074:T:C
Stomach	eqtl	1.5e-08	+0.25	15:58638989:T:C
Testis	eqtl	1.2e-07	+0.21	15:58618625:G:A
Colon Sigmoid	eqtl	1.3e-07	+0.27	15:58558261:CG:C
Adipose Subcutaneous	eqtl	6.7e-07	+0.19	15:58620382:G:A
Brain Cerebellum	eqtl	7.4e-07	+0.26	15:58565746:A:T
Adipose Subcutaneous	sqtl	1.2e-05	-0.26	15:58823796:A:G
Artery Aorta	eqtl	4.7e-05	+0.23	15:58606485:C:T
Esophagus Gastroesophageal Junction	eqtl	5.8e-05	+0.22	15:58610884:A:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
150239	33.5507	1815
150240	5.5399	1539
207542	0.3640	180
150242	0.1181	31
150241	0.0753	24

Top tissues by expression

showing 100 of 298 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.42	gold quality
amniotic fluid	UBERON:0000173	98.38	gold quality
trigeminal ganglion	UBERON:0001675	98.04	gold quality
visceral pleura	UBERON:0002401	98.04	gold quality
monocyte	CL:0000576	97.96	gold quality
mononuclear cell	CL:0000842	97.95	gold quality
oocyte	CL:0000023	97.79	gold quality
olfactory bulb	UBERON:0002264	97.78	gold quality
placenta	UBERON:0001987	97.72	gold quality
leukocyte	CL:0000738	97.65	gold quality
colonic epithelium	UBERON:0000397	97.45	gold quality
bone marrow cell	CL:0002092	97.41	gold quality
corpus callosum	UBERON:0002336	97.38	gold quality
pleura	UBERON:0000977	97.36	gold quality
choroid plexus epithelium	UBERON:0003911	97.36	gold quality
ventricular zone	UBERON:0003053	97.32	gold quality
lower lobe of lung	UBERON:0008949	97.28	gold quality
inferior vagus X ganglion	UBERON:0005363	97.25	gold quality
germinal epithelium of ovary	UBERON:0001304	97.20	gold quality
buccal mucosa cell	CL:0002336	97.14	gold quality
mammary duct	UBERON:0001765	97.10	gold quality
endometrium	UBERON:0001295	97.04	gold quality
epithelium of mammary gland	UBERON:0003244	97.04	gold quality
parietal pleura	UBERON:0002400	97.01	gold quality
globus pallidus	UBERON:0001875	96.98	gold quality
medial globus pallidus	UBERON:0002477	96.93	gold quality
subthalamic nucleus	UBERON:0001906	96.89	gold quality
sural nerve	UBERON:0015488	96.89	gold quality
periodontal ligament	UBERON:0008266	96.87	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.84	gold quality
lateral globus pallidus	UBERON:0002476	96.82	gold quality
islet of Langerhans	UBERON:0000006	96.78	gold quality
decidua	UBERON:0002450	96.77	gold quality
palpebral conjunctiva	UBERON:0001812	96.71	gold quality
calcaneal tendon	UBERON:0003701	96.69	gold quality
mucosa of urinary bladder	UBERON:0001259	96.60	gold quality
adrenal tissue	UBERON:0018303	96.60	gold quality
epithelium of nasopharynx	UBERON:0001951	96.59	gold quality
colonic mucosa	UBERON:0000317	96.57	gold quality
renal medulla	UBERON:0000362	96.51	gold quality
seminal vesicle	UBERON:0000998	96.50	gold quality
eye	UBERON:0000970	96.40	gold quality
dorsal root ganglion	UBERON:0000044	96.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.24	gold quality
jejunal mucosa	UBERON:0000399	96.20	gold quality
caput epididymis	UBERON:0004358	96.18	gold quality
urethra	UBERON:0000057	96.17	gold quality
esophagus squamous epithelium	UBERON:0006920	96.11	gold quality
vermiform appendix	UBERON:0001154	96.06	gold quality
nasal cavity epithelium	UBERON:0005384	95.97	gold quality
caecum	UBERON:0001153	95.95	gold quality
medulla oblongata	UBERON:0001896	95.95	gold quality
nephron tubule	UBERON:0001231	95.83	gold quality
superficial temporal artery	UBERON:0001614	95.81	gold quality
gall bladder	UBERON:0002110	95.79	gold quality
pericardium	UBERON:0002407	95.78	gold quality
trabecular bone tissue	UBERON:0002483	95.64	gold quality
skin of hip	UBERON:0001554	95.62	gold quality
tonsil	UBERON:0002372	95.56	gold quality
cranial nerve II	UBERON:0000941	95.48	gold quality
CA1 field of hippocampus	UBERON:0003881	95.48	gold quality
cauda epididymis	UBERON:0004360	95.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.44	gold quality
upper leg skin	UBERON:0004262	95.43	gold quality
embryo	UBERON:0000922	95.41	gold quality
superior vestibular nucleus	UBERON:0007227	95.36	gold quality
pigmented layer of retina	UBERON:0001782	95.34	gold quality
duodenum	UBERON:0002114	95.34	gold quality
tendon	UBERON:0000043	95.31	gold quality
urinary bladder	UBERON:0001255	95.23	gold quality
synovial joint	UBERON:0002217	95.19	gold quality
heart right ventricle	UBERON:0002080	95.14	gold quality
rectum	UBERON:0001052	95.12	gold quality
gingival epithelium	UBERON:0001949	95.09	gold quality
lymph node	UBERON:0000029	95.08	gold quality
bone marrow	UBERON:0002371	95.06	gold quality
smooth muscle tissue	UBERON:0001135	95.00	gold quality
gingiva	UBERON:0001828	95.00	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.99	gold quality
cortical plate	UBERON:0005343	94.94	gold quality
pons	UBERON:0000988	94.92	gold quality
endothelial cell	CL:0000115	94.90	gold quality
blood	UBERON:0000178	94.88	gold quality
secondary oocyte	CL:0000655	94.80	gold quality
pylorus	UBERON:0001166	94.80	gold quality
tendon of biceps brachii	UBERON:0008188	94.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.78	gold quality
postcentral gyrus	UBERON:0002581	94.75	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.61	gold quality
epithelial cell of pancreas	CL:0000083	94.55	gold quality
parietal lobe	UBERON:0001872	94.53	gold quality
kidney epithelium	UBERON:0004819	94.53	gold quality
myocardium	UBERON:0002349	94.49	gold quality
mammary gland	UBERON:0001911	94.46	gold quality
thoracic mammary gland	UBERON:0005200	94.45	gold quality
tibia	UBERON:0000979	94.40	gold quality
squamous epithelium	UBERON:0006914	94.40	gold quality
ventral tegmental area	UBERON:0002691	94.39	gold quality
corpus epididymis	UBERON:0004359	94.38	gold quality
oral cavity	UBERON:0000167	94.37	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	6420.87
E-HCAD-31	yes	4054.75
E-ANND-3	yes	11.20

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	71.9
Cerebellum	tissue	62.9	not detected
Corpus callosum	tissue	58.9
Midbrain	tissue	55.7
Superior colliculi	tissue	55.4
Medulla oblongata	tissue	54.0
Thalamus	tissue	53.1
Substantia nigra	tissue	52.4
Cerebral cortex	tissue	50.6	low
Somatosensory cortex	tissue	50.6
Pons	tissue	49.2
Occipital cortex	tissue	48.3
Hippocampal formation	tissue	47.3
Motor cortex	tissue	45.9
Retrosplenial and cingulate cortex	tissue	45.3
Putamen	tissue	45.2
Entorhinal cortex	tissue	44.6
Periaqueductal gray	tissue	43.1
Septum	tissue	42.2
Frontal cortex	tissue	41.8
Hypothalamus	tissue	41.4
Retrosplenial cortex	tissue	41.4
Caudate putamen	tissue	40.8
Prefrontal cortex	tissue	40.6
Temporal cortex	tissue	40.0
Insular cortex	tissue	39.7
Thymus	tissue	38.8
Ventral forebrain	tissue	38.3
Nucleus accumbens	tissue	37.9
Amygdala	tissue	35.8
Hippocampus	tissue	35.5	low
Postcentral gyrus	tissue	35.5
Choroid plexus	tissue	34.3
Basal ganglia	tissue	33.1	not detected
Locus coeruleus	tissue	30.1
Olfactory bulb	tissue	29.8
Spleen	tissue	27.3	not detected
Placenta	tissue	27.1	low
Thyroid gland	tissue	26.7	low
Urinary bladder	tissue	26.2	medium
Prostate	tissue	23.6	medium
Lymph node	tissue	20.8	not detected
Colon	tissue	20.8	low
Lung	tissue	19.7	medium
Stomach 1	tissue	19.0	medium
Appendix	tissue	17.9	low
Gallbladder	tissue	17.7	low
Bone marrow	tissue	17.3	not detected
Kidney	tissue	16.8	low
Rectum	tissue	16.1	low
Small intestine	tissue	15.8	low
Tonsil	tissue	15.3	not detected
Endometrium 1	tissue	15.2	low
Cervix	tissue	15.1	low
Liver	tissue	15.0	low
Skin 1	tissue	14.8	not detected
Duodenum	tissue	14.7	not detected
Breast	tissue	14.2	low
Esophagus	tissue	14.2	not detected
Adipose tissue	tissue	14.0	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal spinal cord (71.9), Parieto-temporal junction (white matter) (64.0), Corpus callosum, splenium (white matter) (60.5), Ventral spinal cord (59.3), White matter (58.9).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
ERBB4	Repression

Upstream regulators (CollecTRI, top): AP1, HDAC1, PAX2, RARB, SOX2, SP1, TBX2, USF1

miRNA regulators (miRDB)

Targeting ADAM10 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 288 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-513B-5P	99.99	69.96	2150
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-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.276, missense Z 3.92 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000260408 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
15:58,597,550–58,611,897	150 / 268.5	0.56	no
15:58,611,898–58,621,531	53 / 62.0	0.85	no
15:58,621,532–58,640,905	97 / 221.4	0.44	no
15:58,640,906–58,749,534	310 / 362.4	0.86	no

Literature-anchored findings (GeneRIF, showing 40)

• Atrial fibrillation is associated with an increase in the expression of ADAM10 in the heart atrium (PMID:11839628)
• [alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients. (PMID:12080182)
• ADAM10 mRNA levels were twofold higher in the hippocampus and cerebellum of Alzheimer’s disease patients compared to controls, but without relationship to the severity of anatomical damage. (PMID:12438920)
• The results indicate that ADAM9, ADAM10, and ADAM17, members of the disintegrin and metalloprotease family, catalyze alpha-secretory cleavage and therefore act as alpha-secretases in A172 cells. (PMID:12535668)
• Review. The mode of activation of EGFR in response to bacterial lipoteichoic acid involves cleavage of the transmembrane ligand HBEGF by ADAM 10. (PMID:12568494)
• Our present findings suggest important implications for understanding CD44-dependent signal transduction and a potential role of PS/gamma-secretase activity in the functional regulation of adhesion molecules. (PMID:12629514)
• gamma-secretase cleavage of CT99 is a prerequisite for BACE-mediated processing at Abeta-34 site and therefore, BACE and gamma-secretase activity can be mutually dependent. (PMID:12665519)
• under inflammatory conditions, ADAM-10, expressed by perivascular macrophages, and ADAM-17, expressed by invading T cells, may actively contribute to the pathogenesis of inflammatory disorders of the CNS. (PMID:12730960)
• variation at the ADAM10 gene locus is not associated with Creutzfeldt-Jakob disease (PMID:12782344)
• gamma secretase is regulated by nicastrin (PMID:12815056)
• cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (PMID:12832423)
• gamma-secretase is engaged directly by Notch activation, which leads to diminished PS1 expression, suggesting a complex set of feedback interactions following Notch activation (PMID:12960155)
• APH-1 plays a GXXXG-dependent scaffolding role in both the initial assembly and subsequent maturation and maintenance of the active gamma-secretase complex. (PMID:14627705)
• Purified cholesterol-rich microdomains from a low-density membrane fraction demonstrate gamma-secretase/ADAM10 activity, indicating that amyloid beta protein production can take place in rafts. (PMID:14636066)
• ADAM 10, a putative alpha-secretase involved in Notch signaling, was found in neurons of the perinatal cortex. During aging there is an increase in intraneuronal staining intensity and in the number of cortical nerve cells that contain the enzyme (PMID:14707550)
• ADAM10 is the major alpha-secretase cleaving amyloid precursor protein, with TACE playing a minor role; neither ADAM10 nor TACE is involved in the shedding of angiotensin converting enzyme (PMID:15182369)
• NRADD is an additional gamma-secretase substrate (PMID:15280425)
• IL-8 induces shedding of EGFR ligands because of an ADAM10-dependent pathway in gastric cancer cells (PMID:15300588)
• ADAM10 mediates constitutive and activated pro-BTC shedding (PMID:15507448)
• Expression of a dominant-negative form of kuzbanian in transgenic mice leads to reduced T-cell receptor beta expression in double-negative thymocytes and to a partial block between the double-negative to double-positive stages of development. (PMID:15905513)
• ADAM10 has a role in E-cadherin shedding and epithelial cell-cell adhesion, migration, and beta-catenin translocation (PMID:15958533)
• Data suggest a simple mechanism for regulating ADAM10-mediated ephrin proteolysis, which ensures that only Eph bound ephrins are recognized and cleaved. (PMID:16239146)
• High levels of Prpc C-terminal fragment (C1) are associated with the presence of the active ADAM 10 suggesting this zinc metalloprotease as a candidate for the cleavage of PrP(c) in the human brain. (PMID:16263114)
• Result suggests that ADAM10 expression plays a role in the carcinogenesis of oral squamous cell carcinoma (OSCC) and proliferation of OSCC cells, independent of APP processing. (PMID:16309826)
• EGF induces ADAM10-mediated CD44 cleavage through Rac1 and mitogen-activated protein kinase activation, and thereby promotes tumour cell migration and invasion. (PMID:16390331)
• ADAM10 is a major determinant of HER2 shedding, the inhibition of which, may provide a novel therapeutic approach for treating a variety of breast cancers with active HER2 signaling. (PMID:16627989)
• ADAM10 mediates cleavage of a receptor tyrosine phosphatase and regulation of beta catenin’s transcriptional activity. (PMID:16648485)
• ADAM10-mediated release of CD46 from apoptotic vesicles may represent a form of strategy to allow restricted complement activation to deal with modified self (PMID:16735514)
• ADAM10 is the protease responsible for constitutive and regulated Pcdh gamma shedding events that modulate the cell adhesion role of Pcdh gamma. (PMID:16751190)
• ADAM9 does not behave as a genuine alpha-secretase but rather acts as an important upstream regulator of ADAM10 activity. (PMID:16806063)
• furin enhances alpha-secretase activity via the cleavage of ADAM10 and TACE, and attenuated furin activity is connected to the production of Abeta (PMID:16942750)
• ADAM-10 transgenic mice display significantly elevated cortical cholinergic, glutaminergic and GABAergic presynaptic bouton densities at an early developmental time point. (PMID:17187903)
• These findings suggest that ADAM10 represents an important molecular modulator of FasL-mediated cell death. (PMID:17290285)
• ADAM10 and SPPL2a were identified as two proteases implicated in FasL processing and release of the FasL intracellular domain, which has been shown to be important for retrograde FasL signaling (PMID:17557115)
• ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. (PMID:17699774)
• In human prostate cancer, the nuclear translocation of ADAM-10 coupled with the androgen receptor is involved in tumor growth and progression. (PMID:17727679)
• the ADAM10 prodomain inhibits betacellulin shedding, demonstrating that it could be of potential use as a therapeutic agent to treat cancer. (PMID:17895248)
• SPPL2a and SPPL2b mediate the intramembrane cleavage, whereas neither SPP nor SPPL3 is capable of processing the Bri2 N-terminal fragment. (PMID:17965014)
• ADAM10 is identified as the TSHR cleavage enzyme and it is shown that TSH regulates its activation. (PMID:18074395)
• ADAM10-mediated E-cadherin proteolysis leads to the impaired cohesion of keratinocytes observed in eczematous dermatitis. (PMID:18200054)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	adam10b	ENSDARG00000015502
danio_rerio	adam10a	ENSDARG00000053468
danio_rerio	adam9b	ENSDARG00000057138
mus_musculus	Adam10	ENSMUSG00000054693
rattus_norvegicus	Adam10	ENSRNOG00000054257
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), ADAMDEC1 (ENSG00000134028), ADAM30 (ENSG00000134249), ADAM19 (ENSG00000135074), ADAM21 (ENSG00000139985), ADAM15 (ENSG00000143537), ADAM12 (ENSG00000148848), ADAM33 (ENSG00000149451), ADAM8 (ENSG00000151651), ADAM17 (ENSG00000151694), ADAM29 (ENSG00000168594), ADAM9 (ENSG00000168615), ADAM18 (ENSG00000168619), ADAM32 (ENSG00000197140)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:109548) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 59 distinct phenotype terms.

Mouse phenotype (MP)	Records
thymus hypoplasia	2
abnormal T cell differentiation	2
decreased double-positive T cell number	2
decreased CD4-positive, alpha-beta T cell number	2
embryonic lethality during organogenesis, complete penetrance	2
decreased hematocrit	1
increased leukocyte cell number	1
increased neutrophil cell number	1
failure of vascular branching	1
distended pericardium	1
abnormal spleen morphology	1
enlarged spleen	1
spleen hyperplasia	1
small thymus	1
abnormal embryonic neuroepithelial layer differentiation	1
abnormal pontine flexure morphology	1
abnormal blood vessel morphology	1
abnormal somite development	1
decreased embryo size	1
abnormal visceral yolk sac morphology	1
abnormal umbilical cord morphology	1
abnormal embryo implantation	1
impaired embryo implantation	1
intracranial hemorrhage	1
reduced female fertility	1

+34 more (showing top 25).

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
Trichophyton benhamiae CBS 112371	D4B1G0	97.9%	Diamond
Trichophyton verrucosum HKI 0517	D4DCV9	97.9%	Diamond
Sus scrofa	O77633	97.1%	Diamond
Bos taurus	Q10741	97.1%	Diamond
Xenopus laevis	Q8JIY1	79.8%	Diamond
Macaca fascicularis	Q28483	56.7%	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
MINDY2-DT	ncRNA	101928725
LIPC	protein-coding	3990
LIPC-AS1	ncRNA	101928694
AQP9	protein-coding	366
MINDY2	protein-coding	54629

Protein

Protein identifiers

Disintegrin and metalloproteinase domain-containing protein 10 — O14672 (reviewed: O14672)

Alternative names: CDw156, Kuzbanian protein homolog, Mammalian disintegrin-metalloprotease

All UniProt accessions (8): O14672, A0A087WYG1, B5MC71, C9J9B4, H0YK32, H0YK87, H0YNC5, H3BS53

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins, including adhesion proteins, growth factor precursors and cytokines being essential for development and tissue homeostasis. Associates with six members of the tetraspanin superfamily TspanC8 which regulate its exit from the endoplasmic reticulum and its substrate selectivity. Cleaves the membrane-bound precursor of TNF at ‘76-Ala-|-Val-77’ to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP). Contributes to the normal cleavage of the cellular prion protein. Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity. Also controls the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis. Required for the development of type 1 transitional B cells into marginal zone B cells, probably by cleaving Notch. Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form. Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B. Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3. Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the release of secreted forms of IL6R and IL11RA. Enhances the cleavage of CHL1 by BACE1. Cleaves NRCAM. Cleaves TREM2, resulting in shedding of the TREM2 ectodomain. Involved in the development and maturation of glomerular and coronary vasculature. During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions. May regulate the EFNA5-EPHA3 signaling. Regulates leukocyte transmigration as a sheddase for the adherens junction protein VE-cadherin/CDH5 in endothelial cells. (Microbial infection) Promotes the cytotoxic activity of S.aureus hly by binding to the toxin at zonula adherens and promoting formation of toxin pores.

Subunit / interactions. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells. Interacts with the clathrin adapter AP2 complex subunits AP2A1, AP2A2, AP2B1, and AP2M1; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons. Forms a ternary complex composed of ADAM10, EPHA4 and CADH1; within the complex, ADAM10 cleaves CADH1 which disrupts adherens junctions. Interacts with EPHA2. Interacts with NGF in a divalent cation-dependent manner. Interacts with TSPAN14; the interaction promotes ADAM10 maturation and cell surface expression. Interacts with TSPAN5, TSPAN10, TSPAN14, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate ADAM10 substrate specificity, endocytosis and turnover. Interacts (via extracellular domain) with TSPAN33 (via extracellular domain) and (via cytoplasmic domain) with AFDN; interaction with TSPAN33 allows the docking of ADAM10 to zonula adherens through a PDZ11-dependent interaction between TSPAN33 and PLEKHA7 while interaction with AFDN locks ADAM10 at zonula adherens. Interacts with DLG1; this interaction recruits ADAM10 to the cell membrane during long-term depression in hippocampal neurons. Interacts (via extracellular domain) with BACE1 (via extracellular domain). Interacts with FAM171A1. (Microbial infection) Interacts with S.aureus hly; this interaction is necessary for toxin pore formation, disruption of focal adhesions and S.aureus hly-mediated cytotoxicity.

Subcellular location. Cell membrane. Golgi apparatus membrane. Cytoplasmic vesicle. Clathrin-coated vesicle. Cell projection. Axon. Dendrite. Cell junction. Adherens junction. Cytoplasm.

Tissue specificity. Expressed in the brain (at protein level). Expressed in spleen, lymph node, thymus, peripheral blood leukocyte, bone marrow, cartilage, chondrocytes and fetal liver.

Post-translational modifications. The precursor is cleaved by furin and PCSK7.

Disease relevance. Reticulate acropigmentation of Kitamura (RAK) [MIM:615537] A rare cutaneous pigmentation disorder characterized by reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation, affecting the dorsa of the hands and feet and appearing in the first or second decade of life. The macules gradually darken and extend to the proximal regions of the extremities. The manifestations tend to progress until middle age, after which progression of the eruptions stops. The pigmentary augmentation is found on the flexor aspects of the wrists, neck, patella and olecranon. Other features include breaks in the epidermal ridges on the palms and fingers, palmoplantar pits, occasionally plantar keratoderma, and partial alopecia. The disease is caused by variants affecting the gene represented in this entry. Alzheimer disease 18 (AD18) [MIM:615590] A late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Catalytically inactive when the propeptide is intact and associated with the mature enzyme. The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-173) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme. The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 complex but not the individual proteins. Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33. Stalk region is sufficient for interaction with TSPAN15.

Induction. In osteoarthritis affected-cartilage.

Isoforms (2)

UniProt ID	Names	Canonical?
O14672-1	1	yes
O14672-2	2

RefSeq proteins (2): NP_001101, NP_001307499 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001590	Peptidase_M12B	Domain
IPR001762	Disintegrin_dom	Domain
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR034025	ADAM10_ADAM17	Domain
IPR036436	Disintegrin_dom_sf	Homologous_superfamily
IPR049038	ADAM10_Cys-rich	Domain
IPR051489	ADAM10_17	Family

Pfam: PF00200, PF13574, PF21299

Enzyme classification (BRENDA)

• EC 3.4.24.81 — ADAM10 endopeptidase (BRENDA: 8 organisms, 153 substrates, 85 inhibitors, 2 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GLU(EDANS)-PRO-LEU-ALA-GLN-ALA-VAL-ARG-SER-SER(G	0.0085	1
GLU(EDANS)-PRO-LEU-ALA-GLN-ALA-VAL-ARG-SER-SER-S	0.012	1

UniProt features (105 total): helix 23, strand 21, disulfide bond 17, turn 7, sequence variant 5, binding site 4, glycosylation site 4, mutagenesis site 4, short sequence motif 3, sequence conflict 3, topological domain 2, domain 2, region of interest 2, signal peptide 1, propeptide 1, active site 1, site 1, modified residue 1, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
6BE6	ADAM10 Extracellular Domain	X-RAY DIFFRACTION	2.8
6BDZ	ADAM10 Extracellular Domain Bound by the 11G2 Fab	X-RAY DIFFRACTION	3.1
8ESV	Structure of human ADAM10-Tspan15 complex bound to 11G2 vFab	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14672-F1	80.17	0.38

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 6BDZ, 8ESV

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, CD markers, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutational cancer driver genes, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; vesicles

Antibody reliability (HPA): IH approved · IF supported

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 (2)

Position	Role
384
213–214	cleavage; by furin and pcsk7

Ligand- & substrate-binding residues (4)

Position	Role
173	Zn(2+)
383	Zn(2+)
387	Zn(2+)
393	Zn(2+)

Post-translational modifications (1)

Type	Positions
Phosphothreonine	719

Disulfide bonds (17)

Type	Positions
Disulfide bond	222–313, 344–451, 399–435, 460–495, 471–484, 473–479, 483–515, 503–511, 510–536, 524–543, 530–562, 555–567, 572–598, 580–607, 582–597, 594–639, 632–645

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	267, 278, 439, 551

Mutagenesis-validated functional residues (4)

Position	Phenotype
384	loss of proteolytic activity. abrogates app cleavage. reduces notch signaling.
638–646	strongly reduces interaction and adam10 maturation.
638–646	strongly reduces interaction and prevents adam10 maturation.
653–656	strongly reduces interaction and prevents adam10 maturation.

Function

Pathways and Gene Ontology

Reactome pathways

10 curated (TAS) of 39; 11 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

39 pathways:

ID	Pathway	Evidence
R-HSA-2691232	Constitutive Signaling by NOTCH1 HD Domain Mutants ⚕	curated
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants ⚕	curated
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants ⚕	curated
R-HSA-2660826	Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant ⚕	curated
R-HSA-977225	Amyloid fiber formation	curated
R-HSA-1474228	Degradation of the extracellular matrix	curated
R-HSA-9013507	NOTCH3 Activation and Transmission of Signal to the Nucleus	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-8957275	Post-translational protein phosphorylation	curated
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-2691230	Signaling by NOTCH1 HD Domain Mutants in Cancer ⚕	—
R-HSA-2894858	Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer ⚕	—
R-HSA-2644602	Signaling by NOTCH1 PEST Domain Mutants in Cancer ⚕	—
R-HSA-2644603	Signaling by NOTCH1 in Cancer ⚕	—
R-HSA-2660825	Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant ⚕	—
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus	electronic
R-HSA-422475	Axon guidance	—
R-HSA-1442490	Collagen degradation	electronic
R-HSA-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	—
R-HSA-3928665	EPH-ephrin mediated repulsion of cells	electronic
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-2979096	NOTCH2 Activation and Transmission of Signal to the Nucleus	electronic
R-HSA-9013700	NOTCH4 Activation and Transmission of Signal to the Nucleus	electronic
R-HSA-9675108	Nervous system development	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-162582	Signal Transduction	—
R-HSA-177929	Signaling by EGFR	electronic
R-HSA-157118	Signaling by NOTCH	—
R-HSA-1980143	Signaling by NOTCH1	—
R-HSA-1980145	Signaling by NOTCH2	—
R-HSA-9012852	Signaling by NOTCH3	—
R-HSA-9013694	Signaling by NOTCH4	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—

MSigDB gene sets: 504 (showing top): REACTOME_SIGNALING_BY_NOTCH, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, GOBP_REGULATION_OF_T_CELL_CHEMOTAXIS, GOBP_CELL_CHEMOTAXIS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_MIGRATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH

GO Biological Process (33): in utero embryonic development (GO:0001701), membrane protein ectodomain proteolysis (GO:0006509), negative regulation of cell adhesion (GO:0007162), Notch signaling pathway (GO:0007219), integrin-mediated signaling pathway (GO:0007229), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), regulation of Notch signaling pathway (GO:0008593), negative regulation of gene expression (GO:0010629), positive regulation of T cell chemotaxis (GO:0010820), protein processing (GO:0016485), extracellular matrix disassembly (GO:0022617), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), positive regulation of tumor necrosis factor production (GO:0032760), adherens junction organization (GO:0034332), response to tumor necrosis factor (GO:0034612), epidermal growth factor receptor ligand maturation (GO:0038004), monocyte activation (GO:0042117), amyloid precursor protein catabolic process (GO:0042987), pore complex assembly (GO:0046931), constitutive protein ectodomain proteolysis (GO:0051089), cochlea development (GO:0090102), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696), postsynapse organization (GO:0099173), regulation of postsynapse organization (GO:0099175), protein catabolic process at postsynapse (GO:0140249), regulation of vasculature development (GO:1901342), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265), proteolysis (GO:0006508), negative regulation of amyloid precursor protein biosynthetic process (GO:0042985), signaling receptor ligand precursor processing (GO:0140448), negative regulation of amyloid-beta formation (GO:1902430)

GO Molecular Function (12): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), integrin binding (GO:0005178), metallopeptidase activity (GO:0008237), SH3 domain binding (GO:0017124), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), metallodipeptidase activity (GO:0070573), metalloendopeptidase activity involved in amyloid precursor protein catabolic process (GO:1902945), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (23): Golgi membrane (GO:0000139), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), Golgi-associated vesicle (GO:0005798), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), cell surface (GO:0009986), postsynaptic density (GO:0014069), membrane (GO:0016020), clathrin-coated vesicle (GO:0030136), axon (GO:0030424), dendrite (GO:0030425), specific granule membrane (GO:0035579), pore complex (GO:0046930), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), perinuclear endoplasmic reticulum (GO:0097038), synaptic membrane (GO:0097060), tetraspanin-enriched microdomain (GO:0097197), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

16 top-level categories:

Category	Pathways
Metabolism of proteins	2
Degradation of the extracellular matrix	1
Extracellular matrix organization	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1
Signaling by NOTCH1 HD Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Signaling by NOTCH2	1
EPH-Ephrin signaling	1
Innate Immune System	1
Post-translational protein modification	1
Signaling by NOTCH3	1
Signaling by NOTCH4	1
Signal Transduction	1

GO top-level categories

showing 60 of 84 GO namespaces:

Category	Terms
cellular anatomical structure	4
cell surface receptor signaling pathway	2
positive regulation of cellular process	2
peptidase activity	2
endoplasmic reticulum	2
neuron projection	2
secretory granule membrane	2
chordate embryonic development	1
membrane protein proteolysis	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
cell communication	1
signaling	1
cell population proliferation	1
regulation of cell population proliferation	1
Notch signaling pathway	1
regulation of signal transduction	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
T cell chemotaxis	1
regulation of T cell chemotaxis	1
positive regulation of lymphocyte chemotaxis	1
positive regulation of T cell migration	1
proteolysis	1
protein maturation	1
cellular component disassembly	1
extracellular matrix organization	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
cell-cell junction organization	1
response to cytokine	1
membrane protein ectodomain proteolysis	1
peptide hormone processing	1
myeloid leukocyte activation	1
amyloid precursor protein metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
protein domain specific binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
metalloexopeptidase activity	1
dipeptidase activity	1
metalloendopeptidase activity	1
amyloid precursor protein catabolic process	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 29 of 68 annotations. The rest are phylogenetic / computational / electronic (IEA).

29 experimentally-supported GO terms:

GO term	NS	Evidence
amyloid precursor protein catabolic process	BP	mutant phenotype
constitutive protein ectodomain proteolysis	BP	direct assay
membrane protein ectodomain proteolysis	BP	direct assay
monocyte activation	BP	mutant phenotype
negative regulation of cell adhesion	BP	direct assay
negative regulation of gene expression	BP	mutant phenotype
pore complex assembly	BP	mutant phenotype
positive regulation of T cell chemotaxis	BP	mutant phenotype
positive regulation of cell growth	BP	mutant phenotype
positive regulation of cell migration	BP	mutant phenotype
positive regulation of cell population proliferation	BP	mutant phenotype
positive regulation of tumor necrosis factor production	BP	direct assay
positive regulation of tumor necrosis factor-mediated signaling pathway	BP	direct assay
response to tumor necrosis factor	BP	direct assay
Golgi apparatus	CC	direct assay
Golgi-associated vesicle	CC	direct assay
cell surface	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
membrane	CC	high-throughput assay
perinuclear endoplasmic reticulum	CC	direct assay
plasma membrane	CC	direct assay
pore complex	CC	mutant phenotype
synaptic membrane	CC	direct assay
tetraspanin-enriched microdomain	CC	direct assay
endopeptidase activity	MF	mutant phenotype
metalloendopeptidase activity	MF	direct assay
metallopeptidase activity	MF	direct assay
protein homodimerization activity	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,827 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAM10	APP	P05067	869
ADAM10	BACE1	P56817	869
ADAM10	PSEN1	P49768	837
ADAM10	NCSTN	Q92542	804
ADAM10	PSEN2	P49810	775
ADAM10	CDH1	P12830	746
ADAM10	CXCL16	Q9H2A7	738
ADAM10	CX3CL1	P78423	735
ADAM10	MMEL1	Q495T6	724
ADAM10	PSENEN	Q9NZ42	706
ADAM10	CDH2	P19022	703
ADAM10	KL	Q9UEF7	703
ADAM10	EFNA2	O43921	690
ADAM10	EGF	P01133	689
ADAM10	TNF	P01375	678

IntAct

Human interaction partners of ADAM10 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 89 partners by confidence:

Partner	Interaction type	MIscore	Records
TSPAN15	association	0.840	9
TSPAN5	association	0.800	11
CD9	association	0.750	15
TSPAN14	association	0.740	7
CD81	association	0.740	2
APP	proximity	0.660	7
TSPAN33	physical association	0.620	3
GRB2	direct interaction	0.600	5
LCK	direct interaction	0.600	3
GRAP2	direct interaction	0.540	3
PACSIN3	direct interaction	0.540	3
SRC	direct interaction	0.540	3
ABL1	direct interaction	0.540	2
SH3GL1	direct interaction	0.540	2
SNX18	direct interaction	0.540	2
CD151	association	0.530	4
GPIHBP1	association	0.530	1
HFE	association	0.530	1
LDLRAD1	association	0.530	1
PTGFRN	association	0.530	1
TSPAN12	association	0.500	2
BACE1	physical association	0.450	2
ARHGAP32	direct interaction	0.440	1
ARHGAP33	direct interaction	0.440	1
ARHGEF16	direct interaction	0.440	1
ARHGEF19	direct interaction	0.440	1
ARHGEF38	direct interaction	0.440	1
ARHGEF4	direct interaction	0.440	1
CASK	direct interaction	0.440	1
CRK	direct interaction	0.440	1

BioGRID (111 interactions; top human partners by supporting records): TSPAN5 (Affinity Capture-Western; 3 records), MPPE1 (Affinity Capture-MS; 2 records), SLC15A3 (Affinity Capture-MS; 2 records), TAZ (Affinity Capture-MS; 2 records), TMPRSS2 (Affinity Capture-MS; 2 records), TSPAN15 (Affinity Capture-Western; 2 records), ADAM30 (Affinity Capture-MS), ADAM33 (Affinity Capture-MS), ANKH (Affinity Capture-MS), ANPEP (Affinity Capture-MS), APEX1 (Affinity Capture-RNA), ASIC4 (Affinity Capture-MS), B3GALT4 (Affinity Capture-MS), B3GNT2 (Affinity Capture-MS), B3GNT3 (Affinity Capture-MS)

SIGNOR signaling

14 signaling interactions:

A	Effect	B	Mechanism
SP1	“up-regulates quantity by expression”	ADAM10	“transcriptional regulation”
ADAM10	“up-regulates activity”	NOTCH	cleavage
USF1	“up-regulates quantity by expression”	ADAM10	“transcriptional regulation”
ADAM10	“up-regulates activity”	NOTCH1	cleavage
ADAM10	“up-regulates activity”	BTC	cleavage
ADAM10	“up-regulates activity”	EGF	cleavage
ADAM10	“up-regulates activity”	ERBB2	cleavage
ADAM10	“up-regulates activity”	CDH1	cleavage
ADAM10	“up-regulates activity”	CD44	cleavage
ELAVL1	“up-regulates quantity”	ADAM10	“post transcriptional regulation”
ELAVL2	“up-regulates quantity”	ADAM10	“post transcriptional regulation”
ELAVL3	“up-regulates quantity”	ADAM10	“post transcriptional regulation”
ELAVL4	“up-regulates quantity”	ADAM10	“post transcriptional regulation”
TSPAN33	“up-regulates activity”	ADAM10	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Regulation of KIT signaling	5	48.5×	6e-06
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	41.9×	8e-06
Regulation of signaling by CBL	5	40.0×	9e-06
Signaling by CSF1 (M-CSF) in myeloid cells	6	33.5×	3e-06
Co-stimulation by CD28	5	30.7×	2e-05
EPHA-mediated growth cone collapse	5	30.7×	2e-05
Signaling by SCF-KIT	7	28.0×	1e-06
FCGR3A-mediated phagocytosis	8	24.2×	6e-07

GO biological processes:

GO term	Partners	Fold	FDR
plasma membrane tubulation	6	80.2×	4e-08
negative regulation of endocytosis	5	55.7×	5e-06
Fc-gamma receptor signaling pathway involved in phagocytosis	5	41.8×	2e-05
leukocyte migration	5	37.1×	2e-05
negative regulation of inflammatory response to antigenic stimulus	5	35.8×	3e-05
ephrin receptor signaling pathway	8	32.8×	4e-08
positive regulation of actin filament polymerization	5	19.7×	3e-04
regulation of actin cytoskeleton organization	7	13.1×	9e-05

Disease & clinical

Genetic variants

Variant evidence for ADAM10: 146 ClinVar records (13 pathogenic / likely pathogenic); 13 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	1
Uncertain significance	72
Likely benign	13
Benign	31

Top pathogenic / likely-pathogenic (13)

Showing all 13 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
57220	GRCh38/hg38 15q21.3-22.2(chr15:57456076-61907285)x1	Pathogenic	criteria provided, single submitter	1
57881	GRCh38/hg38 15q21.2-22.2(chr15:50864913-59646577)x1	Pathogenic	criteria provided, single submitter	1
1807706	GRCh37/hg19 15q21.1-22.2(chr15:48589845-63543438)x3	Pathogenic	criteria provided, single submitter	1
2685517	GRCh37/hg19 15q21.3-22.2(chr15:54020810-62086530)x1	Pathogenic	criteria provided, single submitter	1
3391925	GRCh37/hg19 15q21.3-22.31(chr15:57544843-64324372)x1	Pathogenic	criteria provided, single submitter	1
88840	NM_001110.4(ADAM10):c.1511G>A (p.Ser504Asn)	Pathogenic	no assertion criteria provided	1
88841	NM_001110.4(ADAM10):c.429T>A (p.Tyr143Ter)	Pathogenic	no assertion criteria provided	1
88842	NM_001110.4(ADAM10):c.1264del (p.Thr422fs)	Pathogenic	no assertion criteria provided	1
88843	NM_001110.4(ADAM10):c.1571G>A (p.Cys524Tyr)	Pathogenic	no assertion criteria provided	1
395193	GRCh37/hg19 15q21.3-22.2(chr15:54713558-62769295)x1	Pathogenic	no assertion criteria provided	1
442636	GRCh37/hg19 15q21.3-22.2(chr15:58088503-62221756)x1	Pathogenic	no assertion criteria provided	1
685183	GRCh37/hg19 15q21.1-22.2(chr15:48000433-60747551)x3	Pathogenic	no assertion criteria provided	1
442376	GRCh37/hg19 15q21.3(chr15:57518653-58974175)x3	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ADAM10’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; 34 predictions of 2,001):

Position(s)	Effect	Δscore	Sites
15:58621469–58621470	donor_loss	1.0000	5
15:58621473	donor_gain	1.0000
15:58621507	donor_gain	1.0000
15:58621622–58621623	acceptor_loss	1.0000	5
15:58621631	acceptor_gain	1.0000
15:58633194–58633195	donor_loss	1.0000	5
15:58633360–58633361	acceptor_loss	1.0000	5
15:58633366–58633367	acceptor_gain	1.0000	2
15:58640775–58640776	donor_loss	1.0000	4
15:58640961–58640962	acceptor_loss	1.0000	5

AlphaMissense

2,650 missense substitutions predicted likely pathogenic (of 4,980 scored), across 531 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
M417	9	0.997	1.000
M182	9	0.973	0.999
M692	9	0.961	1.000
H383	8	1.000	1.000
H387	8	1.000	1.000
H393	8	1.000	1.000
D229	8	0.999	1.000
N359	8	0.999	1.000
D394	8	0.999	1.000
D472	8	0.999	1.000
D640	8	0.998	1.000
F323	8	0.995	1.000
N429	8	0.995	1.000
F432	8	0.995	1.000
F262	8	0.994	1.000
F389	8	0.994	0.999
F452	8	0.994	1.000
N462	8	0.994	0.999
F318	8	0.993	0.999
S436	8	0.993	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.99e-06
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000206
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000394
Lung Adenocarcinoma (TCGA)	unfavorable	0.000944

Disease associations

OMIM: gene MIM:602192 | disease phenotypes: MIM:615537

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
reticulate acropigmentation of Kitamura	Strong	Autosomal dominant	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Pigmentary skin disorders	green

Mondo (1): reticulate acropigmentation of Kitamura (MONDO:0014234)

Orphanet (1): Reticulate acropigmentation of Kitamura (Orphanet:178307)

HPO phenotypes

5 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000962	Hyperkeratosis
HP:0003621	Juvenile onset
HP:0011463	Childhood onset
HP:0012733	Macule

GWAS associations

13 associations:

Study	Trait	p-value
GCST010241_126	Apolipoprotein A1 levels	1e-12
GCST009391_1082	Metabolite levels	4e-12
GCST90012877_6	Alzheimer’s disease or family history of Alzheimer’s disease	3e-11
GCST007320_73	Alzheimer’s disease or family history of Alzheimer’s disease	1e-9
GCST007511_2	Alzheimer’s disease (late onset)	7e-9
GCST007576_197	Chronotype	1e-8
GCST007201_66	Schizophrenia	4e-8
GCST007321_8	Family history of Alzheimer’s disease	3e-7
GCST007637_3	Diffusing capacity of carbon monoxide	4e-6
GCST90012877_5	Alzheimer’s disease or family history of Alzheimer’s disease	4e-6
GCST009391_1099	Metabolite levels	5e-6
GCST011065_10	Levodopa-induced dyskinesia in levodopa treated Parkinson’s disease	7e-6
GCST007201_409	Schizophrenia	8e-6

EFO canonical traits (from GWAS)

8 canonical traits:

EFO ID	Trait name
EFO:0009268	family history of Alzheimer’s disease
EFO:1001870	late-onset Alzheimers disease
EFO:0008328	chronotype measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0010366	lysophosphatidylethanolamine 16:0 measurement
EFO:0010367	lysophosphatidylethanolamine 18:0 measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0010747	response to levodopa

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5028 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,457 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL206815	APRATASTAT	2	271
CHEMBL19611	ILOMASTAT	2	12,186

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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
ilomastat	Inhibition	8.09	pIC50
compound 25 [PMID: 18068976]	Inhibition	7.8	pIC50
GI254023X	Inhibition	5.28	pIC50

Binding affinities (BindingDB)

570 measured of 649 human assays (673 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(R)-N*4*-Hydroxy-N*1*-[2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide	IC50	0.104 nM
marimastat	IC50	0.41 nM
CHEMBL4078433	IC50	2 nM
CHEMBL1229516	IC50	2.1 nM
(S)-tetrahydrofuran-3-yl 4-(hydroxycarbamoyl)-4-((4-phenyl-5,6-dihydropyridin-1(2H)-ylsulfonyl)methyl)piperidine-1-carboxylate	IC50	4 nM
(R)-2-(4-(but-2-ynyloxy)phenylsulfonamido)-4-(1,3-dioxoisoindolin-2-yl)-N-hydroxybutanamide	IC50	4.2 nM
(6S,7S)-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	5 nM
CHEMBL4435465	IC50	5.3 nM
CHEMBL5206579	IC50	5.3 nM
Grassystatin B	IC50	7.3 nM
TMI-05	IC50	8 nM
(2S,3S,5RS)-N-hydroxy-5-(2-oxo-2-(pyrrolidin-1-yl)ethyl)-2-(4-phenylpiperazine-1-carbonyl)piperidine-3-carboxamide	IC50	8 nM
(S)-tetrahydrofuran-3-yl 4-((4-(4-cyanophenyl)piperidin-1-ylsulfonyl)methyl)-4-(hydroxycarbamoyl)piperidine-1-carboxylate	IC50	9 nM
(2S,3S)-N-hydroxy-5-(N-methylisobutyramido)-2-(4-phenyl-1,2,3,6-tetrahydropyridine-1-carbonyl)piperidine-3-carboxamide	IC50	11 nM
isopropyl-(5S,6S)-5-(hydroxycarbamoyl)-6-(4-phenyl-1,2,3,6-tetrahydropyridine-1-carbonyl)piperidin-3-yl(methyl)carbamate	IC50	11 nM
CGS 27023	IC50	11 nM
(2S,3S)-N-hydroxy-5-(N-methylbenzamido)-2-(4-phenyl-1,2,3,6-tetrahydropyridine-1-carbonyl)piperidine-3-carboxamide	IC50	12 nM
(6S,7S)-N-hydroxy-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide	IC50	13 nM
(6S,7S)-6-(4-m-tolyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	13 nM
(S)-tetrahydrofuran-3-yl 4-(hydroxycarbamoyl)-4-((4-phenylpiperazin-1-ylsulfonyl)methyl)piperidine-1-carboxylate	IC50	13 nM
(6S,7S)-6-[4-(3,5-difluoro-phenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	14 nM
(2S,3S)-N-hydroxy-5-(2-oxo-2-(pyrrolidin-1-yl)ethyl)-2-(4-phenyl-1,2,3,6-tetrahydropyridine-1-carbonyl)piperidine-3-carboxamide	IC50	17 nM
(R)-benzyl 3-(4-(but-2-ynyloxy)phenylsulfonamido)-4-(hydroxyamino)-4-oxobutylcarbamate	IC50	17 nM
(S)-tetrahydrofuran-3-yl 4-(hydroxycarbamoyl)-4-((4-phenylpiperidin-1-ylsulfonyl)methyl)piperidine-1-carboxylate	IC50	18 nM
(6S,7S)-6-[4-(3-ethyl-phenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	21 nM
(R)-2-(4-(but-2-ynyloxy)-N-isobutylphenylsulfonamido)-4-(1,3-dioxoisoindolin-2-yl)-N-hydroxybutanamide	IC50	21 nM
(6S,7S)-6-[4-(3-cyclopropyl-phenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	24 nM
(6S,7S)-6-[4-(3-chloro-phenyl)-piperazine-1-carbonyl]-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	32 nM
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
(6S,7S)-7-hydroxycarbamoyl-6-(4-phenyl-3,4-dihydro-2H-pyridine-1-carbonyl)-5-aza-spiro[2.5]octane-5-carboxylic acid isobutyl ester	IC50	35 nM
(6S,7S)-7-hydroxycarbamoyl-6-(4-phenyl-3,4-dihydro-2H-pyridine-1-carbonyl)-5-aza-spiro[2.5]octane-5-carboxylic acid benzyl ester	IC50	37 nM
(6S,7S)-7-hydroxycarbamoyl-6-(4-phenyl-3,4-dihydro-2H-pyridine-1-carbonyl)-5-aza-spiro[2.5]octane-5-carboxylic acid methyl ester	IC50	39 nM
(6S,7S)-6-[4-(3-methoxy-phenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	50 nM
(6S,7S)-5-acetyl-6-(4-phenyl-3,4-dihydro-2H-pyridine-1-carbonyl)-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	50 nM
(S)-tetrahydrofuran-3-yl 4-(hydroxycarbamoyl)-4-((3-phenyl-2H-pyrrol-1(5H)-ylsulfonyl)methyl)piperidine-1-carboxylate	IC50	52 nM
(6S,7S)-5-methanesulfonyl-6-(4-phenyl-3,4-dihydro-2H-pyridine-1-carbonyl)-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	53 nM
(6S,7S)-6-(4-m-tolyl-piperazine-1-carbonyl)-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	63 nM
(6S,7S)-N-hydroxy-5-methyl-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide	IC50	64 nM
(1S,2S,5RS)-N-hydroxy-5-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)-2-(4-phenylpiperazine-1-carbonyl)cyclohexanecarboxamide	IC50	68 nM
N-hydroxy-4-[4-(4-hydroxybut-2-ynoxy)phenyl]sulfonyl-2,2-dimethylthiomorpholine-3-carboxamide	IC50	71 nM	US-9115102: N-[2-hydroxycarbamoyl-2-(piperazinyl) ethyl] benzamide compounds, their preparation and their use as TACE inhibitors
(3R,5S,6S)-5-(hydroxycarbamoyl)-6-(4-phenyl-1,2,3,6-tetrahydropyridine-1-carbonyl)piperidin-3-yl pyrrolidine-1-carboxylate	IC50	78 nM
(2S,3S,5RS)-N-hydroxy-1-methyl-5-(2-oxo-2-(piperidin-1-yl)ethyl)-2-(4-phenylpiperazine-1-carbonyl)piperidine-3-carboxamide	IC50	81 nM
(6S,7S)-5-methanesulfonyl-6-(4-phenyl-piperazine-1-carbonyl)-5-aza-spiro[2.5]octane-7-carboxylic acid hydroxyamide	IC50	86 nM
(2S,3S,5RS)-N-hydroxy-1-methyl-5-(2-oxo-2-(pyrrolidin-1-yl)ethyl)-2-(4-phenylpiperazine-1-carbonyl)piperidine-3-carboxamide	IC50	92 nM
(2R,3S)-2-(4-(but-2-ynyloxy)phenylsulfonamido)-N,3-dihydroxybutanamide	IC50	96 nM
(1S,2S,5S)-N-hydroxy-5-(2-oxo-2-(piperidin-1-yl)ethyl)-2-(4-phenylpiperazine-1-carbonyl)cyclohexanecarboxamide	IC50	100 nM
(5S,6S)-5-(hydroxycarbamoyl)-6-(4-phenyl-1,2,3,6-tetrahydropyridine-1-carbonyl)piperidin-3-yl pyrrolidine-1-carboxylate	IC50	102 nM
(5S,6S)-5-(hydroxycarbamoyl)-6-(4-phenylpiperidine-1-carbonyl)piperidin-3-yl pyrrolidine-1-carboxylate	IC50	102 nM
(6S,7S)-7-hydroxycarbamoyl-6-(4-phenyl-piperazine-1-carbonyl)-5-aza-spiro[2.5]octane-5-carboxylic acid tetrahydro-pyran-4-yl ester	IC50	106 nM
(5S,6S)-N-hydroxy-6-(4-phenylpiperazine-1-carbonyl)spiro[2.5]octane-5-carboxamide	IC50	106 nM

ChEMBL bioactivities

248 potent at pChembl≥5 of 267 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.28	IC50	5.3	nM	CHEMBL4435465
8.28	IC50	5.3	nM	CHEMBL5206579
8.21	IC50	6.2	nM	CHEMBL442432
8.19	IC50	6.5	nM	CHEMBL253021
8.15	IC50	7.1	nM	CHEMBL251820
8.11	IC50	7.8	nM	CHEMBL400528
8.09	IC50	8.1	nM	ILOMASTAT
8.05	IC50	9	nM	CHEMBL569388
8.04	IC50	9.2	nM	CHEMBL3770688
8.04	IC50	9.1	nM	CHEMBL253021
8.02	IC50	9.6	nM	CHEMBL584116
8.00	IC50	10	nM	CHEMBL251820
7.96	IC50	11	nM	CHEMBL253230
7.96	IC50	11	nM	CHEMBL254492
7.96	IC50	11	nM	CHEMBL572301
7.96	IC50	11	nM	CHEMBL566233
7.92	IC50	12	nM	CHEMBL253665
7.92	IC50	12	nM	CHEMBL570760
7.89	IC50	13	nM	CHEMBL375418
7.89	IC50	13	nM	CHEMBL400528
7.89	IC50	13	nM	CHEMBL399351
7.85	IC50	14	nM	CHEMBL251847
7.85	IC50	14	nM	CHEMBL439405
7.85	IC50	14	nM	CHEMBL253665
7.85	IC50	14	nM	CHEMBL576061
7.82	IC50	15	nM	CHEMBL253920
7.82	IC50	15	nM	CHEMBL399351
7.82	IC50	15	nM	CHEMBL496628
7.80	IC50	16	nM	CHEMBL253460
7.80	IC50	16	nM	CHEMBL252612
7.80	IC50	16	nM	CHEMBL442432
7.77	IC50	17	nM	CHEMBL569166
7.75	IC50	18	nM	CHEMBL373532
7.75	IC50	18	nM	CHEMBL252612
7.75	IC50	18	nM	CHEMBL252023
7.75	IC50	18	nM	CHEMBL253035
7.75	IC50	18	nM	CHEMBL585299
7.72	IC50	19	nM	CHEMBL442443
7.72	IC50	19	nM	CHEMBL403185
7.72	IC50	19	nM	CHEMBL398743
7.72	IC50	19	nM	CHEMBL253020
7.72	IC50	19	nM	CHEMBL495596
7.70	IC50	20	nM	CHEMBL585886
7.70	IC50	20	nM	CHEMBL584334
7.68	IC50	21	nM	CHEMBL496829
7.66	IC50	22	nM	CHEMBL434567
7.66	IC50	22	nM	CHEMBL404409
7.66	IC50	22	nM	CHEMBL439405
7.66	IC50	22	nM	CHEMBL1287851
7.64	IC50	23	nM	CHEMBL375418

PubChem BioAssay actives

238 with measured affinity, of 355 total; 50 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)-2-[(1S)-1-[acetyl(hydroxy)amino]ethyl]-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-5-phenylpentanamide	1628279: Inhibition of ADAM10 (unknown origin) assessed as blockage of TNF-alpha shedding	ic50	0.0053	uM
N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-5-phenylpentanamide	1895849: Inhibition of human ADAM10 using (biotin-SPLAQAVRSSSRTP(3H)S-NH2) as a substrate by streptavidin-coated scintillation proximity assay	ic50	0.0053	uM
(2-hydroxycyclopentyl) 4-(hydroxycarbamoyl)-4-[[4-(2-methylphenyl)piperidin-1-yl]sulfonylmethyl]piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0062	uM
[(2S)-pyrrolidin-2-yl]methyl 4-[[4-(4-cyano-2-methylphenyl)piperidin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0065	uM
[(3S)-oxolan-3-yl] 4-(hydroxycarbamoyl)-4-[(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)sulfonylmethyl]piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0071	uM
pyrrolidin-3-yl 4-[[4-(4-cyano-2-methylphenyl)piperidin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate	313836: Inhibition of ADAM10	ic50	0.0078	uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	241679: In vitro inhibition of A disintegrin and metalloprotease domain 10 (ADAM10)	ic50	0.0081	uM
[(5S,6S)-5-(hydroxycarbamoyl)-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)piperidin-3-yl] pyrrolidine-1-carboxylate	447376: Inhibition of ADAM-10	ic50	0.0090	uM
benzyl N-[(4R)-4-[[4-(4-cyano-2-methylphenyl)piperazin-1-yl]sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]carbamate	1281791: Inhibition of recombinant human ADAM-10 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate after 1 hr by fluorometric assay	ic50	0.0092	uM
[(3S,5S,6S)-5-(hydroxycarbamoyl)-1-methyl-6-(4-phenylpiperazine-1-carbonyl)piperidin-3-yl] piperidine-1-carboxylate	447376: Inhibition of ADAM-10	ic50	0.0096	uM
(3-methyloxolan-3-yl) 4-(hydroxycarbamoyl)-4-[[4-(2-methylphenyl)piperidin-1-yl]sulfonylmethyl]piperidine-1-carboxylate	313836: Inhibition of ADAM10	ic50	0.0110	uM
[(2R)-pyrrolidin-2-yl]methyl 4-[[4-(4-cyano-2-methylphenyl)piperidin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate	313836: Inhibition of ADAM10	ic50	0.0110	uM
propan-2-yl N-[(5S,6S)-5-(hydroxycarbamoyl)-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)piperidin-3-yl]-N-methylcarbamate	447376: Inhibition of ADAM-10	ic50	0.0110	uM
[(3S,5S,6S)-5-(hydroxycarbamoyl)-6-(4-phenylpiperazine-1-carbonyl)piperidin-3-yl] pyrrolidine-1-carboxylate	447376: Inhibition of ADAM-10	ic50	0.0110	uM
[(3S)-oxolan-3-yl] 4-[[4-(4-cyano-2-methylphenyl)piperidin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate	313836: Inhibition of ADAM10	ic50	0.0120	uM
(2S,3S)-5-[benzoyl(methyl)amino]-N-hydroxy-2-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)piperidine-3-carboxamide	447376: Inhibition of ADAM-10	ic50	0.0120	uM
(6S,7S)-N-hydroxy-6-(3-phenyl-2,5-dihydropyrrole-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide	313636: Inhibition of HER2 sheddase in BT474 cells by extracellular domain shedding assay	ic50	0.0130	uM
[(3S)-oxolan-3-yl] 4-(hydroxycarbamoyl)-4-[(4-phenylpiperazin-1-yl)sulfonylmethyl]piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0130	uM
(4,4-dimethyloxolan-3-yl) 4-(hydroxycarbamoyl)-4-[[4-(2-methylphenyl)piperidin-1-yl]sulfonylmethyl]piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0140	uM
(6S,7S)-6-[4-(3-chlorophenyl)piperazine-1-carbonyl]-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide	313637: Binding affinity to ADAM10	ic50	0.0140	uM
(2S,3S)-N-hydroxy-5-(2-oxo-2-pyrrolidin-1-ylethyl)-2-[(3R)-3-phenylpyrrolidine-1-carbonyl]piperidine-3-carboxamide	447376: Inhibition of ADAM-10	ic50	0.0140	uM
(6S,7S)-6-[4-(3,5-difluorophenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide	313637: Binding affinity to ADAM10	ic50	0.0150	uM
(1S,2S,5S)-N-hydroxy-5-(2-oxo-2-piperidin-1-ylethyl)-2-(4-phenylpiperazine-1-carbonyl)cyclohexane-1-carboxamide	375733: Inhibition of human recombinant ADAM10	ic50	0.0150	uM
pyrrolidin-3-yl 4-(hydroxycarbamoyl)-4-[[4-(2-methylphenyl)piperidin-1-yl]sulfonylmethyl]piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0160	uM
(6S,7S)-N-hydroxy-6-[4-(3-propan-2-ylphenyl)piperidine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide	313637: Binding affinity to ADAM10	ic50	0.0160	uM
(2S,3S)-N-hydroxy-5-(2-oxo-2-pyrrolidin-1-ylethyl)-2-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)piperidine-3-carboxamide	447376: Inhibition of ADAM-10	ic50	0.0170	uM
[(3S)-oxolan-3-yl] 4-(hydroxycarbamoyl)-4-[[4-(2-methylphenyl)piperidin-1-yl]sulfonylmethyl]piperidine-1-carboxylate	313836: Inhibition of ADAM10	ic50	0.0180	uM
[(3S)-oxolan-3-yl] 4-(hydroxycarbamoyl)-4-[[4-(2-methylphenyl)-3,6-dihydro-2H-pyridin-1-yl]sulfonylmethyl]piperidine-1-carboxylate	313836: Inhibition of ADAM10	ic50	0.0180	uM
(6S,7S)-N-hydroxy-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide	313636: Inhibition of HER2 sheddase in BT474 cells by extracellular domain shedding assay	ic50	0.0180	uM
[(3S,5S,6S)-5-(hydroxycarbamoyl)-1-methyl-6-(4-phenylpiperazine-1-carbonyl)piperidin-3-yl] pyrrolidine-1-carboxylate	447376: Inhibition of ADAM-10	ic50	0.0180	uM
[(2R)-pyrrolidin-2-yl]methyl 4-[[4-(4-cyano-2-methylphenyl)-3,6-dihydro-2H-pyridin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0190	uM
2-methylpropyl (6S,7S)-7-(hydroxycarbamoyl)-6-(4-phenyl-3,4-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate	313637: Binding affinity to ADAM10	ic50	0.0190	uM
methyl (6S,7S)-7-(hydroxycarbamoyl)-6-(4-phenylpiperidine-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate	313637: Binding affinity to ADAM10	ic50	0.0190	uM
[(2R)-pyrrolidin-2-yl]methyl 4-(hydroxycarbamoyl)-4-[[4-(2-methylphenyl)piperidin-1-yl]sulfonylmethyl]piperidine-1-carboxylate	313836: Inhibition of ADAM10	ic50	0.0190	uM
(2S,3S)-N-hydroxy-5-(2-oxo-2-pyrrolidin-1-ylethyl)-2-(4-phenylpiperazine-1-carbonyl)piperidine-3-carboxamide	375733: Inhibition of human recombinant ADAM10	ic50	0.0190	uM
[(3S,5S,6S)-5-(hydroxycarbamoyl)-1-methyl-6-(4-phenylpiperazine-1-carbonyl)piperidin-3-yl] azetidine-1-carboxylate	447376: Inhibition of ADAM-10	ic50	0.0200	uM
methyl (2S,3S,5S)-3-(hydroxycarbamoyl)-2-(4-phenylpiperazine-1-carbonyl)-5-(pyrrolidine-1-carbonyloxy)piperidine-1-carboxylate	447376: Inhibition of ADAM-10	ic50	0.0200	uM
(1S,2S,5S)-N-hydroxy-5-(2-oxo-2-piperidin-1-ylethyl)-2-[4-(3-propan-2-ylphenyl)piperidine-1-carbonyl]cyclohexane-1-carboxamide	375733: Inhibition of human recombinant ADAM10	ic50	0.0210	uM
[(3S)-oxolan-3-yl] 4-(hydroxycarbamoyl)-4-[(4-phenylpiperidin-1-yl)sulfonylmethyl]piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0220	uM
methyl (6S,7S)-7-(hydroxycarbamoyl)-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate	1235676: Inhibition of human ADAM10	ic50	0.0220	uM
(5R)-5-[(5-methoxy-3-oxo-1H-isoindol-2-yl)methyl]-5-(2-pyridin-3-ylethynyl)imidazolidine-2,4-dione	538184: Inhibition of ADAM10	ic50	0.0220	uM
[(2S)-pyrrolidin-2-yl]methyl 4-(hydroxycarbamoyl)-4-[[4-(2-methylphenyl)piperidin-1-yl]sulfonylmethyl]piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0230	uM
(2S,3S)-N-hydroxy-5-[methyl(2-methylpropanoyl)amino]-2-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)piperidine-3-carboxamide	447376: Inhibition of ADAM-10	ic50	0.0230	uM
[(3S)-oxolan-3-yl] 4-[[4-(4-cyano-2-methylphenyl)piperazin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0250	uM
(6S,7S)-N-hydroxy-6-[4-(3-methylphenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2.5]octane-7-carboxamide	313637: Binding affinity to ADAM10	ic50	0.0250	uM
methyl (6S,7S)-7-(hydroxycarbamoyl)-6-(3-phenyl-2,5-dihydropyrrole-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate	313637: Binding affinity to ADAM10	ic50	0.0260	uM
oxan-4-yl (6S,7S)-7-(hydroxycarbamoyl)-6-(4-phenylpiperazine-1-carbonyl)-5-azaspiro[2.5]octane-5-carboxylate	313636: Inhibition of HER2 sheddase in BT474 cells by extracellular domain shedding assay	ic50	0.0260	uM
[(3R)-oxolan-3-yl] 4-[[4-(4-cyano-2-methylphenyl)piperazin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate	344625: Inhibition of ADAM10	ic50	0.0260	uM
[(3S,5S,6S)-5-(hydroxycarbamoyl)-1-methyl-6-(4-phenylpiperazine-1-carbonyl)piperidin-3-yl] azocane-1-carboxylate	447376: Inhibition of ADAM-10	ic50	0.0260	uM
[(2S)-pyrrolidin-2-yl]methyl 4-[[4-(4-cyano-2-methylphenyl)-3,6-dihydro-2H-pyridin-1-yl]sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate	313835: Inhibition of HER2 sheddase in human BT474 cells	ic50	0.0270	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects localization, increases expression	4
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression, increases expression	4
Air Pollutants	decreases expression, increases abundance, increases expression	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
sodium arsenite	affects methylation, decreases expression	2
cobaltous chloride	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	increases expression, affects cotreatment	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
enzalutamide	affects expression	1
picoxystrobin	decreases expression	1
Bortezomib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Antimycin A	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Biological Products	decreases expression	1
Cadmium	increases abundance, increases palmitoylation, decreases reaction	1

ChEMBL screening assays

64 unique, capped per target: 60 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001997	Binding	Inhibition of ADAM10	Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3’ pocket. — *Bioorg Med Chem Lett*
CHEMBL4018054	ADMET	Inhibition of recombinant human C-terminal His10-tagged ADAM10 expressed in baculovirus infected Sf21 cells using Abz-LANAVRSSSR-(DapDnp)-NH2 as substrate by fluorescence assay	First insight into structure-activity relationships of selective meprin β inhibitors. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

12 cell lines: 7 cancer cell line, 5 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B8AW	Abcam HCT 116 ADAM10 KO	Cancer cell line	Male
CVCL_B8S6	Abcam MCF-7 ADAM10 KO	Cancer cell line	Female
CVCL_B9CY	Abcam A-549 ADAM10 KO	Cancer cell line	Male
CVCL_D1RH	Abcam U-87MG ADAM10 KO	Cancer cell line	Male
CVCL_D7JJ	Ubigene A-549 ADAM10 KO	Cancer cell line	Male
CVCL_E4TR	KOLF2.1J ADAM10 PTC PTC/PTC	Induced pluripotent stem cell	Male
CVCL_E7JF	KOLF2.1J ADAM10 Q170H SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7JG	KOLF2.1J ADAM10 Q170H SNV/WT	Induced pluripotent stem cell	Male
CVCL_E7JI	KOLF2.1J ADAM10 R181G SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7JJ	KOLF2.1J ADAM10 R181G SNV/WT	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

22 trials:

NCT	Phase	Status	Title
NCT00273897	Phase 2	COMPLETED	Electrical Polarization of the Brain in Corticobasal Syndrome
NCT04734379	Phase 2	UNKNOWN	Rho Kinase (ROCK) Inhibitor in Tauopathies - 1
NCT05983588	Phase 2	COMPLETED	PROFIL Study to Investigate the Effect of GPB on NfL Levels in Patients With Corticobasal Syndrome (CBS)
NCT06162013	Phase 2	RECRUITING	The NADAPT Study: a Randomized Double-blind Trial of NAD Replenishment Therapy for Atypical Parkinsonism
NCT02133846	Phase 1	COMPLETED	Safety Study of TPI-287 to Treat CBS and PSP
NCT04100889	Not specified	WITHDRAWN	A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Alzheimer’s Disease
NCT05637801	Not specified	COMPLETED	A Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (HOPE Study)
NCT02365922	Not specified	COMPLETED	Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)
NCT02964637	Not specified	RECRUITING	Diagnosing Frontotemporal Lobar Degeneration
NCT02966145	Not specified	COMPLETED	4-Repeat Tauopathy Neuroimaging Initiative - Cycle 2
NCT03552484	Not specified	COMPLETED	In-Home Care for Patients With PSP and Related Disorders
NCT04715399	Not specified	RECRUITING	UPenn Observational Research Repository on Neurodegenerative Disease
NCT05073471	Not specified	ACTIVE_NOT_RECRUITING	Music and Brain Stimulation for Upper Extremity Performance in Patients With Corticobasal Syndrome
NCT05653778	Not specified	RECRUITING	Scrambler Therapy for Corticobasal Syndrome-Associated Pain
NCT06224920	Not specified	COMPLETED	Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer’s Disease
NCT06529744	Not specified	RECRUITING	Improving Prognostic Confidence in Neurodegenerative Diseases Causing Dementia Using Peripheral Biomarkers and Integrative Modeling
NCT06613204	Not specified	RECRUITING	STELLA-FTD: Examination of a Behavior Change Intervention for FTD Family Care Partners
NCT06647641	Not specified	RECRUITING	The CurePSP Genetics Program
NCT06870838	Not specified	ACTIVE_NOT_RECRUITING	Neuroinflammation in FTLD
NCT07000851	Not specified	RECRUITING	Imaging Studies in Corticobasal Syndrome
NCT07333898	Not specified	NOT_YET_RECRUITING	Digital Measurements of Motor and Voice Functions in FTD
NCT07569367	Not specified	NOT_YET_RECRUITING	A Wearable Sensor Platform for Remote Monitoring of Individuals on the Frontotemporal Dementia Spectrum

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ADAM10 across ~30M SureChEMBL compounds — explore on Sugi Predict.