PADI2

Summary

PADI2 (peptidyl arginine deiminase 2, HGNC:18341) is a protein-coding gene on chromosome 1p36.13, encoding Protein-arginine deiminase type-2 (Q9Y2J8). Catalyzes the deimination of arginine residues of proteins.

This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. The type II enzyme is the most widely expressed family member. Known substrates for this enzyme include myelin basic protein in the central nervous system and vimentin in skeletal muscle and macrophages. This enzyme is thought to play a role in the onset and progression of neurodegenerative human disorders, including Alzheimer disease and multiple sclerosis, and it has also been implicated in glaucoma pathogenesis. This gene exists in a cluster with four other paralogous genes.

Source: NCBI Gene 11240 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 120 total
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007365

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18341
Approved symbol	PADI2
Name	peptidyl arginine deiminase 2
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0994, PDI2
Ensembl gene	ENSG00000117115
Ensembl biotype	protein_coding
OMIM	607935
Entrez	11240

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000375481, ENST00000375486, ENST00000466151, ENST00000479534, ENST00000908715, ENST00000908716, ENST00000908717, ENST00000908718, ENST00000908719, ENST00000922909, ENST00000945841

RefSeq mRNA: 1 — MANE Select: NM_007365 NM_007365

CCDS: CCDS177

Canonical transcript exons

ENST00000375486 — 16 exons

Exon	Start	End
ENSE00000753361	17104878	17105061
ENSE00000753362	17102987	17103059
ENSE00000753363	17095909	17095970
ENSE00000753365	17092408	17092533
ENSE00000753367	17084599	17084702
ENSE00000753368	17083726	17083837
ENSE00000753373	17074856	17074949
ENSE00000855565	17093567	17093684
ENSE00000855570	17082545	17082652
ENSE00001467224	17066761	17069277
ENSE00001691404	17075679	17075823
ENSE00003491056	17071406	17071491
ENSE00003527847	17070088	17070216
ENSE00003597492	17079264	17079415
ENSE00003692176	17086521	17086699
ENSE00003849568	17119280	17119451

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 99.32.

FANTOM5 (CAGE): breadth broad, TPM avg 20.7159 / max 2528.7177, expressed in 781 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10575	20.7132	781
10573	0.0027	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	99.32	gold quality
globus pallidus	UBERON:0001875	98.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.79	gold quality
spinal cord	UBERON:0002240	98.67	gold quality
gluteal muscle	UBERON:0002000	98.63	gold quality
inferior olivary complex	UBERON:0002127	98.52	gold quality
inferior vagus X ganglion	UBERON:0005363	98.20	gold quality
middle frontal gyrus	UBERON:0002702	97.94	gold quality
lateral globus pallidus	UBERON:0002476	97.92	gold quality
subthalamic nucleus	UBERON:0001906	97.81	gold quality
medulla oblongata	UBERON:0001896	97.74	gold quality
gastrocnemius	UBERON:0001388	97.72	gold quality
tibialis anterior	UBERON:0001385	97.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.32	gold quality
mucosa of transverse colon	UBERON:0004991	97.32	gold quality
cranial nerve II	UBERON:0000941	97.28	gold quality
ventral tegmental area	UBERON:0002691	97.26	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.21	gold quality
midbrain	UBERON:0001891	97.20	gold quality
substantia nigra	UBERON:0002038	97.19	gold quality
substantia nigra pars compacta	UBERON:0001965	97.11	gold quality
quadriceps femoris	UBERON:0001377	97.02	gold quality
deltoid	UBERON:0001476	97.02	gold quality
corpus callosum	UBERON:0002336	97.00	gold quality
rectum	UBERON:0001052	96.99	gold quality
vastus lateralis	UBERON:0001379	96.99	gold quality
skeletal muscle tissue	UBERON:0001134	96.97	gold quality
colonic mucosa	UBERON:0000317	96.94	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.72	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	24.84
E-HCAD-25	yes	14.44
E-MTAB-9067	yes	11.38
E-ANND-3	yes	8.11
E-MTAB-9801	yes	7.83
E-CURD-11	no	124.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

miRNA regulators (miRDB)

119 targeting PADI2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6756-5P	99.82	67.97	2466

Literature-anchored findings (GeneRIF, showing 40)

• molecular cloning and gene organization; expressed by all the living epidermal layers, suggesting that PAD type II is functionally important during terminal differentiation of epidermal keratinocytes (PMID:12392711)
• first report to demonstrate a measurable response in the amounts of peptidylarginine deiminase type II mRNA, protein and activity in human astrocytes by prolonged hypoxic exposure (PMID:15555572)
• hPADI2 and hPADI4 have different roles under physiological and pathological conditions (PMID:15629448)
• The amount of peptidyl arginine deiminase type II enzyme and citrullinated myelin basic protein was increased in multiple sclerosis (PMID:17469138)
• PAD-2 & PAD-4 are only isotypes expressed in synovial tissue in rheumatoid arthritis & other arthritides; inflammatory cells are major source, but PAD-4 also comes from hyperplastic synoviocytes; both isotypes probably involved in citrullination of fibrin (PMID:17968929)
• These data provide new structure-function dimensions for chemokines in leukocyte mobilization, disclosing an anti-inflammatory role for PAD. (PMID:18645041)
• The citrullinating enzyme PAD-4 was detected in synovial fluid from patients with rheumatoid arthritis and spondylarthritides. (PMID:18668562)
• Results describe the in vitro kinetic properties of the human peptidylarginine deiminase isoform 2 (hPAD2), and explore the putative inhibitory action of the methyl ester side chain of paclitaxel. (PMID:18923545)
• PADI2 does not contribute to genetic susceptibility to schizophrenia. (PMID:19478818)
• PAD2 is expressed in human monocytic leukaemia THP-1 cells during differentiation into macrophages (PMID:19564157)
• PAD2 activation and aberrant citrullinated proteins could play a role in pathogenesis and have value as a marker for the postmortem classification of neurodegenerative diseases. (PMID:20013286)
• This is the first report demonstrating that like in primary open angle glaucoma, normal tension glaucoma also possesses elevated levels of both PAD2 and protein-bound citrulline. (PMID:20806090)
• Defective regulation of PAD2 in the periphery blood, without the immunological shelter of the blood-brain barrier, may contribute to the development of the autoimmune responses in MS. (PMID:21878453)
• Normal human and canine mammary epithelium showed strong cytoplasmic and nuclear expression of PAD2, but there was reduced PAD2 expression in mammary carcinomas from both species. (PMID:22520816)
• Contact between stimulated T cells and monocyte-macrophages or cytokine-activated monocyte-macrophages constitutes a highly likely source of PAD2 and PAD4, which are observed in inflamed synovial tissues. (PMID:22614825)
• 17beta-estradiol stimulation induces the recruitment of PAD2 to target promoters by ERalpha, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation. (PMID:22853951)
• PAD2 binds directly to the promoters of the PTN and MAGEA12 genes and that the likely mechanism by which PAD2 regulates expression of these genes is via citrullination of arginine residues 2-8-17 on histone H3 tails. (PMID:22911765)
• These findings suggest that PAD2 and citrullinated proteins may play a key role in the brain pathology of prion diseases. [review] (PMID:23022892)
• Our observations show increased levels of protein deimination but not PAD2 in age related macular degeneration retinas and retinal pigment epithelium suggesting reduced rate of turnover of deiminated proteins. (PMID:23562679)
• Data suggest peptidylarginine deiminase 2 (PAD2) as a possible biomarker in various inflammatory diseases. (PMID:24384061)
• PAD2 and PAD4 have distinct substrate specificities. (PMID:24594197)
• PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. (PMID:24850148)
• PAD2 appears to use a substrate-assisted mechanism of catalysis in which the positively charged substrate guanidinium depresses the pKa of the nucleophilic cysteine (PMID:24989433)
• these studies provide the first genetic evidence that PAD2 functions as an oncogene and suggest that PAD2 may promote tumor progression by enhancing inflammation within the tumor microenvironment. (PMID:25213324)
• PAD2 activity was detected in synovial fluid samples from patients with rheumatoid arthritis. (PMID:25475141)
• Protein arginine deiminase 2 binds six calcium ions in an ordered fashion. (PMID:25621824)
• Report increased levels of extracellular PAD2 in the lungs of smokers. (PMID:25897949)
• PAD2 activity was significantly higher in cell-free synovial fluid of rheumatoid arthritis patients compared to osteoarthritis patients. (PMID:26245941)
• We identified the presence of PADI3 mRNA expression in synovial tissue and PADI2 and PADI4 mRNA expressions in fibroblast-like synoviocytes from patients with rheumatoid arthritis. (PMID:26255191)
• this study shows that a miR-4728 downregulates PADI2, a novel rheumatoid arthritis risk gene (PMID:26927695)
• Downregulation of PADI2 is an early event in the pathogenesis of colorectal cancer associated with poor prognosis and points toward a possible role of citrullination in modulating tumor cells and their microenvironment. (PMID:27280713)
• Deimination of myelin basic protein (MBP) by peptidylarginine deiminase (PAD) prevents its binding to the proteasome and decelerates its degradation by the proteasome in mammalian cells. Potential anticancer drug tetrazole analogue of chloramidine 2, at concentrations greater than 1 microM inhibits the enzymatic activity of PAD in vitro. (PMID:27599511)
• Multiple proteins citrullinated by hypoxia-induced PADs were identified. In addition, the extracellular domain of vascular endothelial growth factor receptor 2 was citrullinated by human PAD2 in vitro. CONCLUSION: Our data may contribute to understanding of pathophysiology of malignant gliomas from the aspects of protein citrullination. (PMID:27818200)
• Data suggest that protein-arginine deiminase 2 (PADI2) suppresses the proliferation of colonic epithelial cells through catalysis of protein citrullination, and that downregulation of PADI2 expression might therefore contribute to colon carcinogenesis. (PMID:28403548)
• These data suggest that overexpression of the human PAD2 transgene in the epidermis of transgenic mice increases the malignant conversion rate of benign tumors by promoting an inflammatory microenvironment. (PMID:28766045)
• Peptidyl arginine deiminase 2 (PADI2) is required for activation of androgen receptor (AR) signaling under androgen-deprived condition. (PMID:28819028)
• Brain gene expression of PADI2, ZNF385A, PSD2, and A2ML1 and DNA methylation dysregulations are implicated in the alteration of brain tissue properties associated with late-life cognitive decline above and beyond the influence of common neuropathologic conditions. (PMID:29084334)
• the mRNA expression of PADI2, PADI4 and Sp1 is upregulated in rheumatoid arthritis bone marrow CD34+ cells independently of the systemic inflammation or treatment regimen. (PMID:29148420)
• Chronic gingival inflammation is associated with increased local citrullination and PAD2 and PAD4 expression in periodontitis. (PMID:30064459)
• In most rheumatoid arthritis patients, PAD2 and PAD4 are equally efficient in generating citrullinated target sites for anti-citrullinated protein antibodies (ACPAs) in fibrinogen and ENO1. The binding of autoantibodies to histone H3 was generally higher after citrullination with PAD4 than with PAD2. Citrullinated human serum albumin is not a target for ACPAs. (PMID:30161253)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	padi2	ENSDARG00000044167
mus_musculus	Padi2	ENSMUSG00000028927
rattus_norvegicus	Padi2	ENSRNOG00000007574

Paralogs (4): PADI3 (ENSG00000142619), PADI1 (ENSG00000142623), PADI4 (ENSG00000159339), PADI6 (ENSG00000276747)

Protein

Protein identifiers

Protein-arginine deiminase type-2 — Q9Y2J8 (reviewed: Q9Y2J8)

Alternative names: PAD-H19, Peptidylarginine deiminase II, Protein-arginine deiminase type II

All UniProt accessions (2): B4DIU3, Q9Y2J8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the deimination of arginine residues of proteins.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in keratinocytes in epidermis (at protein level).

Cofactor. Binding of Ca(2+) triggers a conformation change that is essential for catalytic activity.

Similarity. Belongs to the protein arginine deiminase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2J8-1	1	yes
Q9Y2J8-2	2

RefSeq proteins (1): NP_031391* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004303	PAD	Family
IPR008972	Cupredoxin	Homologous_superfamily
IPR013530	PAD_C	Domain
IPR013732	PAD_N	Domain
IPR013733	Prot_Arg_deaminase_cen_dom	Domain
IPR036556	PAD_central_sf	Homologous_superfamily
IPR038685	PAD_N_sf	Homologous_superfamily

Pfam: PF03068, PF08526, PF08527

Enzyme classification (BRENDA):

• EC 3.5.3.15 — protein-arginine deiminase (BRENDA: 14 organisms, 435 substrates, 132 inhibitors, 239 Km, 204 kcat entries)
• EC 3.5.3.6 — arginine deiminase (BRENDA: 57 organisms, 93 substrates, 106 inhibitors, 139 Km, 115 kcat entries)

Substrate kinetics (BRENDA)

95 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-ALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.1–30	62
L-ARGININE	0.09–55.5	55
L-ARG	0.004–38	26
NALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.27–2.77	21
NALPHA-BENZOYL L-ARGININE ETHYL ESTER	0.44–1.7	20
[HISTONE H4]-L-ARG	0.088–0.35	17
N-ALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.1–30	15
BENZOYL-L-ARG	0.0029–33.6	6
L-CANAVANINE	0.044–2.3	6
ACETYL-L-ARG METHYL ESTER	1.19–66.3	5
BENZOYL-ARG ETHYL ESTER	0.33–0.78	4
BENZOYL-L-ARG ETHYL ESTER	0.35–7.5	4
N-ALPHA-BENZOYL-L-ARGININE AMIDE	0.16–17.5	4
AC-SER-GLY-ARG-GLY-ACETYL-LYS-GLY-GLY-ACETYL-LYS	0.15–1.07	3
AC-SER-GLY-ARG-GLY-LYS-GLY-GLY-LYS-GLY-LEU-GLY-L	0.15–0.59	3

Catalyzed reactions (Rhea), 1 shown:

• L-arginyl-[protein] + H2O = L-citrullyl-[protein] + NH4(+) (RHEA:18089)

UniProt features (111 total): strand 46, binding site 22, helix 21, mutagenesis site 14, turn 4, chain 1, active site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
4N2K	X-RAY DIFFRACTION	1.57
4N2M	X-RAY DIFFRACTION	1.6
9B96	X-RAY DIFFRACTION	1.64
4N20	X-RAY DIFFRACTION	1.66
4N2B	X-RAY DIFFRACTION	1.69
4N2A	X-RAY DIFFRACTION	1.7
9DOL	X-RAY DIFFRACTION	1.77
4N2F	X-RAY DIFFRACTION	1.8
4N2N	X-RAY DIFFRACTION	1.8
4N2H	X-RAY DIFFRACTION	1.81
4N2G	X-RAY DIFFRACTION	1.85
4N2E	X-RAY DIFFRACTION	1.86
4N28	X-RAY DIFFRACTION	1.88
4N22	X-RAY DIFFRACTION	1.89
4N2I	X-RAY DIFFRACTION	1.9
4N25	X-RAY DIFFRACTION	1.93
4N26	X-RAY DIFFRACTION	1.94
9B97	X-RAY DIFFRACTION	1.95
4N24	X-RAY DIFFRACTION	1.97
4N2D	X-RAY DIFFRACTION	2
9B98	X-RAY DIFFRACTION	2
4N2L	X-RAY DIFFRACTION	2.1
9OVQ	X-RAY DIFFRACTION	2.17
4N2C	X-RAY DIFFRACTION	3.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2J8-F1	94.35	0.83

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): 647 (nucleophile)

Ligand- & substrate-binding residues (22): 158; 158; 166; 166; 169; 171; 177; 180; 180; 354; 123; 389 …

Mutagenesis-validated functional residues (14):

Position	Phenotype
123	mildly reduced enzyme activity.
125	mildly reduced enzyme activity.
166	reduced enzyme activity.
169	mildly reduced enzyme activity.
177	reduced enzyme activity.
348	loss of enzyme activity.
350	strongly reduced enzyme activity.
354	loss of enzyme activity.
370	reduced enzyme activity.
373	strongly reduced enzyme activity.
374	reduced enzyme activity.
389	reduced enzyme activity.
412	strongly reduced enzyme activity.
647	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 318 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS, SRF_Q5_01, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION

GO Biological Process (7): chromatin remodeling (GO:0006338), substantia nigra development (GO:0021762), estrogen receptor signaling pathway (GO:0030520), transcription initiation-coupled chromatin remodeling (GO:0045815), negative regulation of chemokine-mediated signaling pathway (GO:0070100), negative regulation of lymphocyte chemotaxis (GO:1901624), cellular response to leukemia inhibitory factor (GO:1990830)

GO Molecular Function (8): protein-arginine deiminase activity (GO:0004668), calcium ion binding (GO:0005509), nuclear estrogen receptor binding (GO:0030331), protein homodimerization activity (GO:0042803), histone arginine deiminase activity (GO:0140794), histone H3R26 arginine deiminase activity (GO:0140798), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (7): euchromatin (GO:0000791), extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin organization	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
chromatin organization	1
midbrain development	1
neural nucleus development	1
nuclear receptor-mediated steroid hormone signaling pathway	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
negative regulation of cytokine-mediated signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
chemokine-mediated signaling pathway	1
regulation of chemokine-mediated signaling pathway	1
negative regulation of leukocyte chemotaxis	1
lymphocyte chemotaxis	1
regulation of lymphocyte chemotaxis	1
negative regulation of lymphocyte migration	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines	1
metal ion binding	1
nuclear receptor binding	1
identical protein binding	1
protein dimerization activity	1
protein-arginine deiminase activity	1
histone modifying activity	1
histone H3 arginine deiminase activity	1
catalytic activity	1
cation binding	1
chromatin	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PADI2	POFUT2	Q9Y2G5	777
PADI2	H3C14	Q71DI3	692
PADI2	H3-7	Q5TEC6	692
PADI2	H3-4	Q16695	684
PADI2	H3-5	Q6NXT2	683
PADI2	H3-3A	P06351	682
PADI2	H3C1	P02295	682
PADI2	CA1	P00915	593
PADI2	CTSG	P08311	588
PADI2	PRTN3	P15637	579
PADI2	MBP	P02686	528
PADI2	ESR1	P03372	519
PADI2	FLG2	Q5D862	516
PADI2	FLG	P20930	507
PADI2	TP53	P04637	493

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MYC		psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
CSH1	H6PD	psi-mi:“MI:0914”(association)	0.350
RIPK4	PADI2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): PADI2 (Synthetic Lethality), PADI2 (Affinity Capture-MS), PADI2 (Affinity Capture-MS), PADI2 (Affinity Capture-MS), PADI2 (Affinity Capture-MS), PADI2 (Two-hybrid), PADI2 (Affinity Capture-MS)

ESM2 similar proteins: A6NC97, A8MVJ9, F4IRQ5, F4ISV6, F4IY62, G5ECQ8, O02849, O15091, O64967, O88806, P10759, P17532, P20717, P23109, P53215, P70708, Q05B50, Q08642, Q0EAB8, Q2HZ26, Q3V1D3, Q4R366, Q54E29, Q5K651, Q5M965, Q6BKD4, Q6CW75, Q6CY84, Q6DDV1, Q6FPX3, Q75DJ3, Q7SDM8, Q86VD1, Q8C5W4, Q8CGU9, Q8CGV2, Q8IVG5, Q8IWU9, Q8L627, Q9CY52

Diamond homologs: O02849, O88806, O88807, P20717, P70708, Q08642, Q6TGC4, Q8K3V4, Q9ULC6, Q9ULW8, Q9UM07, Q9Y2J8, Q9Z183, Q9Z184, Q9Z185

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	6
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1831 predictions. Top by Δscore:

Variant	Effect	Δscore
1:17070082:CCTCA:C	donor_loss	1.0000
1:17070083:CTCAC:C	donor_loss	1.0000
1:17070084:TCAC:T	donor_loss	1.0000
1:17070085:CA:C	donor_loss	1.0000
1:17070086:A:AC	donor_gain	1.0000
1:17070086:A:AG	donor_loss	1.0000
1:17070086:AC:A	donor_gain	1.0000
1:17070087:C:A	donor_loss	1.0000
1:17070087:C:CC	donor_gain	1.0000
1:17070087:CC:C	donor_gain	1.0000
1:17070212:CAGCG:C	acceptor_gain	1.0000
1:17070213:AGCG:A	acceptor_gain	1.0000
1:17070214:GCG:G	acceptor_gain	1.0000
1:17070215:CG:C	acceptor_gain	1.0000
1:17070215:CGC:C	acceptor_gain	1.0000
1:17070217:C:CC	acceptor_gain	1.0000
1:17070221:G:C	acceptor_gain	1.0000
1:17070221:G:GC	acceptor_gain	1.0000
1:17071402:TCAC:T	donor_loss	1.0000
1:17071403:CACC:C	donor_loss	1.0000
1:17071404:ACC:A	donor_loss	1.0000
1:17071405:C:CA	donor_loss	1.0000
1:17071487:CAAGC:C	acceptor_gain	1.0000
1:17071488:AAGC:A	acceptor_gain	1.0000
1:17071489:AGC:A	acceptor_gain	1.0000
1:17071490:GC:G	acceptor_gain	1.0000
1:17071491:CC:C	acceptor_gain	1.0000
1:17071492:C:CA	acceptor_loss	1.0000
1:17071492:C:CC	acceptor_gain	1.0000
1:17071493:T:A	acceptor_loss	1.0000

AlphaMissense

4384 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:17079332:A:C	S414R	1.000
1:17079332:A:T	S414R	1.000
1:17079334:T:G	S414R	1.000
1:17075738:A:G	W466R	0.999
1:17075738:A:T	W466R	0.999
1:17079344:G:C	N410K	0.999
1:17079344:G:T	N410K	0.999
1:17083734:A:G	W348R	0.999
1:17083734:A:T	W348R	0.999
1:17069083:C:A	R653S	0.998
1:17069083:C:G	R653S	0.998
1:17069084:C:A	R653M	0.998
1:17069084:C:G	R653T	0.998
1:17069099:C:T	G648D	0.998
1:17069115:C:A	G643W	0.998
1:17069149:G:C	F631L	0.998
1:17069149:G:T	F631L	0.998
1:17069151:A:G	F631L	0.998
1:17069240:G:T	P601H	0.998
1:17075716:T:A	D473V	0.998
1:17079342:A:G	L411P	0.998
1:17079348:C:A	G409V	0.998
1:17079348:C:T	G409E	0.998
1:17082651:T:A	D351V	0.998
1:17082651:T:G	D351A	0.998
1:17083732:C:A	W348C	0.998
1:17083732:C:G	W348C	0.998
1:17069064:A:G	W660R	0.997
1:17069064:A:T	W660R	0.997
1:17069114:C:A	G643V	0.997

dbSNP variants (sampled 300 via entrez): RS1000042855 (1:17097534 G>A), RS1000146890 (1:17086644 A>C,G), RS1000192763 (1:17081891 T>A), RS1000293448 (1:17109006 G>C), RS1000321427 (1:17104231 A>G), RS1000324623 (1:17110176 C>T), RS1000430890 (1:17076652 C>T), RS1000434757 (1:17097260 G>C), RS1000440626 (1:17109954 GAGGCCTC>G), RS1000445379 (1:17072081 G>A), RS1000454632 (1:17073398 C>A), RS1000550701 (1:17104992 A>G), RS1000589107 (1:17067555 G>T), RS1000614232 (1:17120710 G>A), RS1000665224 (1:17104821 T>A,C)

Disease associations

OMIM: gene MIM:607935 | disease phenotypes: MIM:180300

GenCC curated gene-disease

Mondo (2): rheumatoid arthritis (MONDO:0008383), interstitial lung disease (MONDO:0015925)

Orphanet (2): Interstitial lung disease (Orphanet:182095), NON RARE IN EUROPE: Rheumatoid arthritis (Orphanet:284130)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001370	Rheumatoid arthritis

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST004639_29	Prudent dietary pattern	6.000000e-06
GCST006959_15	Rheumatoid arthritis	1.000000e-06
GCST006959_161	Rheumatoid arthritis	2.000000e-10
GCST008473_5	Visceral fat	2.000000e-06
GCST012227_1381	Hip circumference adjusted for BMI	3.000000e-09
GCST012227_1382	Hip circumference adjusted for BMI	6.000000e-10
GCST90002384_528	Hemoglobin	8.000000e-11
GCST90007003_5	Gut microbiota relative abundance (Ruminococcus belonging to family Lachnospiraceae)	8.000000e-06
GCST90020024_7	A body shape index	2.000000e-09
GCST90020027_1777	Waist-hip index	1.000000e-08
GCST90020029_1251	Waist circumference adjusted for body mass index	9.000000e-19
GCST90020029_1252	Waist circumference adjusted for body mass index	7.000000e-09
GCST90020029_1253	Waist circumference adjusted for body mass index	7.000000e-15

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004509	hemoglobin measurement
EFO:0007874	gut microbiome measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001172	Arthritis, Rheumatoid	C05.550.114.154; C05.799.114; C17.300.775.099; C20.111.199
D017563	Lung Diseases, Interstitial	C08.381.483

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1909487 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,337 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL11417	STREPTONIGRIN	2	43,337

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

ChEMBL bioactivities

47 potent at pChembl≥5 of 59 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	CHEMBL58150
6.50	IC50	320	nM	CHEMBL57818
6.46	IC50	350	nM	CHEMBL5542325
6.40	EC50	400	nM	CHEMBL4214962
6.13	IC50	740	nM	CHEMBL60908
6.08	IC50	830	nM	CHEMBL5532370
6.00	IC50	1000	nM	CHEMBL5562134
5.99	IC50	1030	nM	CHEMBL5555170
5.94	IC50	1140	nM	CHEMBL5563751
5.92	EC50	1200	nM	CHEMBL4204476
5.90	IC50	1270	nM	CHEMBL5564382
5.88	IC50	1320	nM	CHEMBL5564422
5.87	IC50	1360	nM	CHEMBL5560601
5.84	IC50	1430	nM	CHEMBL5559926
5.82	IC50	1510	nM	CHEMBL5527968
5.81	IC50	1550	nM	CHEMBL3113470
5.79	IC50	1630	nM	CHEMBL5556269
5.71	IC50	1930	nM	CHEMBL5562016
5.68	EC50	2100	nM	CHEMBL4202689
5.68	IC50	2100	nM	CHEMBL5559509
5.68	IC50	2080	nM	CHEMBL5565461
5.65	IC50	2260	nM	CHEMBL5560885
5.64	IC50	2280	nM	CHEMBL5563821
5.63	IC50	2320	nM	CHEMBL5562945
5.62	EC50	2400	nM	CHEMBL4217485
5.57	EC50	2700	nM	CHEMBL4211403
5.56	IC50	2730	nM	CHEMBL5555615
5.53	IC50	2970	nM	CHEMBL5562648
5.53	IC50	2950	nM	CHEMBL5558736
5.52	IC50	3000	nM	CHEMBL5542302
5.52	IC50	3040	nM	CHEMBL5556573
5.44	IC50	3640	nM	CHEMBL5560217
5.42	IC50	3770	nM	CHEMBL5567700
5.39	IC50	4050	nM	CHEMBL5555765
5.37	IC50	4320	nM	CHEMBL5563295
5.34	IC50	4590	nM	CHEMBL5564029
5.33	IC50	4650	nM	CHEMBL5561457
5.28	IC50	5280	nM	CHEMBL3682418
5.27	IC50	5400	nM	CHEMBL5566624
5.23	EC50	5900	nM	CHEMBL4202689
5.21	IC50	6200	nM	CHEMBL1910971
5.20	IC50	6320	nM	CHEMBL1714002
5.12	EC50	7500	nM	CHEMBL4204476
5.12	EC50	7600	nM	CHEMBL4217485
5.09	Ki	8080	nM	CHEMBL57818
5.08	EC50	8300	nM	CHEMBL4211403
5.02	EC50	9500	nM	CHEMBL4214962

PubChem BioAssay actives

47 with measured affinity, of 180 total; 41 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
6-(7-amino-5,8-dioxoquinolin-2-yl)pyridine-2-carboxylic acid	1069621: Inhibition of recombinant wild-type PAD2 (unknown origin) using N-alpha-Benzoyl-L-arginine ethyl ester as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	0.2000	uM
7-amino-2-pyridin-2-ylquinoline-5,8-dione	1069621: Inhibition of recombinant wild-type PAD2 (unknown origin) using N-alpha-Benzoyl-L-arginine ethyl ester as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	0.3200	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1H-indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	0.3500	uM
N-[(1S)-4-[(1-amino-2-fluoroethylidene)amino]-1-(4-methoxy-1-methylbenzimidazol-2-yl)butyl]-3-oxo-1,2-dihydroisoindole-4-carboxamide	1364671: Binding affinity to human PAD2 expressed in HEK293T cells assessed as decrease in histone H3 citrulination incubated for 3 hrs in presence of ionomycin/CaCl2 by SDS-PAGE analysis	ec50	0.4000	uM
7-aminoquinoline-5,8-dione	1069621: Inhibition of recombinant wild-type PAD2 (unknown origin) using N-alpha-Benzoyl-L-arginine ethyl ester as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	0.7400	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-methyl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	0.8300	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(2,2-dimethoxyethyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.0000	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(2-methylpropyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.0300	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-propan-2-yl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.1400	uM
N-[(1S)-4-[(1-amino-2-chloroethylidene)amino]-1-(1H-benzimidazol-2-yl)butyl]-4-phenylbenzamide	1364671: Binding affinity to human PAD2 expressed in HEK293T cells assessed as decrease in histone H3 citrulination incubated for 3 hrs in presence of ionomycin/CaCl2 by SDS-PAGE analysis	ec50	1.2000	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-cyclopropyl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.2700	uM
(3S)-N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-2,3,4,4a,9,9a-hexahydro-1H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.3200	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-pentan-3-yl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.3600	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1H-indole-5-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.4300	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(2,6-dimethoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.5100	uM
7-amino-6-bromoquinoline-5,8-dione	1069621: Inhibition of recombinant wild-type PAD2 (unknown origin) using N-alpha-Benzoyl-L-arginine ethyl ester as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	1.5500	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(2,4,6-trimethoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.6300	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1,2,3,4-tetrahydroquinoxaline-6-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	1.9300	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-3H-benzimidazole-5-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	2.0800	uM
N-[(1S)-4-[(1-amino-2-fluoroethylidene)amino]-1-(5-methoxy-1-methylbenzimidazol-2-yl)butyl]-3-oxo-1,2-dihydroisoindole-4-carboxamide	1364671: Binding affinity to human PAD2 expressed in HEK293T cells assessed as decrease in histone H3 citrulination incubated for 3 hrs in presence of ionomycin/CaCl2 by SDS-PAGE analysis	ec50	2.1000	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-5-fluoro-1H-indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	2.1000	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(4-hydroxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	2.2600	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]quinoxaline-6-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	2.2800	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-cyclohexyl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	2.3200	uM
N-[(1S)-4-[(1-amino-2-fluoroethylidene)amino]-1-(1-ethyl-4-methoxybenzimidazol-2-yl)butyl]-3-oxo-1,2-dihydroisoindole-4-carboxamide	1364671: Binding affinity to human PAD2 expressed in HEK293T cells assessed as decrease in histone H3 citrulination incubated for 3 hrs in presence of ionomycin/CaCl2 by SDS-PAGE analysis	ec50	2.4000	uM
N-[(1S)-4-[(1-amino-2-fluoroethylidene)amino]-1-(4-ethoxy-1-methylbenzimidazol-2-yl)butyl]-3-oxo-1,2-dihydroisoindole-4-carboxamide	1364671: Binding affinity to human PAD2 expressed in HEK293T cells assessed as decrease in histone H3 citrulination incubated for 3 hrs in presence of ionomycin/CaCl2 by SDS-PAGE analysis	ec50	2.7000	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	2.7300	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(4-fluorophenyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	2.9500	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-phenyl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	2.9700	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(4-cyanophenyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	3.0000	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	3.0400	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-pentyl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	3.6400	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-thiophen-2-yl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	3.7700	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(4-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	4.0500	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-tert-butyl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	4.3200	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-(3,4-dimethoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	4.5900	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1-pyridin-4-yl-9H-pyrido[3,4-b]indole-3-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	4.6500	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-6-(dimethylamino)naphthalene-2-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	5.2800	uM
N-[(2S)-5-[(1-amino-2-chloroethylidene)amino]-1-(benzylamino)-1-oxopentan-2-yl]-1H-benzimidazole-2-carboxamide	2071730: Inhibition of PAD2 (unknown origin) using Nalpha-benzoyl-L-arginine ethyl ester as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins by colorimetric analysis	ic50	5.4000	uM
2-[[(2S)-1-amino-5-[(1-amino-2-chloroethylidene)amino]-1-oxopentan-2-yl]carbamoyl]benzoic acid;2,2,2-trifluoroacetic acid	627373: Irreversible inhibition of PAD2 assessed as hydrolysis of benzoyl-L-arginine ethyl ester preincubated for 15 mins measured after 15 mins by fluorometric analysis	ic50	6.2000	uM
7-bromo-6-methoxyquinoline-5,8-dione	1069621: Inhibition of recombinant wild-type PAD2 (unknown origin) using N-alpha-Benzoyl-L-arginine ethyl ester as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	6.3200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	increases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
terbufos	increases methylation	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

30 unique, capped per target: 30 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1913981	Binding	Irreversible inhibition of PAD2 assessed as residual activity at 1 mM measured after 20 hrs by colorimetric assay in presence of 2 mM benzoyl-L-arginine ethyl ester	The development of N-α-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l-ornithine amide (o-F-amidine) and N-α-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-l-ornithine amide (o-Cl-amidine) as second generation protein arginine deiminase (PAD) inhibitors. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1LB	Abcam Jurkat PADI2 KO	Cancer cell line	Male
CVCL_D1PI	Abcam K-562 PADI2 KO	Cancer cell line	Female
CVCL_D2L4	Abcam Raji PADI2 KO	Cancer cell line	Male
CVCL_D8RZ	Ubigene HCT 116 PADI2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00056667	PHASE4	COMPLETED	Relaxation Response Training for the Treatment of Rheumatoid Arthritis
NCT00094341	PHASE4	COMPLETED	Preference of Rheumatoid Arthritis (RA) Patients of Enbrel® (Etanercept) Auto-Injector Versus Enbrel® Pre-Filled Syringes
NCT00099554	PHASE4	COMPLETED	Effectiveness and Safety of Enbrel® (Etanercept) in Rheumatoid Arthritis Subjects Who Have Failed Remicade® (Infliximab)
NCT00111410	PHASE4	COMPLETED	Evaluating the Effect of Anakinra (r-metHuIL-1ra) on Vaccine AntibodyResponse in Subjects With Rheumatoid Arthritis (RA)
NCT00115219	PHASE4	COMPLETED	Evaluating Efficacy and Safety of Etanercept 50 mg Twice Weekly (BIW) in Rheumatoid Arthritis (RA) Subjects Who Are Sub-Optimal Responders to Etanercept 50 mg Once Weekly (QW)
NCT00121043	PHASE4	COMPLETED	Evaluating Kineret® (Anakinra) in Rheumatoid Arthritis (RA) Subjects Using aSelf-Reported Questionnaire
NCT00132418	PHASE4	COMPLETED	Study of Enbrel in Rheumatoid Arthritis (RA) Subjects With Comorbid Disorders
NCT00157872	PHASE4	COMPLETED	A Study of Rofecoxib Versus Naproxen in the Treatment of Chinese Patient With Rheumatoid Arthritis (0966-231)
NCT00195494	PHASE4	COMPLETED	Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis
NCT00208364	PHASE4	TERMINATED	A Two Centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Metal-on-Metal Bearing in Primary Total Hip Replacement
NCT00208377	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy ASR™ System in Primary Hip Resurfacing Surgery
NCT00208390	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement
NCT00208429	PHASE4	WITHDRAWN	A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement
NCT00208455	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy PROXIMA™ Hip in Primary Total Hip Replacement
NCT00209859	PHASE4	COMPLETED	Methotrexate and Cyclosporine in Treatment of Early Rheumatoid Arthritis
NCT00216177	PHASE4	UNKNOWN	Comparison of Adalimumab and Infliximab Treatment of Rheumatoid Arthritis
NCT00233558	PHASE4	TERMINATED	Open-Label Steroid Reduction Study of Adalimumab With Methotrexate in Patients With Active Rheumatoid Arthritis
NCT00234234	PHASE4	COMPLETED	Predictors of the Response to Adalimumab in Rheumatoid Arthritis
NCT00234897	PHASE4	COMPLETED	Efficacy of HUMIRA in Subjects With Active Rheumatoid Arthritis
NCT00244556	PHASE4	COMPLETED	Study Comparing Enbrel (Etanercept) Plus Methotrexate Versus Enbrel Alone in Active Rheumatoid Arthritis Despite Current Methotrexate Therapy
NCT00252668	PHASE4	COMPLETED	Study Evaluating the Combination of Etanercept and Methotrexate in Rheumatoid Arthritis Subjects
NCT00259610	PHASE4	COMPLETED	Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)
NCT00291915	PHASE4	UNKNOWN	Multicenter Randomized Prospective Trial Comparing Methotrexate Alone or in Combination With Adalimumab in Early Arthritis
NCT00319917	PHASE4	COMPLETED	A Double Blind Placebo Controlled Study to Assess the Efficacy on Joint Damage in RA Patients
NCT00334620	PHASE4	COMPLETED	Effectiveness of Radon Spa Therapy in Multimodal Rehabilitative Treatment of Rheumatoid Arthritis
NCT00346294	PHASE4	COMPLETED	An Open-Label Study to Assess the Rate of Failure of an Enbrel® (Etanercept) SureClick™ Auto-injector in Subjects With Rheumatoid Arthritis
NCT00356473	PHASE4	COMPLETED	Effects of Atorvastatin on Disease Activity and HDL Cholesterol Function in Patients With Rheumatoid Arthritis
NCT00369187	PHASE4	COMPLETED	Study of a Large Protein Molecule Administered With Escalating Doses of Recombinant Human Hyaluronidase
NCT00385528	PHASE4	COMPLETED	Effects of a Multi-Faceted Psychiatric Intervention Targeted at the Complex Medically Ill: a Randomized Controlled Trial
NCT00396747	PHASE4	COMPLETED	A Comparison of Methotrexate Alone or Combined to Infliximab or to Pulse Methylprednisolone in Early Rheumatoid Arthritis: A Magnetic Resonance Imaging Study
NCT00420927	PHASE4	COMPLETED	Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis
NCT00422227	PHASE4	COMPLETED	Study Comparing Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis in the Asia Pacific Region
NCT00424502	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a TNF-Blocker.
NCT00434200	PHASE4	UNKNOWN	Rheumatoid Arthritis Patients in Training
NCT00439062	PHASE4	COMPLETED	Treatment of Rheumatoid Arthritis With Roxithromycin
NCT00447759	PHASE4	COMPLETED	The Standard Care Versus Celecoxib Outcome Trial
NCT00462072	PHASE4	COMPLETED	Centocor Microarray Study of Patients
NCT00462345	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.
NCT00480272	PHASE4	COMPLETED	Prospective Study on Intensive Early Rheumatoid Arthritis Treatment
NCT00502853	PHASE4	COMPLETED	A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.