DNASE2

Summary

DNASE2 (deoxyribonuclease 2, lysosomal, HGNC:2960) is a protein-coding gene on chromosome 19p13.13, encoding Deoxyribonuclease-2-alpha (O00115). Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA.

This gene encodes a member of the DNase family. The protein, located in the lysosome, hydrolyzes DNA under acidic conditions and mediates the breakdown of DNA during erythropoiesis and apoptosis. Two codominant alleles have been characterized, DNASE2L (low activity) and DNASE2H (high activity), that differ at one nucleotide in the promoter region. The DNASE2*H allele is represented in this record.

Source: NCBI Gene 1777 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 196 total — 3 pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes
• MANE Select transcript: NM_001375

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2960
Approved symbol	DNASE2
Name	deoxyribonuclease 2, lysosomal
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105612
Ensembl biotype	protein_coding
OMIM	126350
Entrez	1777

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000222219, ENST00000586547, ENST00000588777, ENST00000592506, ENST00000698691, ENST00000698692, ENST00000698693, ENST00000880269, ENST00000951022

RefSeq mRNA: 1 — MANE Select: NM_001375 NM_001375

CCDS: CCDS12284

Canonical transcript exons

ENST00000222219 — 6 exons

Exon	Start	End
ENSE00000682693	12880972	12881152
ENSE00000682695	12880802	12880880
ENSE00000682697	12878382	12878579
ENSE00001184279	12875209	12876363
ENSE00002936594	12881290	12881449
ENSE00003620137	12878670	12878834

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.6113 / max 701.3361, expressed in 1798 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179413	15.7245	1751
179414	14.3891	1763
179412	6.2990	872
179411	1.1986	283

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	95.89	silver quality
stromal cell of endometrium	CL:0002255	94.74	gold quality
lateral globus pallidus	UBERON:0002476	94.01	gold quality
parotid gland	UBERON:0001831	93.56	gold quality
descending thoracic aorta	UBERON:0002345	93.34	gold quality
cardia of stomach	UBERON:0001162	93.27	silver quality
monocyte	CL:0000576	93.23	gold quality
vena cava	UBERON:0004087	93.13	silver quality
mononuclear cell	CL:0000842	92.99	gold quality
leukocyte	CL:0000738	92.95	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.89	gold quality
substantia nigra pars compacta	UBERON:0001965	92.76	gold quality
pylorus	UBERON:0001166	92.74	gold quality
subthalamic nucleus	UBERON:0001906	92.65	silver quality
substantia nigra pars reticulata	UBERON:0001966	92.58	silver quality
lymph node	UBERON:0000029	92.52	gold quality
thoracic aorta	UBERON:0001515	92.52	gold quality
granulocyte	CL:0000094	92.48	gold quality
ventral tegmental area	UBERON:0002691	92.48	silver quality
gall bladder	UBERON:0002110	92.43	gold quality
ascending aorta	UBERON:0001496	92.42	gold quality
endometrium epithelium	UBERON:0004811	92.04	silver quality
superior surface of tongue	UBERON:0007371	91.98	gold quality
right coronary artery	UBERON:0001625	91.97	gold quality
aorta	UBERON:0000947	91.79	gold quality
inferior vagus X ganglion	UBERON:0005363	91.70	silver quality
nipple	UBERON:0002030	91.57	gold quality
renal medulla	UBERON:0000362	91.56	gold quality
popliteal artery	UBERON:0002250	91.25	gold quality
tibial artery	UBERON:0007610	91.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	13.84
E-ANND-3	yes	7.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF1, SP1, SP3

miRNA regulators (miRDB)

37 targeting DNASE2, 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-507	99.97	70.11	1915
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-325	99.58	66.55	358
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-597-5P	96.82	67.57	732

Literature-anchored findings (GeneRIF, showing 10)

• upregulation of expression during myelomonocytic differentiation of HL-60 and THP-1 cells (PMID:12147225)
• Sp1 and Sp3 are involved in up-regulation of this enzyme’s transcriptoin during cell differentiation of hl-60 cells. (PMID:12694199)
• the enzyme is a monomeric phospholipase D-family member with a pseudodimeric protein fold (PMID:17192590)
• The association of SNPs in the 5’-regulatory region of the DNA degrading enzyme DNASE2 with Rheumatoid Arthritis implies a role for this enzyme in the pathogenesis of this autoimmune disease. (PMID:18812394)
• study demonstrated the relationship of genotypes/haplotypes with the in vivo DNase II and promoter activities; significant correlations between genotype in each rheumatoid arthritis (RA)-related SNP and enzymatic activity levels were found; alleles associated with RA exhibited a reduction in serum DNase II activity. (PMID:23019102)
• 15 nonsynonymous human DNase II SNPs were genotyped in three ethnic groups including 16 different populations using the PCR-restriction fragment length polymorphism technique. (PMID:24242851)
• Single nucleotide polymorphisms producing a loss-of-function variant of the enzymes in DNASE1, DNASE1L3, and DNASE2, possibly serving as a genetic risk factor for autoimmune diseases, were confirmed. (PMID:27116004)
• DNase2 participate in the degradation of DNA during cornification in the interfollicular epidermis of mice.Cornification of epidermal keratinocytes depends on the cooperation of DNase1L2 and DNase2. (PMID:28743926)
• Study identifies biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity causing type I interferonopathy in three patients from two unrelated families. (PMID:29259162)
• Study of the copy number variations (CNVs) for DNASE1L3 and DNASE2 in Japanese and German populations found that only 2 diploid copy numbers for these DNASE CNVs was distributed in both populations; no copy loss or gain was evident for any of the autoimmune-related DNase genes. These human autoimmune-related DNase genes show low genetic diversity of CNVs resulting in alterations of the in vivo levels of DNase activity. (PMID:31022206)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnase2	ENSDARG00000073893
mus_musculus	Dnase2a	ENSMUSG00000003812
rattus_norvegicus	Dnase2	ENSRNOG00000023830
drosophila_melanogaster	DNaseII	FBGN0000477
caenorhabditis_elegans		WBGENE00000799
caenorhabditis_elegans		WBGENE00003828
caenorhabditis_elegans		WBGENE00007056

Paralogs (1): DNASE2B (ENSG00000137976)

Protein

Protein identifiers

Deoxyribonuclease-2-alpha — O00115 (reviewed: O00115)

Alternative names: Acid DNase, Deoxyribonuclease II alpha, Lysosomal DNase II, R31240_2

All UniProt accessions (3): O00115, A0A8V8TNK3, K7ENE5

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA. Plays a major role in the clearance of nucleic acids generated through apoptosis, hence preventing autoinflammation. Necessary for proper fetal development and for definitive erythropoiesis in fetal liver and bone marrow, where it degrades nuclear DNA expelled from erythroid precursor cells.

Subcellular location. Lysosome.

Tissue specificity. Expressed in monocytes/macrophages (at protein level).

Post-translational modifications. Glycosylated. Genetic variations that affect N-glycosylation sites reduce activity, but enzymatic deglycosylation has no effect.

Disease relevance. Autoinflammatory-pancytopenia syndrome (AIPCS) [MIM:619858] An autosomal recessive disorder characterized by severe anemia and thrombocytopenia apparent from early infancy, hepatosplenomegaly, and recurrent fevers associated with a hyperinflammatory state. Additional systemic features may include chronic diarrhea, proteinuria with renal disease, liver fibrosis with elevated liver enzymes, deforming arthropathy, and vasculitic skin lesions. Some patients may have motor delay or learning difficulties associated with subcortical white matter lesions on brain imaging. The disease is caused by variants affecting the gene represented in this entry. The genetic variation producing the missense variant p.G116A, associated with AIPCS, has been shown to predominantly affect splicing, leading to in-frame deletion of exon 4, encoding amino acids 116 to 171. The protein resulting from this aberrant splicing may be unstable.

Similarity. Belongs to the DNase II family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00115-1	1	yes
O00115-2	2

RefSeq proteins (1): NP_001366* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004947	DNase_II	Family

Pfam: PF03265

Enzyme classification (BRENDA):

• EC 3.1.22.1 — deoxyribonuclease II (BRENDA: 30 organisms, 69 substrates, 60 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SUPERCOILED PLASMID DNA	—	6

UniProt features (31 total): mutagenesis site 13, sequence variant 6, glycosylation site 4, disulfide bond 3, signal peptide 1, chain 1, splice variant 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00115-F1	91.52	0.84

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): 295

Disulfide bonds (3): 19–159, 267–347, 308–327

Glycosylation sites (4): 86, 212, 266, 290

Mutagenesis-validated functional residues (13):

Position	Phenotype
19	loss of activity.
86	reduced n-glycosylation, complete loss of n-glycosylation; when associated with q-212; q-266 and q-290.
151	loss of activity.
159	loss of activity.
212	reduced n-glycosylation, complete loss of n-glycosylation; when associated with q-86; q-266 and q-290.
266	reduced n-glycosylation, complete loss of n-glycosylation; when associated with q-86; q-212 and q-290.
267	loss of activity.
290	reduced n-glycosylation, complete loss of n-glycosylation; when associated with q-86; q-212 and q-266.
295	loss of activity, but not of dna-binding.
299	no effect.
308	loss of activity.
327	loss of activity.
347	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-432720	Lysosome Vesicle Biogenesis

MSigDB gene sets: 0 (showing top):

GO Biological Process (6): DNA metabolic process (GO:0006259), apoptotic DNA fragmentation (GO:0006309), enucleate erythrocyte differentiation (GO:0043353), regulation of immune response (GO:0050776), DNA catabolic process (GO:0006308), apoptotic process (GO:0006915)

GO Molecular Function (7): DNA binding (GO:0003677), deoxyribonuclease II activity (GO:0004531), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), DNA endonuclease activity (GO:0004520), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): lysosome (GO:0005764), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA nuclease activity	2
nucleic acid metabolic process	1
DNA catabolic process	1
apoptotic nuclear changes	1
erythrocyte differentiation	1
regulation of immune system process	1
immune response	1
regulation of response to stimulus	1
DNA metabolic process	1
nucleic acid catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleic acid binding	1
DNA endonuclease activity, producing 3’-phosphomonoesters	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
endonuclease activity	1
binding	1
catalytic activity	1
lytic vacuole	1
extracellular vesicle	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNASE2	DFFB	O76075	838
DNASE2	DNASE1	P24855	838
DNASE2	DFFA	O00273	798
DNASE2	DNASE1L3	Q13609	684
DNASE2	DNASE1L2	Q92874	680
DNASE2	IFNB1	P01574	586
DNASE2	RNASEH2C	Q8TDP1	568
DNASE2	IFNA13	P01562	556
DNASE2	DNASE1L1	P49184	554
DNASE2	IFNA13	A0A087WWS6	545
DNASE2	CGAS	Q8N884	535
DNASE2	RNASEH2B	Q5TBB1	522
DNASE2	IFNAR1	P17181	501
DNASE2	CASP3	P42574	483
DNASE2	RNASEH2A	O75792	482

IntAct

10 interactions, top by confidence:

A	B	Type	Score
DNASE2	CANX	psi-mi:“MI:0915”(physical association)	0.690
	VPS37C	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DNASE2	C1QL1	psi-mi:“MI:0914”(association)	0.350
FBXO6	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DNASE2	RUVBL2	psi-mi:“MI:0915”(physical association)	0.000
DNASE2	RUVBL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): CANX (Affinity Capture-MS), DNASE2 (Affinity Capture-RNA), RUVBL2 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), DNASE2 (Affinity Capture-MS), DNASE2 (Affinity Capture-RNA), DNASE2 (Proximity Label-MS), DNASE2 (Affinity Capture-RNA), CANX (Affinity Capture-MS), DNASE2 (Affinity Capture-MS), DNASE2 (Affinity Capture-MS), DNASE2 (Affinity Capture-MS), DNASE2 (Affinity Capture-MS), DNASE2 (Affinity Capture-MS), DNASE2 (Proximity Label-MS)

ESM2 similar proteins: O00115, O08590, O15547, O46406, O62855, O70423, O95897, P10820, P14222, P34387, P35763, P36633, P56541, P56542, Q04912, Q16853, Q17778, Q24K15, Q29437, Q2KJC3, Q2T8B0, Q3JJK4, Q3V5L5, Q4R9E0, Q5R9I0, Q5SSH8, Q62190, Q63IT3, Q6AX53, Q6NUS6, Q6TMA8, Q71SY6, Q75WF2, Q765H6, Q812C9, Q8JZQ5, Q8R2Q6, Q8WZ79, Q91ZV7, Q93086

Diamond homologs: O00115, O62855, P34387, P34508, P56541, P56542, Q17778, Q75WF2, Q8WZ79, Q9QY48, Q9QZK8, Q9QZK9, Q2T8B0, Q3JJK4, Q63IT3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	92
Likely benign	84
Benign	7

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1686899	NM_001375.3(DNASE2):c.347G>C (p.Gly116Ala)	Pathogenic
1686900	NM_001375.3(DNASE2):c.362A>T (p.Asp121Val)	Pathogenic
1686901	NM_001375.3(DNASE2):c.284A>G (p.Tyr95Cys)	Pathogenic

SpliceAI

481 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12876359:CAGGT:C	acceptor_gain	1.0000
19:12876364:C:CC	acceptor_gain	1.0000
19:12878375:GACTC:G	donor_loss	1.0000
19:12878376:ACTCA:A	donor_loss	1.0000
19:12878377:CTCA:C	donor_loss	1.0000
19:12878378:TCACC:T	donor_loss	1.0000
19:12878379:CACCA:C	donor_loss	1.0000
19:12878381:CCAT:C	donor_gain	1.0000
19:12878575:CTTGC:C	acceptor_gain	1.0000
19:12878578:GC:G	acceptor_gain	1.0000
19:12878578:GCC:G	acceptor_loss	1.0000
19:12878579:CC:C	acceptor_gain	1.0000
19:12878580:C:CC	acceptor_gain	1.0000
19:12878581:T:C	acceptor_loss	1.0000
19:12878588:C:CT	acceptor_gain	1.0000
19:12878589:A:T	acceptor_gain	1.0000
19:12880800:AC:A	donor_gain	1.0000
19:12880801:CC:C	donor_gain	1.0000
19:12881286:TCA:T	donor_loss	1.0000
19:12881288:A:AC	donor_gain	1.0000
19:12881288:ACC:A	donor_loss	1.0000
19:12881289:C:A	donor_loss	1.0000
19:12881289:C:CC	donor_gain	1.0000
19:12876361:GGT:G	acceptor_gain	0.9900
19:12876362:GTCTG:G	acceptor_loss	0.9900
19:12876365:T:A	acceptor_loss	0.9900
19:12878374:AGACT:A	donor_loss	0.9900
19:12878380:A:AC	donor_gain	0.9900
19:12878381:C:CC	donor_gain	0.9900
19:12878576:TTGC:T	acceptor_gain	0.9900

AlphaMissense

2356 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12881149:G:C	F30L	0.987
19:12881149:G:T	F30L	0.987
19:12881151:A:G	F30L	0.987
19:12876308:G:C	F255L	0.982
19:12876308:G:T	F255L	0.982
19:12876310:A:G	F255L	0.982
19:12881005:G:C	S78R	0.981
19:12881005:G:T	S78R	0.981
19:12881007:T:G	S78R	0.981
19:12878788:A:C	S131R	0.980
19:12878788:A:T	S131R	0.980
19:12878790:T:G	S131R	0.980
19:12881056:C:A	W61C	0.979
19:12881056:C:G	W61C	0.979
19:12876181:A:G	W298R	0.977
19:12876181:A:T	W298R	0.977
19:12878776:G:C	F135L	0.977
19:12878776:G:T	F135L	0.977
19:12878778:A:G	F135L	0.977
19:12881137:C:A	K34N	0.977
19:12881137:C:G	K34N	0.977
19:12876193:C:G	D294H	0.976
19:12876179:C:A	W298C	0.975
19:12876179:C:G	W298C	0.975
19:12876183:T:A	K297I	0.972
19:12876186:G:T	S296Y	0.969
19:12881058:A:G	W61R	0.968
19:12881058:A:T	W61R	0.968
19:12876093:C:G	C327S	0.966
19:12876094:A:T	C327S	0.966

dbSNP variants (sampled 300 via entrez): RS1000431261 (19:12883351 A>T), RS1001303266 (19:12881322 G>A,T), RS1001651198 (19:12881076 C>T), RS1001779175 (19:12875058 G>A), RS1001787344 (19:12875333 G>C), RS1002167240 (19:12875703 C>G,T), RS1002290291 (19:12879911 C>T), RS1002518341 (19:12876013 G>C), RS1002709616 (19:12880148 G>A,C), RS1002920237 (19:12883145 T>C), RS1002938869 (19:12880807 G>A), RS1003455324 (19:12876431 C>A,G,T), RS1004076936 (19:12879254 G>A), RS1004711087 (19:12882135 C>A,T), RS1005081028 (19:12877655 C>T)

Disease associations

OMIM: gene MIM:126350 | disease phenotypes: MIM:619858, MIM:610333, MIM:152700, MIM:601744

GenCC curated gene-disease

Disease	Classification	Inheritance
autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency	Strong	Autosomal recessive

Mondo (3): autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency (MONDO:0800132), Aicardi-Goutieres syndrome 4 (MONDO:0012472), systemic lupus erythematosus (MONDO:0007915)

Orphanet (2): Aicardi-Goutières syndrome (Orphanet:51), Systemic lupus erythematosus (Orphanet:536)

HPO phenotypes

24 total (25 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000793	Membranoproliferative glomerulonephritis
HP:0001270	Motor delay
HP:0001395	Hepatic fibrosis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001876	Pancytopenia
HP:0001945	Fever
HP:0001954	Recurrent fever
HP:0002028	Chronic diarrhea
HP:0002194	Delayed gross motor development
HP:0002611	Cholestatic liver disease
HP:0003040	Arthropathy
HP:0003577	Congenital onset
HP:0003623	Neonatal onset
HP:0009125	Lipodystrophy
HP:0009710	Chilblains
HP:0012156	Hemophagocytosis
HP:0031693	Severe Epstein Barr virus infection
HP:0032252	Granuloma
HP:0100651	Type I diabetes mellitus
HP:4000055	Intestinal inflammation
HP:0002725	Systemic lupus erythematosus

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002595_9	Clozapine-induced agranulocytosis	1.000000e-06
GCST004628_113	Immature fraction of reticulocytes	6.000000e-09
GCST006011_58	Mean corpuscular volume	4.000000e-32
GCST006804_132	Red cell distribution width	5.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590
C563681	Aicardi-Goutieres Syndrome 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1250342 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.70	Ki	200	nM	CHEMBL1240687

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 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-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-sulfanylpropanoic acid	507758: Binding affinity to Dnase 2	ki	0.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Cisplatin	affects expression, affects cotreatment, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
sodium arsenite	increases expression	2
Tunicamycin	increases expression	2
bisphenol A	increases expression	1
arsenite	affects expression	1
cobaltous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
entinostat	increases expression	1
pinostrobin	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
PP242	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Cadmium	affects localization, decreases reaction	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1244651	Binding	Binding affinity to Dnase 2	Phage-encoded combinatorial chemical libraries based on bicyclic peptides. — Nat Chem Biol

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E8F4	THP1-Dual KO-DNase2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients