RNASE2

Summary

RNASE2 (ribonuclease A family member 2, HGNC:10045) is a protein-coding gene on chromosome 14q11.2, encoding Non-secretory ribonuclease (P10153). This is a non-secretory ribonuclease.

The protein encoded by this gene is a non-secretory ribonuclease that belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein antimicrobial activity against viruses.

Source: NCBI Gene 6036 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• MANE Select transcript: NM_002934

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10045
Approved symbol	RNASE2
Name	ribonuclease A family member 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	EDN, RAF3
Ensembl gene	ENSG00000169385
Ensembl biotype	protein_coding
OMIM	131410
Entrez	6036

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000304625

RefSeq mRNA: 1 — MANE Select: NM_002934 NM_002934

CCDS: CCDS9561

Canonical transcript exons

ENST00000304625 — 2 exons

Exon	Start	End
ENSE00001124161	20955767	20956436
ENSE00001285128	20955487	20955536

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 99.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7787 / max 176.2572, expressed in 128 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138487	0.7481	126
138486	0.0306	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.52	gold quality
bone marrow	UBERON:0002371	98.92	gold quality
bone marrow cell	CL:0002092	97.66	gold quality
monocyte	CL:0000576	97.08	gold quality
mononuclear cell	CL:0000842	96.92	gold quality
leukocyte	CL:0000738	96.86	gold quality
granulocyte	CL:0000094	94.47	gold quality
blood	UBERON:0000178	93.60	gold quality
olfactory bulb	UBERON:0002264	87.78	gold quality
type B pancreatic cell	CL:0000169	86.87	gold quality
right lung	UBERON:0002167	85.83	gold quality
spleen	UBERON:0002106	85.49	gold quality
germinal epithelium of ovary	UBERON:0001304	82.90	gold quality
right adrenal gland cortex	UBERON:0035827	79.25	gold quality
right coronary artery	UBERON:0001625	78.75	gold quality
upper lobe of left lung	UBERON:0008952	78.49	gold quality
upper lobe of lung	UBERON:0008948	78.14	gold quality
right adrenal gland	UBERON:0001233	77.66	gold quality
left adrenal gland cortex	UBERON:0035825	77.05	gold quality
left adrenal gland	UBERON:0001234	76.91	gold quality
adrenal cortex	UBERON:0001235	76.01	gold quality
descending thoracic aorta	UBERON:0002345	75.78	gold quality
lower lobe of lung	UBERON:0008949	75.53	silver quality
left uterine tube	UBERON:0001303	75.41	gold quality
hair follicle	UBERON:0002073	74.54	gold quality
amniotic fluid	UBERON:0000173	74.50	gold quality
endothelial cell	CL:0000115	74.43	gold quality
mucosa of stomach	UBERON:0001199	73.81	gold quality
epithelial cell of pancreas	CL:0000083	73.72	gold quality
left coronary artery	UBERON:0001626	73.63	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	7288.46
E-GEOD-89232	yes	1840.59
E-CURD-112	yes	925.20
E-HCAD-10	yes	713.17
E-ANND-5	yes	473.26
E-HCAD-6	yes	355.05
E-ANND-3	yes	29.32
E-MTAB-9067	yes	23.17
E-CURD-122	yes	13.44
E-MTAB-10042	yes	12.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CEBPA, CEBPG, GATA1, GATA2, HNF4A, MAZ, SP1, SPI1, ZNF362

miRNA regulators (miRDB)

28 targeting RNASE2, 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-548AW	99.99	72.57	3559
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-3936	97.64	64.47	732
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-3139	96.68	66.77	652
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-4765	93.11	66.17	737

Literature-anchored findings (GeneRIF, showing 37)

• atomic resolution structure (PMID:11876642)
• crystal structure of a post-translationally modified form of eosinophil-derived neurotoxin (EDN) with four extra residues on its N terminus ((-4)EDN) has been solved and refined at atomic resolution (1 A) (PMID:11916383)
• EDN and ECP are paralogs in human and Old World monkeys. (PMID:11959927)
• evidence for glycosylphosphatidylinositol (GPI)-anchored neurotoxin on granulocytes (PMID:12606041)
• data suggest that peripheral blood eosinophils from subjects with untreated asthma have increased inflammatory capacity, as reflected by greater intracellular concentrations of EDN (PMID:15356558)
• Results reveal the dendritic cell-activating activity of eosinophil-derived neurotoxin and suggest that it is a likely participant of inflammatory and immune responses–an endogenous multifunctional immune alarmin. (PMID:15528350)
• Results describe the crystal structure of placental ribonuclease inhibitor in complex with eosinophil-derived neurotoxin, and a mutational analysis based on this structure. (PMID:15755456)
• May possibly be associated with the development of tropical pulmonary eosinophilia. (PMID:16014847)
• Elevated glycosylated form of EDN in urine is associated with ovarian cancer (PMID:16428483)
• EGO is a novel ncRNA gene expressed during eosinophil development and is necessary for normal MBP and EDN transcript expression. (PMID:17351112)
• Data show that uEPX/c levels did not correlate with established markers of asthma severity and eosinophilic airway inflammation in atopic asthmatic children. (PMID:17641730)
• MAZ and Sp1 play important roles on the transcriptional activation of the human edn promoter through specific binding to a 34-nt segment present in representative primate eosinophil rnase promoters. (PMID:17927842)
• Urinary concentrations of eosinophil-derived neurotoxin in patients with atopic dermatitis show a significant positive correlation with disease severity. (PMID:17965582)
• EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2-myeloid differentiation factor 88 signaling pathway (PMID:18195069)
• In three continental population groups (Asia, Europe, Africa), the angiogenin and RNase 2 genes appear to exhibit markedly less genetic heterogeneity with regard to T195C and A238G (ANG) and C425A (RNASE2) SNPs. (PMID:18636464)
• No variation in genes encoding eosinophil-derived neurotoxin for Atopic dermatitis pathogenesis in this German cohort. (PMID:19014520)
• the roles of the six discrete segments in transcription regulation were investigated and the -350/-329 region (ednR2) was shown to be involved in the regulation of edn expression (PMID:19115260)
• ECP and EDN disrupt skin integrity and cause inflammation (PMID:19717523)
• Eosinophil protein X in urine from asymptomatic neonates is a biomarker significantly associated with later development of allergic sensitization, nasal eosinophilia, and eczema during the first 6 years of life (PMID:21680952)
• findings show substantial amounts of EPX/EDN localise in an extra-granular, low equilibrium density compartment of eosinophils (PMID:23053729)
• A higher level of serum EDN was found specifically in patients with ALS, indicating that EDN may participate in the pathophysiology of Amyotrophic lateral sclerosis. (PMID:23533305)
• mRNA levels of eosinophil granule proteins, rather than sputum eosinophil%, may reflect airway hyperresponsiveness and airflow limitation. (PMID:24814827)
• increased in feces after the ingestion of enterocolitis-causative foods (PMID:24890227)
• RNASE2 gene expression was differentially expressed in rheumatoid arthritis patients considering a sequence polymorphism. (PMID:25221852)
• Serum EDN level may be a useful marker for monitoring persistent airflow limitation in adult patients with asthma who had positive results for house-dust-specific IgE antibodies. (PMID:26534742)
• In healthy children, 95th Percentile values ranged from 1519 mg/kg at 0 months to 54.4 mg/kg at 144 months for fecal calprotectin (fCP) and from 9.9 mg/kg at 0 months to 0.2 mg/kg at 144 months for fecal eosinophil-derived neurotoxin (fEDN). There was a significant association between age and fCP concentrations and age and fEDN concentrations and a significant association between fEDN and fCP. (PMID:28169973)
• EDN serum level could be considered a candidate molecule as a clinical biomarker for evaluating atopic dermatitis activity and a predictor of relapse (PMID:28866306)
• the rs3827907 C-allele appeared to particularly influence inhaled corticosteroid treatment response in the presence of eosinophilic inflammation (PMID:30367910)
• Immune Sensing of Synthetic, Bacterial, and Protozoan RNA by Toll-like Receptor 8 Requires Coordinated Processing by RNase T2 and RNase 2. (PMID:32294405)
• Combined assessment of serum eosinophil-derived neurotoxin and YKL-40 may identify Asthma-COPD overlap. (PMID:32571644)
• Blood eosinophil cationic protein and eosinophil-derived neurotoxin are associated with different asthma expression and evolution in adults. (PMID:34615736)
• RNASE2 Mediates Age-Associated B Cell Expansion Through Monocyte Derived IL-10 in Patients With Systemic Lupus Erythematosus. (PMID:35265065)
• RNase2 is a possible trigger of acute-on-chronic inflammation leading to mRNA vaccine-associated cardiac complication. (PMID:37105176)
• The Role of Eosinophil-Derived Neurotoxin and Vascular Endothelial Growth Factor in the Pathogenesis of Eosinophilic Asthma. (PMID:37174726)
• Eosinophil-derived neurotoxin levels in early childhood and association with preschool asthma - A prospective observational study. (PMID:37795650)
• Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil-derived neurotoxin. (PMID:38374551)
• The antimicrobial protein, RNase 2 exhibits antiviral against respiratory syncytial virus. (PMID:9826755)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnase2a	ENSMUSG00000047222
mus_musculus	Ear14	ENSMUSG00000050766
mus_musculus	Rnase2b	ENSMUSG00000059606
mus_musculus	Ear6	ENSMUSG00000062148
mus_musculus	Ear2	ENSMUSG00000072596
mus_musculus	Ear1	ENSMUSG00000072601
mus_musculus	Ear10	ENSMUSG00000090166
rattus_norvegicus	Rnase2	ENSRNOG00000032133
rattus_norvegicus	Ear1	ENSRNOG00000062969
rattus_norvegicus	Rnase17	ENSRNOG00000063957
rattus_norvegicus	Ear1l1	ENSRNOG00000070444
rattus_norvegicus		ENSRNOG00000077288
rattus_norvegicus		ENSRNOG00000085776

Paralogs (12): RNASE1 (ENSG00000129538), RNASE7 (ENSG00000165799), RNASE3 (ENSG00000169397), RNASE6 (ENSG00000169413), RNASE8 (ENSG00000173431), RNASE11 (ENSG00000173464), RNASE10 (ENSG00000182545), RNASE9 (ENSG00000188655), RNASE13 (ENSG00000206150), ANG (ENSG00000214274), RNASE12 (ENSG00000258436), RNASE4 (ENSG00000258818)

Protein

Protein identifiers

Non-secretory ribonuclease — P10153 (reviewed: P10153)

Alternative names: Eosinophil-derived neurotoxin, RNase UpI-2, Ribonuclease 2, Ribonuclease US

All UniProt accessions (2): P10153, W0UV60

UniProt curated annotations — full annotation on UniProt →

Function. This is a non-secretory ribonuclease. It is a pyrimidine specific nuclease with a slight preference for U. Cytotoxin and helminthotoxin. Selectively chemotactic for dendritic cells. Possesses a wide variety of biological activities.

Subunit / interactions. Interacts with and forms a tight 1:1 complex with RNH1. Dimerization of two such complexes may occur.

Subcellular location. Lysosome. Cytoplasmic granule.

Tissue specificity. Liver, lung, spleen, leukocytes and body fluids.

Post-translational modifications. A particular signal processing and glycosylation pattern may differentiate the UpI2 RNase, found specifically in pregnant women urine, from other nonsecretory RNases.

Domain organisation. The N-terminal region is necessary for mediating chemotactic activity.

Similarity. Belongs to the pancreatic ribonuclease family.

RefSeq proteins (1): NP_002925* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001427	RNaseA	Family
IPR023411	RNaseA_AS	Active_site
IPR023412	RNaseA_domain	Domain
IPR036816	RNaseA-like_dom_sf	Homologous_superfamily

Pfam: PF00074

UniProt features (33 total): glycosylation site 6, strand 6, disulfide bond 4, sequence conflict 4, helix 4, sequence variant 2, active site 2, signal peptide 1, chain 1, turn 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
9R6D	X-RAY DIFFRACTION	0.94
1GQV	X-RAY DIFFRACTION	0.98
2BZZ	X-RAY DIFFRACTION	0.98
1K2A	X-RAY DIFFRACTION	1
9GQM	X-RAY DIFFRACTION	1.01
9GQP	X-RAY DIFFRACTION	1.01
9QR7	X-RAY DIFFRACTION	1.01
9QYO	X-RAY DIFFRACTION	1.02
9R6E	X-RAY DIFFRACTION	1.02
9RAN	X-RAY DIFFRACTION	1.02
9GO7	X-RAY DIFFRACTION	1.04
9GO8	X-RAY DIFFRACTION	1.04
9GQ0	X-RAY DIFFRACTION	1.04
9GO4	X-RAY DIFFRACTION	1.17
8QEW	X-RAY DIFFRACTION	1.2
6SSO	X-RAY DIFFRACTION	1.21
2C01	X-RAY DIFFRACTION	1.24
9GNT	X-RAY DIFFRACTION	1.31
5E13	X-RAY DIFFRACTION	1.34
1HI2	X-RAY DIFFRACTION	1.6
8F5X	X-RAY DIFFRACTION	1.7
1HI3	X-RAY DIFFRACTION	1.8
1HI4	X-RAY DIFFRACTION	1.8
1HI5	X-RAY DIFFRACTION	1.8
2C05	X-RAY DIFFRACTION	1.86
2BEX	X-RAY DIFFRACTION	1.99
2C02	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10153-F1	91.67	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 (2): 42 (proton acceptor); 156 (proton donor)

Ligand- & substrate-binding residues (1): 65–69

Post-translational modifications (1): 60

Disulfide bonds (4): 50–110, 64–123, 82–138, 89–98

Glycosylation sites (6): 111, 119, 34, 44, 86, 92

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 190 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOCC_SECRETORY_GRANULE, GOMF_NUCLEASE_ACTIVITY, MODULE_45, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_511, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, MODULE_16

GO Biological Process (4): innate immune response in mucosa (GO:0002227), RNA catabolic process (GO:0006401), chemotaxis (GO:0006935), defense response to virus (GO:0051607)

GO Molecular Function (8): nucleic acid binding (GO:0003676), ribonuclease A activity (GO:0004522), RNA nuclease activity (GO:0004540), hydrolase activity (GO:0016787), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
nuclease activity	2
catalytic activity	2
mucosal immune response	1
innate immune response	1
RNA metabolic process	1
nucleic acid catabolic process	1
response to chemical	1
taxis	1
defense response	1
response to virus	1
RNA endonuclease activity	1
phosphorus-oxygen lyase activity	1
catalytic activity, acting on RNA	1
catalytic activity, acting on a nucleic acid	1
cellular anatomical structure	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1
lytic vacuole	1

Protein interactions and networks

STRING

1044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNASE2	EPX	P11678	999
RNASE2	RNASE3	P12724	964
RNASE2	PRG2	P13727	944
RNASE2	ANG	P03950	926
RNASE2	RNASET2	O00584	815
RNASE2	EDNRA	P25101	787
RNASE2	CD300A	Q9UGN4	706
RNASE2	RNASEL	Q05823	686
RNASE2	IL5	P05113	669
RNASE2	LILRB3	O75022	622
RNASE2	CCL11	P50877	591
RNASE2	IL5RA	Q01344	582
RNASE2	CLC	Q05315	581
RNASE2	RNASE11	Q8TAA1	581
RNASE2	EDN3	P14138	573

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RNASE2	DLG2	psi-mi:“MI:0915”(physical association)	0.560
RNH1	RNASE2	psi-mi:“MI:0407”(direct interaction)	0.440
	RNASE2	psi-mi:“MI:0902”(rna cleavage)	0.440
RNASE2	PCP2	psi-mi:“MI:0915”(physical association)	0.400
RNASE2	DLG2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): PCP2 (Affinity Capture-MS), RNASE2 (Two-hybrid), RNASE2 (Positive Genetic), GEMIN4 (Two-hybrid), RNASE2 (Reconstituted Complex)

ESM2 similar proteins: A5HAK0, O18937, O35290, O35291, O35292, P00686, P10152, P10153, P12724, P27043, P30374, P31346, P47778, P47779, P47780, P47781, P47782, P47783, P47784, P47785, P70709, P80287, P97425, P97426, P97802, Q3TMQ6, Q861Y1, Q861Y2, Q861Y3, Q861Y4, Q861Y5, Q8SPN5, Q8SPY2, Q8SPY3, Q8SPY4, Q8SPY5, Q8SPY7, Q8SPY8, Q8SPY9, Q8SQ09

Diamond homologs: A1YLB9, B3EWJ0, O18937, O35290, O35291, O35292, O46525, O46526, O46527, O46528, O46529, O46530, O46531, O46532, O46533, O46534, O55004, P00657, P00680, P00682, P00685, P03950, P08904, P10153, P12724, P15466, P15467, P15468, P16414, P24717, P34096, P47778, P47779, P47780, P47781, P47782, P47783, P47784, P47785, P47786

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EPX	“up-regulates activity”	RNASE2	“post translational modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

185 predictions. Top by Δscore:

Variant	Effect	Δscore
14:20955534:TGGG:T	donor_loss	1.0000
14:20955535:GG:G	donor_gain	1.0000
14:20955535:GGGT:G	donor_loss	1.0000
14:20955536:GG:G	donor_gain	1.0000
14:20955536:GGT:G	donor_loss	1.0000
14:20955537:G:GG	donor_gain	1.0000
14:20955538:T:G	donor_loss	0.9900
14:20955533:CTGG:C	donor_gain	0.9800
14:20955534:TGG:T	donor_gain	0.9600
14:20955535:GGG:G	donor_gain	0.9600
14:20955532:ACTGG:A	donor_gain	0.9500
14:20955761:TTACA:T	acceptor_loss	0.9400
14:20955762:TACAG:T	acceptor_loss	0.9400
14:20955764:CAGGA:C	acceptor_loss	0.9400
14:20955765:A:AT	acceptor_loss	0.9400
14:20955766:G:A	acceptor_loss	0.9400
14:20955765:A:AG	acceptor_gain	0.9100
14:20955766:G:GG	acceptor_gain	0.9100
14:20955766:GGA:G	acceptor_gain	0.9000
14:20955766:GGAA:G	acceptor_gain	0.8500
14:20955765:AG:A	acceptor_gain	0.8000
14:20955766:GG:G	acceptor_gain	0.8000
14:20956176:A:AG	acceptor_gain	0.7800
14:20956177:G:GG	acceptor_gain	0.7800
14:20955539:AAG:A	donor_loss	0.7500
14:20955766:GGAAA:G	acceptor_gain	0.7400
14:20955648:G:GT	donor_gain	0.7200
14:20956072:A:AG	acceptor_gain	0.7100
14:20956073:G:GG	acceptor_gain	0.7100
14:20956183:T:G	acceptor_gain	0.6900

AlphaMissense

1069 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:20955883:T:C	F38L	0.992
14:20955885:T:A	F38L	0.992
14:20955885:T:G	F38L	0.992
14:20955979:T:C	F70L	0.992
14:20955981:C:A	F70L	0.992
14:20955981:C:G	F70L	0.992
14:20955980:T:G	F70C	0.989
14:20955884:T:G	F38C	0.988
14:20955961:T:A	C64S	0.984
14:20955962:G:C	C64S	0.984
14:20956099:T:A	C110S	0.984
14:20956100:G:C	C110S	0.984
14:20955966:A:C	K65N	0.983
14:20955966:A:T	K65N	0.983
14:20956138:T:A	C123S	0.982
14:20956139:G:C	C123S	0.982
14:20955995:T:G	F75C	0.981
14:20956063:T:A	C98S	0.979
14:20956064:G:C	C98S	0.979
14:20956232:C:A	P154Q	0.979
14:20956072:A:C	S101R	0.977
14:20956074:T:A	S101R	0.977
14:20956074:T:G	S101R	0.977
14:20956183:T:A	C138S	0.977
14:20956184:G:A	C138Y	0.977
14:20956184:G:C	C138S	0.977
14:20956066:C:G	H99D	0.976
14:20956015:T:A	C82S	0.975
14:20956016:G:C	C82S	0.975
14:20956036:T:A	C89S	0.975

dbSNP variants (sampled 300 via entrez): RS1001771426 (14:20954293 T>A,C), RS1002111098 (14:20954544 G>A,T), RS1003172789 (14:20955525 C>T), RS1003771626 (14:20956882 C>G,T), RS1004228302 (14:20956647 G>A), RS1004271740 (14:20955932 T>C), RS1007560167 (14:20953585 G>A), RS1010973512 (14:20956834 T>G), RS10132319 (14:20955642 A>C,G), RS10142760 (14:20954909 C>T), RS1014380473 (14:20954013 G>C), RS10145713 (14:20956348 G>A,C), RS1017611519 (14:20954295 T>A,C), RS1018059214 (14:20953622 C>A,G), RS1018654862 (14:20954972 T>C)

Disease associations

OMIM: gene MIM:131410 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000705_7	Crohn’s disease	6.000000e-08
GCST006585_944	Blood protein levels	2.000000e-26

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5120 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.75	Ki	180	nM	CHEMBL401150
6.75	Ki	180	nM	CHEMBL455775

PubChem BioAssay actives

2 with measured affinity, of 13 total; 2 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,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [[(2R,3S,5R)-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate	345853: Inhibition of human EDN	ki	0.1800	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,5R)-5-(2,4-dioxopyrimidin-1-yl)-2-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate	718195: Inhibition of EDN	ki	0.1800	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Tretinoin	affects cotreatment, decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Salmeterol Xinafoate	decreases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Beclomethasone	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cyclophosphamide	decreases expression	1
Cytarabine	increases expression	1
Fonofos	increases methylation	1
Ozone	affects expression, increases abundance	1
Parathion	increases methylation	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Asbestos, Serpentine	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Antirheumatic Agents	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2215700	Binding	Inhibition of EDN	Triazole pyrimidine nucleosides as inhibitors of Ribonuclease A. Synthesis, biochemical, and structural evaluation. — Bioorg Med Chem

Clinical trials (associated diseases)

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