RNASE1

Summary

RNASE1 (ribonuclease A family member 1, pancreatic, HGNC:10044) is a protein-coding gene on chromosome 14q11.2, encoding Ribonuclease pancreatic (P07998). Endonuclease that catalyzes the cleavage of RNA on the 3’ side of pyrimidine nucleotides. In precision oncology, RAC1 P29S is associated with resistance to Dabrafenib + Vemurafenib in Melanoma (CIViC Level B); 2 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 77.1% of cell lines).

This gene encodes a member of the pancreatic-type of secretory ribonucleases, a subset of the ribonuclease A superfamily. The encoded endonuclease cleaves internal phosphodiester RNA bonds on the 3’-side of pyrimidine bases. It prefers poly(C) as a substrate and hydrolyzes 2’,3’-cyclic nucleotides, with a pH optimum near 8.0. The encoded protein is monomeric and more commonly acts to degrade ds-RNA over ss-RNA. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified.

Source: NCBI Gene 6035 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 132 total — 10 pathogenic, 17 likely-pathogenic
• GTEx eGene: eQTL in 25 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 68
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 77.1% of screened cell lines
• Constraint (gnomAD): pLI 0.14 (intermediate), LOEUF 1.91 (unconstrained)
• MANE Select transcript: NM_002933

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10044
Approved symbol	RNASE1
Name	ribonuclease A family member 1, pancreatic
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	RAC1
Ensembl gene	ENSG00000129538
Ensembl biotype	protein_coding
OMIM	180440
Entrez	6035

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 16 protein_coding

MANE Select: ENST00000397967

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

ENST00000397967, ENST00000340900, ENST00000397970, ENST00000412779, ENST00000555698, ENST00000884083, ENST00000884084, ENST00000884085, ENST00000884086, ENST00000884087, ENST00000884088, ENST00000884089, ENST00000960487, ENST00000960488, ENST00000960489, ENST00001134923

RefSeq mRNA: 4 — MANE Select: NM_002933 NM_002933, NM_198232, NM_198234, NM_198235

CCDS: CCDS9559

Canonical transcript exons

ENST00000397967 — 2 exons

Exon	Start	End
ENSE00001867062	20802797	20802844
ENSE00001929748	20801228	20802093

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.90.

FANTOM5 (CAGE): breadth broad, TPM avg 145.4140 / max 18126.0918, expressed in 744 samples.

Highest expression (Bgee): testis, lung, upper lobe of lung, upper lobe of left lung, synovial joint.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RNASE1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	8.3e-23	-0.35	14:20807826:G:A
Lung	eqtl	2.0e-09	-0.19	14:20710228:C:G
Stomach	eqtl	2.0e-09	-0.25	14:20807826:G:A
Whole Blood	eqtl	5.4e-09	+0.47	14:20802929:G:C
Adrenal Gland	eqtl	5.2e-08	-0.23	14:20728872:C:A
Heart Atrial Appendage	eqtl	4.0e-07	-0.20	14:20732555:C:T
Artery Aorta	eqtl	3.2e-06	-0.18	14:20730487:T:C
Adipose Subcutaneous	eqtl	3.9e-06	-0.13	14:20730487:T:C
Artery Tibial	eqtl	4.1e-06	-0.14	14:20735667:A:G
Nerve Tibial	eqtl	2.4e-05	-0.17	14:20710854:T:C
Adipose Visceral Omentum	eqtl	2.4e-05	+0.16	14:20812589:T:C
Heart Left Ventricle	eqtl	7.4e-04	-0.14	14:20770159:G:A
Colon Sigmoid	eqtl	1.6e-03	+0.22	14:20793396:C:G
Esophagus Muscularis	eqtl	3.6e-03	-0.09	14:20710228:C:G
Adipose Visceral Omentum	sqtl	4.3e-03	-0.23	14:20812519:G:A
Cells EBV-transformed lymphocytes	eqtl	5.7e-03	-0.25	14:20730487:T:C
Muscle Skeletal	eqtl	8.8e-03	+0.11	14:20812519:G:A
Esophagus Gastroesophageal Junction	eqtl	8.9e-03	-0.44	14:21551050:C:G
Skin Sun Exposed Lower leg	eqtl	1.1e-02	+0.10	14:20812519:G:A
Artery Coronary	eqtl	1.4e-02	-0.20	14:20730010:C:T

FANTOM5 promoters

showing 10 of 14 alternative TSS:

Promoter ID	TPM avg	Samples expressed
142066	125.7577	717
142067	8.6711	536
142063	4.1873	132
142060	1.8323	287
142054	1.0058	204
142064	0.9282	75
142059	0.8687	180
142061	0.8183	199
142062	0.3817	136
142055	0.3117	112

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.90	gold quality
right testis	UBERON:0004534	99.90	gold quality
right lung	UBERON:0002167	99.64	gold quality
upper lobe of lung	UBERON:0008948	99.61	gold quality
upper lobe of left lung	UBERON:0008952	99.61	gold quality
synovial joint	UBERON:0002217	99.58	gold quality
testis	UBERON:0000473	99.53	gold quality
gall bladder	UBERON:0002110	99.50	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.48	gold quality
body of pancreas	UBERON:0001150	99.47	gold quality
decidua	UBERON:0002450	99.45	gold quality
peritoneum	UBERON:0002358	99.43	gold quality
omental fat pad	UBERON:0010414	99.43	gold quality
layer of synovial tissue	UBERON:0007616	99.42	gold quality
adult organism	UBERON:0007023	99.40	gold quality
mucosa of stomach	UBERON:0001199	99.37	gold quality
right coronary artery	UBERON:0001625	99.37	gold quality
right adrenal gland cortex	UBERON:0035827	99.37	gold quality
inferior vagus X ganglion	UBERON:0005363	99.35	gold quality
corpus callosum	UBERON:0002336	99.33	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.32	gold quality
body of stomach	UBERON:0001161	99.30	gold quality
apex of heart	UBERON:0002098	99.30	gold quality
spinal cord	UBERON:0002240	99.29	gold quality
right uterine tube	UBERON:0001302	99.23	gold quality
rectum	UBERON:0001052	99.19	gold quality
right adrenal gland	UBERON:0001233	99.16	gold quality
lung	UBERON:0002048	99.13	gold quality
middle frontal gyrus	UBERON:0002702	99.12	gold quality
lower lobe of lung	UBERON:0008949	99.12	gold quality
mucosa of transverse colon	UBERON:0004991	99.08	gold quality
spleen	UBERON:0002106	99.06	gold quality
trachea	UBERON:0003126	99.03	gold quality
left adrenal gland	UBERON:0001234	98.95	gold quality
putamen	UBERON:0001874	98.93	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.93	gold quality
left adrenal gland cortex	UBERON:0035825	98.93	gold quality
left uterine tube	UBERON:0001303	98.92	gold quality
transverse colon	UBERON:0001157	98.86	gold quality
adipose tissue	UBERON:0001013	98.84	gold quality
adrenal cortex	UBERON:0001235	98.84	gold quality
metanephros cortex	UBERON:0010533	98.84	gold quality
stomach	UBERON:0000945	98.80	gold quality
right atrium auricular region	UBERON:0006631	98.80	gold quality
lateral globus pallidus	UBERON:0002476	98.79	gold quality
cranial nerve II	UBERON:0000941	98.75	gold quality
coronary artery	UBERON:0001621	98.73	gold quality
cardiac atrium	UBERON:0002081	98.73	gold quality
subthalamic nucleus	UBERON:0001906	98.71	gold quality
left coronary artery	UBERON:0001626	98.70	gold quality
fundus of stomach	UBERON:0001160	98.68	gold quality
descending thoracic aorta	UBERON:0002345	98.67	gold quality
ventral tegmental area	UBERON:0002691	98.65	gold quality
right ovary	UBERON:0002118	98.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.62	gold quality
heart left ventricle	UBERON:0002084	98.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.56	gold quality
cardiac ventricle	UBERON:0002082	98.54	gold quality
amygdala	UBERON:0001876	98.52	gold quality
midbrain	UBERON:0001891	98.52	gold quality
substantia nigra	UBERON:0002038	98.52	gold quality
heart	UBERON:0000948	98.49	gold quality
caudate nucleus	UBERON:0001873	98.49	gold quality
lower esophagus	UBERON:0013473	98.48	gold quality
superior vestibular nucleus	UBERON:0007227	98.47	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.44	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.44	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.39	gold quality
pons	UBERON:0000988	98.37	gold quality
skin of hip	UBERON:0001554	98.37	gold quality
pericardium	UBERON:0002407	98.34	gold quality
tendon of biceps brachii	UBERON:0008188	98.34	gold quality
sigmoid colon	UBERON:0001159	98.32	gold quality
placenta	UBERON:0001987	98.32	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.30	gold quality
thoracic aorta	UBERON:0001515	98.29	gold quality
medulla oblongata	UBERON:0001896	98.28	gold quality
heart right ventricle	UBERON:0002080	98.27	gold quality
connective tissue	UBERON:0002384	98.25	gold quality
myocardium	UBERON:0002349	98.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.22	gold quality
ascending aorta	UBERON:0001496	98.19	gold quality
smooth muscle tissue	UBERON:0001135	98.17	gold quality
tibial nerve	UBERON:0001323	98.17	gold quality
adrenal gland	UBERON:0002369	98.11	gold quality
large intestine	UBERON:0000059	98.10	gold quality
colon	UBERON:0001155	98.08	gold quality
left ventricle myocardium	UBERON:0006566	98.03	gold quality
pancreas	UBERON:0001264	97.95	gold quality
hypothalamus	UBERON:0001898	97.95	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.93	gold quality
superficial temporal artery	UBERON:0001614	97.92	gold quality
prefrontal cortex	UBERON:0000451	97.90	gold quality
intestine	UBERON:0000160	97.89	gold quality
body of uterus	UBERON:0009853	97.80	gold quality
minor salivary gland	UBERON:0001830	97.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.77	gold quality
pylorus	UBERON:0001166	97.76	gold quality
globus pallidus	UBERON:0001875	97.75	gold quality
small intestine	UBERON:0002108	97.75	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 32.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	12752.11
E-MTAB-6678	yes	10914.47
E-MTAB-8322	yes	8798.36
E-MTAB-6701	yes	7947.51
E-MTAB-7407	yes	7077.58
E-HCAD-36	yes	5563.43
E-HCAD-15	yes	5351.96
E-MTAB-8142	yes	5130.80
E-MTAB-9906	yes	4955.99
E-HCAD-10	yes	4794.24
E-GEOD-134144	yes	3957.54
E-GEOD-84465	yes	3923.75
E-MTAB-6653	yes	3214.44
E-GEOD-124263	yes	2967.86
E-CURD-112	yes	2169.89

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 155 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pancreas	tissue	8599.3	high
Stomach 1	tissue	945.6	high
Placenta	tissue	842.3	not detected
Lung	tissue	730.8	not detected
Adipose tissue	tissue	613.5	not detected
Testis	tissue	601.5	low
Adrenal gland	tissue	472.2	not detected
Hippocampal formation	tissue	441.4
Rectum	tissue	398.6	high
Spinal cord	tissue	382.8
Gallbladder	tissue	380.5	not detected
Amygdala	tissue	375.0
Colon	tissue	354.4	high
Hippocampal formation	tissue	350.7
Urinary bladder	tissue	349.3	not detected
Basal ganglia	tissue	341.0	medium
Cerebral cortex	tissue	326.8	medium
Motor cortex	tissue	326.8
Septum	tissue	324.9
Heart muscle	tissue	323.4	not detected
Periaqueductal gray	tissue	321.7
Entorhinal cortex	tissue	313.9
Ovary	tissue	311.6	not detected
Prefrontal cortex	tissue	311.1
Temporal cortex	tissue	310.8
Corpus callosum	tissue	307.7
Midbrain	tissue	307.0
Medulla oblongata	tissue	297.6
Insular cortex	tissue	296.2
Thalamus	tissue	289.4
Substantia nigra	tissue	286.5
Thalamus	tissue	283.8
Retrosplenial cortex	tissue	278.9
Ventral forebrain	tissue	278.8
Hypothalamus	tissue	277.7
Pons	tissue	277.5
Breast	tissue	273.6	not detected
Caudate putamen	tissue	272.3
Hypothalamus	tissue	269.6
Superior colliculi	tissue	269.0
Midbrain	tissue	268.7
Smooth muscle	tissue	266.6	not detected
Retrosplenial and cingulate cortex	tissue	262.2
Tongue	tissue	261.8
Medulla oblongata	tissue	260.6
Cerebral cortex	tissue	259.4	low
Motor cortex	tissue	259.4
Septum	tissue	258.5
Prefrontal cortex	tissue	257.2
Spleen	tissue	257.0	not detected
Pons	tissue	254.4
Nucleus accumbens	tissue	254.4
Spinal cord	tissue	252.8
Ventral forebrain	tissue	247.5
Putamen	tissue	245.2
Amygdala	tissue	243.2
Substantia nigra	tissue	242.0
Periaqueductal gray	tissue	239.2
Temporal cortex	tissue	238.0
Somatosensory cortex	tissue	235.1

Brain sub-regions (HPA Brain Atlas): detected in 381; highest nTPM — Temporal white matter (654.1), Corpus callosum, genu (white matter) (613.3), Area striata (white matter) (586.2), Parieto-temporal junction (white matter) (581.9), Corpus callosum, splenium (white matter) (549.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBP

miRNA regulators (miRDB)

Targeting RNASE1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

20 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
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-4533	100.00	69.48	2758
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-5194	96.77	63.91	1021

Functional genomics

gnomAD constraint: pLI 0.141, LOEUF 1.91, missense Z 0.19 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000397967 — one region, missense o/e 1.01. DepMap (CRISPR cell-line fitness): dependent in 77.1% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SNU-1544 (-0.506), TUHR10TKB (-0.504).

Literature-anchored findings (GeneRIF, showing 24)

• Human endothelial cells selectively express large amounts of pancreatic-type ribonuclease (RNase 1) (PMID:12210760)
• Results show that Glycine 38 is crucial for the full catalytic activity of the human enzyme on duplex RNA as its substitution with aspartate or alanine results in a drastic reduction in the dsRNA cleavage activity of HPR. (PMID:12237131)
• Results reveal the dendritic cell-activating activity of pancreatic ribonuclease and suggest that it is a likely participant of inflammatory and immune responses–an endogenous multifunctional immune alarmin. (PMID:15528350)
• Altogether the results suggest that the pressure-folding transition state of ribonuclease A looks like a collapsed globule with some secondary structure and a weakened hydrophobic core. This is the first direct comparison using a set of mutants. (PMID:16597833)
• RNase-1 has ribonuclease H activity. (PMID:16738129)
• Human pancreatic-ribonuclease interacts with importin alpha through different basic residues, including Lys1 and the arginine clusters 31-33 and 89-91. (PMID:16780873)
• The results were confirmed at the level of mRNA and protein, and suggested that four genes (OPCML, RNASE1, YES1 and ACK1) could play a key role in the tumorigenesis and metastasis of gastric cancer. (PMID:17109515)
• Structural and energetic aspects of the interaction between human RI (hRI) and human pancreatic ribonuclease (RNase 1), is reported. (PMID:17350650)
• Coulombic forces mediate extracellular and intracellular equilibria in a dichotomous manner that both endangers cells and defends them from the potentially lethal enzymatic activity of ribonucleases. (PMID:17705507)
• irrespective of differences in ethnic groups, RNASE1 might show markedly low heterogeneity in its genetic structure with regard to these SNPs (PMID:18219569)
• Multiple side chain conformations observed for key surface residues are proposed to be crucial for membrane binding as well as translocation and efficient RNA hydrolysis. (PMID:18495155)
• Studies illustrate of the making dimeric pancreatic RNase through removal by directed mutagenesis of most of the N-terminal alpha-helix to the remainder of the protein. (PMID:19156888)
• The nuclear transport of PE5 is critical for its cytotoxicity. (PMID:20352290)
• Vascular RNase1 and RNase5 are mainly produced by vascular endothelial cells and can serve, depending on the vascular bed, different functions in vascular homeostasis and endothelial cell responses. (PMID:21103661)
• In human pancreatic ribonuclease both glutamine 28 and arginine 39 are important for the cleavage of dsRNA. (PMID:21408145)
• The role on the dimerization process of different residues of a domain-swapped dimer human pancreatic ribonuclease variant. (PMID:21767499)
• The reduced conformational flexibility of eosinophil cationic protein can be dynamically and functionally reproduced in the RNase A scaffold. (PMID:23135272)
• Deletion of five residues in the hinge loop of pancreatic ribonuclease induces formation of a domain-swapped dimer that leads to the generation of linear aggregates of pancreatic RNase, revealed by the crystal packing. (PMID:24100329)
• Focusing on the increase in an N-glycosylated Asn residue of serum pancreatic ribonuclease 1, specifically Asn(88), affords a new diagnostic marker for pancreatic cancer (PMID:25336120)
• Data suggest that ribonuclease inhibitor (RNH1) protects HeLa cells from ribonuclease 1 (RNase 1). (PMID:27806571)
• N-glycosylation of human RNase 1 improves its resistance to both thermal denaturation and proteolytic degradation but reduces its catalytic activity.N-glycosylation of Asn34 in human RNase 1 significantly improves overall protein stability while maintaining robust catalytic activity. (PMID:30633504)
• Chromatin immunoprecipitation kinetics revealed that HDAC2 accumulates at the RNASE1 promoter upon TNF-alpha stimulation, indicating an essential role for HDAC2 in regulating RNase1 expression. Thus, proinflammatory stimulation induced recruitment of HDAC2 to attenuate histone acetylation at the RNASE1 promoter site. (PMID:31039328)
• Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment. (PMID:32609822)
• Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation. (PMID:33986289)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnase1	ENSMUSG00000035896
rattus_norvegicus	Rnase1l1	ENSRNOG00000025615
rattus_norvegicus	Rnase1	ENSRNOG00000063584
rattus_norvegicus	Rnase1l2	ENSRNOG00000069584

Paralogs (12): RNASE7 (ENSG00000165799), RNASE2 (ENSG00000169385), RNASE3 (ENSG00000169397), RNASE6 (ENSG00000169413), RNASE8 (ENSG00000173431), RNASE11 (ENSG00000173464), RNASE10 (ENSG00000182545), RNASE9 (ENSG00000188655), RNASE13 (ENSG00000206150), ANG (ENSG00000214274), RNASE12 (ENSG00000258436), RNASE4 (ENSG00000258818)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97919) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased body weight	1
abnormal skin morphology	1
abnormal blood coagulation	1
abnormal enzyme/coenzyme activity	1
decreased prepulse inhibition	1
abnormal blood homeostasis	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Chlorocebus aethiops	P61821	100.0%	Diamond
Miopithecus talapoin	P61822	100.0%	Diamond
Bos taurus	P61823	100.0%	Diamond
Bison bison	P61824	100.0%	Diamond
Capra hircus	P67926	100.0%	Diamond
Ovis aries	P67927	100.0%	Diamond
Gorilla gorilla gorilla	Q71MJ0	100.0%	Diamond
Pan troglodytes	Q8HZQ0	99.3%	Diamond
Papio hamadryas	Q8SQ09	99.3%	Diamond
Cervus elaphus	P00663	99.2%	Diamond
Dama dama	P00665	99.2%	Diamond
Camelus dromedarius	P67928	99.2%	Diamond
Camelus bactrianus	P67929	99.2%	Diamond
Lithobates pipiens	P85072	99.1%	Diamond
Macaca mulatta	Q8SPN5	98.7%	Diamond
Pongo abelii	Q5NVS4	98.6%	Diamond
Aepyceros melampus	P07847	98.4%	Diamond
Ateles geoffroyi	Q8SQ06	98.1%	Diamond
Saimiri sciureus	Q8SQ08	98.1%	Diamond
Connochaetes taurinus	P00660	97.6%	Diamond
Axis porcinus	P87351	97.6%	Diamond
Nomascus leucogenys	Q8SQ11	97.4%	Diamond
Oryx leucoryx	Q29606	97.3%	Diamond
Rattus exulans	Q8VD92	97.3%	Diamond
Semnopithecus entellus	P19644	96.9%	Diamond
Pygathrix nemaeus	Q8SPN3	96.9%	Diamond
Capreolus capreolus	P00664	96.8%	Diamond
Rangifer tarandus	P00666	96.8%	Diamond
Alces alces alces	P00667	96.8%	Diamond
Saguinus oedipus	Q8SQ07	96.8%	Diamond
Pongo pygmaeus	Q8SQ12	96.8%	Diamond
Lagothrix lagotricha	Q8SQ05	96.2%	Diamond
Aotus trivirgatus	O46528	96.0%	Diamond
Antilocapra americana	P00668	96.0%	Diamond
Mesocricetus auratus	P00682	96.0%	Diamond
Eudorcas thomsonii	P07848	96.0%	Diamond
Cricetulus griseus	P24717	96.0%	Diamond
Giraffa camelopardalis	Q29542	95.3%	Diamond
Bubalus bubalis	P00657	95.2%	Diamond
Tragelaphus oryx	P00658	94.4%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
RNASE2	protein-coding	6036
RNASE3	protein-coding	6037
RNASE6	protein-coding	6039
EDDM3B	protein-coding	64184
EDDM3A	protein-coding	10876

Protein

Protein identifiers

Ribonuclease pancreatic — P07998 (reviewed: P07998)

Alternative names: HP-RNase, RIB-1, RNase UpI-1, Ribonuclease 1, Ribonuclease A

All UniProt accessions (3): G3V357, P07998, W0UV93

UniProt curated annotations — full annotation on UniProt →

Function. Endonuclease that catalyzes the cleavage of RNA on the 3’ side of pyrimidine nucleotides. Acts on single-stranded and double-stranded RNA.

Subunit / interactions. Monomer. Interacts with and forms tight 1:1 complexes with RNH1. Dimerization of two such complexes may occur. Interaction with RNH1 inhibits this protein.

Subcellular location. Secreted.

Tissue specificity. Pancreas and other tissues and body fluids (indicating it may have other physiological functions besides its role in digestion).

Post-translational modifications. N-linked glycans are of complex type.

Similarity. Belongs to the pancreatic ribonuclease family.

RefSeq proteins (4): NP_002924, NP_937875, NP_937877, NP_937878 (=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

Enzyme classification (BRENDA)

• EC 4.6.1.18 — pancreatic ribonuclease (BRENDA: 31 organisms, 87 substrates, 129 inhibitors, 97 Km, 47 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CYTIDINE-2’,3’-CYCLIC MONOPHOSPHATE	0.31–13	24
POLY(C)	0.0409–4	17
CYTIDINYL-3’,5’-ADENOSINE	0.38–22	10
POLY(A)-POLY(U)	0.0115–0.1059	10
POLY(A)POLY(U)	0.032–0.389	10
CYCLIC 2’,3’-CYTIDINE MONOPHOSPHATE	0.0023–0.44	4
TRNA	0.0005–5	4
PENTACYTIDYLIC ACID	0.015–0.038	3
CYCLIC 2’,3’-CMP	0.46–1	2
POLY (C)	0.34–0.47	2
CYCLIC 2’,3’-UMP	3	1
UPA	0.79	1
RNA	—	0

UniProt features (45 total): strand 8, mutagenesis site 6, sequence conflict 6, binding site 5, disulfide bond 4, helix 4, glycosylation site 3, turn 3, active site 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

12 structures by resolution:

PDB	Title	Method	Resolution (Å)
2E0J	Mutant Human Ribonuclease 1 (R31L, R32L)	X-RAY DIFFRACTION	1.6
2E0L	Mutant Human Ribonuclease 1 (Q28L, R31L, R32L)	X-RAY DIFFRACTION	1.6
1DZA	3-D structure of a HP-RNase	X-RAY DIFFRACTION	1.65
2E0M	Mutant Human Ribonuclease 1 (T24L, Q28L, R31L, R32L)	X-RAY DIFFRACTION	1.7
1E21	Ribonuclease 1 des1-7 Crystal Structure at 1.9A	X-RAY DIFFRACTION	1.9
1Z7X	X-ray structure of human ribonuclease inhibitor complexed with ribonuclease I	X-RAY DIFFRACTION	1.95
2Q4G	Ensemble refinement of the protein crystal structure of human ribonuclease inhibitor …	X-RAY DIFFRACTION	1.95
1H8X	Domain-swapped Dimer of a Human Pancreatic Ribonuclease Variant	X-RAY DIFFRACTION	2
2E0O	Mutant Human Ribonuclease 1 (V52L, D53L, N56L, F59L)	X-RAY DIFFRACTION	2
3F8G	The X-ray structure of a dimeric variant of human pancreatic ribonuclease with high …	X-RAY DIFFRACTION	2.6
4KXH	The X-ray crystal structure of a dimeric variant of human pancreatic ribonuclease	X-RAY DIFFRACTION	2.7
2K11	Solution structure of human pancreatic ribonuclease	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07998-F1	92.87	0.78

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Lyases, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2)

Position	Role
40	proton acceptor
147	proton donor

Ligand- & substrate-binding residues (5)

Position	Role
113	substrate
35	substrate
38	substrate
69–73	substrate
94	substrate

Disulfide bonds (4)

Type	Positions
Disulfide bond	54–112, 68–123, 86–138, 93–100

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	62, 104, 116

Mutagenesis-validated functional residues (6)

Position	Phenotype
67	substantially decreases binding affinity for rnh1 but maintains high conformational stability; when associated with d-95, a-116, d-117 and …
95	substantially decreases binding affinity for rnh1 but maintains high conformational stability; when associated with d-67, a-116, d-117 and …
116–117	no effect on inhibition by rnh1.
116	substantially decreases binding affinity for rnh1 but maintains high conformational stability; when associated with d-67, d-95, d-117 and …
117	substantially decreases binding affinity for rnh1 but maintains high conformational stability; when associated with d-67, d-95, a-116 and …
119	substantially decreases binding affinity for rnh1 but maintains high conformational stability; when associated with d-67, d-95, a-116 and …

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells	curated
R-HSA-9612973	Autophagy	—
R-HSA-9613829	Chaperone Mediated Autophagy	electronic
R-HSA-1266738	Developmental Biology	—
R-HSA-9734767	Developmental Cell Lineages	—
R-HSA-9820448	Developmental Cell Lineages of the Exocrine Pancreas	—
R-HSA-9615710	Late endosomal microautophagy	electronic

MSigDB gene sets: 194 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, MODULE_52, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, WALLACE_PROSTATE_CANCER_RACE_UP, GRUETZMANN_PANCREATIC_CANCER_DN, MCLACHLAN_DENTAL_CARIES_UP, GOMF_NUCLEASE_ACTIVITY, GOZGIT_ESR1_TARGETS_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MODULE_66, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GOMF_RNA_ENDONUCLEASE_ACTIVITY, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM

GO Biological Process (1): defense response to Gram-positive bacterium (GO:0050830)

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 (2): extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Autophagy	2
Developmental Cell Lineages of the Exocrine Pancreas	1
Developmental Biology	1
Developmental Cell Lineages	1

GO top-level categories

10 GO namespaces:

Category	Terms
binding	2
nuclease activity	2
catalytic activity	2
defense response to bacterium	1
RNA endonuclease activity	1
phosphorus-oxygen lyase activity	1
catalytic activity, acting on RNA	1
catalytic activity, acting on a nucleic acid	1
extracellular vesicle	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay
RNA nuclease activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,525 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNASE1	RNASET2	O00584	784
RNASE1	RNASEL	Q05823	655
RNASE1	GLUD1	P00367	638
RNASE1	PNP	P00491	634
RNASE1	GLUD2	P49448	605
RNASE1	ALB	P02768	570
RNASE1	MB	P02144	570
RNASE1	PRTFDC1	Q9NRG1	550
RNASE1	CYCS	P00001	493
RNASE1	EPX	P11678	490
RNASE1	LALBA	P00709	490
RNASE1	DNASE1	P24855	490
RNASE1	HPRT1	P00492	455
RNASE1	ANXA5	P08758	441
RNASE1	TG	P01266	440

IntAct

Human interaction partners of RNASE1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
RNH1	physical association	0.850	9
TRIM7	physical association	0.560	3
RELA	physical association	0.370	1
HNRNPA1	association	0.350	1

BioGRID (18 interactions; top human partners by supporting records): RNH1 (Affinity Capture-MS; 5 records), BUD31 (Affinity Capture-MS; 2 records), C2orf49 (Affinity Capture-MS; 2 records), NMNAT1 (Affinity Capture-MS; 2 records), ADAR (Affinity Capture-MS), B3GNT2 (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS), NUDCD2 (Affinity Capture-MS), RELA (Two-hybrid), STRBP (Affinity Capture-MS), TRIM7 (Two-hybrid)

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

The RAC1 P29S mutation is the third most common protein-coding hotspot mutation in melanomas, ocurring in 4-9%. A preclinical study has shown that this mutation confers resistance to BRAF inhibition in-vitro.

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — HNSC, MEL, SKCM.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for RNASE1: 132 ClinVar records (27 pathogenic / likely pathogenic); 1 CIViC cancer variant; 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	17
Uncertain significance	65
Likely benign	14
Benign	5

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 27 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
986286	NM_006908.5(RAC1):c.77A>G (p.Asn26Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
974895	NM_006908.5(RAC1):c.198A>T (p.Arg66Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
445280	NM_006908.5(RAC1):c.53G>A (p.Cys18Tyr)	Pathogenic	criteria provided, single submitter	2
2446363	NM_006908.5(RAC1):c.181C>G (p.Gln61Glu)	Pathogenic	criteria provided, single submitter	2
1727258	NM_006908.5(RAC1):c.475G>A (p.Ala159Thr)	Pathogenic	criteria provided, single submitter	1
1727259	NM_006908.5(RAC1):c.184G>A (p.Glu62Lys)	Pathogenic	criteria provided, single submitter	1
2503252	NM_006908.5(RAC1):c.394A>G (p.Lys132Glu)	Pathogenic	criteria provided, single submitter	1
3341010	NM_006908.5(RAC1):c.122C>T (p.Ser41Phe)	Pathogenic	criteria provided, single submitter	1
445282	NM_006908.5(RAC1):c.470G>A (p.Cys157Tyr)	Likely pathogenic	criteria provided, single submitter	2
445285	NM_006908.5(RAC1):c.151G>C (p.Val51Leu)	Likely pathogenic	criteria provided, single submitter	2
1333690	NM_006908.5(RAC1):c.191A>G (p.Tyr64Cys)	Likely pathogenic	criteria provided, single submitter	2
1027690	NM_006908.5(RAC1):c.168G>C (p.Trp56Cys)	Likely pathogenic	criteria provided, single submitter	1
1176531	NM_006908.5(RAC1):c.493C>G (p.Leu165Val)	Likely pathogenic	criteria provided, single submitter	1
2431922	NM_006908.5(RAC1):c.190T>C (p.Tyr64His)	Likely pathogenic	criteria provided, single submitter	1
3235757	NM_006908.5(RAC1):c.129T>A (p.Asn43Lys)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore RNASE1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 42 predictions of 825):

Position(s)	Effect	Δscore	Sites
14:20802094–20802095	acceptor_loss	1.0000	6
7:6387210–6387211	acceptor_loss	1.0000	6
7:6387284–6387285	donor_loss	1.0000	5
7:6400124–6400125	acceptor_loss	1.0000	6
7:6374771–6374772	donor_loss	0.9900	5
7:6400189–6400190	donor_loss	0.9900	5
7:6402016	donor_gain	0.9900
7:6402024	donor_gain	0.9900
7:6402314–6402315	acceptor_loss	0.9900	6
14:20802098	acceptor_gain	0.9800

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

8 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	6.87e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.12e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	2.76e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000102
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000116
Breast Invasive Carcinoma (validation)	unfavorable	0.000203
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.00028
Lung Adenocarcinoma (TCGA)	favorable	0.000307

Disease associations

OMIM: gene MIM:180440 | disease phenotypes: MIM:617751, MIM:617755

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
intellectual disability, autosomal dominant 48	Strong	Autosomal dominant	5

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (2): intellectual disability, autosomal dominant 48 (MONDO:0030913), neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (MONDO:0060596)

Orphanet (2): Microcephaly-corpus callosum and cerebellar vermis hypoplasia-facial dysmorphism-intellectual disability syndrom (Orphanet:500159), BPTF-related intellectual disability-facial dysmorphism-skeletal anomalies syndrome (Orphanet:686482)

HPO phenotypes

showing 60 of 68 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000194	Open mouth
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000363	Abnormal earlobe morphology
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000637	Long palpebral fissure
HP:0000664	Synophrys
HP:0000708	Atypical behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000752	Hyperactivity
HP:0000819	Diabetes mellitus
HP:0000964	Eczematoid dermatitis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0001357	Plagiocephaly
HP:0001382	Joint hypermobility
HP:0001511	Intrauterine growth retardation
HP:0001537	Umbilical hernia
HP:0001627	Abnormal heart morphology
HP:0001629	Ventricular septal defect
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001655	Patent foramen ovale
HP:0001999	Abnormal facial shape
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002195	Dysgenesis of the cerebellar vermis
HP:0002198	Dilated fourth ventricle
HP:0002280	Enlarged cisterna magna
HP:0002360	Sleep disturbance
HP:0002365	Hypoplasia of the brainstem
HP:0002465	Poor speech
HP:0002518	Abnormal periventricular white matter morphology
HP:0002553	Highly arched eyebrow
HP:0002650	Scoliosis
HP:0002786	Tracheobronchomalacia
HP:0003086	Acromesomelia
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0006532	Recurrent pneumonia
HP:0006956	Lateral ventricle dilatation
HP:0007033	Cerebellar dysplasia
HP:0008527	Congenital sensorineural hearing impairment
HP:0008872	Feeding difficulties in infancy
HP:0008947	Floppy infant

GWAS associations

10 associations:

Study	Trait	p-value
GCST010241_17	Apolipoprotein A1 levels	5e-35
GCST006585_1878	Blood protein levels	3e-25
GCST004621_164	Red cell distribution width	8e-9
GCST005951_100	Body mass index	1e-8
GCST008870_42	Keratinocyte cancer (MTAG)	1e-8
GCST007930_70	Medication use (agents acting on the renin-angiotensin system)	2e-8
GCST010245_78	LDL cholesterol levels	5e-8
GCST001762_611	Obesity-related traits	8e-8
GCST005194_240	Coronary artery disease	1e-7
GCST008871_73	Basal cell carcinoma	1e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0005190	urinary nitrogen measurement
EFO:0009188	Red cell distribution width
EFO:0004340	body mass index
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0010176	keratinocyte carcinoma
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5425 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication, from 3 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

3 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
RAC1 P29S	Dabrafenib + Vemurafenib	Melanoma	Resistance	CIViC B	EID7669
RAC1 P29S	PLX4720	Skin Melanoma	Resistance	CIViC D	EID8056
RAC1 P29S	Vemurafenib + Dabrafenib	Melanoma	Resistance	CIViC D	EID873

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

P29S (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

10 measured of 14 human assays (15 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
1-[3-(4-CARBOXYPIPERIDIN-1-YL)-3-DEOXY-BETA-D-ARABINOFURANOSYL]PYRIMIDINE-2,4(1H,3H)-DIONE	KI	103000 nM
3’-[1-(4-ethoxycarbonylpiperdinyl)]-3’-deoxy-ara-uridine	KI	120000 nM
2-((2S,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-ylamino)-2-oxoacetic acid	KI	132000 nM
CHEMBL408119	IC50	167000 nM
CHEMBL266234	IC50	197000 nM
CHEMBL259808	IC50	341000 nM
5’-phospho-2’-deoxyuridine 3-pyrophosphate (P’->5’) adenosine 3’-phosphate	KI	360000 nM
CHEMBL401150	KI	360000 nM
3-((2S,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-ylamino)-3-oxopropanoic acid	KI	380000 nM
4-((2S,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-ylamino)-4-oxobutanoic acid	KI	918000 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.57	Ki	27	nM	CHEMBL401150
7.57	Ki	27	nM	CHEMBL455775

PubChem BioAssay actives

2 with measured affinity, of 45 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	345852: Inhibition of RNase A	ki	0.0270	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	718194: Inhibition of RNase A	ki	0.0270	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation, affects expression	3
tetrabromobisphenol A	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases abundance	2
2,4,6-tribromophenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
sodium bichromate	decreases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	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
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	affects expression	1
Allergens	affects cotreatment, decreases abundance, increases expression	1
Aspirin	increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	affects cotreatment, decreases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Calcitriol	decreases expression	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Silicon Dioxide	decreases expression	1

ChEMBL screening assays

17 unique, capped per target: 16 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1026631	Binding	Induction of protein photodamage of ribonuclease A assessed as increase in protein carbonyl content at 10 uM treated 30 mins before 2.5 J/cm'2 UVA irradiation by electrophoresis	Thiopyrano[2,3-e]indol-2-ones: angelicin heteroanalogues with potent photoantiproliferative activity. — *Bioorg Med Chem*
CHEMBL2209165	ADMET	Prodrug activation assessed as half life for ribonuclease 1 mediated 4-hydroxytamoxifen release in MES-NaOH buffer at pH 6.0 by HPLC analysis	Ribonuclease-Activated Cancer Prodrug. — *ACS Med Chem Lett*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1D9	Ubigene THP-1 RNASE1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RNASE1 across ~30M SureChEMBL compounds — explore on Sugi Predict.