RNASE3

Summary

RNASE3 (ribonuclease A family member 3, HGNC:10046) is a protein-coding gene on chromosome 14q11.2, encoding Eosinophil cationic protein (P12724). Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. In precision oncology, RAF1 Amplification confers sensitivity to Paclitaxel + Sorafenib + Carboplatin in Skin Melanoma (CIViC Level B); 3 further curated variant–drug associations are listed below.

The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein exhibits antimicrobial activity against pathogenic bacteria

Source: NCBI Gene 6037 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 28 total
• Phenotypes (HPO): 163
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_002935

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10046
Approved symbol	RNASE3
Name	ribonuclease A family member 3
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ECP, RAF1
Ensembl gene	ENSG00000169397
Ensembl biotype	protein_coding
OMIM	131398
Entrez	6037

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000304639

RefSeq mRNA: 1 — MANE Select: NM_002935 NM_002935

CCDS: CCDS9560

Canonical transcript exons

ENST00000304639 — 2 exons

Exon	Start	End
ENSE00001124180	20891682	20892348
ENSE00001137146	20891385	20891451

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 99.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2602 / max 176.2572, expressed in 30 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138483	0.2602	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.40	gold quality
bone marrow	UBERON:0002371	98.07	gold quality
bone marrow cell	CL:0002092	96.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.26	gold quality
mononuclear cell	CL:0000842	86.64	gold quality
monocyte	CL:0000576	86.63	gold quality
leukocyte	CL:0000738	85.75	gold quality
blood	UBERON:0000178	78.64	gold quality
granulocyte	CL:0000094	74.86	gold quality
spleen	UBERON:0002106	71.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.37	gold quality
sperm	CL:0000019	67.81	gold quality
male germ cell	CL:0000015	66.47	gold quality
right lung	UBERON:0002167	64.70	gold quality
Brodmann (1909) area 10	UBERON:0013541	63.31	gold quality
upper arm skin	UBERON:0004263	62.75	gold quality
upper lobe of left lung	UBERON:0008952	60.71	gold quality
pancreatic ductal cell	CL:0002079	60.41	silver quality
tongue squamous epithelium	UBERON:0006919	60.01	gold quality
upper lobe of lung	UBERON:0008948	58.72	gold quality
saphenous vein	UBERON:0007318	58.40	gold quality
gluteal muscle	UBERON:0002000	57.98	gold quality
body of tongue	UBERON:0011876	57.88	gold quality
triceps brachii	UBERON:0001509	57.82	gold quality
amniotic fluid	UBERON:0000173	57.76	silver quality
dorsal root ganglion	UBERON:0000044	57.50	gold quality
thymus	UBERON:0002370	57.50	silver quality
trigeminal ganglion	UBERON:0001675	56.99	gold quality
tibia	UBERON:0000979	56.82	silver quality
lateral globus pallidus	UBERON:0002476	56.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-89232	yes	690.93
E-CURD-112	yes	31.88
E-MTAB-9067	yes	22.78
E-CURD-122	yes	10.58
E-ANND-3	yes	6.67
E-MTAB-9801	yes	5.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, NFATC2

miRNA regulators (miRDB)

25 targeting RNASE3, 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-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
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-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-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-1295B-5P	99.03	67.50	810
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-6515-5P	97.08	65.48	1219
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 40)

• EDN and ECP are paralogs in human and Old World monkeys. (PMID:11959927)
• Measurement of ECP polymorphism is a significant indicator for the disease activity in asthmatic patient. (PMID:12524255)
• serum levels elevated in asthmatic patients during acute attack (PMID:12530121)
• results suggest a differential release of ECP by the serum eosinophil, depending on the disease status and asthma exacerbation severity (PMID:12974194)
• Presence of ECP in human milk is associated with development of cow milk allergy and atopic dermatitis in the breast-fed infant, but has no direct association with the maternal atopy. (PMID:14630983)
• ECP contributes to surfactant dysfunction in asthma, which in turn could lead to airway obstruction. (PMID:15007353)
• The presence of Torque tenovirus (TTV) and TTV load correlate with concentrations of serum eosinophil cationic protein in children with acute respiratory disease (PMID:15295703)
• conformational transitions at the level of sidechain interactions (PMID:15317478)
• serum ECP asthma patients, during and after a mild pollen season (PMID:15928844)
• The involvement of some cationic and aromatic surface exposed residues of eosinophil cationic protein in the inhibition of proliferation of mammalian cell lines was assessed. (PMID:16010966)
• Among mite-allergic patients T-bet expression was down-regulated, which had no relation to ECP concentration and allergic symptoms. (PMID:16874959)
• These results demonstrate that eosinophils degranulate in vivo at the host-parasite interface, and that the released ECP reaches concentrations that could be harmful for the parasite, Echinococcus granulosus. (PMID:16879306)
• ECP is present in the middle ear effusion of otitis media of effusion. There was a positive correlation between ECP level and IgE level. (PMID:16883790)
• The high thermal stability of ECP may contribute to its resistance to degradation when the protein is secreted to the extracellular medium during the immune response. (PMID:17088327)
• Tryptophan solvent exposure and the depth of the protein insertion in the lipid bilayer were monitored by the degree of protein fluorescence quenching by KI and brominated phospholipids, respectively. (PMID:17223693)
• study concludes that ECP is present in several molecular forms with varying biological activities; some of this functional heterogeneity is based on the genetic polymorphism of the ECP gene and some on post-translational modifications (PMID:17250693)
• the A-G-G haplotype in the RNASE3 gene influences the development of asthma, in particular, an allergic form of asthma (PMID:17362255)
• In the asthma group, there was no correlation between methacholine end-point concentration and the eosinophil counts or serum ECP levels. In contrast, AMP end-point concentration correlated with the eosinophil counts and with serum ECP levels. (PMID:17573858)
• ECP stimulates TGF-beta(1)-release by human lung fibroblasts, suggesting a potential mechanism for eosinophils in the fibrotic response. (PMID:17587163)
• neutrophils from allergic patients were able to produce ECP by an IgE-dependent mechanism. (PMID:17675527)
• Both genetic and post-translational causes of the molecular heterogeneity of the eosinophil cationic protein, was detected. (PMID:17726151)
• ECP might be used as a disease activity marker in Churg-Strauss syndrome (PMID:17804567)
• Determined faecal and serum ECP levels add background information concerning reference levels at paediatric age for further studies indifferent clinical settings. (PMID:17852809)
• Eosinophil cationic protein may serve as a possible contributor to the pathophysiology of exercise-induced bronchoconstriction in asthmatic children. (PMID:17885861)
• Transcriptional regulation of human eosinophil RNases by an evolutionary- conserved sequence motif in primate genome. (PMID:17927842)
• cell surface-bound heparan sulfate proteoglycans serve as the major receptor for ECP internalization (PMID:17944807)
• The cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present. (PMID:18087674)
• ECP can bind with high affinity to the bacteria-wall components, a first-encounter step which is key to its antimicrobial mechanism of action. (PMID:18293932)
• Results describe the release of eosinophil cationic protein from intact tissue biopsies from patients with nasal polyps. (PMID:18345486)
• the tight interaction between ECP and heparin acts as the primary step for ECP endocytosis (PMID:18593710)
• higher expression levels in adenoid tissue of children with house dust mite allergies (PMID:18657051)
• These results may indicate the absence of a correlation between clinical status and quality of life and levels of eosinophilic cationic protein in tissues with allergic inflammation. (PMID:18716399)
• No variation in genes eosinophil cationic protein for Atopic dermatitis pathogenesis in this German cohort. (PMID:19014520)
• The expression level of ECP mRNA was up-regulated in nasal polyps. (PMID:19086659)
• Serum eosinophil cationic protein and eosinophil peroxidase in patients with seasonal rhinitis demonstrated a high predictive ability for later development of asthma. (PMID:19133919)
• Data show that conformational diversity of ECP is observed for the loop segments 17-22, 65-68, and 92-95 and most exposed sidechains. (PMID:19189375)
• ECP stimulates migration of human lung fibroblasts (PMID:19284504)
• Using phospholipid vesicles as membrane models, RNase 3 triggers first the vesicle aggregation, while RNase 7 induces leakage well before the aggregation step. (PMID:19366593)
• Bactericidal and membrane disruption activities of the eosinophil cationic protein are located in N-terminal. (PMID:19450231)
• decreased levels following alpine mountain climate therapy in patients with allergic diseases and chronic obstructive pulmonary disease (PMID:19476022)

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), RNASE2 (ENSG00000169385), RNASE6 (ENSG00000169413), RNASE8 (ENSG00000173431), RNASE11 (ENSG00000173464), RNASE10 (ENSG00000182545), RNASE9 (ENSG00000188655), RNASE13 (ENSG00000206150), ANG (ENSG00000214274), RNASE12 (ENSG00000258436), RNASE4 (ENSG00000258818)

Protein

Protein identifiers

Eosinophil cationic protein — P12724 (reviewed: P12724)

Alternative names: Ribonuclease 3

All UniProt accessions (1): P12724

UniProt curated annotations — full annotation on UniProt →

Function. Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarization of preferentially Gram-negative, but also Gram-positive strains. Promotes E.coli outer membrane detachment, alteration of the overall cell shape and partial loss of cell content.

Subunit / interactions. Interacts with bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In vitro interacts with and insert into lipid bilayers composed of dioleoyl phosphatidylcholine and dioleoyl phosphatidylglycerol. In vitro, tends to form amyloid-like aggregates at pH 3, but not at pH 5, nor 7.

Subcellular location. Secreted.

Similarity. Belongs to the pancreatic ribonuclease family.

RefSeq proteins (1): NP_002926* (*=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 (36 total): strand 9, helix 5, disulfide bond 4, glycosylation site 3, sequence variant 3, turn 2, active site 2, site 2, signal peptide 1, chain 1, mutagenesis site 1, region of interest 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
4X08	X-RAY DIFFRACTION	1.34
4OWZ	X-RAY DIFFRACTION	1.47
4OXB	X-RAY DIFFRACTION	1.5
4OXF	X-RAY DIFFRACTION	1.5
4A2O	X-RAY DIFFRACTION	1.69
4A2Y	X-RAY DIFFRACTION	1.7
1DYT	X-RAY DIFFRACTION	1.75
1H1H	X-RAY DIFFRACTION	2
1QMT	X-RAY DIFFRACTION	2.4
2KB5	SOLUTION NMR
2LVZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12724-F1	90.69	0.81

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 (4): 42 (proton acceptor); 155 (proton donor); 60 (may be involved in lps-binding); 62 (may be involved in lps- and lta-binding)

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 (3): 92, 119, 84

Mutagenesis-validated functional residues (1):

Position	Phenotype
40	loss of in vitro formation of amyloid-like aggregates.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-6803157	Antimicrobial peptides

MSigDB gene sets: 1052 (showing top): PID_BCR_5PATHWAY, PID_SHP2_PATHWAY, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOMF_ENDONUCLEASE_ACTIVITY, BIOCARTA_FMLP_PATHWAY, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GRUETZMANN_PANCREATIC_CANCER_DN

GO Biological Process (10): innate immune response in mucosa (GO:0002227), RNA catabolic process (GO:0006401), chemotaxis (GO:0006935), antibacterial humoral response (GO:0019731), induction of bacterial agglutination (GO:0043152), innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), defense response to bacterium (GO:0042742)

GO Molecular Function (6): lipopolysaccharide binding (GO:0001530), nucleic acid binding (GO:0003676), endonuclease activity (GO:0004519), RNA nuclease activity (GO:0004540), hydrolase activity (GO:0016787), nuclease activity (GO:0004518)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), azurophil granule lumen (GO:0035578)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	3
antimicrobial humoral response	2
nuclease 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
antibacterial humoral response	1
immune response	1
defense response to symbiont	1
defense response	1
response to bacterium	1
lipid binding	1
carbohydrate derivative binding	1
binding	1
catalytic activity, acting on RNA	1
catalytic activity	1
catalytic activity, acting on a nucleic acid	1
cellular anatomical structure	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1

Protein interactions and networks

STRING

786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNASE3	EPX	P11678	999
RNASE3	RNASE2	P10153	964
RNASE3	ANG	P03950	879
RNASE3	IL5	P05113	840
RNASE3	PRG2	P13727	803
RNASE3	CCL11	P50877	697
RNASE3	CSF2	P04141	672
RNASE3	MPO	P05164	668
RNASE3	AZU1	P20160	667
RNASE3	IL3	P08700	663
RNASE3	RNASET2	O00584	654
RNASE3	CTSG	P08311	604
RNASE3	IL4	P05112	603
RNASE3	IL13	P35225	600
RNASE3	RNASEL	Q05823	578

IntAct

11 interactions, top by confidence:

A	B	Type	Score
RNASE3	GGPS1	psi-mi:“MI:0914”(association)	0.640
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
	POLR3A	psi-mi:“MI:0914”(association)	0.350
	POLRMT	psi-mi:“MI:0914”(association)	0.350
	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
RNASE3	RNASEH1	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): POTEI (Affinity Capture-MS), RNH1 (Affinity Capture-MS), GTPBP2 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), BLK (Affinity Capture-MS), ACTB (Affinity Capture-MS), GNAZ (Affinity Capture-MS), GGPS1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), EFR3B (Affinity Capture-MS), RNF123 (Affinity Capture-MS), RNH1 (Affinity Capture-MS), POTEI (Affinity Capture-MS), UBAC1 (Affinity Capture-MS)

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”	RNASE3	“post translational modification”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — BLCA.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3170 predictions. Top by Δscore:

Variant	Effect	Δscore
3:12582114:A:AG	acceptor_gain	1.0000
3:12582115:G:GG	acceptor_gain	1.0000
3:12582115:GTT:G	acceptor_gain	1.0000
3:12584653:AGGAT:A	acceptor_gain	1.0000
3:12584654:GGAT:G	acceptor_gain	1.0000
3:12584655:GAT:G	acceptor_gain	1.0000
3:12584657:TC:T	acceptor_loss	1.0000
3:12584658:C:CC	acceptor_gain	1.0000
3:12584658:CTGA:C	acceptor_loss	1.0000
3:12584664:C:CT	acceptor_gain	1.0000
3:12584665:A:T	acceptor_gain	1.0000
3:12584841:CCTTA:C	donor_loss	1.0000
3:12584842:CTTA:C	donor_loss	1.0000
3:12584843:TTA:T	donor_loss	1.0000
3:12584844:TA:T	donor_loss	1.0000
3:12584846:C:CA	donor_loss	1.0000
3:12584869:T:TA	donor_gain	1.0000
3:12584977:ATGAT:A	acceptor_gain	1.0000
3:12584978:TGAT:T	acceptor_gain	1.0000
3:12584979:GAT:G	acceptor_gain	1.0000
3:12584980:AT:A	acceptor_gain	1.0000
3:12584981:TC:T	acceptor_loss	1.0000
3:12584982:C:CA	acceptor_loss	1.0000
3:12584982:C:CC	acceptor_gain	1.0000
3:12584983:T:A	acceptor_loss	1.0000
3:12585117:CTTA:C	donor_loss	1.0000
3:12585118:TTAC:T	donor_loss	1.0000
3:12585120:A:AC	donor_gain	1.0000
3:12585120:A:AG	donor_loss	1.0000
3:12585121:C:CC	donor_gain	1.0000

AlphaMissense

1047 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:20891910:T:G	F75C	0.990
14:20891895:T:G	F70C	0.989
14:20891798:T:C	F38L	0.986
14:20891799:T:G	F38C	0.986
14:20891800:T:A	F38L	0.986
14:20891800:T:G	F38L	0.986
14:20891894:T:C	F70L	0.985
14:20891896:T:A	F70L	0.985
14:20891896:T:G	F70L	0.985
14:20892014:T:A	C110S	0.975
14:20892015:G:C	C110S	0.975
14:20891987:A:C	S101R	0.969
14:20891989:T:A	S101R	0.969
14:20891989:T:G	S101R	0.969
14:20891951:T:A	C89S	0.965
14:20891952:G:C	C89S	0.965
14:20891978:T:A	C98S	0.965
14:20891979:G:C	C98S	0.965
14:20892098:T:A	C138S	0.965
14:20892099:G:C	C138S	0.965
14:20891930:T:A	C82S	0.962
14:20891931:G:C	C82S	0.962
14:20891981:C:G	H99D	0.962
14:20892053:T:A	C123S	0.961
14:20892054:G:C	C123S	0.961
14:20891881:A:C	K65N	0.960
14:20891881:A:T	K65N	0.960
14:20892144:C:A	P153Q	0.959
14:20892099:G:A	C138Y	0.957
14:20891876:T:A	C64S	0.956

dbSNP variants (sampled 300 via entrez): RS1000935682 (14:20889682 A>G), RS1001389449 (14:20890122 T>C), RS1001488629 (14:20891184 C>T), RS1001836040 (14:20891038 T>A), RS1002419494 (14:20889499 G>A), RS1002880229 (14:20889620 T>C), RS1003826104 (14:20892402 T>A), RS1004837594 (14:20890979 A>G), RS1006298907 (14:20889472 A>G), RS1014090715 (14:20891291 T>C), RS1014142909 (14:20891491 C>A,T), RS1016523802 (14:20890241 C>T), RS1017671205 (14:20890138 C>A), RS1018037908 (14:20889687 A>G), RS1020045396 (14:20891074 C>A,T)

Disease associations

OMIM: gene MIM:131398 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

163 total (30 of 163 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000078	Abnormality of the genital system
HP:0000144	Decreased fertility
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000391	Thickened helices
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000476	Cystic hygroma
HP:0000486	Strabismus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_244	Blood protein levels	1.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 4 predictive associations from 4 curated evidence items; also 1 functional.

Variant	Therapy	Indication	Effect	Level	CIViC
RAF1 Amplification	Paclitaxel + Sorafenib + Carboplatin	Skin Melanoma	Sensitivity/Response	CIViC B	EID1496
RAF1 Amplification	Trametinib + B-Raf/VEGFR-2 Inhibitor RAF265	Bladder Carcinoma	Sensitivity/Response	CIViC D	EID11767
RAF1 Amplification	Sorafenib	Hepatocellular Carcinoma	Sensitivity/Response	CIViC D	EID9113
RAF1 R391W	Vemurafenib	Melanoma	Resistance	CIViC D	EID4824

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11710163	Efficacy	3	carboplatin;cisplatin;docetaxel;gemcitabine;paclitaxel	Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11710163	RAF1	3	3.50	1	carboplatin;cisplatin;docetaxel;gemcitabine;paclitaxel

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Beclomethasone	affects reaction, increases expression, decreases expression, affects cotreatment	6
Salmeterol Xinafoate	increases expression, decreases expression, affects cotreatment, affects reaction	2
perfluorooctanoic acid	affects expression	1
zafirlukast	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
montelukast	decreases expression	1
CP 31398	decreases expression	1
perfluorohexanesulfonic acid	increases expression	1
Formoterol Fumarate	decreases expression	1
Allergens	affects cotreatment, increases expression, affects reaction	1
Vehicle Emissions	increases expression	1
Cadmium	decreases expression, increases abundance	1
Dust	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Budesonide	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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