RNH1

Summary

RNH1 (ribonuclease/angiogenin inhibitor 1, HGNC:10074) is a protein-coding gene on chromosome 11p15.5, encoding Ribonuclease inhibitor (P13489). Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and angiogenin (ANG).

Placental ribonuclease inhibitor (PRI) is a member of a family of proteinaceous cytoplasmic RNase inhibitors that occur in many tissues and bind to both intracellular and extracellular RNases (summarized by Lee et al., 1988 [PubMed 3219362]). In addition to control of intracellular RNases, the inhibitor may have a role in the regulation of angiogenin (MIM 105850). Ribonuclease inhibitor, of 50,000 Da, binds to ribonucleases and holds them in a latent form. Since neutral and alkaline ribonucleases probably play a critical role in the turnover of RNA in eukaryotic cells, RNH may be essential for control of mRNA turnover; the interaction of eukaryotic cells with ribonuclease may be reversible in vivo.

Source: NCBI Gene 6050 — RefSeq curated summary.

At a glance

• Gene–disease (curated): encephalitis, acute, infection-induced, susceptibility to, 12 (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 121 total
• MANE Select transcript: NM_203387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10074
Approved symbol	RNH1
Name	ribonuclease/angiogenin inhibitor 1
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	RAI
Ensembl gene	ENSG00000023191
Ensembl biotype	protein_coding
OMIM	173320
Entrez	6050

Gene structure

Transcript identifiers

Ensembl transcripts: 130 — 121 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000354420, ENST00000356187, ENST00000397604, ENST00000397614, ENST00000397615, ENST00000438658, ENST00000524464, ENST00000524780, ENST00000525522, ENST00000525701, ENST00000526295, ENST00000527485, ENST00000528713, ENST00000529115, ENST00000529306, ENST00000529368, ENST00000529768, ENST00000531149, ENST00000531223, ENST00000531540, ENST00000532055, ENST00000533410, ENST00000533592, ENST00000534797, ENST00000903633, ENST00000903634, ENST00000903635, ENST00000903636, ENST00000903637, ENST00000903638, ENST00000903639, ENST00000903640, ENST00000903641, ENST00000903642, ENST00000903643, ENST00000903644, ENST00000903645, ENST00000903646, ENST00000903647, ENST00000903648, ENST00000903649, ENST00000903650, ENST00000903651, ENST00000903652, ENST00000903653, ENST00000903654, ENST00000903655, ENST00000903656, ENST00000903657, ENST00000903658, ENST00000903659, ENST00000903660, ENST00000903661, ENST00000903662, ENST00000903663, ENST00000903664, ENST00000903665, ENST00000903666, ENST00000903667, ENST00000903668, ENST00000903669, ENST00000903670, ENST00000903671, ENST00000903672, ENST00000903673, ENST00000903674, ENST00000903675, ENST00000903676, ENST00000903677, ENST00000903678, ENST00000903679, ENST00000903680, ENST00000903681, ENST00000940514, ENST00000940515, ENST00000940516, ENST00000940517, ENST00000940518, ENST00000940519, ENST00000940520, ENST00000940521, ENST00000972464, ENST00000972465, ENST00000972466, ENST00000972467, ENST00000972468, ENST00000972469, ENST00000972470, ENST00000972471, ENST00000972472, ENST00000972473, ENST00000972474, ENST00000972475, ENST00000972476, ENST00000972477, ENST00000972478, ENST00000972479, ENST00000972480, ENST00000972481, ENST00000972482, ENST00000972483, ENST00000972484, ENST00000972485, ENST00000972486, ENST00000972487, ENST00000972488, ENST00000972489, ENST00000972490, ENST00000972491, ENST00000972492, ENST00000972493, ENST00000972494, ENST00000972495, ENST00000972496, ENST00000972497, ENST00000972498, ENST00000972499, ENST00000972500, ENST00000972501, ENST00000972502, ENST00000972503, ENST00000972504, ENST00000972505, ENST00000972506, ENST00000972507, ENST00000972508, ENST00000972509, ENST00000972510, ENST00000972511, ENST00000972512

RefSeq mRNA: 8 — MANE Select: NM_203387 NM_002939, NM_203383, NM_203384, NM_203385, NM_203386, NM_203387, NM_203388, NM_203389

CCDS: CCDS7697

Canonical transcript exons

ENST00000354420 — 11 exons

Exon	Start	End
ENSE00000656254	499829	499999
ENSE00001369908	504824	504996
ENSE00001827718	494515	494778
ENSE00002169729	507113	507242
ENSE00003500305	502062	502249
ENSE00003504169	500484	500654
ENSE00003515066	498457	498627
ENSE00003525736	499015	499185
ENSE00003599043	498763	498933
ENSE00003600488	497971	498141
ENSE00003670636	494883	495053

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 117.9741 / max 488.4674, expressed in 1828 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117774	64.9235	1823
117772	29.5735	1815
117769	17.8420	1216
117767	3.5166	1020
117770	1.2102	631
117768	0.4390	231
117764	0.1549	56
117771	0.0891	31
117763	0.0619	22
117761	0.0594	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	98.95	gold quality
zone of skin	UBERON:0000014	98.85	gold quality
skin of abdomen	UBERON:0001416	98.83	gold quality
ectocervix	UBERON:0012249	98.55	gold quality
right coronary artery	UBERON:0001625	98.54	gold quality
esophagus mucosa	UBERON:0002469	98.53	gold quality
vagina	UBERON:0000996	98.45	gold quality
lower esophagus	UBERON:0013473	98.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.45	gold quality
left uterine tube	UBERON:0001303	98.43	gold quality
left coronary artery	UBERON:0001626	98.43	gold quality
right atrium auricular region	UBERON:0006631	98.43	gold quality
esophagus	UBERON:0001043	98.42	gold quality
upper lobe of left lung	UBERON:0008952	98.40	gold quality
mucosa of stomach	UBERON:0001199	98.38	gold quality
ascending aorta	UBERON:0001496	98.38	gold quality
thoracic aorta	UBERON:0001515	98.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.38	gold quality
lower esophagus mucosa	UBERON:0035834	98.35	gold quality
apex of heart	UBERON:0002098	98.33	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.29	gold quality
endocervix	UBERON:0000458	98.27	gold quality
popliteal artery	UBERON:0002250	98.24	gold quality
tibial artery	UBERON:0007610	98.24	gold quality
adipose tissue	UBERON:0001013	98.22	gold quality
right lung	UBERON:0002167	98.21	gold quality
descending thoracic aorta	UBERON:0002345	98.20	gold quality
omental fat pad	UBERON:0010414	98.18	gold quality
body of uterus	UBERON:0009853	98.17	gold quality
right ovary	UBERON:0002118	98.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting RNH1, 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-340-5P	100.00	72.50	4437
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-580-5P	99.28	70.94	1776

Literature-anchored findings (GeneRIF, showing 26)

• Human ribonuclease inhibitor gene has antiangiogenic and antitumor effects when expressed in hematopoietic cells in mouse melanoma models. (PMID:15592448)
• 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)
• Structural and energetic aspects of the interaction between human RI (hRI) and human pancreatic ribonuclease (RNase 1), is reported. (PMID:17350650)
• The conformational and oxidative stabilities of both RIs increase upon complex formation with ribonucleases. Thus, RI has evolved to maintain its inhibition of invading ribonucleases, even when confronted with extreme environmental stress. (PMID:17956129)
• This the first measurement of the inhibition of the ribonucleolytic activity of onconase by ribonuclease inhibitor protein. (PMID:18930025)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• This protein has been found differentially expressed in the anterior cingulate cortex in men patients with schizophrenia. (PMID:20381070)
• the anti-tumor effect of RNH1 is also involved in suppressing growth and metastasis (PMID:21125316)
• RNH1 (as a recombinant fusion protein) is localized to mitochondria, nuclei, and cytosol in HeLa and HCT cells; RNH1 appears to bind to various mitochondrial proteins. (PMID:21276451)
• PTEN-mediated miR-21 regulation is achieved by inhibiting the interaction between the Drosha complex and RNH1, revealing previously unidentified role of PTEN in the oncogenic miR-21 biogenesis (PMID:22162762)
• RNH1 as a regulator of HDACi resistance in gastric cancer (PMID:23584480)
• RI might play a novel role in the development of bladder cancer through regulating EMT and the ILK signaling pathway. (PMID:23703635)
• RNH1 bound to RNase 7 and suppressed its antimicrobial activity by blocking its ability to bind the cell wall of uropathogenic bacteria. (PMID:24107847)
• RI could play a novel role in inhibiting metastasis of bladder cancer through regulating EMT and ILK signaling pathways. (PMID:24768914)
• angiogenin and ILK signaling pathway plays a pivotal role in mediating the inhibitory effects of RI on melanoma cells growth (PMID:24769129)
• a novel mechanism of ANG in regulating PI3K/AKT/mTOR signaling pathway via RI, is reported. (PMID:25193113)
• Results show that a low expression of RNH1 in metastasis of bladder cancer and suggest that it might regulate the function of ILK through mutual binding. (PMID:27576342)
• Data suggest that ribonuclease inhibitor (RNH1) protects HeLa cells from ribonuclease 1 (RNase 1). (PMID:27806571)
• This study first time revealed in vivo role of RNH1. This study report that RNH1 is important for embryonic development and erythropoiesis. RNH1 binds to ribosomes and regulates erythropoiesis by controlling translation of the erythroid transcription factor GATA1. (PMID:29408805)
• RNH1 might represent the first direct regulator of IRE1 RNase activity (PMID:30109813)
• Angiogenin (ANG)-Ribonuclease Inhibitor (RNH1) System in Protein Synthesis and Disease. (PMID:33525475)
• LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity. (PMID:35256513)
• Ribonuclease inhibitor 1 (RNH1) deficiency cause congenital cataracts and global developmental delay with infection-induced psychomotor regression and anemia. (PMID:36935417)
• Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy. (PMID:37191094)
• Functional status analysis of RNH1 in bladder cancer for predicting immunotherapy response. (PMID:37537337)
• New link between RNH1 and E2F1: regulates the development of lung adenocarcinoma. (PMID:38783241)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnh1	ENSMUSG00000038650
rattus_norvegicus	Rnh1	ENSRNOG00000016416
drosophila_melanogaster	LRR	FBGN0033212
caenorhabditis_elegans	crml-1	WBGENE00010641

Paralogs (4): CARMIL1 (ENSG00000079691), PPP1R37 (ENSG00000104866), CARMIL2 (ENSG00000159753), CARMIL3 (ENSG00000186648)

Protein

Protein identifiers

Ribonuclease inhibitor — P13489 (reviewed: P13489)

Alternative names: Placental ribonuclease inhibitor, Ribonuclease/angiogenin inhibitor 1

All UniProt accessions (11): A0A0J9YXC4, A0A140VJT8, P13489, E9PIK5, E9PIM9, E9PLZ3, E9PMA9, E9PMI1, E9PMJ3, E9PR82, H0YCR7

UniProt curated annotations — full annotation on UniProt →

Function. Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and angiogenin (ANG). May play a role in redox homeostasis. Required to inhibit the cytotoxic tRNA ribonuclease activity of ANG in the cytoplasm in absence of stress. Relocates to the nucleus in response to stress, relieving inhibition of ANG in the cytoplasm, and inhibiting the angiogenic activity of ANG in the nucleus.

Subunit / interactions. Forms high-affinity heterodimers with RNASE1, ANG and RNASE2.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. The N-terminus is blocked. At least 30 of the 32 cysteine residues are in the reduced form.

Disease relevance. Encephalitis, acute, infection-induced, 12 (IIAE12) [MIM:620461] An autosomal recessive disorder apparent in infancy or early childhood, and characterized by acute encephalopathy triggered by viral infections and febrile illness. Neurologic features of the acute episodes include seizures, hemiplegia, decreased consciousness, hypotonia, abnormal posturing, feeding problems, and respiratory insufficiency. Disease severity is variable, ranging from death to normal neurologic outcomes. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. The LRR domain forms a horseshoe-shaped structure that interacts tightly with target RNases via a large protein interaction surface on its interior side.

RefSeq proteins (8): NP_002930, NP_976317, NP_976318, NP_976319, NP_976320, NP_976321, NP_976322, NP_976323 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR006553	Leu-rich_rpt_Cys-con_subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041302	LRR_RI_cap	Repeat
IPR050637	NLRP_innate_immun_reg	Family

Pfam: PF13516, PF18779

UniProt features (80 total): strand 23, helix 19, repeat 15, mutagenesis site 7, sequence variant 6, sequence conflict 4, modified residue 3, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1Z7X	X-RAY DIFFRACTION	1.95
2Q4G	X-RAY DIFFRACTION	1.95
2BEX	X-RAY DIFFRACTION	1.99
1A4Y	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13489-F1	96.44	0.97

Functional residue map

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

Post-translational modifications (3): 2, 82, 91

Mutagenesis-validated functional residues (7):

Position	Phenotype
262	binding affinity decreased 5000-fold over the wild type for rnase2; when associated with a-264 and a-319.
264	substantially decreased binding affinity for rnase2. binding affinity decreased 5000-fold over the wild type for rnase2;
319	substantially decreased binding affinity for rnase2. binding affinity decreased 5000-fold over the wild type for rnase2;
376	40-fold reduction in binding affinity for rnase2.
435–436	substantially decreases binding affinity for rnase1, ang and rnase2.
458	25-fold reduction in binding affinity for rnase2.
461	a significant decrease in binding affinity with rnase1, slight decrease for the ang ligand, no real change in binding af

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 292 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_TRNA_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, GOLDRATH_ANTIGEN_RESPONSE, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GERY_CEBP_TARGETS, JAZAG_TGFB1_SIGNALING_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_REGULATION_OF_ARP2_3_COMPLEX_MEDIATED_ACTIN_NUCLEATION

GO Biological Process (7): mRNA catabolic process (GO:0006402), cell migration (GO:0016477), regulation of Arp2/3 complex-mediated actin nucleation (GO:0034315), tRNA stabilization (GO:0036416), regulation of angiogenesis (GO:0045765), cytoplasmic translation (GO:0002181), negative regulation of translation in response to stress (GO:0032055)

GO Molecular Function (2): ribonuclease inhibitor activity (GO:0008428), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), lamellipodium (GO:0030027), angiogenin-PRI complex (GO:0032311), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
translation	2
RNA catabolic process	1
negative regulation of gene expression	1
mRNA metabolic process	1
cell motility	1
Arp2/3 complex-mediated actin nucleation	1
regulation of actin nucleation	1
regulation of tRNA stability	1
RNA stabilization	1
negative regulation of tRNA catabolic process	1
angiogenesis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
negative regulation of translation	1
cellular response to stress	1
regulation of translation in response to stress	1
RNA nuclease activity	1
nuclease inhibitor activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cell leading edge	1
plasma membrane bounded cell projection	1
extracellular protein-containing complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

1035 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNH1	ANG	P03950	937
RNH1	DGCR8	Q8WYQ5	859
RNH1	FBXO38	Q6PIJ6	844
RNH1	FBXO33	Q7Z6M2	826
RNH1	FBXO39	Q8N4B4	826
RNH1	DROSHA	Q9NRR4	816
RNH1	XPO5	Q9HAV4	776
RNH1	DICER1	Q9UPY3	774
RNH1	ZNF699	Q32M78	687
RNH1	KLF7	O75840	649
RNH1	AGO2	Q9UKV8	594
RNH1	AGO1	Q9UL18	570
RNH1	TUT4	Q5TAX3	541
RNH1	RNASE2	P10153	535
RNH1	NAIP	Q13075	534

IntAct

120 interactions, top by confidence:

A	B	Type	Score
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
RNASE1	RNH1	psi-mi:“MI:0915”(physical association)	0.850
RNASE1	RNH1	psi-mi:“MI:0914”(association)	0.850
RNH1	RNASE1	psi-mi:“MI:0407”(direct interaction)	0.850
RNASE1	RNH1	psi-mi:“MI:0407”(direct interaction)	0.850
SDCBP	RNH1	psi-mi:“MI:0915”(physical association)	0.830
RNH1	SDCBP	psi-mi:“MI:0915”(physical association)	0.830
ANG	RNH1	psi-mi:“MI:0915”(physical association)	0.750
RNH1	ANG	psi-mi:“MI:0407”(direct interaction)	0.750
ANG	RNH1	psi-mi:“MI:0407”(direct interaction)	0.750
ANG	RNH1	psi-mi:“MI:0914”(association)	0.750
rep	CCDC22	psi-mi:“MI:0914”(association)	0.670
RNASE3	GGPS1	psi-mi:“MI:0914”(association)	0.640
RNH1	RNASE1	psi-mi:“MI:0902”(rna cleavage)	0.620
RNH1	RNASE1	psi-mi:“MI:0407”(direct interaction)	0.620
RNASE1	RNH1	psi-mi:“MI:0407”(direct interaction)	0.620
RNASE7	RNH1	psi-mi:“MI:0915”(physical association)	0.590
RNH1	WFS1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (277): SDCBP (Two-hybrid), RNH1 (Affinity Capture-MS), RNH1 (Affinity Capture-MS), RNH1 (Proximity Label-MS), CDC20 (Affinity Capture-MS), LMO7 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), MAP4K4 (Affinity Capture-MS), RNH1 (Affinity Capture-MS), RNH1 (Affinity Capture-MS), RNH1 (Affinity Capture-MS), RNH1 (Affinity Capture-MS), RNH1 (Affinity Capture-MS), RNH1 (Affinity Capture-MS), RNH1 (Affinity Capture-MS)

ESM2 similar proteins: A5PJJ5, A6NHZ5, E9Q5R7, G1T469, G3XA59, P02750, P10775, P13489, P22792, P29315, P59046, P59047, Q14392, Q149C3, Q14BP6, Q15048, Q32PG9, Q3UJB3, Q3V3V9, Q3ZBI5, Q53B87, Q53B88, Q569B5, Q5BK65, Q5DU56, Q5RF01, Q63035, Q640Z9, Q647I9, Q6F5E8, Q6QMY6, Q6UY01, Q6UY18, Q6ZQY2, Q7RTR2, Q86W24, Q86W25, Q86YC3, Q8BMT4, Q8CBR6

Diamond homologs: A1Z198, A6QLE5, A8Y3R9, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, P10775, P13489, P29315, P59044, P59046, P59047, Q0GKD5, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q5RAV7, Q63035, Q6B966, Q86W24, Q86W25, Q86W26, Q8CCN1, Q8HXK9, Q8HZP9, Q8R4B8, Q91VI7, Q91WS2, Q96P20, Q9C000, Q9EPB4, Q9I9N6, Q9ULZ3, Q9Y2G2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to xenobiotic stimulus	6	14.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000327523 (11:497091 C>A,T), RS1000439430 (11:508631 G>C), RS1000472844 (11:499740 C>G,T), RS1000529147 (11:496742 C>A), RS1000628005 (11:501539 G>A), RS1000748008 (11:508455 G>A), RS1000784615 (11:505098 T>A,C,G), RS1000858254 (11:504837 T>C), RS1000934327 (11:504763 T>C), RS1001007786 (11:505099 G>A,C), RS1001234201 (11:496156 A>C), RS1001342387 (11:503907 C>T), RS1001409812 (11:503692 C>A,G,T), RS1001489251 (11:500263 G>A), RS1001585697 (11:503177 T>G)

Disease associations

OMIM: gene MIM:173320 | disease phenotypes: MIM:620461

GenCC curated gene-disease

Disease	Classification	Inheritance
encephalitis, acute, infection-induced, susceptibility to, 12	Strong	Autosomal recessive

Mondo (1): encephalitis, acute, infection-induced, susceptibility to, 12 (MONDO:0957561)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002783_397	Body mass index	5.000000e-06
GCST002783_484	Body mass index	3.000000e-06
GCST002783_81	Body mass index	8.000000e-06
GCST003818_19	Resting heart rate	5.000000e-08
GCST90002385_492	High light scatter reticulocyte count	7.000000e-11
GCST90002386_413	High light scatter reticulocyte percentage of red cells	5.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	6
bisphenol A	decreases expression, decreases methylation, increases expression, affects expression	4
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
lead acetate	affects cotreatment, decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
manganese chloride	increases abundance, increases expression	1
ochratoxin A	increases expression	1
coumarin	decreases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
epigallocatechin gallate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	increases abundance, increases expression	1
Antimony Potassium Tartrate	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7ZI	Ubigene A-549 RNH1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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