ERI3

Summary

ERI3 (ERI1 exoribonuclease family member 3, HGNC:17276) is a protein-coding gene on chromosome 1p34.1, encoding ERI1 exoribonuclease 3 (O43414).

Enables RNA binding activity.

Source: NCBI Gene 79033 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_024066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17276
Approved symbol	ERI3
Name	ERI1 exoribonuclease family member 3
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22943, PINT1
Ensembl gene	ENSG00000117419
Ensembl biotype	protein_coding
OMIM	609917
Entrez	79033

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000372257, ENST00000372259, ENST00000452396, ENST00000456170, ENST00000457571, ENST00000462341, ENST00000479101, ENST00000489710, ENST00000495828, ENST00000649995, ENST00000862446, ENST00000862447, ENST00000862448, ENST00000862449, ENST00000862450, ENST00000930633, ENST00000930634, ENST00000930635, ENST00000930636, ENST00000930637, ENST00000930638

RefSeq mRNA: 5 — MANE Select: NM_024066 NM_001301698, NM_001301699, NM_001301700, NM_001301701, NM_024066

CCDS: CCDS30696

Canonical transcript exons

ENST00000372257 — 9 exons

Exon	Start	End
ENSE00001234631	44284835	44284907
ENSE00001559578	44221070	44221640
ENSE00001788345	44352850	44352925
ENSE00001810117	44354892	44355257
ENSE00003479401	44339045	44339322
ENSE00003510458	44313169	44313228
ENSE00003564175	44319628	44319744
ENSE00003600189	44247939	44248038
ENSE00003785744	44308310	44308401

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 97.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.2764 / max 238.7078, expressed in 1808 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12074	24.6623	1801
12075	2.5944	1475
12072	1.5495	1126
12071	0.7591	492
12076	0.4405	211
12070	0.2572	79
12073	0.0136	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.76	gold quality
right testis	UBERON:0004534	97.70	gold quality
right frontal lobe	UBERON:0002810	97.04	gold quality
anterior cingulate cortex	UBERON:0009835	96.94	gold quality
cingulate cortex	UBERON:0003027	96.86	gold quality
prefrontal cortex	UBERON:0000451	96.60	gold quality
ventricular zone	UBERON:0003053	95.94	gold quality
caudate nucleus	UBERON:0001873	95.79	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.68	gold quality
frontal pole	UBERON:0002795	95.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.45	gold quality
cortical plate	UBERON:0005343	95.28	gold quality
adenohypophysis	UBERON:0002196	95.15	gold quality
nucleus accumbens	UBERON:0001882	95.14	gold quality
middle frontal gyrus	UBERON:0002702	95.09	gold quality
amygdala	UBERON:0001876	95.07	gold quality
testis	UBERON:0000473	95.03	gold quality
apex of heart	UBERON:0002098	94.82	gold quality
right uterine tube	UBERON:0001302	94.77	gold quality
ganglionic eminence	UBERON:0004023	94.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.72	gold quality
gastrocnemius	UBERON:0001388	94.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.53	gold quality
muscle of leg	UBERON:0001383	94.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.92	gold quality
mucosa of transverse colon	UBERON:0004991	93.83	gold quality
putamen	UBERON:0001874	93.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.67	gold quality
lower esophagus	UBERON:0013473	93.66	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.54
E-GEOD-125970	yes	4.16
E-MTAB-6142	no	180.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting ERI3, 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-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-3620-5P	97.42	63.95	792

Literature-anchored findings (GeneRIF, showing 1)

• The conclude of this study that the particular LINE-1 element within the ERI3 gene does not associate with the schizophrenia phenotype in European Americans. (PMID:29123232)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eri3	ENSMUSG00000033423
rattus_norvegicus	Eri3	ENSRNOG00000019381
caenorhabditis_elegans		WBGENE00019724
caenorhabditis_elegans		WBGENE00019825

Paralogs (2): ERI1 (ENSG00000104626), ERI2 (ENSG00000196678)

Protein

Protein identifiers

ERI1 exoribonuclease 3 — O43414 (reviewed: O43414)

Alternative names: Prion interactor 1, Prion protein-interacting protein

All UniProt accessions (7): A0A3B3ISV9, A0A3B3ITJ5, A0A3B3IU35, O43414, F6QUN3, F6UGJ8, H0Y4B0

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with PRNP.

Cofactor. Binds 2 magnesium ions per subunit.

Isoforms (3)

UniProt ID	Names	Canonical?
O43414-1	1	yes
O43414-2	2
O43414-3	3

RefSeq proteins (5): NP_001288627, NP_001288628, NP_001288629, NP_001288630, NP_076971* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR013520	Ribonucl_H	Domain
IPR036397	RNaseH_sf	Homologous_superfamily
IPR047201	ERI-1_3’hExo-like	Domain
IPR051274	3-5_Exoribonuclease	Family

Pfam: PF00929

UniProt features (30 total): helix 9, binding site 7, strand 6, splice variant 2, turn 2, active site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7LPZ	X-RAY DIFFRACTION	1.55
7LQ0	X-RAY DIFFRACTION	1.6
7K05	X-RAY DIFFRACTION	1.85
7LPY	X-RAY DIFFRACTION	1.85
7K06	X-RAY DIFFRACTION	1.95
2XRI	X-RAY DIFFRACTION	2.15
7K07	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43414-F1	75.08	0.61

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): 152 (proton acceptor); 307 (proton acceptor)

Ligand- & substrate-binding residues (7): 312; 150; 150; 152; 152; 249; 307

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOMF_RNA_NUCLEASE_ACTIVITY, GGTGTGT_MIR329, GOMF_NUCLEASE_ACTIVITY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, chr1p34, GOBP_REGULATION_OF_CHROMATIN_ORGANIZATION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_RRNA_3_END_PROCESSING, GOMF_EXONUCLEASE_ACTIVITY

GO Biological Process (0):

GO Molecular Function (7): 3’-5’-RNA exonuclease activity (GO:0000175), RNA binding (GO:0003723), metal ion binding (GO:0046872), nucleic acid binding (GO:0003676), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
nucleic acid binding	1
cation binding	1
binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1

Protein interactions and networks

STRING

1412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERI3	PRNP	P04156	764
ERI3	SYN3	O14994	704
ERI3	GRB2	P29354	703
ERI3	SYN2	Q92777	672
ERI3	SYN1	P17600	580
ERI3	ERI1	Q8IV48	539
ERI3	TMEM53	Q6P2H8	534
ERI3	RNF220	Q5VTB9	530
ERI3	CCDC24	Q8N4L8	526
ERI3	DICER1	Q9UPY3	466
ERI3	SPCS2	Q15005	461
ERI3	TRAPPC1	Q9Y5R8	454
ERI3	LANCL1	O43813	446
ERI3	TRAPPC4	Q9Y296	442
ERI3	SRCIN1	Q9C0H9	404

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CELF5	CASC3	psi-mi:“MI:0914”(association)	0.530
ERI3	nleF	psi-mi:“MI:0915”(physical association)	0.370
PCNA	ERI3	psi-mi:“MI:0915”(physical association)	0.370
ERI3	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
ERI3	TFAP2A	psi-mi:“MI:0915”(physical association)	0.370
Cct2	OSBPL9	psi-mi:“MI:0914”(association)	0.350
RAPGEF2	BDP1	psi-mi:“MI:0914”(association)	0.350
Stmn1	FXR1	psi-mi:“MI:0914”(association)	0.350
Cenpf	WDR91	psi-mi:“MI:0914”(association)	0.350
Mark2	ERI3	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
RIN3		psi-mi:“MI:0914”(association)	0.350
S	COPE	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SPX	ERI3	psi-mi:“MI:0914”(association)	0.350
POLE3	ERI3	psi-mi:“MI:0914”(association)	0.350
CZIB	ERI3	psi-mi:“MI:0914”(association)	0.350
LAMTOR5	ERI3	psi-mi:“MI:0914”(association)	0.350
KCNJ5	ERI3	psi-mi:“MI:0914”(association)	0.350
MT1F	ERI3	psi-mi:“MI:0914”(association)	0.350
CUTA	ERI3	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), ERI3 (Affinity Capture-RNA), ERI3 (Two-hybrid), ERI3 (Negative Genetic), ERI3 (Affinity Capture-MS), ERI3 (Two-hybrid), ERI3 (Affinity Capture-MS)

ESM2 similar proteins: A4Q9F4, A6QLH5, D3Z7P3, D3ZVU9, E9PV86, M0R7T9, O35652, O43414, O54804, O60242, O60347, O70512, O94925, P08887, P0C7M8, P13264, P35790, P85298, Q01134, Q08DW9, Q13202, Q13505, Q2HJ53, Q2TBM7, Q3UGX3, Q4R766, Q4R7M4, Q58DH2, Q5XI70, Q62225, Q6AYT7, Q6DN14, Q80T74, Q80UW0, Q80ZF8, Q86W50, Q8C460, Q8N2K0, Q8NBA8, Q8NHH1

Diamond homologs: A6QLH5, A8K979, O43414, O44406, Q08I43, Q10905, Q502M8, Q5BKS4, Q5FVR4, Q5HZL1, Q7TMF2, Q8C460, Q8IV48, Q8W566, Q95RQ4, Q9NG98

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2476 predictions. Top by Δscore:

Variant	Effect	Δscore
1:44221638:CGT:C	acceptor_gain	1.0000
1:44221641:C:CC	acceptor_gain	1.0000
1:44286791:T:TA	donor_gain	1.0000
1:44286792:C:A	donor_gain	1.0000
1:44308309:CATGA:C	donor_gain	1.0000
1:44313164:CCTA:C	donor_loss	1.0000
1:44313165:CTAC:C	donor_loss	1.0000
1:44319627:CCT:C	donor_gain	1.0000
1:44319750:G:GC	acceptor_gain	1.0000
1:44319754:C:CT	acceptor_gain	1.0000
1:44319755:A:T	acceptor_gain	1.0000
1:44355063:C:CA	donor_gain	1.0000
1:44221636:GTCGT:G	acceptor_gain	0.9900
1:44221637:TCGT:T	acceptor_gain	0.9900
1:44221638:CGTC:C	acceptor_gain	0.9900
1:44221639:GT:G	acceptor_gain	0.9900
1:44221639:GTCTA:G	acceptor_loss	0.9900
1:44221642:T:G	acceptor_loss	0.9900
1:44248037:GCCT:G	acceptor_gain	0.9900
1:44248039:C:CC	acceptor_gain	0.9900
1:44308308:A:AC	donor_gain	0.9900
1:44308309:C:CC	donor_gain	0.9900
1:44308398:CCCT:C	acceptor_gain	0.9900
1:44308399:CCTC:C	acceptor_gain	0.9900
1:44308402:C:G	acceptor_gain	0.9900
1:44313167:A:AC	donor_gain	0.9900
1:44313167:ACCT:A	donor_gain	0.9900
1:44313168:C:CC	donor_gain	0.9900
1:44313168:CCT:C	donor_gain	0.9900
1:44313168:CCTC:C	donor_gain	0.9900

AlphaMissense

2199 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:44221583:A:G	F330S	1.000
1:44221604:A:G	L323P	1.000
1:44221604:A:T	L323H	1.000
1:44221622:G:T	A317D	1.000
1:44221623:C:G	A317P	1.000
1:44221627:G:C	N315K	1.000
1:44221627:G:T	N315K	1.000
1:44221633:G:C	C313W	1.000
1:44221634:C:A	C313F	1.000
1:44221634:C:T	C313Y	1.000
1:44221635:A:G	C313R	1.000
1:44221636:G:C	D312E	1.000
1:44221636:G:T	D312E	1.000
1:44221637:T:A	D312V	1.000
1:44221637:T:C	D312G	1.000
1:44221637:T:G	D312A	1.000
1:44221638:C:A	D312Y	1.000
1:44221638:C:G	D312H	1.000
1:44247944:C:A	G309V	1.000
1:44247944:C:T	G309D	1.000
1:44247945:C:A	G309C	1.000
1:44247945:C:G	G309R	1.000
1:44247949:G:C	H307Q	1.000
1:44247949:G:T	H307Q	1.000
1:44247951:G:C	H307D	1.000
1:44247959:C:A	G304V	1.000
1:44247959:C:T	G304D	1.000
1:44247960:C:G	G304R	1.000
1:44248035:A:C	Y279D	1.000
1:44284838:T:A	K276N	1.000

dbSNP variants (sampled 300 via entrez): RS1000025757 (1:44271058 C>T), RS1000036743 (1:44225304 T>C,G), RS1000041562 (1:44313707 T>A), RS1000059905 (1:44356209 C>T), RS1000074235 (1:44314060 A>G), RS1000092684 (1:44260457 G>A), RS1000099202 (1:44269062 C>T), RS1000110104 (1:44356475 A>G), RS1000111012 (1:44256301 G>A,T), RS1000117932 (1:44339957 G>T), RS1000152515 (1:44225592 G>A), RS1000179893 (1:44250908 G>A), RS1000190341 (1:44340315 T>C), RS1000194602 (1:44322608 AATG>A), RS1000202485 (1:44345601 C>T)

Disease associations

OMIM: gene MIM:609917 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005173_61	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	7.000000e-06
GCST012354_2	Anxiety	9.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0009863	anxiety measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases expression	2
arsenite	affects binding, increases reaction	1
benzo(e)pyrene	increases methylation	1
CGP 52608	increases reaction, affects binding	1
bisphenol B	increases expression	1
bisphenol S	decreases methylation	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	increases expression, affects cotreatment	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Thiram	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1RH	Abcam HeLa ERI3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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