ERI2

Summary

ERI2 (ERI1 exoribonuclease family member 2, HGNC:30541) is a protein-coding gene on chromosome 16p12.3, encoding ERI1 exoribonuclease 2 (A8K979).

Predicted to enable 3’-5’-RNA exonuclease activity.

Source: NCBI Gene 112479 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_001142725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30541
Approved symbol	ERI2
Name	ERI1 exoribonuclease family member 2
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1504, MGC16943, ZGRF5
Ensembl gene	ENSG00000196678
Ensembl biotype	protein_coding
Entrez	112479

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 protein_coding, 6 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000300005, ENST00000357967, ENST00000562215, ENST00000562277, ENST00000562987, ENST00000563117, ENST00000563537, ENST00000564349, ENST00000565884, ENST00000566223, ENST00000567562, ENST00000567859, ENST00000568251, ENST00000568805, ENST00000569729, ENST00000911689

RefSeq mRNA: 2 — MANE Select: NM_001142725 NM_001142725, NM_080663

CCDS: CCDS10590, CCDS45436

Canonical transcript exons

ENST00000357967 — 9 exons

Exon	Start	End
ENSE00003490396	20803603	20803670
ENSE00003505610	20799957	20800038
ENSE00003526583	20802796	20802923
ENSE00003586126	20803433	20803516
ENSE00003692065	20799263	20799351
ENSE00003890038	20806408	20806472
ENSE00003891460	20800302	20800402
ENSE00003894628	20796340	20799067
ENSE00003894982	20801203	20801359

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 90.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.6292 / max 104.4166, expressed in 1669 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156705	6.6292	1669
156699	5.9701	1624
156698	1.3152	611
156700	0.0243	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	90.91	gold quality
secondary oocyte	CL:0000655	89.93	gold quality
rectum	UBERON:0001052	88.80	gold quality
right uterine tube	UBERON:0001302	88.56	gold quality
tibia	UBERON:0000979	88.00	gold quality
esophagus squamous epithelium	UBERON:0006920	87.43	gold quality
right adrenal gland	UBERON:0001233	87.08	gold quality
hair follicle	UBERON:0002073	87.04	gold quality
right adrenal gland cortex	UBERON:0035827	86.84	gold quality
right testis	UBERON:0004534	86.69	gold quality
choroid plexus epithelium	UBERON:0003911	86.62	gold quality
squamous epithelium	UBERON:0006914	86.60	gold quality
left testis	UBERON:0004533	86.32	gold quality
body of pancreas	UBERON:0001150	86.07	gold quality
cervix squamous epithelium	UBERON:0006922	85.95	silver quality
endothelial cell	CL:0000115	85.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.60	gold quality
testis	UBERON:0000473	85.40	gold quality
visceral pleura	UBERON:0002401	85.39	gold quality
gingival epithelium	UBERON:0001949	85.37	gold quality
ventricular zone	UBERON:0003053	85.34	gold quality
germinal epithelium of ovary	UBERON:0001304	85.28	gold quality
left adrenal gland	UBERON:0001234	85.15	gold quality
ganglionic eminence	UBERON:0004023	84.81	gold quality
trabecular bone tissue	UBERON:0002483	84.76	gold quality
epithelium of esophagus	UBERON:0001976	84.68	gold quality
amniotic fluid	UBERON:0000173	84.62	gold quality
palpebral conjunctiva	UBERON:0001812	84.60	gold quality
left adrenal gland cortex	UBERON:0035825	84.54	gold quality
right lobe of liver	UBERON:0001114	84.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.87
E-GEOD-124858	no	170.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting ERI2, 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-548C-3P	99.99	74.01	7587
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-6783-5P	97.67	67.21	1528

Literature-anchored findings (GeneRIF, showing 1)

• This paper describes a detailed biochemical and genetic characterization of the exonuclease Snipper, the Drosophila ortholog of EXOD1. It identifies EXOD1 as a member of a new subclass of exonucleases called the 3’hExo/ERI-1 subfamily of DEDDh nucleases. (PMID:17135487)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	eri2	ENSDARG00000104392
mus_musculus	Eri2	ENSMUSG00000030929
rattus_norvegicus	Eri2	ENSRNOG00000014673
drosophila_melanogaster	Snp	FBGN0265192

Paralogs (2): ERI1 (ENSG00000104626), ERI3 (ENSG00000117419)

Protein

Protein identifiers

ERI1 exoribonuclease 2 — A8K979 (reviewed: A8K979)

Alternative names: Exonuclease domain-containing protein 1

All UniProt accessions (2): A8K979, H3BN77

UniProt curated annotations — full annotation on UniProt →

Cofactor. Binds 2 magnesium ions per subunit.

Similarity. Belongs to the ERI2 family.

Isoforms (4)

UniProt ID	Names	Canonical?
A8K979-1	1	yes
A8K979-2	2
A8K979-3	3
A8K979-4	4

RefSeq proteins (2): NP_001136197, NP_542394 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010666	Znf_GRF	Domain
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, PF06839

UniProt features (42 total): binding site 11, helix 9, strand 7, splice variant 5, sequence variant 3, active site 2, chain 1, domain 1, zinc finger region 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7N8V	X-RAY DIFFRACTION	2.1
7N8W	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8K979-F1	59.66	0.31

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): 43 (proton acceptor); 213 (proton acceptor)

Ligand- & substrate-binding residues (11): 213; 218; 597; 599; 622; 634; 41; 41; 43; 43; 156

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 208 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, MARTINEZ_RB1_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_REGULATION_OF_CHROMATIN_ORGANIZATION, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_RRNA_3_END_PROCESSING, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOMF_EXONUCLEASE_ACTIVITY

GO Biological Process (0):

GO Molecular Function (7): 3’-5’-RNA exonuclease activity (GO:0000175), nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

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
binding	1
transition metal ion binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1
cation binding	1

Protein interactions and networks

STRING

558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERI2	XRN2	Q9H0D6	946
ERI2	DNASE1L2	Q92874	712
ERI2	DXO	O77932	684
ERI2	TJAP1	Q5JTD0	648
ERI2	TDRD12	Q587J7	603
ERI2	INTS14	Q96SY0	474
ERI2	EXD1	Q8NHP7	447
ERI2	ERI1	Q8IV48	445
ERI2	L3MBTL2	Q969R5	433
ERI2	ACSM3	Q53FZ2	424
ERI2	TBC1D8B	Q0IIM8	422
ERI2	OR5H14	A6NHG9	419
ERI2	WDR83	Q9BRX9	402
ERI2	KRABD5	Q7Z2F6	396
ERI2	PPIP5K2	O43314	392

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CASQ2	ERI2	psi-mi:“MI:0915”(physical association)	0.400
ERI2	DNAJC12	psi-mi:“MI:0915”(physical association)	0.400
PB2		psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350

BioGRID (8): FLNC (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), FLNC (Affinity Capture-MS), ERI2 (Synthetic Lethality), CASQ2 (Proximity Label-MS), DNAJC12 (Affinity Capture-MS), ERI2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0G2L7I0, A0A1L8G2K9, A0A1P8AW69, A5D979, A8K979, B3H578, B4R4H1, D3ZVU1, F4HTH8, F4HXQ7, F4I8S3, F6UH96, G3X912, O64571, P0DKJ8, P62283, P62285, P62286, P62287, P62288, P62289, P62290, P62293, P62294, Q0IGK1, Q2PS26, Q56NI9, Q5QGU6, Q60GC1, Q6DJS0, Q6DRC5, Q6NYJ3, Q6PF04, Q7ZXG4, Q8BMI4, Q8BP27, Q8CIB9, Q8IZT6, Q8N4S0, Q94F87

Diamond homologs: A6QLH5, A8K979, O43414, O44406, Q08I43, Q10905, Q502M8, Q5BKS4, Q5FVR4, Q5HZL1, Q7TMF2, Q8C460, Q8IV48, Q8W566, Q95RQ4, Q9NG98, A0A0L0P6P7, C7J0A2, F4ISQ7, O60126, O61660, O70157, O95985, O96651, P13099, Q0J0S6, Q0VGT4, Q13472, Q5E9N9, Q68G58, Q6F598, Q86YA3, Q8T2T7, Q8TAT5, Q9LVP1, Q9UBZ4, Q9Z321

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

7183 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20780854:G:GT	donor_gain	1.0000
16:20780855:A:T	donor_gain	1.0000
16:20790684:ACGTA:A	donor_gain	1.0000
16:20790686:GTA:G	donor_gain	1.0000
16:20790687:TA:T	donor_gain	1.0000
16:20790688:AG:A	donor_loss	1.0000
16:20790689:G:GG	donor_gain	1.0000
16:20790690:TAA:T	donor_loss	1.0000
16:20792078:A:G	donor_gain	1.0000
16:20796117:GTTTA:G	donor_gain	1.0000
16:20796118:TTTAT:T	donor_gain	1.0000
16:20796121:A:AG	donor_gain	1.0000
16:20796121:A:G	donor_gain	1.0000
16:20796125:G:GG	donor_gain	1.0000
16:20799348:AACCC:A	acceptor_loss	1.0000
16:20799349:ACCC:A	acceptor_loss	1.0000
16:20799350:CC:C	acceptor_gain	1.0000
16:20799350:CCCTG:C	acceptor_loss	1.0000
16:20799351:CC:C	acceptor_gain	1.0000
16:20799351:CCTG:C	acceptor_loss	1.0000
16:20799352:C:CC	acceptor_gain	1.0000
16:20799353:T:A	acceptor_loss	1.0000
16:20800417:T:TC	acceptor_gain	1.0000
16:20801227:A:C	donor_gain	1.0000
16:20801232:A:AC	donor_gain	1.0000
16:20801233:C:CC	donor_gain	1.0000
16:20801235:T:TA	donor_gain	1.0000
16:20801359:CCTG:C	acceptor_loss	1.0000
16:20801360:C:CA	acceptor_loss	1.0000
16:20802790:TCATA:T	donor_loss	1.0000

AlphaMissense

4562 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20801209:A:G	W152R	0.999
16:20801209:A:T	W152R	0.999
16:20800328:A:G	W179R	0.997
16:20800328:A:T	W179R	0.997
16:20800400:A:G	W155R	0.997
16:20800400:A:T	W155R	0.997
16:20800381:A:G	L161P	0.996
16:20800396:T:G	D156A	0.996
16:20802857:A:T	V81D	0.996
16:20798011:A:G	C597R	0.995
16:20799976:G:C	F208L	0.995
16:20799976:G:T	F208L	0.995
16:20799978:A:G	F208L	0.995
16:20800318:A:G	L182P	0.995
16:20801214:A:T	V150D	0.995
16:20801305:A:G	W120R	0.995
16:20801305:A:T	W120R	0.995
16:20797885:A:G	W639R	0.994
16:20797885:A:T	W639R	0.994
16:20797936:A:G	C622R	0.994
16:20799309:A:G	M229T	0.994
16:20799327:G:T	A223D	0.994
16:20799336:C:G	R220P	0.994
16:20800396:T:A	D156V	0.994
16:20800398:C:A	W155C	0.994
16:20800398:C:G	W155C	0.994
16:20802868:G:C	F77L	0.994
16:20802868:G:T	F77L	0.994
16:20802870:A:G	F77L	0.994
16:20802902:A:G	L66P	0.994

dbSNP variants (sampled 300 via entrez): RS1000296370 (16:20793948 A>G), RS1000551004 (16:20793865 G>A), RS1000776653 (16:20806614 A>G,T), RS1000794830 (16:20784666 T>A,G), RS1000849229 (16:20807856 G>C), RS1000853138 (16:20807178 C>T), RS1001133002 (16:20799916 T>A), RS1001163441 (16:20785031 T>C), RS1001240538 (16:20785941 C>G), RS1001502383 (16:20799674 A>G), RS1001689953 (16:20785563 G>A), RS1001867789 (16:20787907 C>G), RS1001965601 (16:20799572 G>A), RS1002140589 (16:20782359 C>A,G), RS1002207393 (16:20793631 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
quercitrin	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
pentanal	decreases expression	1
jinfukang	decreases expression	1
NSC668394	decreases expression	1
Sunitinib	decreases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Cisplatin	increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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