EPM2AIP1

Summary

EPM2AIP1 (EPM2A interacting protein 1, HGNC:19735) is a protein-coding gene on chromosome 3p22.2, encoding EPM2A-interacting protein 1 (Q7L775).

The EPM2A gene, which encodes laforin, is mutated in an autosomal recessive form of adolescent progressive myoclonus epilepsy. The protein encoded by this gene binds to laforin, but its function is not known. This gene is intronless.

Source: NCBI Gene 9852 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 97 total — 19 pathogenic
• MANE Select transcript: NM_014805

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19735
Approved symbol	EPM2AIP1
Name	EPM2A interacting protein 1
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0766, FLJ11207
Ensembl gene	ENSG00000178567
Ensembl biotype	protein_coding
OMIM	607911
Entrez	9852

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000322716, ENST00000623924, ENST00000624586

RefSeq mRNA: 1 — MANE Select: NM_014805 NM_014805

CCDS: CCDS46790

Canonical transcript exons

ENST00000322716 — 1 exons

Exon	Start	End
ENSE00001336002	36985043	36993131

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0328 / max 256.9575, expressed in 1799 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41675	7.6519	1716
41674	4.3275	1621
41673	3.8536	1309
41676	3.4768	1397
41677	1.0447	590
41670	0.9230	553
41678	0.3949	221
41679	0.1942	63
41672	0.1661	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.34	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.48	gold quality
trabecular bone tissue	UBERON:0002483	97.05	gold quality
caput epididymis	UBERON:0004358	96.96	gold quality
superior vestibular nucleus	UBERON:0007227	96.87	gold quality
pons	UBERON:0000988	96.79	gold quality
pigmented layer of retina	UBERON:0001782	96.70	gold quality
cerebellar vermis	UBERON:0004720	96.70	gold quality
ventral tegmental area	UBERON:0002691	96.57	gold quality
postcentral gyrus	UBERON:0002581	96.41	gold quality
parietal lobe	UBERON:0001872	96.32	gold quality
corpus epididymis	UBERON:0004359	96.31	gold quality
left ventricle myocardium	UBERON:0006566	96.30	gold quality
inferior vagus X ganglion	UBERON:0005363	96.27	gold quality
myocardium	UBERON:0002349	96.21	gold quality
pylorus	UBERON:0001166	96.19	gold quality
biceps brachii	UBERON:0001507	96.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.98	gold quality
tibia	UBERON:0000979	95.95	gold quality
nipple	UBERON:0002030	95.92	gold quality
CA1 field of hippocampus	UBERON:0003881	95.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.88	gold quality
cauda epididymis	UBERON:0004360	95.87	gold quality
entorhinal cortex	UBERON:0002728	95.85	gold quality
lateral globus pallidus	UBERON:0002476	95.70	gold quality
renal medulla	UBERON:0000362	95.63	gold quality
seminal vesicle	UBERON:0000998	95.49	gold quality
subthalamic nucleus	UBERON:0001906	95.46	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

283 targeting EPM2AIP1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 2)

• The EPM2AIP1 gene was identified and characterized in a screen for laforin-interacting proteins with a human brain cDNA library; the specificity of the interaction was confirmed; subcellular colocalization of laforin and EPM2AIP1 protein was demonstrated (PMID:12782127)
• The -93G>A polymorphism modifies the efficiency of MLH1/EPM2AIP1 transcription. (PMID:21206982)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Epm2aip1	ENSMUSG00000046785
rattus_norvegicus	Epm2aip1	ENSRNOG00000043006

Paralogs (18): GTF2IRD1 (ENSG00000006704), ZMYM2 (ENSG00000121741), ZMYM5 (ENSG00000132950), THAP12 (ENSG00000137492), ZMYM4 (ENSG00000146463), ZMYM3 (ENSG00000147130), ZMYM6 (ENSG00000163867), KIAA1958 (ENSG00000165185), GTF2IRD2B (ENSG00000174428), GTF2IRD2 (ENSG00000196275), ZMYM1 (ENSG00000197056), QRICH1 (ENSG00000198218), FAM200C (ENSG00000221886), FAM200A (ENSG00000221909), SCAND3 (ENSG00000232040), ZBED5 (ENSG00000236287), FAM200B (ENSG00000237765), GTF2I (ENSG00000263001)

Protein

Protein identifiers

EPM2A-interacting protein 1 — Q7L775 (reviewed: Q7L775)

Alternative names: Laforin-interacting protein

All UniProt accessions (3): A0A096LNL1, A0A096LPB0, Q7L775

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with EPM2A.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Expressed in heart, brain, placenta, liver, pancreas, kidney and skeletal muscle.

RefSeq proteins (1): NP_055620* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040647	SPIN-DOC_Znf-C2H2	Domain

Pfam: PF18658

UniProt features (7 total): sequence conflict 3, sequence variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L775-F1	85.37	0.46

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 (1): 146

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 231 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GCM_GSPT1, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GCM_ZNF198, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POSITIVE_REGULATION_OF_GLYCOGEN_METABOLIC_PROCESS, LOPES_METHYLATED_IN_COLON_CANCER_DN, GOBP_RESPONSE_TO_INSULIN, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr3p22

GO Biological Process (3): glycogen biosynthetic process (GO:0005978), response to insulin (GO:0032868), positive regulation of glycogen biosynthetic process (GO:0045725)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
glycogen metabolic process	1
glucan biosynthetic process	1
response to peptide hormone	1
glycogen biosynthetic process	1
regulation of glycogen biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of glycogen metabolic process	1
protein binding	1
binding	1
endoplasmic reticulum membrane	1
cytoplasmic side of membrane	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPM2AIP1	EPM2A	O95278	930
EPM2AIP1	NFU1	Q9UMS0	691
EPM2AIP1	NHLRC1	Q6VVB1	689
EPM2AIP1	PPP1R3C	Q9UQK1	664
EPM2AIP1	LYG1	Q8N1E2	571
EPM2AIP1	TXNL1	O43396	560
EPM2AIP1	AMY1B	P04745	548
EPM2AIP1	MLH1	P40692	515
EPM2AIP1	AMY2A	P04746	514
EPM2AIP1	IFT70A	Q86WT1	507
EPM2AIP1	NAA38	Q9BRA0	491
EPM2AIP1	LRRFIP2	Q9Y608	473
EPM2AIP1	SHROOM4	Q9ULL8	449
EPM2AIP1	RTF2	Q9BY42	448
EPM2AIP1	ZSWIM3	Q96MP5	446

IntAct

185 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
PGBD1	ZNF24	psi-mi:“MI:0914”(association)	0.900
SERPINF1	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.850
MAD2L1	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.740
ZBTB14	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.720
ACTN1	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.720
EPM2AIP1	VPS52	psi-mi:“MI:0915”(physical association)	0.720
EPM2AIP1	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
PRTFDC1	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.720
EPM2AIP1	ZBTB14	psi-mi:“MI:0915”(physical association)	0.720
EPM2AIP1	ACTN1	psi-mi:“MI:0915”(physical association)	0.720
VPS52	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.720
EPM2AIP1	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (95): EPM2AIP1 (Two-hybrid), EPM2AIP1 (Two-hybrid), EPM2AIP1 (Two-hybrid), EPM2AIP1 (Two-hybrid), EPM2AIP1 (Two-hybrid), EPM2AIP1 (Two-hybrid), EPM2AIP1 (Two-hybrid), EPM2AIP1 (Two-hybrid), EPM2AIP1 (Two-hybrid), PRTFDC1 (Two-hybrid), TRIM54 (Two-hybrid), CCNB1IP1 (Two-hybrid), C1orf50 (Two-hybrid), CPSF7 (Two-hybrid), KCTD1 (Two-hybrid)

ESM2 similar proteins: A0A140LIF8, A0A2P1BRP3, A0JN92, A1A4Y4, B1ARD8, G1SRW8, P0C7P3, P0DMR5, P27473, P59045, P86448, P86449, Q08AF3, Q0E2Q3, Q0GUM3, Q2T9S8, Q32KW9, Q3T9E4, Q3TL54, Q53G44, Q5NCI0, Q5RFJ8, Q5U311, Q60766, Q62293, Q66X01, Q66X03, Q66X22, Q6AYC2, Q6AYF9, Q6NXR0, Q7L775, Q7TSV6, Q84WJ0, Q8BV66, Q8BZS9, Q8C6J9, Q8CBA2, Q8NHS2, Q8TCB0

Diamond homologs: Q7L775, Q8VEH5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	0
Uncertain significance	69
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1454711	NC_000003.11:g.(?37034542)(37059100_?)del	Pathogenic
154796	GRCh38/hg38 3p22.2(chr3:36828515-37007227)x1	Pathogenic
2422637	NC_000003.11:g.(?37034542)(37061964_?)del	Pathogenic
2422638	NC_000003.11:g.(?37034542)(37042554_?)del	Pathogenic
2422645	NC_000003.11:g.(?37034542)(37035164_?)del	Pathogenic
3246795	NC_000003.11:g.(?36856133)(37076835_?)del	Pathogenic
3246808	NC_000003.11:g.(?37034542)(37035174_?)del	Pathogenic
3246809	NC_000003.11:g.(?37034542)(37035260_?)del	Pathogenic
3246810	NC_000003.11:g.(?37034289)(37092144_?)del	Pathogenic
455070	NC_000003.11:g.(?37034542)(37050402_?)del	Pathogenic
455071	NC_000003.12:g.(?36993051)(37017605_?)del	Pathogenic
455073	NC_000003.12:g.(?36993051)(37050659_?)del	Pathogenic
525977	NC_000003.12:g.(?36993051)(37004480_?)del	Pathogenic
583740	NC_000003.12:g.(?36993051)(37050663_?)del	Pathogenic
583896	NC_000003.12:g.(?36993051)(37008915_?)del	Pathogenic
584333	NC_000003.12:g.(?36993051)(37028942_?)del	Pathogenic
642035	NC_000003.12:g.(?36993051)(36996719_?)del	Pathogenic
645371	NC_000003.12:g.(?36993051)(37012109_?)del	Pathogenic
830919	NC_000003.12:g.(?36993031)(37050673_?)del	Pathogenic

SpliceAI

668 predictions. Top by Δscore:

Variant	Effect	Δscore
3:36990377:T:TA	donor_gain	1.0000
3:36987624:A:C	acceptor_gain	0.9900
3:36990373:CACCT:C	donor_gain	0.9900
3:36990381:AAT:A	donor_gain	0.9900
3:36990373:CA:C	donor_gain	0.9800
3:36991627:T:TA	donor_gain	0.9800
3:36992275:ACGG:A	donor_gain	0.9800
3:36992276:CGGC:C	donor_gain	0.9800
3:36987624:A:AC	acceptor_gain	0.9700
3:36990371:CACA:C	donor_loss	0.9700
3:36990374:A:AT	donor_loss	0.9700
3:36990375:C:CG	donor_loss	0.9700
3:36990436:C:CC	acceptor_gain	0.9700
3:36987623:CA:C	acceptor_gain	0.9600
3:36991625:AGT:A	donor_gain	0.9600
3:36991729:T:TA	donor_gain	0.9600
3:36992877:CCG:C	donor_gain	0.9600
3:36992464:TGC:T	donor_gain	0.9500
3:36990372:A:AC	donor_gain	0.9400
3:36990373:C:CC	donor_gain	0.9400
3:36991705:T:C	donor_gain	0.9400
3:36991879:A:AC	donor_gain	0.9300
3:36991880:C:CC	donor_gain	0.9300
3:36987279:GATGC:G	acceptor_loss	0.9200
3:36987280:ATGC:A	acceptor_loss	0.9200
3:36987285:T:G	acceptor_loss	0.9200
3:36987286:A:C	acceptor_loss	0.9100
3:36992478:AGGG:A	donor_gain	0.9100
3:36990440:A:T	acceptor_gain	0.9000
3:36992275:A:AC	donor_gain	0.9000

AlphaMissense

3992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:36991494:A:C	F528L	0.998
3:36991494:A:T	F528L	0.998
3:36991495:A:G	F528S	0.998
3:36991496:A:G	F528L	0.998
3:36992491:C:G	R196P	0.998
3:36991440:C:A	K546N	0.997
3:36991440:C:G	K546N	0.997
3:36991549:A:G	L510P	0.997
3:36991558:A:G	L507P	0.997
3:36992350:C:T	G243E	0.997
3:36992351:C:G	G243R	0.997
3:36992351:C:T	G243R	0.997
3:36992492:G:T	R196S	0.996
3:36992496:A:C	F194L	0.996
3:36992496:A:T	F194L	0.996
3:36992498:A:G	F194L	0.996
3:36992548:A:T	L177H	0.996
3:36992552:A:G	S176P	0.996
3:36992555:A:C	Y175D	0.996
3:36991425:A:C	F551L	0.995
3:36991425:A:T	F551L	0.995
3:36991427:A:G	F551L	0.995
3:36991483:A:G	L532S	0.995
3:36991606:G:T	P491Q	0.995
3:36992500:A:T	V193D	0.995
3:36991324:C:G	R585P	0.994
3:36991582:G:T	A499E	0.994
3:36992347:A:G	L244P	0.994
3:36992596:A:G	L161P	0.994
3:36991602:A:C	F492L	0.993

dbSNP variants (sampled 300 via entrez): RS1000009385 (3:36991731 C>A,T), RS1000080361 (3:36994441 C>T), RS1000269549 (3:36987600 A>C,G), RS1000281426 (3:36994277 T>G), RS1000491699 (3:36988187 A>G,T), RS1000607663 (3:36993295 A>C), RS1000817042 (3:36986583 C>A), RS1000842754 (3:36987916 G>A,C), RS1000863739 (3:36988992 T>TC), RS1001456127 (3:36995063 A>T), RS1001663690 (3:36988614 T>C,G), RS1001842460 (3:36993824 T>C), RS1001943212 (3:36986654 T>A), RS1002704217 (3:36985775 G>C), RS1003334377 (3:36985503 G>A)

Disease associations

OMIM: gene MIM:607911 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003158_2	Subjective response to lithium treatment	8.000000e-07
GCST004521_90	Autism spectrum disorder or schizophrenia	1.000000e-11
GCST010244_107	Triglyceride levels	6.000000e-09
GCST90013407_184	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-49

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800734	EPM2AIP1, MLH1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
perfluorooctane sulfonic acid	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	decreases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1

Clinical trials (associated diseases)

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