EEPD1

Summary

EEPD1 (endonuclease/exonuclease/phosphatase family domain containing 1, HGNC:22223) is a protein-coding gene on chromosome 7p14.2, encoding Endonuclease/exonuclease/phosphatase family domain-containing protein 1 (Q7L9B9).

Predicted to enable DNA binding activity and catalytic activity. Involved in positive regulation of cholesterol efflux. Located in plasma membrane.

Source: NCBI Gene 80820 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 106 total
• MANE Select transcript: NM_030636

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22223
Approved symbol	EEPD1
Name	endonuclease/exonuclease/phosphatase family domain containing 1
Location	7p14.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1706
Ensembl gene	ENSG00000122547
Ensembl biotype	protein_coding
OMIM	617192
Entrez	80820

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 retained_intron

ENST00000242108, ENST00000444777, ENST00000468591, ENST00000487069, ENST00000874230, ENST00000874231, ENST00000874232, ENST00000936250, ENST00000960495, ENST00000960496

RefSeq mRNA: 1 — MANE Select: NM_030636 NM_030636

CCDS: CCDS34619

Canonical transcript exons

ENST00000242108 — 8 exons

Exon	Start	End
ENSE00000976554	36238985	36239036
ENSE00001152794	36281115	36281225
ENSE00001152811	36153254	36153674
ENSE00001155725	36299007	36301538
ENSE00001155731	36154133	36155202
ENSE00003518739	36296993	36297187
ENSE00003589096	36287639	36287777
ENSE00003688602	36284686	36284820

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 96.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.7982 / max 178.4895, expressed in 1371 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78119	4.8093	1140
78125	1.0721	393
78118	0.7578	419
78124	0.6166	270
78132	0.2125	78
78126	0.1815	82
78131	0.0634	30
78133	0.0464	15
78134	0.0386	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.98	gold quality
gastrocnemius	UBERON:0001388	93.89	gold quality
muscle of leg	UBERON:0001383	93.04	gold quality
gall bladder	UBERON:0002110	90.98	gold quality
ganglionic eminence	UBERON:0004023	90.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.59	gold quality
body of stomach	UBERON:0001161	89.75	gold quality
omental fat pad	UBERON:0010414	89.58	gold quality
peritoneum	UBERON:0002358	89.48	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.26	gold quality
right lobe of liver	UBERON:0001114	89.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.22	gold quality
lower esophagus	UBERON:0013473	89.20	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.93	gold quality
pancreatic ductal cell	CL:0002079	88.53	silver quality
apex of heart	UBERON:0002098	88.41	gold quality
skin of abdomen	UBERON:0001416	87.99	gold quality
body of pancreas	UBERON:0001150	87.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.72	gold quality
endocervix	UBERON:0000458	87.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.30	gold quality
skin of leg	UBERON:0001511	87.25	gold quality
descending thoracic aorta	UBERON:0002345	87.17	gold quality
spinal cord	UBERON:0002240	87.04	gold quality
lower esophagus mucosa	UBERON:0035834	86.97	gold quality
stomach	UBERON:0000945	86.57	gold quality
popliteal artery	UBERON:0002250	86.46	gold quality
tibial artery	UBERON:0007610	86.44	gold quality
tibialis anterior	UBERON:0001385	86.10	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting EEPD1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-548AR-3P	99.85	71.26	3889

Literature-anchored findings (GeneRIF, showing 5)

• These data demonstrate that genome stability during replication stress is maintained by EEPD1, which initiates HR and inhibits cNHEJ and MMEJ. (PMID:26684013)
• EEPD1 performs a gatekeeper function for replication fork repair by mediating the fork cleavage that permits initiation of HR-mediated repair and restart of stressed forks (PMID:28049724)
• EEPD1 is a novel LXR-regulated gene in macrophages and that it promotes cellular cholesterol efflux by controlling cellular levels and activity of ABCA1. (PMID:28082258)
• The mechanism by which RAD52 depletion causes synthetic lethality in BRCA1 mutant cancer cells depends on the 5’ endonuclease EEPD1, which normally functions to cleave stressed replication forks to initiate HR repair. (PMID:29145865)
• Super-enhancer-associated EEPD1 facilitates EMT-mediated metastasis by regulating the PI3K/AKT/mTOR pathway in gastric cancer. (PMID:37976838)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	eepd1	ENSDARG00000071116
mus_musculus	Eepd1	ENSMUSG00000036611
rattus_norvegicus	Eepd1	ENSRNOG00000006931

Protein

Protein identifiers

Endonuclease/exonuclease/phosphatase family domain-containing protein 1 — Q7L9B9 (reviewed: Q7L9B9)

All UniProt accessions (2): H7C4A5, Q7L9B9

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (1): NP_085139* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003583	Hlx-hairpin-Hlx_DNA-bd_motif	Domain
IPR004509	Competence_ComEA_HhH	Domain
IPR005135	Endo/exonuclease/phosphatase	Domain
IPR010994	RuvA_2-like	Homologous_superfamily
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily
IPR051675	Endo/Exo/Phosphatase_dom_1	Family

Pfam: PF03372, PF12836

UniProt features (22 total): modified residue 9, sequence variant 3, region of interest 3, compositionally biased region 3, initiator methionine 1, chain 1, lipid moiety-binding region 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9YSF	X-RAY DIFFRACTION	1.59
9YXY	X-RAY DIFFRACTION	2
9YI2	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L9B9-F1	74.72	0.40

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 (10): 21, 25, 106, 110, 160, 173, 265, 428, 2, 16

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux

MSigDB gene sets: 146 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_POSITIVE_REGULATION_OF_CHOLESTEROL_EFFLUX, GOBP_REGULATION_OF_CHOLESTEROL_EFFLUX, GOBP_POSITIVE_REGULATION_OF_STEROL_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_CHOLESTEROL_EFFLUX, RGTTAMWNATT_HNF1_01, GOBP_DNA_DAMAGE_RESPONSE, GOBP_REGULATION_OF_STEROL_TRANSPORT, HNF1_C, GOBP_STEROL_TRANSPORT, HNF1_01, GOBP_POSITIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_TRANSPORT

GO Biological Process (2): DNA repair (GO:0006281), positive regulation of cholesterol efflux (GO:0010875)

GO Molecular Function (3): DNA binding (GO:0003677), catalytic activity (GO:0003824), protein binding (GO:0005515)

GO Cellular Component (1): plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
NR1H2 and NR1H3-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	1
DNA damage response	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
cholesterol efflux	1
nucleic acid binding	1
molecular_function	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EEPD1	EXO1	Q9UQ84	676
EEPD1	EME2	A4GXA9	534
EEPD1	DNA2	P51530	469
EEPD1	EXO5	Q9H790	456
EEPD1	SHISA3	A0PJX4	453
EEPD1	SETMAR	Q53H47	433
EEPD1	MUS81	Q96NY9	433
EEPD1	TXNDC8	Q6A555	423
EEPD1	RAD52	P43351	419
EEPD1	COX7A2L	O14548	370
EEPD1	ADGRL1	O94910	353
EEPD1	ADGRL2	O95490	353
EEPD1	ADGRL3	Q9HAR2	353
EEPD1	FHIP2A	Q5W0V3	350
EEPD1	MTMR8	Q96EF0	347

IntAct

36 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
EEPD1	GRIP1	psi-mi:“MI:0915”(physical association)	0.560
FYTTD1	UBA6	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
	EEPD1	psi-mi:“MI:0407”(direct interaction)	0.440
MED21	MED19	psi-mi:“MI:0914”(association)	0.350
TIGD5	P4HA2	psi-mi:“MI:0914”(association)	0.350
SDC1	ARVCF	psi-mi:“MI:0914”(association)	0.350
PCDHGC3	HRAS	psi-mi:“MI:0914”(association)	0.350
NCSTN	YES1	psi-mi:“MI:0914”(association)	0.350
ISG20	SRC	psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350
CERS2	VPS37C	psi-mi:“MI:0914”(association)	0.350
MALL	GPR89A	psi-mi:“MI:0914”(association)	0.350
ANKRD50	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
GAGE5	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
DPM2	WDR46	psi-mi:“MI:0914”(association)	0.350
STARD6	GSTA4	psi-mi:“MI:0914”(association)	0.350
FEM1A	RNF113A	psi-mi:“MI:0914”(association)	0.350
PIGT	AKAP8	psi-mi:“MI:0914”(association)	0.350
PCDHGC3	FYN	psi-mi:“MI:0914”(association)	0.350
NCSTN	ALOX5	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), EEPD1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A2R8Y7D0, A3KMV1, A6NDN8, B9EHT4, D3YWQ0, F1MAB7, O23702, O54788, O75426, O76075, P04413, P0C5J9, P49897, P55073, Q1LZC5, Q28969, Q2T9Z2, Q2VPJ9, Q39491, Q3MHJ7, Q3TGW2, Q4R327, Q57VU6, Q58CZ0, Q5BIR3, Q5I3B1, Q5R4R7, Q5R686, Q5SPX3, Q5XI74, Q6DN07, Q6NXT1, Q6P7W2, Q6QN11, Q6X4W1, Q7L9B9, Q7TPD7, Q80TL4, Q8K485, Q8TBC3

Diamond homologs: A6QPL4, P0AAR8, P0AAR9, P39694, Q14807, Q3MHJ7, Q3TGW2, Q3V300, Q57134, Q5I0E8, Q5REP4, Q5XI74, Q6P3R1, Q6TEQ0, Q7L9B9, A8WFU8, P46837, P57072, P71353, Q45388, Q497V5, Q51062, Q51152, Q5RDI0, Q6IND4, Q8N5C6, Q9I869

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2715 predictions. Top by Δscore:

Variant	Effect	Δscore
7:36164806:G:GG	donor_gain	1.0000
7:36238983:A:AG	acceptor_gain	1.0000
7:36238983:AG:A	acceptor_loss	1.0000
7:36238984:G:GC	acceptor_loss	1.0000
7:36238984:G:GG	acceptor_gain	1.0000
7:36238984:GC:G	acceptor_gain	1.0000
7:36243866:G:GT	donor_gain	1.0000
7:36281113:A:AG	acceptor_gain	1.0000
7:36281114:G:GG	acceptor_gain	1.0000
7:36281221:AGAAG:A	donor_loss	1.0000
7:36281222:GAAGG:G	donor_loss	1.0000
7:36281223:AAGGT:A	donor_loss	1.0000
7:36281224:AGGTA:A	donor_loss	1.0000
7:36281225:GGTA:G	donor_loss	1.0000
7:36281226:GT:G	donor_loss	1.0000
7:36281227:T:G	donor_loss	1.0000
7:36284781:G:T	donor_gain	1.0000
7:36284815:TTC:T	donor_gain	1.0000
7:36284872:A:T	donor_gain	1.0000
7:36296985:A:AG	acceptor_gain	1.0000
7:36296986:C:G	acceptor_gain	1.0000
7:36296988:TCCAG:T	acceptor_loss	1.0000
7:36296991:A:AG	acceptor_gain	1.0000
7:36296991:AGG:A	acceptor_loss	1.0000
7:36296992:G:A	acceptor_loss	1.0000
7:36296992:G:GA	acceptor_gain	1.0000
7:36296992:GGA:G	acceptor_gain	1.0000
7:36297160:A:AG	donor_gain	1.0000
7:36297161:G:GG	donor_gain	1.0000
7:36297189:T:A	donor_loss	1.0000

AlphaMissense

3739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:36154449:T:A	I42N	1.000
7:36154453:C:A	N43K	1.000
7:36154453:C:G	N43K	1.000
7:36154458:C:A	A45D	1.000
7:36154473:T:A	L50Q	1.000
7:36154473:T:C	L50P	1.000
7:36154482:T:C	L53P	1.000
7:36154506:C:A	A61E	1.000
7:36154515:T:A	I64N	1.000
7:36154527:G:C	R68P	1.000
7:36154544:T:C	F74L	1.000
7:36154545:T:C	F74S	1.000
7:36154546:C:A	F74L	1.000
7:36154546:C:G	F74L	1.000
7:36154563:T:C	L80P	1.000
7:36154572:T:A	V83D	1.000
7:36154596:T:C	L91P	1.000
7:36154449:T:G	I42S	0.999
7:36154452:A:T	N43I	0.999
7:36154457:G:C	A45P	0.999
7:36154473:T:G	L50R	0.999
7:36154505:G:C	A61P	0.999
7:36154515:T:G	I64S	0.999
7:36154523:T:G	Y67D	0.999
7:36154526:C:G	R68G	0.999
7:36154544:T:G	F74V	0.999
7:36154545:T:G	F74C	0.999
7:36154559:G:C	D79H	0.999
7:36154560:A:C	D79A	0.999
7:36154560:A:G	D79G	0.999

dbSNP variants (sampled 300 via entrez): RS1000011213 (7:36228028 T>C), RS1000013117 (7:36191917 C>A,T), RS1000047791 (7:36269693 T>C), RS1000115245 (7:36185769 C>T), RS1000141587 (7:36228060 C>T), RS1000177805 (7:36217476 C>T), RS1000178127 (7:36262705 C>G,T), RS1000195956 (7:36239825 A>C,T), RS1000201432 (7:36256832 A>C), RS1000211484 (7:36203825 C>T), RS1000222926 (7:36178742 C>T), RS1000266499 (7:36206027 G>T), RS1000309449 (7:36297338 T>C), RS1000313639 (7:36161053 G>A), RS1000322853 (7:36301983 T>C)

Disease associations

OMIM: gene MIM:617192 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001061_6	Platelet count	5.000000e-06
GCST001762_559	Obesity-related traits	3.000000e-06
GCST003194_24	Fibrinogen levels	3.000000e-09
GCST004121_32	Fibrinogen levels	4.000000e-08
GCST004122_6	Fibrinogen levels	9.000000e-09
GCST006626_16	Pulse pressure	1.000000e-09
GCST007205_6	Schizophrenia	1.000000e-06
GCST007614_47	C-reactive protein levels	1.000000e-08
GCST010002_347	Refractive error	3.000000e-08
GCST010241_425	Apolipoprotein A1 levels	2.000000e-12
GCST010242_18	HDL cholesterol levels	1.000000e-16
GCST010242_242	HDL cholesterol levels	1.000000e-08
GCST010245_60	LDL cholesterol levels	2.000000e-11
GCST90002385_186	High light scatter reticulocyte count	6.000000e-10
GCST90002397_500	Mean spheric corpuscular volume	2.000000e-12
GCST90002405_227	Reticulocyte count	7.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004736	aspartate aminotransferase measurement
EFO:0005763	pulse pressure measurement
EFO:0004458	C-reactive protein measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation	3
Lead	affects expression, affects methylation	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
NSC 689534	affects binding, decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, affects expression	1
Amiodarone	increases expression	1
Arbutin	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Calcitriol	decreases expression	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	increases expression	1
Estradiol	affects expression	1
Lipopolysaccharides	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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