EAPP

Summary

EAPP (E2F associated phosphoprotein, HGNC:19312) is a protein-coding gene on chromosome 14q13.1, encoding E2F-associated phosphoprotein (Q56P03). May play an important role in the fine-tuning of both major E2F1 activities, the regulation of the cell-cycle and the induction of apoptosis. It is a selective cancer dependency (DepMap: 64.9% of cell lines).

This gene encodes a phosphoprotein that interacts with several members of the E2F family of proteins. The protein localizes to the nucleus, and is present throughout the cell cycle except during mitosis. It functions to modulate E2F-regulated transcription and stimulate proliferation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55837 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 61 total
• Cancer dependency (DepMap): dependent in 64.9% of screened cell lines
• MANE Select transcript: NM_018453

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19312
Approved symbol	EAPP
Name	E2F associated phosphoprotein
Location	14q13.1
Locus type	gene with protein product
Status	Approved
Aliases	BM036, FLJ20578
Ensembl gene	ENSG00000129518
Ensembl biotype	protein_coding
OMIM	609486
Entrez	55837

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000250454, ENST00000554792, ENST00000555683, ENST00000555705, ENST00000867834, ENST00000912552

RefSeq mRNA: 2 — MANE Select: NM_018453 NM_001318916, NM_018453

CCDS: CCDS41941

Canonical transcript exons

ENST00000250454 — 6 exons

Exon	Start	End
ENSE00000889626	34529358	34529475
ENSE00000998932	34515938	34516586
ENSE00001288967	34524697	34524807
ENSE00001310426	34539555	34539701
ENSE00003478801	34536094	34536275
ENSE00003625453	34533444	34533539

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 97.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.2884 / max 1041.5104, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142789	42.0315	1817
142788	0.2568	117

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.79	gold quality
palpebral conjunctiva	UBERON:0001812	95.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.45	gold quality
rectum	UBERON:0001052	95.43	gold quality
eye	UBERON:0000970	94.51	gold quality
mucosa of transverse colon	UBERON:0004991	94.43	gold quality
skin of leg	UBERON:0001511	94.35	gold quality
left ovary	UBERON:0002119	94.20	gold quality
nasal cavity mucosa	UBERON:0001826	94.06	gold quality
skin of abdomen	UBERON:0001416	94.02	gold quality
leukocyte	CL:0000738	93.98	gold quality
zone of skin	UBERON:0000014	93.98	gold quality
ganglionic eminence	UBERON:0004023	93.95	gold quality
monocyte	CL:0000576	93.90	gold quality
transverse colon	UBERON:0001157	93.90	gold quality
mononuclear cell	CL:0000842	93.89	gold quality
ovary	UBERON:0000992	93.84	gold quality
granulocyte	CL:0000094	93.65	gold quality
right ovary	UBERON:0002118	93.64	gold quality
right adrenal gland cortex	UBERON:0035827	93.50	gold quality
tibial artery	UBERON:0007610	93.48	gold quality
popliteal artery	UBERON:0002250	93.47	gold quality
mucosa of stomach	UBERON:0001199	93.41	gold quality
islet of Langerhans	UBERON:0000006	93.39	gold quality
bronchial epithelial cell	CL:0002328	93.35	gold quality
right adrenal gland	UBERON:0001233	93.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.28	gold quality
caput epididymis	UBERON:0004358	93.25	gold quality
artery	UBERON:0001637	93.19	gold quality
descending thoracic aorta	UBERON:0002345	93.18	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: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
ABCB1	Activation
CDKN1A	Unknown
CDKN2A	Repression
MAOB	Repression

Upstream regulators (CollecTRI, top): EGR1, SP1, SP3

miRNA regulators (miRDB)

29 targeting EAPP, 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-551B-5P	99.96	71.28	3493
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4774-3P	98.90	67.82	737
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-4791	96.51	67.76	659
HSA-MIR-563	96.26	66.13	450
HSA-MIR-668-3P	96.18	65.80	673
HSA-MIR-380-5P	95.68	67.32	512

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 64.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• EAPP modulates E2F-regulated transcription, stimulates proliferation, and may be involved in the malignant transformation of cells. (PMID:15716352)
• Regulation of the EAPP promoter by GC-box binding proteins is reported. (PMID:18588995)
• results indicate that the level of EAPP is critical for cellular homeostasis (PMID:21258403)
• Independently of EAPP, E2F1 also increases the activity of the MDR1 promoter. (PMID:23542036)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	eapp	ENSDARG00000017272
mus_musculus	Eapp	ENSMUSG00000054302
rattus_norvegicus	Eapp	ENSRNOG00000004509
caenorhabditis_elegans		WBGENE00018609

Protein

Protein identifiers

E2F-associated phosphoprotein — Q56P03 (reviewed: Q56P03)

All UniProt accessions (3): Q56P03, G3V2W9, G3V5N6

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in the fine-tuning of both major E2F1 activities, the regulation of the cell-cycle and the induction of apoptosis. Promotes S-phase entry, and inhibits p14(ARP) expression.

Subunit / interactions. Interacts with E2F1. The C-terminal half binds the N-terminal of E2F1. Also interacts with E2F2 and E2F3, but not E2F4.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed. Highest levels in heart, placenta, skeletal muscle and pancreas. Lower levels in brain, lung and kidney. In the brain, expressed in all regions with high levels in the cerebellum and cerebral cortex. Expressed in COS1 and transformed skin fibroblasts.

RefSeq proteins (2): NP_001305845, NP_060923* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019370	E2F-assoc_phosphoprotein	Family

Pfam: PF10238

UniProt features (17 total): modified residue 5, compositionally biased region 4, region of interest 3, sequence conflict 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q56P03-F1	75.38	0.28

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 (5): 37, 109, 111, 1, 17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GENTILE_UV_HIGH_DOSE_DN, GOBP_NEGATIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GENTILE_UV_RESPONSE_CLUSTER_D7, YNGTTNNNATT_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, chr14q13, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B

GO Biological Process (3): positive regulation of cell population proliferation (GO:0008284), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), negative regulation of transcription elongation by RNA polymerase II (GO:0034244)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription elongation by RNA polymerase II	2
regulation of transcription elongation by RNA polymerase II	2
cellular anatomical structure	2
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
positive regulation of DNA-templated transcription, elongation	1
positive regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EAPP	E2F2	Q14209	657
EAPP	E2F3	O00716	607
EAPP	E2F4	Q16254	602
EAPP	PRPF8	Q6P2Q9	569
EAPP	E2F1	Q01094	544
EAPP	SLC7A6OS	Q96CW6	539
EAPP	EFTUD2	Q15029	529
EAPP	ZNHIT2	Q9UHR6	490
EAPP	DRG2	P55039	472
EAPP	TSSC4	Q9Y5U2	460
EAPP	AAR2	Q9Y312	450
EAPP	THYN1	Q9P016	437
EAPP	PPP2R3C	Q969Q6	426
EAPP	TTC27	Q6P3X3	425
EAPP	GK5	Q6ZS86	423

IntAct

60 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
PRPF6	SART1	psi-mi:“MI:0914”(association)	0.750
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
AAR2	EAPP	psi-mi:“MI:0915”(physical association)	0.660
PRPF8	PRPF4	psi-mi:“MI:0914”(association)	0.640
DDX23	PRPF4	psi-mi:“MI:0914”(association)	0.640
EFTUD2	SART1	psi-mi:“MI:0914”(association)	0.610
BYSL	EAPP	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8	EAPP	psi-mi:“MI:0915”(physical association)	0.560
SLX1A	BACH1	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
KIAA1143	AQR	psi-mi:“MI:0914”(association)	0.530
EAPP	SNRNP200	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
EFTUD2	AQR	psi-mi:“MI:0914”(association)	0.530
AAR2	SNRNP200	psi-mi:“MI:0914”(association)	0.530
TSSC4	SNRNP200	psi-mi:“MI:0914”(association)	0.530
Prpf8		psi-mi:“MI:0915”(physical association)	0.400

BioGRID (137): EAPP (Affinity Capture-MS), EAPP (Affinity Capture-MS), EAPP (Affinity Capture-MS), SNRNP200 (Affinity Capture-MS), GPATCH1 (Affinity Capture-MS), DHX35 (Affinity Capture-MS), AAR2 (Affinity Capture-MS), ECD (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CRNKL1 (Affinity Capture-MS), IGHA1 (Affinity Capture-MS), WDR83 (Affinity Capture-MS), EAPP (Affinity Capture-MS), EAPP (Two-hybrid), AAR2 (Co-fractionation)

ESM2 similar proteins: A0JMA8, A1L2S8, A4IG66, A7S7Z9, A8X2R2, A9ULX8, B3P7K6, E7F187, F1NVK6, F6UF99, G5EF60, O95071, O95159, P38349, P51592, P51950, P62447, P70302, P91682, P97496, Q0VFM0, Q16N38, Q1L0X2, Q1L8G6, Q20448, Q298N4, Q29EP6, Q2YDD3, Q4W9V0, Q56P03, Q5AX35, Q5BU09, Q5RFL4, Q5U245, Q62671, Q66IE4, Q6IQA2, Q6ZPS6, Q7YU29, Q80TP3

Diamond homologs: Q56P03, Q5BU09

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EAPP	“up-regulates quantity by expression”	ABCB1	“transcriptional regulation”
EAPP	“down-regulates quantity by repression”	MAOB	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of non-coding RNA	6	108.8×	7e-10
mRNA Splicing - Minor Pathway	10	64.0×	3e-14
snRNP Assembly	7	42.3×	1e-08
SARS-CoV-2 modulates host translation machinery	6	38.4×	3e-07
mRNA Splicing - Major Pathway	17	26.5×	1e-18
mRNA Splicing	8	25.1×	3e-08
Processing of Capped Intron-Containing Pre-mRNA	8	18.8×	3e-07
CHD1 and CHD2 subfamily	6	18.6×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal tri-snRNP complex assembly	5	119.5×	2e-08
spliceosomal snRNP assembly	9	111.3×	5e-15
RNA splicing, via transesterification reactions	5	66.4×	4e-07
U2-type prespliceosome assembly	5	66.4×	4e-07
spliceosomal complex assembly	5	64.0×	4e-07
mRNA splicing, via spliceosome	17	33.1×	1e-19
RNA splicing	13	24.4×	3e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

706 predictions. Top by Δscore:

Variant	Effect	Δscore
14:34529356:ACCC:A	donor_gain	1.0000
14:34529357:CCCC:C	donor_gain	1.0000
14:34533440:TTAC:T	donor_loss	1.0000
14:34533441:TACCT:T	donor_loss	1.0000
14:34533442:A:AC	donor_gain	1.0000
14:34533442:AC:A	donor_gain	1.0000
14:34533442:ACCTG:A	donor_gain	1.0000
14:34533443:C:CA	donor_gain	1.0000
14:34533443:CC:C	donor_gain	1.0000
14:34533443:CCT:C	donor_gain	1.0000
14:34533443:CCTG:C	donor_gain	1.0000
14:34533443:CCTGC:C	donor_gain	1.0000
14:34533535:AGATC:A	acceptor_gain	1.0000
14:34533536:GATC:G	acceptor_gain	1.0000
14:34533537:ATC:A	acceptor_gain	1.0000
14:34533537:ATCC:A	acceptor_loss	1.0000
14:34533538:TC:T	acceptor_gain	1.0000
14:34533539:CC:C	acceptor_gain	1.0000
14:34533539:CCTA:C	acceptor_loss	1.0000
14:34533540:C:CC	acceptor_gain	1.0000
14:34533541:T:G	acceptor_loss	1.0000
14:34533545:C:CT	acceptor_gain	1.0000
14:34533550:C:CT	acceptor_gain	1.0000
14:34533550:C:T	acceptor_gain	1.0000
14:34533551:A:T	acceptor_gain	1.0000
14:34536089:TTTAC:T	donor_loss	1.0000
14:34536092:A:AC	donor_gain	1.0000
14:34536092:A:AG	donor_loss	1.0000
14:34536093:C:CC	donor_gain	1.0000
14:34536153:T:TA	donor_gain	1.0000

AlphaMissense

1902 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:34516368:G:T	A267E	1.000
14:34516393:A:G	C259R	1.000
14:34516550:A:C	F206L	1.000
14:34516550:A:T	F206L	1.000
14:34516552:A:G	F206L	1.000
14:34516559:T:A	R203S	1.000
14:34516559:T:G	R203S	1.000
14:34516560:C:G	R203T	1.000
14:34524735:A:C	C181W	1.000
14:34524737:A:G	C181R	1.000
14:34524742:A:G	L179S	1.000
14:34516329:A:T	V280D	0.999
14:34516334:G:C	F278L	0.999
14:34516334:G:T	F278L	0.999
14:34516336:A:G	F278L	0.999
14:34516338:A:G	F277S	0.999
14:34516340:A:C	H276Q	0.999
14:34516340:A:T	H276Q	0.999
14:34516342:G:C	H276D	0.999
14:34516365:A:T	V268D	0.999
14:34516382:A:C	C262W	0.999
14:34516383:C:G	C262S	0.999
14:34516384:A:G	C262R	0.999
14:34516384:A:T	C262S	0.999
14:34516391:G:C	C259W	0.999
14:34516392:C:G	C259S	0.999
14:34516392:C:T	C259Y	0.999
14:34516393:A:T	C259S	0.999
14:34516398:A:T	V257D	0.999
14:34516538:A:C	C210W	0.999

dbSNP variants (sampled 300 via entrez): RS1000095890 (14:34531948 C>T), RS1000098956 (14:34539276 A>C), RS1000161824 (14:34530520 C>T), RS1000273717 (14:34521916 G>C,T), RS1000287556 (14:34519341 C>G), RS1000297999 (14:34532075 C>A), RS1000383656 (14:34515537 C>A), RS1000878565 (14:34515945 A>G), RS1000916864 (14:34538511 A>C), RS1001097995 (14:34527535 G>C), RS1001137377 (14:34523223 G>A), RS1001276500 (14:34520489 C>T), RS1001286568 (14:34520049 C>T), RS1001480419 (14:34517342 G>A), RS1001481998 (14:34526298 G>A,C)

Disease associations

OMIM: gene MIM:609486 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002112_10	Celiac disease	4.000000e-06
GCST009391_1093	Metabolite levels	3.000000e-06
GCST009863_21	Insulin-related traits (multivariate analysis)	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010446	2-hydroxyglutaric acid measurement
EFO:0004467	insulin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
zinc chromate	increases abundance, increases expression	1
coumarin	affects phosphorylation	1
chromium hexavalent ion	increases abundance, increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	decreases phosphorylation	1
bisphenol S	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Estradiol	increases phosphorylation	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SL33	HAP1 EAPP (-) 1	Cancer cell line	Male
CVCL_SL34	HAP1 EAPP (-) 2	Cancer cell line	Male
CVCL_SL35	HAP1 EAPP (-) 3	Cancer cell line	Male
CVCL_SL36	HAP1 EAPP (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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