PEA15

Summary

PEA15 (proliferation and apoptosis adaptor protein 15, HGNC:8822) is a protein-coding gene on chromosome 1q23.2, encoding Astrocytic phosphoprotein PEA-15 (Q15121). Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade.

This gene encodes a death effector domain-containing protein that functions as a negative regulator of apoptosis. The encoded protein is an endogenous substrate for protein kinase C. This protein is also overexpressed in type 2 diabetes mellitus, where it may contribute to insulin resistance in glucose uptake. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8682 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_003768

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8822
Approved symbol	PEA15
Name	proliferation and apoptosis adaptor protein 15
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	HMAT1, MAT1, PED, PEA-15, MAT1H, HUMMAT1H, PED-PEA15, PED/PEA15
Ensembl gene	ENSG00000162734
Ensembl biotype	protein_coding
OMIM	603434
Entrez	8682

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 21 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000360472, ENST00000368076, ENST00000368077, ENST00000488858, ENST00000853680, ENST00000853683, ENST00000853684, ENST00000853685, ENST00000853686, ENST00000853687, ENST00000853688, ENST00000853689, ENST00000853690, ENST00000853692, ENST00000853693, ENST00000853694, ENST00000853695, ENST00000853696, ENST00000853697, ENST00000853698, ENST00000853701, ENST00000962148

RefSeq mRNA: 4 — MANE Select: NM_003768 NM_001297576, NM_001297577, NM_001297578, NM_003768

CCDS: CCDS1199, CCDS72954, CCDS76227

Canonical transcript exons

ENST00000360472 — 4 exons

Exon	Start	End
ENSE00000000360	160213422	160215372
ENSE00001446275	160205384	160205522
ENSE00003599401	160213110	160213265
ENSE00003662425	160211543	160211716

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 158.8228 / max 2333.7886, expressed in 1822 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6077	105.8639	1814
6075	32.6603	1786
6076	7.8154	1641
6094	5.0042	1430
6078	2.9770	1366
6080	2.1207	961
6096	0.6299	310
6092	0.5255	252
6099	0.3110	113
6098	0.2620	99

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.86	gold quality
medulla oblongata	UBERON:0001896	99.85	gold quality
subthalamic nucleus	UBERON:0001906	99.85	gold quality
spinal cord	UBERON:0002240	99.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.85	gold quality
inferior vagus X ganglion	UBERON:0005363	99.84	gold quality
globus pallidus	UBERON:0001875	99.83	gold quality
medial globus pallidus	UBERON:0002477	99.83	gold quality
superior vestibular nucleus	UBERON:0007227	99.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.82	gold quality
inferior olivary complex	UBERON:0002127	99.82	gold quality
lateral globus pallidus	UBERON:0002476	99.82	gold quality
ventricular zone	UBERON:0003053	99.81	gold quality
ventral tegmental area	UBERON:0002691	99.78	gold quality
substantia nigra pars compacta	UBERON:0001965	99.77	gold quality
olfactory bulb	UBERON:0002264	99.77	gold quality
middle frontal gyrus	UBERON:0002702	99.76	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.75	gold quality
amygdala	UBERON:0001876	99.71	gold quality
hypothalamus	UBERON:0001898	99.70	gold quality
pons	UBERON:0000988	99.68	gold quality
temporal lobe	UBERON:0001871	99.68	gold quality
nucleus accumbens	UBERON:0001882	99.67	gold quality
midbrain	UBERON:0001891	99.66	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.66	gold quality
cranial nerve II	UBERON:0000941	99.65	gold quality
entorhinal cortex	UBERON:0002728	99.65	gold quality
substantia nigra	UBERON:0002038	99.64	gold quality
ganglionic eminence	UBERON:0004023	99.63	gold quality
caudate nucleus	UBERON:0001873	99.59	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	1065.96
E-GEOD-93593	yes	672.92
E-HCAD-5	yes	43.30
E-CURD-122	yes	21.64
E-MTAB-5061	yes	6.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, HNF4A, JUN, NR2F2, PPARG, RUNX3

miRNA regulators (miRDB)

126 targeting PEA15, 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-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3680-3P	99.75	72.51	3095

Literature-anchored findings (GeneRIF, showing 40)

• role of mitogen-activated protein kinase family members in anti-apoptotic function (PMID:11790785)
• role in modulating tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex (PMID:11976344)
• interaction with p90 ribosomal S6 kinase isoenzyme regulates its activity (PMID:12796492)
• phosphorylation by Akt regulates the antiapoptotic function of PED/PEA-15 at least in part by controlling the stability of PED/PEA-15 (PMID:12808093)
• apoptosis following Omi/HtrA2 mitochondrial release is mediated by reduction in ped/pea-15 cellular levels (PMID:15328349)
• PEA-15 is inhibited by adenovirus E1A and has a role in ERK nuclear export and Ras-induced senescence (PMID:15331596)
• The mechanism controlling PEA-15 binding to ERK/MAPK or FADD, and its subsequent role in cell proliferation and apoptosis is reported. (PMID:15916534)
• Raised expression of the antiapoptotic protein pea-15 increases susceptibility to chemically induced skin tumor development (PMID:16044159)
• Human breast cancer cells express high levels of PED and that AKT activity regulates PED protein levels. AKT-dependent increase of PED expression levels represents a key molecular mechanism for chemoresistance in breast cancer. (PMID:16061647)
• cytoplasmic sequestration of the activated form of ERK by PEA15 enables the action of E1A in ovarian neoplasms (PMID:16170361)
• Akt overactivation prevents the nuclear translocation of ERK1/2 and the AngII-induced proliferation through interaction with and stabilization of endogenous PEA-15. (PMID:16822839)
• These data reveal a new function for PEA-15 in the inhibitory control of astrocyte motility through a PKC delta-dependent pathway involving the constitutive expression of a catalytic fragment of PKC delta. (PMID:16987961)
• PEA15 overexpression represents a common defect in first degree relatives of patients with type 2 diabetes and is correlated with reduced insulin sensitivity in these individuals. (PMID:17021921)
• TPA increases PED/PEA-15 expression at the post-translational level by inducing phosphorylation at serine 116 and preventing ubiquitinylation and proteosomal degradation (PMID:17227770)
• In addition to sequestering protein kinases ERK1/2 in the cytoplasm, PEA-15 has the potential to modulate the activity of ERK2 in cells by competing directly with proteins that contain D-recruitment sites. (PMID:17658892)
• Elevated PEA-15 levels provide a survival advantage for glioblastoma cells confronted with a poor microenvironment and low glucose levels. (PMID:17700518)
• PEA-15 functions as a scaffold to enhance extracellular signal-regulated MAP kinase (ERK) activation of ribosomal S6 kinase polypeptide RSK2, an activity that is regulated by phosphorylation. (PMID:18077417)
• transfection with PED siRNA, but not with cFLIP siRNA, sensitized NSCLC cells to TRAIL-induced cell death (PMID:18284607)
• COUP-TFII antagonizes the repression of the PED/PEA-15 gene by HNF-4alpha. (PMID:18765665)
• PEA-15 expression is an important prognostic marker in ovarian cancer. (PMID:19010903)
• PTEN influences Fas signaling, at least in part, by regulating PEA-15 phosphorylation and activity that, in turn, regulate the ability of Bcl-2 to suppress Fas-induced apoptosis. (PMID:19103758)
• Vitamin D3 signalling in the brain enhances the function of phosphoprotein enriched in astrocytes–15 kD (PEA-15) (PMID:19382910)
• Strategies are being devised to target key signaling events in PED/PEA-15 action aimed at improving glucose tolerance and at facilitating cancer cell death. (PMID:19531639)
• Results suggest that PEA-15 expression is likely to be associated with the tumorigenesis of alignant pleural mesothelioma. (PMID:19771552)
• Data show that PEA-15 prevents ERK1/2 localization to the plasma membrane, thereby inhibiting ERK1/2-dependent threonine phosphorylation of FRS2alpha to promote activation of the ERK1/2 MAP kinase pathway. (PMID:20032303)
• The results show that HNF-4alpha serves as a scaffold protein for histone deacetylase activities, thereby inhibiting liver expression of genes including PED. (PMID:20396999)
• PED/PEA-15 modulates Coxsackievirus-adenovirus receptor expression and adenoviral entry, by sequestering ERK1/2. (PMID:20406097)
• PEA-15 promotes autophagy in glioma cells in a JNK-dependent manner (PMID:20452983)
• There was no significant difference in the frequency of three marker haplotype in the PEA15 gene in patient with schizophrenia. (PMID:20537721)
• Data show that PED and Rac1 interact and that this interaction modulates cell migration/invasion processes in cancer cells through ERK1/2 pathway. (PMID:20648624)
• provide molecular basis of the PED/PEA-15 functional interactions and detailed surface for the design and development of PED/PEA-15 binders (PMID:20825483)
• The expressions of PED/PEA-15 and XIAP are elevated in hepatocellular carcinoma as compared with adjacent tissues and normal tissues. (PMID:20979872)
• The protective effect of melatonin is likely mediated, in part, by inhibition of peroxynitrate-mediated nitrosative stress, which in turn relieves imbalance of mitochondrial HtrA2-PED signaling and endothelial cell death. (PMID:21198825)
• The 67 kD laminin receptor is a novel PED/PEA-15 interacting protein. PED/PEA-15 overexpression increases 67LR-mediated cell adhesion and migration to laminin and extracellular matrix invasion. (PMID:21895963)
• Data show that knockdown of PEA-15 expression resulted in reversal of selumetinib-sensitive cells to resistant cells, implying that PEA-15 contributes to selumetinib sensitivity. (PMID:22144664)
• PEA15 impairs cell migration and correlates with clinical features predicting good prognosis in neuroblastoma (PMID:22213050)
• The article hypothesizes that only unphosphorylated PEA-15 can act as a tumor-suppressor and that phosphorylation alters the interaction with binding partners to promote tumor development. (PMID:22694972)
• the solution death effector domain (DED) structure of the PED/PEA-15 protein, a representative member of DED subfamily, using traditional NMR restraints with the addition of residual dipolar coupling restraints was refined. (PMID:22732408)
• NMR chemical shift perturbation and backbone dynamic studies at the fast ps-ns timescale of PED/PEA-15, in its free form and in the complex with ERK2. (PMID:22820249)
• study demonstrates that the PEA-15 protein decreases proliferation, clonogenicity, and invasiveness, but increases resistance to apoptosis in colorectal carcinoma cells (PMID:23481023)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pea15	ENSDARG00000079771
mus_musculus	Pea15a	ENSMUSG00000013698
rattus_norvegicus	Pea15	ENSRNOG00000046996

Protein

Protein identifiers

Astrocytic phosphoprotein PEA-15 — Q15121 (reviewed: Q15121)

Alternative names: 15 kDa phosphoprotein enriched in astrocytes, Phosphoprotein enriched in diabetes

All UniProt accessions (3): B1AKZ4, B1AKZ5, Q15121

UniProt curated annotations — full annotation on UniProt →

Function. Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm. Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface.

Subunit / interactions. Binds RPS6KA3, MAPK3 and MAPK1. Transient interaction with PLD1 and PLD2. Interacts with CASP8 and FADD.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitously expressed. Most abundant in tissues such as heart, brain, muscle and adipose tissue which utilize glucose as an energy source. Lower expression in glucose-producing tissues. Higher levels of expression are found in tissues from individuals with type 2 diabetes than in controls.

Post-translational modifications. Phosphorylated by protein kinase C and calcium-calmodulin-dependent protein kinase. These phosphorylation events are modulated by neurotransmitters or hormones.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15121-1	1	yes
Q15121-2	2

RefSeq proteins (4): NP_001284505, NP_001284506, NP_001284507, NP_003759* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001875	DED_dom	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR029546	PEA15_DED	Domain

Pfam: PF01335

UniProt features (20 total): helix 6, sequence conflict 4, modified residue 4, region of interest 2, chain 1, domain 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4IZA	X-RAY DIFFRACTION	1.93
4IZ5	X-RAY DIFFRACTION	3.19
6P6B	SOLUTION NMR
6P6C	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15121-F1	78.01	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 (4): 61, 90, 104, 116

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-112409	RAF-independent MAPK1/3 activation
R-HSA-5673001	RAF/MAP kinase cascade

MSigDB gene sets: 324 (showing top): GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, AP1_01, GOBP_CARBOHYDRATE_TRANSPORT, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, RIZKI_TUMOR_INVASIVENESS_3D_DN, PATIL_LIVER_CANCER, CHANG_IMMORTALIZED_BY_HPV31_DN, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, GERY_CEBP_TARGETS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, AP1_Q4_01

GO Biological Process (6): MAPK cascade (GO:0000165), apoptotic process (GO:0006915), negative regulation of D-glucose import across plasma membrane (GO:0046325), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), positive regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902043), regulation of apoptotic process (GO:0042981)

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

GO Cellular Component (4): nucleoplasm (GO:0005654), cytosol (GO:0005829), microtubule associated complex (GO:0005875), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
MAPK1/MAPK3 signaling	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
extrinsic apoptotic signaling pathway via death domain receptors	2
regulation of extrinsic apoptotic signaling pathway via death domain receptors	2
intracellular signaling cassette	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
negative regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
negative regulation of extrinsic apoptotic signaling pathway	1
positive regulation of extrinsic apoptotic signaling pathway	1
apoptotic process	1
regulation of programmed cell death	1
binding	1
nuclear lumen	1
cytoplasm	1
microtubule cytoskeleton	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEA15	FADD	Q13158	921
PEA15	MAPK1	P28482	781
PEA15	PLD1	Q13393	731
PEA15	RPS6KA3	P51812	721
PEA15	MAPK3	P27361	687
PEA15	RRAS	P10301	627
PEA15	CASP8	Q14790	597
PEA15	SLC2A4	P14672	496
PEA15	SLC2A1	P11166	495
PEA15	DEDD	O75618	453
PEA15	CFLAR	O15519	432
PEA15	CREB1	P16220	422
PEA15	PRKD1	Q15139	412
PEA15	ANK3	Q12955	391
PEA15	NME1	P15531	391

IntAct

38 interactions, top by confidence:

A	B	Type	Score
MAPK1	PEA15	psi-mi:“MI:0915”(physical association)	0.900
PEA15	MAPK1	psi-mi:“MI:0407”(direct interaction)	0.900
PEA15	MAPK1	psi-mi:“MI:0914”(association)	0.900
MAPK1	PEA15	psi-mi:“MI:0407”(direct interaction)	0.900
PEA15	MAPK1	psi-mi:“MI:0915”(physical association)	0.900
MAPK3	PEA15	psi-mi:“MI:0915”(physical association)	0.740
PEA15	MAPK3	psi-mi:“MI:0915”(physical association)	0.740
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
TERF2IP	PEA15	psi-mi:“MI:0915”(physical association)	0.510
PEA15	SMYD5	psi-mi:“MI:0915”(physical association)	0.400
PEA15	BCAT2	psi-mi:“MI:0915”(physical association)	0.400
	DENR	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
PEA15	PDPK1	psi-mi:“MI:0915”(physical association)	0.370
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
PEA15	CLASP2	psi-mi:“MI:0914”(association)	0.350
OSTN	PEA15	psi-mi:“MI:0914”(association)	0.350
FBF1	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
STIL	ERVK3-1	psi-mi:“MI:2364”(proximity)	0.270
CEP170	ERVK3-1	psi-mi:“MI:2364”(proximity)	0.270
TERF2IP	PEA15	psi-mi:“MI:0915”(physical association)	0.000
MAPK1	PEA15	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (108): PEA15 (Proximity Label-MS), PEA15 (Proximity Label-MS), PEA15 (Proximity Label-MS), PEA15 (Affinity Capture-RNA), ATP1B3 (Two-hybrid), TRAPPC13 (Two-hybrid), CACYBP (Two-hybrid), CEP120 (Two-hybrid), COPS5 (Two-hybrid), DNAJB1 (Two-hybrid), DYRK1A (Two-hybrid), FAM103A1 (Two-hybrid), KLHL12 (Two-hybrid), MTIF3 (Two-hybrid), OSBPL1A (Two-hybrid)

ESM2 similar proteins: A6QLE5, B0FPE9, D4A523, O08736, O14862, O35732, O62640, O77736, O89110, O95786, P25445, P29452, P43527, P55865, P55867, P57730, P70343, Q13158, Q14790, Q15121, Q153Z0, Q504J1, Q5R529, Q5RAV7, Q5U318, Q61160, Q62048, Q63199, Q645M6, Q6GZR1, Q6Q899, Q7RTR0, Q8HXK9, Q8IXQ6, Q8R4B8, Q8WXC3, Q91VJ1, Q920D5, Q92851, Q96P20

Diamond homologs: Q15121, Q5R529, Q5U318, Q62048, Q9Z297

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
AKT1	“up-regulates activity”	PEA15	phosphorylation
PEA15	down-regulates	MAPK1
PEA15	down-regulates	MAPK3
HTRA2	down-regulates	PEA15	binding
CAMK2A	up-regulates	PEA15	phosphorylation
PRKCA	down-regulates	PEA15	phosphorylation
AKT	“up-regulates activity”	PEA15	phosphorylation
RUNX3	“down-regulates quantity by repression”	PEA15	“transcriptional regulation”
PEA15	down-regulates	Gbeta
PEA15	down-regulates	ERK1/2
CAMK2G	unknown	PEA15	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

739 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160205451:G:GT	donor_gain	1.0000
1:160211527:C:A	acceptor_gain	1.0000
1:160211535:A:AG	acceptor_gain	1.0000
1:160211536:A:G	acceptor_gain	1.0000
1:160211537:CCCCA:C	acceptor_loss	1.0000
1:160211538:CCCAG:C	acceptor_loss	1.0000
1:160211539:CCAGT:C	acceptor_loss	1.0000
1:160211540:CAGT:C	acceptor_loss	1.0000
1:160211541:A:AG	acceptor_gain	1.0000
1:160211541:A:T	acceptor_loss	1.0000
1:160211542:G:GG	acceptor_gain	1.0000
1:160211542:GTC:G	acceptor_gain	1.0000
1:160211542:GTCAT:G	acceptor_gain	1.0000
1:160211629:G:GT	donor_gain	1.0000
1:160211649:GA:G	donor_gain	1.0000
1:160211651:G:GG	donor_gain	1.0000
1:160211693:A:T	donor_gain	1.0000
1:160213104:CTCCA:C	acceptor_loss	1.0000
1:160213105:TCCAG:T	acceptor_loss	1.0000
1:160213106:CCAG:C	acceptor_loss	1.0000
1:160213107:CAGAC:C	acceptor_loss	1.0000
1:160213108:A:AC	acceptor_loss	1.0000
1:160213108:A:AG	acceptor_gain	1.0000
1:160213109:G:GA	acceptor_gain	1.0000
1:160213109:GA:G	acceptor_gain	1.0000
1:160213109:GAC:G	acceptor_gain	1.0000
1:160213109:GACA:G	acceptor_gain	1.0000
1:160213109:GACAA:G	acceptor_gain	1.0000
1:160213262:AAAGG:A	donor_loss	1.0000
1:160213263:AAGGT:A	donor_loss	1.0000

AlphaMissense

862 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160211576:T:C	L11P	1.000
1:160211603:T:C	L20P	1.000
1:160211612:T:C	L23P	1.000
1:160211690:T:C	L49P	1.000
1:160213151:C:A	R72S	1.000
1:160213161:T:C	L75P	1.000
1:160213164:T:C	L76P	1.000
1:160213259:T:C	Y108H	1.000
1:160211623:T:C	C27R	0.999
1:160211624:G:A	C27Y	0.999
1:160211625:C:G	C27W	0.999
1:160211677:T:A	W45R	0.999
1:160211677:T:C	W45R	0.999
1:160211708:T:C	L55P	0.999
1:160213125:T:A	I63N	0.999
1:160213129:G:C	E64D	0.999
1:160213129:G:T	E64D	0.999
1:160213130:C:G	H65D	0.999
1:160213131:A:C	H65P	0.999
1:160213132:C:A	H65Q	0.999
1:160213132:C:G	H65Q	0.999
1:160213137:T:C	F67S	0.999
1:160213139:G:A	E68K	0.999
1:160213140:A:T	E68V	0.999
1:160213141:G:C	E68D	0.999
1:160213141:G:T	E68D	0.999
1:160213145:T:C	S70P	0.999
1:160213151:C:G	R72G	0.999
1:160213152:G:C	R72P	0.999
1:160213154:C:A	P73T	0.999

dbSNP variants (sampled 300 via entrez): RS1000028275 (1:160210603 C>A,G), RS1000310062 (1:160209214 C>T), RS1000318267 (1:160203718 G>A), RS1000381176 (1:160215409 T>C), RS1000418349 (1:160203435 C>T), RS1000497076 (1:160214225 G>A), RS1000527044 (1:160207443 C>T), RS1000595428 (1:160208873 G>A,C), RS1001044642 (1:160207734 G>T), RS1001059375 (1:160205449 A>G), RS1001203243 (1:160210167 C>T), RS1001716845 (1:160210482 T>G), RS1002326021 (1:160215751 T>C), RS1002335342 (1:160204027 T>C), RS1002492414 (1:160204349 C>A)

Disease associations

OMIM: gene MIM:603434 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	5
Benzo(a)pyrene	increases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Acetaminophen	increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression	3
Cyclosporine	decreases methylation, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	affects expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Cisplatin	decreases expression, increases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
FR900359	affects phosphorylation	1
lead acetate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
chloropicrin	affects expression	1
AM 251	increases expression	1
candoxin	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
ON 01910	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
eprenetapopt	increases expression, affects reaction	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3DQ	Abcam HEK293T PEA15 KO	Transformed cell line	Female
CVCL_C4J9	SKOV3.ip1 PEA-15-AA	Cancer cell line	Female
CVCL_C4JA	SKOV3.ip1 PEA-15-DD	Cancer cell line	Female
CVCL_C4JB	SKOV3.ip1 PEA-15-WT	Cancer cell line	Female
CVCL_D1TX	Abcam U-87MG PEA15 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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