PEBP1

Summary

PEBP1 (phosphatidylethanolamine binding protein 1, HGNC:8630) is a protein-coding gene on chromosome 12q24.23, encoding Phosphatidylethanolamine-binding protein 1 (P30086). Binds ATP, opioids and phosphatidylethanolamine.

This gene encodes a member of the phosphatidylethanolamine-binding family of proteins and has been shown to modulate multiple signaling pathways, including the MAP kinase (MAPK), NF-kappa B, and glycogen synthase kinase-3 (GSK-3) signaling pathways. The encoded protein can be further processed to form a smaller cleavage product, hippocampal cholinergic neurostimulating peptide (HCNP), which may be involved in neural development. This gene has been implicated in numerous human cancers and may act as a metastasis suppressor gene. Multiple pseudogenes of this gene have been identified in the genome.

Source: NCBI Gene 5037 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 15 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002567

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8630
Approved symbol	PEBP1
Name	phosphatidylethanolamine binding protein 1
Location	12q24.23
Locus type	gene with protein product
Status	Approved
Aliases	RKIP, HCNP, PEBP
Ensembl gene	ENSG00000089220
Ensembl biotype	protein_coding
OMIM	604591
Entrez	5037

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000261313, ENST00000542939, ENST00000874099, ENST00000874100, ENST00000874101, ENST00000942724

RefSeq mRNA: 1 — MANE Select: NM_002567 NM_002567

CCDS: CCDS9187

Canonical transcript exons

ENST00000261313 — 4 exons

Exon	Start	End
ENSE00000755834	118138039	118138148
ENSE00000940085	118136124	118136344
ENSE00001141259	118144586	118145584
ENSE00003643316	118139451	118139551

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 231.1248 / max 2440.1144, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128260	224.8498	1828
128261	6.2749	1709

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	99.95	gold quality
postcentral gyrus	UBERON:0002581	99.92	gold quality
right adrenal gland cortex	UBERON:0035827	99.91	gold quality
parietal lobe	UBERON:0001872	99.90	gold quality
adrenal cortex	UBERON:0001235	99.89	gold quality
right adrenal gland	UBERON:0001233	99.88	gold quality
left adrenal gland	UBERON:0001234	99.87	gold quality
medial globus pallidus	UBERON:0002477	99.87	gold quality
left adrenal gland cortex	UBERON:0035825	99.87	gold quality
superior frontal gyrus	UBERON:0002661	99.86	gold quality
prefrontal cortex	UBERON:0000451	99.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.85	gold quality
frontal cortex	UBERON:0001870	99.83	gold quality
globus pallidus	UBERON:0001875	99.83	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.83	gold quality
superior vestibular nucleus	UBERON:0007227	99.83	gold quality
frontal lobe	UBERON:0016525	99.83	gold quality
cranial nerve II	UBERON:0000941	99.82	gold quality
right frontal lobe	UBERON:0002810	99.82	gold quality
ventral tegmental area	UBERON:0002691	99.81	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.80	gold quality
adrenal gland	UBERON:0002369	99.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.80	gold quality
medulla oblongata	UBERON:0001896	99.79	gold quality
neocortex	UBERON:0001950	99.79	gold quality
cerebellar vermis	UBERON:0004720	99.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.78	gold quality
cerebral cortex	UBERON:0000956	99.77	gold quality
choroid plexus epithelium	UBERON:0003911	99.77	gold quality
inferior vagus X ganglion	UBERON:0005363	99.77	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	3630.84
E-GEOD-135922	yes	1156.82
E-CURD-112	yes	546.63
E-MTAB-6701	yes	116.23
E-GEOD-125970	yes	67.94
E-HCAD-4	yes	67.76
E-HCAD-9	yes	53.87
E-HCAD-35	yes	41.54
E-GEOD-137537	yes	37.39
E-GEOD-134144	yes	36.14
E-HCAD-11	yes	32.03
E-MTAB-8410	yes	27.58
E-MTAB-8142	yes	20.06
E-MTAB-7316	yes	17.37
E-MTAB-10042	yes	14.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, BACH1, CREB1, EZH2, MYC, NFKB, SNAI1, SP1, SPI1, SUZ12, ZHX2

miRNA regulators (miRDB)

26 targeting PEBP1, 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-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-410-5P	96.55	66.28	459
HSA-MIR-759	96.16	66.77	873
HSA-MIR-323B-5P	96.12	66.39	472
HSA-MIR-494-5P	95.31	66.29	463
HSA-MIR-3174	94.63	63.64	577
HSA-MIR-4640-3P	94.58	63.02	263
HSA-MIR-6798-3P	94.55	68.78	325

Literature-anchored findings (GeneRIF, showing 40)

• After stimulation of G-protein-coupled receptors, RKIP dissociates from its known target, Raf-1, to associate with GRK-2 and block its activity [RKIP] (PMID:14654844)
• RKIP may represent a novel effector of signal transduction pathways leading to apoptosis (PMID:14766752)
• Review. The discovery, structure, function, and significance of RKIP in cancer are discussd. (PMID:15327891)
• Low expression of RKIP and its antagonistic action on B-Raf suggests that RKIP may play an important role in melanoma turmorgenesis (PMID:15782137)
• Results suggest that in human breast cancer, RKIP is a metastasis suppressor gene whose expression must be down-regulated for metastases to develop. (PMID:16243812)
• data show for the first time that RKIP is upregulated during macrophage and dendritic cell differentiation. (PMID:16513087)
• Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma (PMID:16865242)
• These results indicate that RKIP regulates Aurora B kinase and the spindle checkpoint via the Raf-1/MEK/ERK cascade and demonstrate that small changes in the MAP kinase (MAPK) pathway can profoundly impact the fidelity of the cell cycle. (PMID:16916643)
• Together these data identify PEBP as a potential in vivo calpain substrate and indicate that increased PEBP levels may contribute to impaired proteasome function. (PMID:17018026)
• down-regulation of RKIP expression is a major factor in activation of the IGF-I/ERK/MAPK pathway during human hepatocarcinogenesis (PMID:17030190)
• The Raf kinase inhibitory protein (RKIP) binds to Raf-1 interfering with binding of the MEK substrate and potentially also Raf-1 activation. (PMID:17097642)
• 2’,5’-oligoadenylate synthetase activation may occur in prostate cancer cells stimulated by cellular mRNAs for RKIP. (PMID:17145707)
• RKIP expression in primary colorectal cancers correlates with overall and disease-free survival, and can be useful for identifying early-stage colorectal cancer patients at risk of relapse (PMID:17179102)
• RKIP overexpression regulates tumor cell sensitivity to TRAIL via inhibition of Yin Yang 1, up-regulation of death receptor 5, and modulation of apoptotic pathways. (PMID:17911631)
• RKIP is a novel component of the Snail transcriptional regulatory network important for the progression and metastasis of cancer. (PMID:17952120)
• combined analysis of N stage, vascular invasion, and RKIP expression is highly predictive of distant metastasis in patients with mismatch repair–proficient colorectal cancer. (PMID:18172264)
• the RKIP conserved pocket may constitute a novel phosphoamino-acid binding motif and is absolutely required for RKIP function (PMID:18294816)
• RKIP could play an important role in the down-regulation of wild-type BRAF, serving thus as an endogenous inhibitor of the MAPK pathway in nasal polyps and their adjacent turbinate mucosa (PMID:18329792)
• RKIP loss by hypermethylation of its promoter could have a significant influence on colorectal cancer aneuploidy, which might explain its association with metastatic progression (PMID:18375747)
• predictive and protective role of cytoplasmic RKIP expression in gastric adenocarcinoma of the intestinal subtype (PMID:18483365)
• RKIP expression was inversely associated with the invasiveness of five ovarian cancer cell lines. (PMID:18567796)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• Non-phosphorylated RKIP is associated with nasopharyngeal carcinoma. (PMID:19096942)
• These results demonstrating the absence of a disease-specific SNP in the HCNPpp promoter region suggest that the decrease in expression of this gene in late-onset AD patients can manifest from transcriptional or posttranscriptional changes in activity. (PMID:19101508)
• RKIP uses a flexible pocket to integrate ligand binding- and phosphorylation-dependent interactions and to modulate the MAPK signaling pathway (PMID:19103740)
• Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7 (PMID:19153603)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Elevated expression of RKIP in nitric-oxide-treated keratinocytes may contribute to the pathological & physiological features of NO-inhibited proliferation. (PMID:19228192)
• Raf kinase inhibitor protein expression was highest in nonneoplastic gastric tissue, low in primary gastric cancer tissue, and lowest in metastatic gastric cancer tissue. (PMID:19291429)
• Both BRAF and RKIP expression levels exhibit a decrease from normal skin tissue and actinic keratosis, going to squamous cell carcinoma. (PMID:19342899)
• loss of RKIP is a functional somatic event in carriers of C-RAF germline mutations, which contributes to the development of t-AML (PMID:19357705)
• RKIP is an invasion suppressor protein in nasopharyngeal carcinoma (PMID:19367706)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• RKIP has a role in potentially sequestering toxic compounds, including locostatin, that may have deleterious effects on cells (PMID:19551145)
• The investigation of PEBP binding properties towards morphine and morphine analogs, is reported. (PMID:19564817)
• loss of RKIP expression could have an important role as prognostic marker in Gastrointestinal stromal tumours (GISTs). (PMID:19705153)
• The expression of RKIP and E-cadherin in prostate cancer tissues was obviously lower than that in the benign prostatic hypertrophy tissues. (PMID:19779262)
• the conserved signal transduction modulator RKIP was shown to enhance several aspects of neuronal differentiation via enhanced crosstalk from PKC to ERK-1/2 and enhancement of G-protein-coupled receptor signaling. (PMID:19955695)
• RKIP could inhibit metastasis, and also inhibit the growth of ovarian cancer cells. (PMID:19957553)
• Bcr-Abl represses the expression of RKIP, continuously activates pERK1/2, and suppresses FoxM1 expression, resulting in proliferation of CML cells. (PMID:20028985)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pbp2	ENSMUSG00000047104
rattus_norvegicus	Pbp2	ENSRNOG00000008667
drosophila_melanogaster	a5	FBGN0011294
drosophila_melanogaster	CG17917	FBGN0037431
drosophila_melanogaster	CG10298	FBGN0037432
drosophila_melanogaster	CG17919	FBGN0037433
drosophila_melanogaster	CG7054	FBGN0038972
drosophila_melanogaster	Pebp1	FBGN0038973
drosophila_melanogaster	CG30060	FBGN0265272
caenorhabditis_elegans		WBGENE00018218

Paralogs (2): PEBP4 (ENSG00000134020), MRPL38 (ENSG00000204316)

Protein

Protein identifiers

Phosphatidylethanolamine-binding protein 1 — P30086 (reviewed: P30086)

Alternative names: HCNPpp, Neuropolypeptide h3, Prostatic-binding protein, Raf kinase inhibitor protein

All UniProt accessions (2): P30086, D9IAI1

UniProt curated annotations — full annotation on UniProt →

Function. Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase. Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation. HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor.

Subunit / interactions. Has a tendency to form dimers by disulfide cross-linking. Interacts with RAF1 and this interaction is enhanced if RAF1 is phosphorylated on residues ‘Ser-338’, ‘Ser-339’, ‘Tyr-340’ and ‘Tyr-341’. Interacts with ALOX15; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade.

Subcellular location. Cytoplasm.

Similarity. Belongs to the phosphatidylethanolamine-binding protein family.

RefSeq proteins (1): NP_002558* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001858	Phosphatidylethanolamine-bd_CS	Conserved_site
IPR008914	PEBP	Family
IPR035810	PEBP_euk	Family
IPR036610	PEBP-like_sf	Homologous_superfamily

Pfam: PF01161

UniProt features (33 total): strand 11, modified residue 7, helix 5, turn 4, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1, peptide 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1BEH	X-RAY DIFFRACTION	1.75
2QYQ	X-RAY DIFFRACTION	1.95
1BD9	X-RAY DIFFRACTION	2.05
2L7W	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30086-F1	97.40	0.98

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 (7): 153, 6, 13, 42, 52, 54, 98

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-5675221	Negative regulation of MAPK pathway
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-9649948	Signaling downstream of RAS mutants

MSigDB gene sets: 209 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, ZHAN_MULTIPLE_MYELOMA_MF_UP, HSIAO_HOUSEKEEPING_GENES, PRAMOONJAGO_SOX4_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, CAIRO_HEPATOBLASTOMA_CLASSES_DN, SCHUHMACHER_MYC_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, JIANG_TIP30_TARGETS_DN, PID_AURORA_B_PATHWAY, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, LIU_CMYB_TARGETS_UP

GO Biological Process (1): negative regulation of MAPK cascade (GO:0043409)

GO Molecular Function (10): RNA binding (GO:0003723), serine-type endopeptidase inhibitor activity (GO:0004867), ATP binding (GO:0005524), phosphatidylethanolamine binding (GO:0008429), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166), protein binding (GO:0005515), lipid binding (GO:0008289), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Oncogenic MAPK signaling	4
RAF/MAP kinase cascade	2
Signaling by RAS mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
nucleic acid binding	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
phospholipid binding	1
protein binding	1
kinase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEBP1	ALOX15	P16050	984
PEBP1	GRK2	P25098	923
PEBP1	RAF1	P04049	894
PEBP1	PRDX2	P31945	665
PEBP1	CHUK	O15111	664
PEBP1	GRK5	P34947	659
PEBP1	ALOX15B	O15296	648
PEBP1	RPS16	P17008	637
PEBP1	DPYSL2	Q16555	632
PEBP1	PKM	P14618	629
PEBP1	LOX	P28300	621
PEBP1	BRAF	P15056	605
PEBP1	PRDX1	P35703	600
PEBP1	MAP2K1	Q02750	570
PEBP1	STAT3	P40763	568

IntAct

96 interactions, top by confidence:

A	B	Type	Score
NFE2L2	MAFG	psi-mi:“MI:0914”(association)	0.940
PEBP1	RAF1	psi-mi:“MI:0915”(physical association)	0.760
PEBP1	RAF1	psi-mi:“MI:0914”(association)	0.760
RAF1	PEBP1	psi-mi:“MI:0915”(physical association)	0.760
PEBP1	RAF1	psi-mi:“MI:0407”(direct interaction)	0.760
Tnfrsf19	PEBP1	psi-mi:“MI:0407”(direct interaction)	0.600
Tnfrsf19	PEBP1	psi-mi:“MI:0915”(physical association)	0.600
PEBP1	PICK1	psi-mi:“MI:0915”(physical association)	0.560
PEBP1	ALOX15	psi-mi:“MI:0915”(physical association)	0.500
PEBP1	STK38	psi-mi:“MI:0915”(physical association)	0.500
TNFRSF19	PEBP1	psi-mi:“MI:0915”(physical association)	0.460
TNFRSF19	PEBP1	psi-mi:“MI:0403”(colocalization)	0.460
LMTK3	GPI	psi-mi:“MI:0914”(association)	0.420
PIK3R1	PEBP1	psi-mi:“MI:0915”(physical association)	0.400
TRAF6	PEBP1	psi-mi:“MI:0915”(physical association)	0.400
ERBB2	PEBP1	psi-mi:“MI:0915”(physical association)	0.370
PEBP1	DNMT1	psi-mi:“MI:0915”(physical association)	0.370
TRPV2	PEBP1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (305): PEBP1 (Affinity Capture-RNA), PEBP1 (Affinity Capture-RNA), PEBP1 (Affinity Capture-MS), ASNS (Co-fractionation), C11orf54 (Co-fractionation), GNPDA2 (Co-fractionation), HSPE1 (Co-fractionation), LGALS3 (Co-fractionation), PEBP1 (Co-fractionation), PEBP1 (Co-fractionation), PEBP1 (Co-fractionation), PEBP1 (Co-fractionation), PEBP1 (Co-fractionation), PEBP1 (Co-fractionation), PEBP1 (Co-fractionation)

ESM2 similar proteins: A0A0Q3IBS1, I1H0V9, O08619, O18733, O54732, O82088, O88917, O94910, O97831, P00488, P08587, P13696, P14780, P22735, P22758, P23606, P30086, P31044, P41245, P41246, P51176, P51511, P52176, P52181, P52183, P54185, P93003, Q3YIX4, Q41261, Q5R4R0, Q656A5, Q80TR1, Q8MK67, Q8VIN1, Q8VWH2, Q93WI9, Q95220, Q9ASJ1, Q9D9G2, Q9FIT4

Diamond homologs: A0A0Q3IBS1, I1H0V9, O16264, O82088, P13696, P14306, P30086, P31044, P31729, P48737, P54185, P54186, P54187, P54188, P54189, P54190, P70296, P93003, Q3YIX4, Q41261, Q5R4R0, Q656A5, Q8MK67, Q8VIN1, Q8VWH2, Q93WI9, Q96S96, Q9ASJ1, Q9D9G2, Q9FIT4, Q9S7R5, Q9SXZ2, Q9XFK7, Q9XH42, Q9XH43, Q9XH44, Q9ZNV5, Q06252, Q3ZBF3, Q5PQN9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRKCD	up-regulates	PEBP1	phosphorylation
CDK5	“down-regulates quantity by destabilization”	PEBP1	phosphorylation
PEBP1	down-regulates	RAF1	binding
PRKCG	“up-regulates activity”	PEBP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	11	9.2×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

574 predictions. Top by Δscore:

Variant	Effect	Δscore
12:118136340:CCCAG:C	donor_loss	1.0000
12:118136341:CCAGG:C	donor_loss	1.0000
12:118136342:CAGG:C	donor_loss	1.0000
12:118136343:AGGT:A	donor_loss	1.0000
12:118136344:GGT:G	donor_loss	1.0000
12:118136346:T:A	donor_loss	1.0000
12:118139447:GCAG:G	acceptor_loss	1.0000
12:118139448:CAG:C	acceptor_gain	1.0000
12:118139448:CAGAG:C	acceptor_loss	1.0000
12:118139449:A:AC	acceptor_loss	1.0000
12:118139449:A:AG	acceptor_gain	1.0000
12:118139449:AGA:A	acceptor_gain	1.0000
12:118139450:G:GC	acceptor_loss	1.0000
12:118139450:G:GG	acceptor_gain	1.0000
12:118139450:GA:G	acceptor_gain	1.0000
12:118139450:GAG:G	acceptor_gain	1.0000
12:118139450:GAGA:G	acceptor_gain	1.0000
12:118139450:GAGAA:G	acceptor_gain	1.0000
12:118139548:ACAG:A	donor_loss	1.0000
12:118139551:GGTT:G	donor_loss	1.0000
12:118139552:G:A	donor_loss	1.0000
12:118139553:T:A	donor_loss	1.0000
12:118144580:CCACA:C	acceptor_loss	1.0000
12:118144581:CACA:C	acceptor_loss	1.0000
12:118144583:CAG:C	acceptor_loss	1.0000
12:118144584:A:AG	acceptor_gain	1.0000
12:118144584:A:AT	acceptor_loss	1.0000
12:118144585:G:A	acceptor_loss	1.0000
12:118144585:G:GG	acceptor_gain	1.0000
12:118139445:A:AG	acceptor_gain	0.9900

AlphaMissense

1216 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:118144591:C:G	H118D	0.999
12:118138112:A:T	D70V	0.998
12:118139461:C:G	H86D	0.998
12:118144591:C:A	H118N	0.998
12:118144675:C:A	R146S	0.998
12:118138111:G:C	D70H	0.997
12:118138113:C:A	D70E	0.997
12:118138113:C:G	D70E	0.997
12:118138117:G:C	D72H	0.997
12:118139455:T:A	W84R	0.996
12:118139455:T:C	W84R	0.996
12:118138112:A:G	D70G	0.995
12:118139463:T:A	H86Q	0.995
12:118139463:T:G	H86Q	0.995
12:118139528:G:A	G108D	0.995
12:118144593:C:A	H118Q	0.995
12:118144593:C:G	H118Q	0.995
12:118144597:T:C	Y120H	0.995
12:118144603:T:A	W122R	0.995
12:118144603:T:C	W122R	0.995
12:118144684:T:C	F149L	0.995
12:118144686:C:A	F149L	0.995
12:118144686:C:G	F149L	0.995
12:118144759:G:C	D174H	0.995
12:118138112:A:C	D70A	0.994
12:118138118:A:T	D72V	0.994
12:118138119:T:A	D72E	0.994
12:118138119:T:G	D72E	0.994
12:118139457:G:C	W84C	0.994
12:118139457:G:T	W84C	0.994

dbSNP variants (sampled 300 via entrez): RS1000015970 (12:118141419 T>G), RS1000324106 (12:118144189 G>C,T), RS1000559345 (12:118137227 C>G,T), RS1000705292 (12:118142696 C>T), RS1000837065 (12:118141763 T>A), RS1001162535 (12:118136085 T>A,C), RS1001645322 (12:118144994 T>C), RS1001678368 (12:118139210 G>T), RS1001841539 (12:118143455 G>A,C,T), RS1001951612 (12:118137673 A>G), RS1001978800 (12:118143854 G>A), RS1001989185 (12:118135529 T>C), RS1002024147 (12:118139043 G>A,C,T), RS1002536354 (12:118134496 G>A), RS1002546618 (12:118145857 A>G)

Disease associations

OMIM: gene MIM:604591 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002472_1	Morphine dose requirement in tonsillectomy and adenoidectomy surgery	3.000000e-07
GCST006585_41	Blood protein levels	4.000000e-111

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105856 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,455 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1289494	TIVOZANIB	4	4,455

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3	nM	TIVOZANIB
7.08	Kd	83.5	nM	CHEMBL5653589
7.08	ED50	83.5	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 188 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Tivozanib	1425107: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148974: Binding affinity to human PEBP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0835	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Copper	decreases expression, affects binding	2
Glucose	increases expression, increases secretion	2
Smoke	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
deguelin	decreases expression	1
7,3’-dihydroxy-4’-methoxyisoflavone	increases expression	1
K 7174	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases 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

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991820	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8MD	Abcam HCT 116 PEBP1 KO	Cancer cell line	Male
CVCL_B9PJ	Abcam A-549 PEBP1 KO	Cancer cell line	Male
CVCL_D2GV	Abcam MCF-7 PEBP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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