PAG1

Summary

PAG1 (phosphoprotein membrane anchor with glycosphingolipid microdomains 1, HGNC:30043) is a protein-coding gene on chromosome 8q21.13, encoding Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (Q9NWQ8). Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells.

The protein encoded by this gene is a type III transmembrane adaptor protein that binds to the tyrosine kinase csk protein. It is thought to be involved in the regulation of T cell activation.

Source: NCBI Gene 55824 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 71 total
• Druggable target: yes
• MANE Select transcript: NM_018440

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30043
Approved symbol	PAG1
Name	phosphoprotein membrane anchor with glycosphingolipid microdomains 1
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Aliases	PAG, CBP
Ensembl gene	ENSG00000076641
Ensembl biotype	protein_coding
OMIM	605767
Entrez	55824

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 24 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000220597, ENST00000519326, ENST00000522811, ENST00000523463, ENST00000884230, ENST00000884231, ENST00000884232, ENST00000884233, ENST00000884234, ENST00000884235, ENST00000884236, ENST00000884237, ENST00000884238, ENST00000884239, ENST00000884240, ENST00000884241, ENST00000884242, ENST00000884243, ENST00000884244, ENST00000884245, ENST00000884246, ENST00000884247, ENST00000884248, ENST00000970331, ENST00000970332, ENST00000970333, ENST00000970334

RefSeq mRNA: 1 — MANE Select: NM_018440 NM_018440

CCDS: CCDS6227

Canonical transcript exons

ENST00000220597 — 9 exons

Exon	Start	End
ENSE00001016729	80991479	80991530
ENSE00001086597	80984776	80985377
ENSE00001086600	80980435	80980494
ENSE00001086601	80987370	80987466
ENSE00001206822	81029996	81030089
ENSE00001206828	80967810	80976906
ENSE00001206829	80993103	80993307
ENSE00001479707	81070112	81070170
ENSE00001479708	81111591	81112068

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5573 / max 431.3695, expressed in 1137 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93728	8.8844	1063
93729	0.6728	354

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.45	gold quality
oocyte	CL:0000023	98.26	gold quality
ileal mucosa	UBERON:0000331	97.78	gold quality
visceral pleura	UBERON:0002401	97.62	gold quality
endothelial cell	CL:0000115	96.72	gold quality
lower lobe of lung	UBERON:0008949	94.76	gold quality
jejunal mucosa	UBERON:0000399	94.44	gold quality
dorsal root ganglion	UBERON:0000044	94.11	gold quality
colonic mucosa	UBERON:0000317	93.47	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.45	gold quality
tibia	UBERON:0000979	92.84	gold quality
blood	UBERON:0000178	92.65	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.38	gold quality
pylorus	UBERON:0001166	92.26	gold quality
trigeminal ganglion	UBERON:0001675	92.17	gold quality
nipple	UBERON:0002030	92.07	gold quality
bone marrow	UBERON:0002371	91.99	gold quality
middle temporal gyrus	UBERON:0002771	91.78	gold quality
inferior vagus X ganglion	UBERON:0005363	91.76	gold quality
trabecular bone tissue	UBERON:0002483	91.55	gold quality
left ventricle myocardium	UBERON:0006566	91.28	gold quality
pigmented layer of retina	UBERON:0001782	91.00	gold quality
retina	UBERON:0000966	90.98	gold quality
embryo	UBERON:0000922	90.65	gold quality
ganglionic eminence	UBERON:0004023	90.65	gold quality
bone marrow cell	CL:0002092	90.53	gold quality
cardia of stomach	UBERON:0001162	90.46	gold quality
upper arm skin	UBERON:0004263	90.27	gold quality
pancreatic ductal cell	CL:0002079	90.14	gold quality
placenta	UBERON:0001987	89.52	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	837.05
E-CURD-112	yes	40.31
E-HCAD-35	yes	29.42
E-MTAB-8142	yes	18.34
E-CURD-119	yes	16.63
E-MTAB-9067	yes	16.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ALB	Activation

miRNA regulators (miRDB)

374 targeting PAG1, 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-6867-5P	100.00	82.21	3464
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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1193	100.00	65.93	529
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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-103A-3P	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 26)

• Study shows EGF-stimulation-induced Csk-binding protein (Cbp) tyrosine phosphorylation followed by Cbp-Csk association, in a SFK-dependent manner. (PMID:16636672)
• High PAG-binding ability with CSK in vitro as well as the human PAG structure characterized by 11 alpha-helix structures including a 3 kDa transmembrane domain are reported. (PMID:16947079)
• PAG negatively regulates Ras proteins, and by knocking down PAG there is enhanced Src kinase activity and Ras activation. (PMID:17389760)
• engagement of the SH2 domain on PAG renders FynT insensitive to Csk negative regulation (PMID:18056706)
• role in control of proliferation and survival in most B-non-Hodgkin lymphomas (PMID:18070987)
• new insights into the function of Cbp in modulating RhoA activation, by which Cbp might contribute to renal cell carcinogenesis (PMID:19581936)
• PAG1 protein was downregulated in PC-3M-1E8 prostate cancer cell line. (PMID:20388373)
• In the membrane environment of ALK+ lymphoma rafts, where the glycosphingolipid to signaling protein ratio is higher than in B-NHL rafts, the Lyn activity is suboptimal and does not allow the formation of an efficient Lyn-Cbp/PAG signalosome (PMID:20561033)
• An over-expression of PAG1 in PC-3M-1E8 cells effectively suppresses the activation of Ras and ERK, as well as the cyclin D1 expression, leading to an inhibition of the proliferation ability of tumor cells. (PMID:21092590)
• Results indicate that Cbp is required for the Csk-mediated inactivation of c-Src and may control the promotion of malignancy in NSCLC tumors that are characterized by c-Src upregulation. (PMID:21156787)
• Cbp down-regulation is primarily mediated by epigenetic histone modifications via oncogenic MAPK/PI3K pathways in a subset of cancer cells. (PMID:21388951)
• expression of CBP gene is decreased in esophageal carcinoma, which might contribute to the tumorigenesis and progression. (PMID:22027792)
• findings support a negative regulatory function for Cbp/PAG in proximal B cell receptor signaling in normal and EBV-transformed B cells (PMID:22659621)
• siRNA directed against PAG1 in a radioresistant (Hep-2max) cell line dramatically enhanced the radiosensitivity and IR-induced cell death. (PMID:22994656)
• The inhibitory function of novobiocin in disrupting the HIF1alpha/p300 complex might be important in tumor cell growth. (PMID:23671581)
• No association Pag1 mutation with patient with Schizophrenia. (PMID:25005592)
• CBP may decrease the metastasis of esophageal carcinoma by inhibiting the activation of Src. (PMID:25684946)
• Up-regulated expression of CBP in Jurkat cells could reduce cell homogeneity and promote cell apoptosis (PMID:26062415)
• The risk-associated allele of rs2370615 predisposes to allergic disease by increasing PAG1 expression, which might promote B cell activation and have a pro-inflammatory effect. (PMID:26211970)
• Low PAG1 expression is associated neuroblastoma. (PMID:26993602)
• Our study highlights the underlying mechanism of cross interaction between ASCs and breast cancer cells, and indicates that PAG1/Cbp in breast cancer cell may modulate tumor progression and acquired chemoresistance in the ASCs-associated breast cancer microenvironment through Src and AKT/mTOR pathways. (PMID:29079189)
• PAG1 conferred inherent radioresistance by activating STAT3. (PMID:29913153)
• PAG1 directs SRC-family kinase intracellular localization to mediate receptor tyrosine kinase-induced differentiation. (PMID:32726167)
• PAG1 stimulates proliferation and metastasis of nasopharyngeal carcinoma through downregulating PTEN. (PMID:33215426)
• Transmembrane adaptor protein PAG is a mediator of PD-1 inhibitory signaling in human T cells. (PMID:34083754)
• The role of phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) in regulating the progression of oral squamous cell carcinoma. (PMID:37852106)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pag1	ENSDARG00000055875
mus_musculus	Pag1	ENSMUSG00000027508
rattus_norvegicus	Pag1	ENSRNOG00000087915

Protein

Protein identifiers

Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 — Q9NWQ8 (reviewed: Q9NWQ8)

Alternative names: Csk-binding protein, Transmembrane adapter protein PAG, Transmembrane phosphoprotein Cbp

All UniProt accessions (1): Q9NWQ8

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Promotes CSK activation and recruitment to lipid rafts, which results in LCK inhibition. Inhibits immunological synapse formation by preventing dynamic arrangement of lipid raft proteins. May be involved in cell adhesion signaling.

Subunit / interactions. Interacts with FYN. When phosphorylated, interacts with CSK. Interacts with NHERF1/EBP50. In resting T-cells, part of a PAG1-NHERF1-MSN complex which is disrupted upon TCR activation. Interacts with LYN on plasma membrane lipid rafts. Identified in a complex with LYN and STAT3.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitously expressed. Present in germinal center B-cells, plasma cells, T-cells, monocytes and platelets (at protein level).

Post-translational modifications. Palmitoylated. Phosphorylated by FYN on Tyr-317 in resting T-cells; which promotes interaction with CSK. Dephosphorylated by PTPRC/CD45 upon TCR activation; which leads to CSK dissociation. May also be dephosphorylated by PTPN11. Hyperphosphorylated in mast cells upon FCER1 activation. Phosphorylated by LYN.

RefSeq proteins (1): NP_060910* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032748	PAG	Family

Pfam: PF15347

UniProt features (39 total): modified residue 13, mutagenesis site 10, region of interest 5, compositionally biased region 3, topological domain 2, lipid moiety-binding region 2, sequence conflict 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWQ8-F1	54.93	0.05

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 (15): 50, 61, 105, 163, 181, 227, 229, 317, 354, 359, 380, 387, 417, 37, 40

Mutagenesis-validated functional residues (10):

Position	Phenotype
105	no effect on interaction with fyn or csk.
163	no effect on interaction with fyn or csk.
181	no effect on interaction with fyn or csk.
227	no effect on interaction with fyn or csk.
299	no effect on interaction with fyn or csk.
317	no effect on interaction with fyn. abolishes interaction with csk.
341	no effect on interaction with fyn or csk.
359	no effect on interaction with fyn or csk.
387	no effect on interaction with fyn or csk.
417	no effect on interaction with fyn or csk.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-180292	GAB1 signalosome
R-HSA-202427	Phosphorylation of CD3 and TCR zeta chains

MSigDB gene sets: 332 (showing top): PID_BCR_5PATHWAY, PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, TSENG_IRS1_TARGETS_UP, REACTOME_GAB1_SIGNALOSOME, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_169, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, PID_CXCR4_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, REACTOME_PHOSPHORYLATION_OF_CD3_AND_TCR_ZETA_CHAINS, GOMF_SH2_DOMAIN_BINDING

GO Biological Process (6): adaptive immune response (GO:0002250), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556), regulation of T cell activation (GO:0050863), negative regulation of T cell activation (GO:0050868), immune system process (GO:0002376)

GO Molecular Function (3): signaling adaptor activity (GO:0035591), SH2 domain binding (GO:0042169), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane raft (GO:0045121), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by EGFR	1
TCR signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
T cell activation	2
immune response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular anatomical structure	1
signal transduction	1
regulation of lymphocyte activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
biological_process	1
protein-macromolecule adaptor activity	1
protein domain specific binding	1
binding	1
membrane	1
cell periphery	1
membrane microdomain	1
cellular anatomical structure	1

Protein interactions and networks

STRING

624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAG1	CSK	P41240	994
PAG1	LYN	P07948	874
PAG1	FYN	P06241	855
PAG1	NHERF1	O14745	838
PAG1	DHCR7	Q9UBM7	769
PAG1	FCER1A	P12319	717
PAG1	EZR	P15311	657
PAG1	SRC	P12931	517
PAG1	ASAP1	Q9ULH1	507
PAG1	THY1	P04216	501
PAG1	ITGB1	P05556	480
PAG1	LCK	P06239	479
PAG1	AKT1	P31749	459
PAG1	ERBB2	P04626	425
PAG1	FDFT1	P37268	424

IntAct

91 interactions, top by confidence:

A	B	Type	Score
CSK	PAG1	psi-mi:“MI:0914”(association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PAG1	LYN	psi-mi:“MI:0915”(physical association)	0.640
PAG1	LYN	psi-mi:“MI:0914”(association)	0.640
LYN	PAG1	psi-mi:“MI:0915”(physical association)	0.640
NHERF1	PAG1	psi-mi:“MI:0915”(physical association)	0.630
FYN	PAG1	psi-mi:“MI:0914”(association)	0.620
FYN	PAG1	psi-mi:“MI:0915”(physical association)	0.620
HOXB5	VPS37C	psi-mi:“MI:0914”(association)	0.530
S1PR2	PALM3	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
SLC25A41	NUDT19	psi-mi:“MI:0914”(association)	0.530
FKBP11	ANKRD13D	psi-mi:“MI:0914”(association)	0.530
GPR141	STXBP3	psi-mi:“MI:0914”(association)	0.530
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530

BioGRID (106): PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Proximity Label-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), PAG1 (Affinity Capture-MS)

ESM2 similar proteins: A6H7B4, B1AXH1, F1RDM5, M3WHG5, O43561, O54957, O70601, O88834, P15391, P16382, P24394, P25917, P25918, Q08DN6, Q13651, Q2TBN9, Q3SYS8, Q3U1F9, Q3UU41, Q58CT8, Q5FVQ5, Q5HYW2, Q5JTC6, Q5M831, Q5S7W5, Q63257, Q6DJE5, Q6P1D7, Q6RFH4, Q6T4R5, Q6WG24, Q7M4L6, Q7TS75, Q863Z5, Q8BHB3, Q8C5R2, Q8CB93, Q8CGK5, Q8IWV1, Q8IY92

Diamond homologs: Q3U1F9, Q9JM80, Q9NWQ8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
FYN	“up-regulates activity”	PAG1	phosphorylation
LYN	“up-regulates activity”	PAG1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	9	75.3×	6e-13
Regulation of KIT signaling	5	48.5×	5e-06
Co-inhibition by CTLA4	5	41.9×	7e-06
CD209 (DC-SIGN) signaling	5	41.9×	7e-06
Signaling by SCF-KIT	9	36.0×	6e-10
Signaling by CSF1 (M-CSF) in myeloid cells	6	33.5×	3e-06
Downstream signal transduction	5	30.7×	2e-05
Co-stimulation by CD28	5	30.7×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
leukocyte migration	5	38.5×	7e-05
T cell costimulation	6	27.7×	6e-05
positive regulation of cell migration	8	6.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2712 predictions. Top by Δscore:

Variant	Effect	Δscore
8:80980428:AACTT:A	donor_loss	1.0000
8:80980429:ACTTA:A	donor_loss	1.0000
8:80980430:CTTA:C	donor_loss	1.0000
8:80980431:TTACC:T	donor_loss	1.0000
8:80980432:TA:T	donor_loss	1.0000
8:80980433:A:AG	donor_loss	1.0000
8:80980493:CT:C	acceptor_gain	1.0000
8:80984771:CCCA:C	donor_loss	1.0000
8:80984772:CCACC:C	donor_loss	1.0000
8:80984773:CAC:C	donor_loss	1.0000
8:80984774:A:T	donor_loss	1.0000
8:80985374:AGAA:A	acceptor_gain	1.0000
8:80985375:GAA:G	acceptor_gain	1.0000
8:80985385:A:T	acceptor_gain	1.0000
8:80987319:T:TA	donor_gain	1.0000
8:80987368:A:AC	donor_gain	1.0000
8:80987368:ACTGT:A	donor_gain	1.0000
8:80987369:C:CT	donor_gain	1.0000
8:80987369:CTGT:C	donor_gain	1.0000
8:80987369:CTGTC:C	donor_gain	1.0000
8:80987401:A:AC	donor_gain	1.0000
8:80987402:C:CC	donor_gain	1.0000
8:80991415:A:AC	donor_gain	1.0000
8:80991416:G:C	donor_gain	1.0000
8:80991424:G:C	donor_gain	1.0000
8:80993097:TCTCA:T	donor_loss	1.0000
8:80993098:CTCA:C	donor_loss	1.0000
8:80993099:TCA:T	donor_loss	1.0000
8:80993100:CA:C	donor_loss	1.0000
8:80993101:ACCT:A	donor_loss	1.0000

AlphaMissense

2849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:80984973:A:G	Y227H	0.995
8:80984969:G:T	A228D	0.992
8:80984972:T:G	Y227S	0.992
8:80985104:G:A	T183I	0.991
8:80984972:T:C	Y227C	0.990
8:80985120:C:G	D178H	0.990
8:80984973:A:C	Y227D	0.988
8:80985107:T:A	E182V	0.988
8:80984967:A:G	S229P	0.985
8:80976894:A:C	Y317D	0.984
8:80985119:T:A	D178V	0.983
8:80985119:T:G	D178A	0.982
8:80984963:A:T	V230E	0.980
8:80984970:C:G	A228P	0.978
8:80985101:A:T	V184E	0.977
8:80985111:A:C	Y181D	0.977
8:80976758:A:T	V362D	0.975
8:80984973:A:T	Y227N	0.975
8:80985245:A:G	I136T	0.974
8:80976893:T:G	Y317S	0.972
8:80985106:T:A	E182D	0.972
8:80985106:T:G	E182D	0.972
8:80985254:A:G	L133P	0.972
8:80985111:A:G	Y181H	0.971
8:80985105:T:G	T183P	0.970
8:80984863:C:A	K263N	0.969
8:80984863:C:G	K263N	0.969
8:80985088:C:A	K188N	0.969
8:80985088:C:G	K188N	0.969
8:80985113:A:G	L180S	0.969

dbSNP variants (sampled 300 via entrez): RS1000004657 (8:80978236 T>G), RS1000031520 (8:81055952 T>C), RS1000060135 (8:81014742 G>C), RS1000062221 (8:80997564 A>G), RS1000078798 (8:81006929 G>A), RS1000092408 (8:81013940 T>A,C,G), RS1000098964 (8:81047852 T>C), RS1000108660 (8:81088911 T>C), RS1000124372 (8:81033490 A>G), RS1000125042 (8:81041046 C>T), RS1000125251 (8:81049372 A>G), RS1000132234 (8:81109869 C>A,T), RS1000207049 (8:81026475 T>C), RS1000209449 (8:81067185 T>C), RS1000217545 (8:80991693 C>A,G,T)

Disease associations

OMIM: gene MIM:605767 | 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
GCST001698_10	Serum total protein levels	6.000000e-08
GCST003081_9	Glucocorticoid-induced osteonecrosis (age 10 years and older)	4.000000e-06
GCST008513_18	Health literacy	4.000000e-06
GCST90011899_67	Aspartate aminotransferase levels	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004536	total blood protein measurement
EFO:0010104	health literacy measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067084 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.06	Kd	873.4	nM	CHEMBL5653589
5.75	ED50	1773	nM	CHEMBL5653589
5.08	Kd	8276	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148930: Binding affinity to human PAG1 incubated for 45 mins by Kinobead based pull down assay	kd	0.8734	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148930: Binding affinity to human PAG1 incubated for 45 mins by Kinobead based pull down assay	kd	8.2765	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	8
(+)-JQ1 compound	increases expression	7
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
bisphenol A	increases expression	2
trichostatin A	affects expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
OTX015	increases expression	1
FR900359	affects phosphorylation	1
mivebresib	increases expression	1
sotorasib	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
2-butenal	decreases expression, increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
cobalt oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651972	Binding	Binding affinity to human PAG1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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