PES1

Summary

PES1 (pescadillo ribosomal biogenesis factor 1, HGNC:8848) is a protein-coding gene on chromosome 22q12.2, encoding Pescadillo homolog (O00541). Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome. It is a common-essential gene (DepMap: required in 96.8% of cancer cell lines).

This gene encodes a nuclear protein that contains a breast cancer associated gene 1 (BRCA1) C-terminal interaction domain. The encoded protein interacts with BOP1 and WDR12 to form the PeBoW complex, which plays a critical role in cell proliferation via pre-rRNA processing and 60S ribosomal subunit maturation. Expression of this gene may play an important role in breast cancer proliferation and tumorigenicity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Pseudogenes of this gene are located on the long arm of chromosome 4 and the short arm of chromosome 9.

Source: NCBI Gene 23481 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 103 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 96.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_014303

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8848
Approved symbol	PES1
Name	pescadillo ribosomal biogenesis factor 1
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	PES, NOP7
Ensembl gene	ENSG00000100029
Ensembl biotype	protein_coding
OMIM	605819
Entrez	23481

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000335214, ENST00000354694, ENST00000402281, ENST00000402284, ENST00000405677, ENST00000406208, ENST00000433575, ENST00000441668, ENST00000466614, ENST00000467368, ENST00000477762, ENST00000488719, ENST00000492986, ENST00000898784, ENST00000898785, ENST00000898786, ENST00000934359, ENST00000934360, ENST00000944364, ENST00000944365

RefSeq mRNA: 4 — MANE Select: NM_014303 NM_001243225, NM_001282327, NM_001282328, NM_014303

CCDS: CCDS13880, CCDS58802, CCDS74842

Canonical transcript exons

ENST00000354694 — 15 exons

Exon	Start	End
ENSE00000652434	30578837	30578998
ENSE00000652440	30579137	30579303
ENSE00000652444	30579751	30579935
ENSE00000652452	30580053	30580178
ENSE00000652454	30580571	30580701
ENSE00000652457	30581012	30581101
ENSE00001613286	30591810	30591910
ENSE00003566398	30581528	30581644
ENSE00003588401	30584546	30584717
ENSE00003589714	30584365	30584454
ENSE00003704090	30588021	30588174
ENSE00003704216	30589191	30589270
ENSE00003708755	30587286	30587395
ENSE00003709188	30576625	30577129
ENSE00003790120	30581334	30581408

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 94.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.3590 / max 439.4994, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193655	50.0936	1816
193654	1.2653	881

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	94.67	gold quality
body of pancreas	UBERON:0001150	94.24	gold quality
islet of Langerhans	UBERON:0000006	93.88	gold quality
skin of leg	UBERON:0001511	93.62	gold quality
mucosa of transverse colon	UBERON:0004991	93.35	gold quality
skin of abdomen	UBERON:0001416	93.21	gold quality
pancreas	UBERON:0001264	93.10	gold quality
left testis	UBERON:0004533	92.93	gold quality
stromal cell of endometrium	CL:0002255	92.82	gold quality
body of stomach	UBERON:0001161	92.66	gold quality
metanephros cortex	UBERON:0010533	92.66	gold quality
right testis	UBERON:0004534	92.62	gold quality
tibial nerve	UBERON:0001323	92.56	gold quality
right ovary	UBERON:0002118	92.51	gold quality
body of uterus	UBERON:0009853	92.43	gold quality
left adrenal gland	UBERON:0001234	92.32	gold quality
right adrenal gland	UBERON:0001233	92.30	gold quality
left adrenal gland cortex	UBERON:0035825	92.22	gold quality
left ovary	UBERON:0002119	92.13	gold quality
right adrenal gland cortex	UBERON:0035827	92.13	gold quality
esophagus mucosa	UBERON:0002469	92.11	gold quality
granulocyte	CL:0000094	92.03	gold quality
cortical plate	UBERON:0005343	92.03	gold quality
ectocervix	UBERON:0012249	91.98	gold quality
left uterine tube	UBERON:0001303	91.97	gold quality
right lobe of thyroid gland	UBERON:0001119	91.82	gold quality
endocervix	UBERON:0000458	91.72	gold quality
right lobe of liver	UBERON:0001114	91.71	gold quality
upper lobe of left lung	UBERON:0008952	91.71	gold quality
esophagus	UBERON:0001043	91.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2, FOS, IRF6, JUN, JUNB, JUND

miRNA regulators (miRDB)

28 targeting PES1, 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-5696	99.98	72.36	4487
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-6805-5P	95.79	64.86	670
HSA-MIR-1914-3P	95.07	63.37	762

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 23)

• Mechanisms for the ability of Pes1 to transform cells, and its failure to immortalize them. (PMID:15273728)
• RRB1 interacts with YPH1 (yeast pescadillo homologue 1) and other members of the Yph1 complex (PMID:15467761)
• Pes1 and Bop1 form a stable complex with a novel member, WDR12 (PeBoW complex). (PMID:16043514)
• Results describe the role of PeBoW-specific proteins Pes1, Bop1, and WDR12 in complex assembly and stability, nucleolar transport, and pre-ribosome association. (PMID:17353269)
• pescadillo might play a role in promoting the proliferation and carcinogenesis of human breast cancer, and thereby might be a potential target for human breast cancer treatment. (PMID:19764998)
• The physical interaction between B23 and PES1 implies that they may participate in ribosome biogenesis in a protein complex. (PMID:20011973)
• expression of PES1 correlated positively with ERalpha expression and negatively with ERbeta expression and predicted good clinical outcome in breast cancer (PMID:22820289)
• Upstream of c-Jun, it was revealed that c-Jun NH2-terminal kinases (JNK) is essential for controlling PES1 expression (PMID:22860098)
• these results uncover a potential role of PES1 in chemoresistance by regulating DNA damage response in colorectal cancer cells. (PMID:23333390)
• PES1 may play important role in the progression of ovarian cancer by inversely regulating the ERalpha and ERbeta expression. (PMID:24376209)
• The DDX27 can interact specifically with the Pes1 and Bop1 but fulfils critical function(s) for proper 3’ end formation of 47S rRNA independently of the PeBoW-complex. (PMID:25825154)
• PES1 may play an important role in development of gastric cancer. (PMID:26423399)
• posttranslational modification of PES1 by SUMOylation may serve as a key factor that regulates the function of PES1 in vivo (PMID:27409667)
• PES1 is transcriptionally regulated by BRD4 and promotes cell proliferation and glycolysis in hepatocellular carcinoma (PMID:30172011)
• upregulated in hepatocellular carcinoma tissues and cells, potentially representing a novel prognostic marker for overall survival (PMID:30630006)
• PES1 promotes the occurrence and development of papillary thyroid cancer by upregulating the ERalpha/ERbeta protein ratio. (PMID:30705367)
• PES1 facilitates telomerase assembly by promoting direct interaction between TERT and TR without affecting TERT and TR levels (PMID:31106266)
• CD44 regulates PES1 in liver cancer stem cells via miR-105-5p to promote cell growth (PMID:31127852)
• Authors showed that PES1 interacted with BRD4 to enhance c-Myc expression, which is the primary cause of cancer cell resistance to BET inhibitors in pancreatic cancer. (PMID:31718704)
• microRNA-1271 impedes the development of prostate cancer by downregulating PES1 and upregulating ERbeta. (PMID:32448371)
• Pescadillo ribosomal biogenesis factor 1 reduction suppresses tumour growth and renders chemosensitivity of head and neck squamous cell carcinoma. (PMID:36217758)
• Overexpression of hepatic pescadillo 1 in obesity induces lipid dysregulation by inhibiting autophagy. (PMID:36775058)
• PES1 is a biomarker of head and neck squamous cell carcinoma and is associated with the tumor microenvironment. (PMID:37076985)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pes	ENSDARG00000018902
mus_musculus	Pes1	ENSMUSG00000020430
rattus_norvegicus	Pes1	ENSRNOG00000004515
drosophila_melanogaster	CG4364	FBGN0032138
caenorhabditis_elegans		WBGENE00003063

Protein

Protein identifiers

Pescadillo homolog — O00541 (reviewed: O00541)

All UniProt accessions (6): O00541, B2RDF2, B5MCF9, F6VXF5, H7BYY8, H7C267

UniProt curated annotations — full annotation on UniProt →

Function. Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.

Subunit / interactions. Component of the PeBoW complex, composed of BOP1, PES1 and WDR12. The complex is held together by BOP1, which interacts with PES1 via its N-terminal domain and with WDR12 via a high-affinity interaction between the seven-bladed beta-propeller domains of the 2 proteins. The PeBoW complex associates with the 66S pre-ribosome. The PeBoW complex also associates with DDX27, PES1 interacts directly with DDX27. Interacts with IRS1 and UBTF. May interact with MAP1B.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Chromosome.

Tissue specificity. Significant levels are detected in a variety of cancer cell lines, including glioblastoma, breast carcinoma, colon carcinoma and cervical carcinoma cells. Levels are abnormally elevated in malignant tumors of astrocytic origin.

Post-translational modifications. Sumoylated.

Induction. By MYC.

Similarity. Belongs to the pescadillo family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00541-1	1	yes
O00541-2	2

RefSeq proteins (4): NP_001230154, NP_001269256, NP_001269257, NP_055118* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR010613	PES	Family
IPR036420	BRCT_dom_sf	Homologous_superfamily

Pfam: PF06732, PF16589

UniProt features (32 total): region of interest 7, strand 5, mutagenesis site 4, sequence variant 3, turn 3, compositionally biased region 2, cross-link 2, helix 2, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FLE	ELECTRON MICROSCOPY	2.48
8FKW	ELECTRON MICROSCOPY	2.5
8FL3	ELECTRON MICROSCOPY	2.53
8FL7	ELECTRON MICROSCOPY	2.55
8FLB	ELECTRON MICROSCOPY	2.55
8FLD	ELECTRON MICROSCOPY	2.58
8FKX	ELECTRON MICROSCOPY	2.59
8FL6	ELECTRON MICROSCOPY	2.62
8FLA	ELECTRON MICROSCOPY	2.63
8FKY	ELECTRON MICROSCOPY	2.67
8FL2	ELECTRON MICROSCOPY	2.67
8FKQ	ELECTRON MICROSCOPY	2.76
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82
8FKP	ELECTRON MICROSCOPY	2.85
8FKS	ELECTRON MICROSCOPY	2.88
8FKR	ELECTRON MICROSCOPY	2.89
8FL4	ELECTRON MICROSCOPY	2.89
8INF	ELECTRON MICROSCOPY	3
8FKZ	ELECTRON MICROSCOPY	3.04
8INE	ELECTRON MICROSCOPY	3.2
8IPY	ELECTRON MICROSCOPY	3.2
8IR3	ELECTRON MICROSCOPY	3.5
8IPX	ELECTRON MICROSCOPY	4.3
2EP8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00541-F1	80.28	0.42

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 (3): 98, 517, 517

Mutagenesis-validated functional residues (4):

Position	Phenotype
327	reduces incorporation into the pebow complex and nucleolar localization and impairs maturation of 28s ribosomal rna.
347	reduces incorporation into the pebow complex and nucleolar localization and impairs maturation of 28s ribosomal rna.
380	slightly impairs nucleolar localization.
397	reduces incorporation into the pebow complex and nucleolar localization and impairs maturation of 28s ribosomal rna.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 0 (showing top):

GO Biological Process (7): maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000463), maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000466), rRNA processing (GO:0006364), cell population proliferation (GO:0008283), ribosomal large subunit biogenesis (GO:0042273), regulation of cell cycle (GO:0051726), ribosome biogenesis (GO:0042254)

GO Molecular Function (3): RNA binding (GO:0003723), ribonucleoprotein complex binding (GO:0043021), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), cytosol (GO:0005829), membrane (GO:0016020), preribosome, large subunit precursor (GO:0030687), PeBoW complex (GO:0070545), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
ribosome biogenesis	2
ribonucleoprotein complex biogenesis	2
nuclear lumen	2
intracellular membraneless organelle	2
maturation of LSU-rRNA	1
maturation of 5.8S rRNA	1
RNA processing	1
rRNA metabolic process	1
cellular process	1
cell cycle	1
regulation of cellular process	1
nucleic acid binding	1
protein-containing complex binding	1
binding	1
cytoplasm	1
preribosome	1
nucleolus	1
90S preribosome	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PES1	BOP1	Q14137	992
PES1	WDR12	Q9GZL7	988
PES1	BRCA1	P38398	701
PES1	NUCLEOLIN	P19338	635
PES1	EBNA1BP2	Q99848	596
PES1	DDX21	Q9NR30	540
PES1	GNL3	Q9BVP2	538
PES1	MRTO4	Q9UKD2	530
PES1	TEX10	Q9NXF1	524
PES1	SURF6	O75683	496
PES1	SUMO1	P55856	492
PES1	EMG1	Q92979	487
PES1	RBM19	Q9Y4C8	487
PES1	GNL2	Q13823	483
PES1	PPAN	Q9NQ55	482

IntAct

131 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
PES1	WDR12	psi-mi:“MI:0915”(physical association)	0.850
WDR12	PES1	psi-mi:“MI:0914”(association)	0.850
BOP1	PES1	psi-mi:“MI:0914”(association)	0.810
PES1	BOP1	psi-mi:“MI:0914”(association)	0.810
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CSNK2A2	PES1	psi-mi:“MI:0914”(association)	0.640
PES1	HTT	psi-mi:“MI:0915”(physical association)	0.560
PES1	ATXN1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA10	POTEF	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
WDR55	PES1	psi-mi:“MI:0914”(association)	0.530
CASQ2	PES1	psi-mi:“MI:0914”(association)	0.530
PES1	FOXM1	psi-mi:“MI:0915”(physical association)	0.500
FOXM1	PES1	psi-mi:“MI:0914”(association)	0.500
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410

BioGRID (394): PES1 (Affinity Capture-RNA), PES1 (Affinity Capture-RNA), PES1 (Affinity Capture-MS), PES1 (Affinity Capture-MS), PES1 (Affinity Capture-MS), PES1 (Affinity Capture-MS), PES1 (Affinity Capture-MS), PES1 (Affinity Capture-MS), PES1 (Affinity Capture-MS), BRIX1 (Co-fractionation), CEBPZ (Co-fractionation), FBL (Co-fractionation), FTSJ3 (Co-fractionation), GNL1 (Co-fractionation), GNL3 (Co-fractionation)

ESM2 similar proteins: A1CHD1, A1CXF4, A3LU56, A4RLI4, A5DGY0, A5DYS6, A6RBB0, A6SK81, A7EGB5, A7TSA8, A8N1X3, A8Q1F0, A9URZ4, B0CQL7, B0WD26, B0Y612, B2WBA7, B3MUX9, B3N8H0, B4G7Y6, B4HW93, B4JZG8, B4KID9, B4LQD0, B4NE56, B4NY70, B4Q865, O00541, O60164, P0CP58, P0CP59, P53261, P79741, Q0CLP9, Q0V577, Q1DLJ4, Q29NB4, Q2HCV1, Q2UGQ8, Q3B8N8

Diamond homologs: A1CHD1, A1CXF4, A3LU56, A4RLI4, A5DGY0, A5DYS6, A6RBB0, A6SK81, A6ZV85, A7EGB5, A7SWH1, A7TSA8, A8JBB2, A8N1X3, A8Q1F0, A8QHQ0, A8X871, A9URZ4, B0CQL7, B0WD26, B0Y612, B2WBA7, B3MUX9, B3N8H0, B4G7Y6, B4HW93, B4JZG8, B4KID9, B4LQD0, B4NE56, B4NY70, B4Q865, B5X171, O00541, O60164, P0CP58, P0CP59, P53261, P79741, Q0CLP9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PES1	up-regulates	Proliferation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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 ALK fusions and activated point mutants	8	14.1×	4e-05
Major pathway of rRNA processing in the nucleolus and cytosol	11	8.0×	4e-05
Diseases of signal transduction by growth factor receptors and second messengers	9	6.0×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	7	14.4×	5e-04
negative regulation of translation	6	10.6×	5e-03
rRNA processing	8	10.2×	6e-04
cytoplasmic translation	6	10.0×	6e-03
regulation of cell cycle	9	6.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2261 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30577125:TTGGC:T	acceptor_gain	1.0000
22:30577126:TGGC:T	acceptor_gain	1.0000
22:30577127:GGC:G	acceptor_gain	1.0000
22:30577128:GC:G	acceptor_gain	1.0000
22:30577129:CC:C	acceptor_gain	1.0000
22:30577129:CCTG:C	acceptor_loss	1.0000
22:30577130:C:CC	acceptor_gain	1.0000
22:30577130:C:G	acceptor_loss	1.0000
22:30577131:T:A	acceptor_loss	1.0000
22:30578832:CTCA:C	donor_loss	1.0000
22:30578833:TCA:T	donor_loss	1.0000
22:30578834:CA:C	donor_loss	1.0000
22:30578835:A:AC	donor_gain	1.0000
22:30578835:A:C	donor_loss	1.0000
22:30578836:C:CC	donor_gain	1.0000
22:30578836:CCT:C	donor_gain	1.0000
22:30578836:CCTCT:C	donor_gain	1.0000
22:30578994:GGCTT:G	acceptor_gain	1.0000
22:30578996:CTT:C	acceptor_gain	1.0000
22:30578997:TT:T	acceptor_gain	1.0000
22:30578998:TCTG:T	acceptor_loss	1.0000
22:30578999:C:CA	acceptor_loss	1.0000
22:30578999:C:CC	acceptor_gain	1.0000
22:30579000:T:A	acceptor_loss	1.0000
22:30579131:CCCTA:C	donor_loss	1.0000
22:30579132:CCTA:C	donor_loss	1.0000
22:30579133:CTA:C	donor_loss	1.0000
22:30579134:TACCT:T	donor_loss	1.0000
22:30579135:AC:A	donor_loss	1.0000
22:30579139:T:A	donor_gain	1.0000

AlphaMissense

3860 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30581606:G:C	F223L	1.000
22:30581606:G:T	F223L	1.000
22:30581608:A:G	F223L	1.000
22:30584449:G:C	F182L	1.000
22:30584449:G:T	F182L	1.000
22:30584451:A:G	F182L	1.000
22:30588086:A:C	Y65D	1.000
22:30588136:G:C	P48R	1.000
22:30588136:G:T	P48H	1.000
22:30588137:G:A	P48S	1.000
22:30588145:G:T	P45H	1.000
22:30588155:C:G	G42R	1.000
22:30588163:A:T	I39N	1.000
22:30588165:G:C	C38W	1.000
22:30588166:C:T	C38Y	1.000
22:30588167:A:G	C38R	1.000
22:30588169:A:G	L37P	1.000
22:30589191:C:A	R35M	1.000
22:30589194:A:G	F34S	1.000
22:30578880:A:G	L547P	0.999
22:30579841:G:C	H422D	0.999
22:30579916:A:G	W397R	0.999
22:30579916:A:T	W397R	0.999
22:30581616:A:C	M220R	0.999
22:30581616:A:T	M220K	0.999
22:30581619:A:T	V219D	0.999
22:30581628:T:A	D216V	0.999
22:30581628:T:C	D216G	0.999
22:30581629:C:G	D216H	0.999
22:30581631:A:T	V215E	0.999

dbSNP variants (sampled 300 via entrez): RS1000066447 (22:30597232 A>T), RS1000170980 (22:30592315 G>A,C), RS1000227099 (22:30579114 C>A,T), RS1000264642 (22:30600224 C>A,T), RS1000268704 (22:30586691 C>G,T), RS1000367825 (22:30600582 C>A,T), RS1000462469 (22:30581279 G>A,C), RS1000536134 (22:30592219 G>A), RS1000738285 (22:30603493 C>A,G,T), RS1000768412 (22:30603731 T>C,G), RS1000781751 (22:30599688 T>C), RS1000969685 (22:30599646 T>C,G), RS1001139786 (22:30590891 G>C), RS1001249877 (22:30599886 G>A), RS1001260862 (22:30578415 C>A)

Disease associations

OMIM: gene MIM:605819 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90006996_3	Gut microbiota relative abundance (Blautia)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725178 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases methylation, increases expression	2
Estradiol	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Aflatoxin B1	affects cotreatment, decreases expression, increases methylation	2
Particulate Matter	increases abundance, increases methylation, decreases expression	2
bisphenol F	affects cotreatment, decreases expression	1
deoxynivalenol	increases expression	1
beta-lapachone	increases expression, decreases expression	1
afimoxifene	decreases reaction, increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	increases expression	1
nivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
licochalcone A	affects expression, affects localization, decreases 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, decreases expression	1
ICG 001	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estrogens	decreases reaction, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697258	Binding	Inhibition of PES1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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