PYGO2

Summary

PYGO2 (pygopus family PHD finger 2, HGNC:30257) is a protein-coding gene on chromosome 1q21.3, encoding Pygopus homolog 2 (Q9BRQ0). Involved in signal transduction through the Wnt pathway.

Predicted to enable several functions, including histone acetyltransferase regulator activity; histone binding activity; and zinc ion binding activity. Predicted to be involved in kidney development and spermatid nucleus differentiation. Predicted to act upstream of or within several processes, including canonical Wnt signaling pathway; lens development in camera-type eye; and regulation of mammary gland epithelial cell proliferation. Part of beta-catenin-TCF complex.

Source: NCBI Gene 90780 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 75 total
• MANE Select transcript: NM_138300

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30257
Approved symbol	PYGO2
Name	pygopus family PHD finger 2
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163348
Ensembl biotype	protein_coding
OMIM	606903
Entrez	90780

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000368456, ENST00000368457, ENST00000483463

RefSeq mRNA: 1 — MANE Select: NM_138300 NM_138300

CCDS: CCDS1075

Canonical transcript exons

ENST00000368457 — 3 exons

Exon	Start	End
ENSE00001073617	154957026	154959846
ENSE00001447170	154961474	154961782
ENSE00003535761	154960977	154961026

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 97.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.2357 / max 152.9730, expressed in 1812 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14863	27.9199	1810
14865	0.4773	288
14864	0.4435	252
14866	0.1783	59
14861	0.1108	37
14862	0.1059	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	97.89	silver quality
upper arm skin	UBERON:0004263	95.79	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.50	silver quality
left ventricle myocardium	UBERON:0006566	94.47	silver quality
oviduct epithelium	UBERON:0004804	92.68	gold quality
nasal cavity epithelium	UBERON:0005384	91.97	silver quality
cardia of stomach	UBERON:0001162	90.95	gold quality
right adrenal gland	UBERON:0001233	90.89	gold quality
adenohypophysis	UBERON:0002196	90.84	gold quality
right adrenal gland cortex	UBERON:0035827	90.83	gold quality
granulocyte	CL:0000094	90.71	gold quality
pituitary gland	UBERON:0000007	90.69	gold quality
oocyte	CL:0000023	90.58	gold quality
lymph node	UBERON:0000029	90.39	gold quality
vena cava	UBERON:0004087	90.38	silver quality
tendon of biceps brachii	UBERON:0008188	90.33	gold quality
adrenal cortex	UBERON:0001235	90.18	gold quality
left adrenal gland	UBERON:0001234	90.09	gold quality
epithelial cell of pancreas	CL:0000083	90.03	gold quality
pylorus	UBERON:0001166	89.96	gold quality
lower esophagus mucosa	UBERON:0035834	89.96	gold quality
left adrenal gland cortex	UBERON:0035825	89.91	gold quality
myocardium	UBERON:0002349	89.80	silver quality
ileal mucosa	UBERON:0000331	89.78	gold quality
nipple	UBERON:0002030	89.78	gold quality
right lobe of thyroid gland	UBERON:0001119	89.38	gold quality
islet of Langerhans	UBERON:0000006	89.33	gold quality
ventral tegmental area	UBERON:0002691	89.33	gold quality
adrenal gland	UBERON:0002369	89.29	gold quality
inferior vagus X ganglion	UBERON:0005363	89.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.88

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PAX6	Activation

Upstream regulators (CollecTRI, top): ELF1, ELK1

miRNA regulators (miRDB)

99 targeting PYGO2, 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-9-5P	100.00	72.28	2361
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-11181-3P	99.75	66.38	2205

Literature-anchored findings (GeneRIF, showing 36)

• The Expression of pygopus 2 protein mRNA levels were significantly higher in the epithelial ovarian cancer cell lines. (PMID:16609037)
• hPygo2 is highly expressed in, and required for the growth of breast carcinoma cells (PMID:17203217)
• These results provide new evidence that Elf-1 is involved in transcriptional activation of hPygo2. (PMID:18314487)
• Data support a model in which the NHD region of Pygopus is required to augment transcriptional activation by a mechanism that includes both transcriptional activation and histone acetylation resulting from the recruitment of the CBP. (PMID:19555349)
• The study demonstrated that Pygo2 was highly expressed in glioma tissue and required for growth of glioblastoma cells. (PMID:20204459)
• Pygo2 is highly expressed in and promotes the growth of glioma cells (PMID:20361361)
• Pygo2 PHD is the only known PHD finger that is capable of interacting simultaneously with two functional ligands, B9L and BCL9 (PMID:20637214)
• Data show that Pygo2 associates with MLL2 histone methyltransferase and STAGA histone acetyltransferase to facilitate their interaction with beta-catenin and Wnt1-induced, TCF/LEF-dependent transactivation in breast cancer cells. (PMID:20937768)
• Pygo2 directly occupies the promoters of multiple histone genes and enhances the acetylation of lysine 56 in histone H3. (PMID:22186018)
• PYGO2 is identified as a new molecular marker of invasive tumors in esophageal squamous cell carcinoma. (PMID:23456637)
• The results of the present study suggest a novel involvement of Pygo in the promotion of rRNA transcription in cancer cells (PMID:23517060)
• SNPs in the coding region of Pygo2 gene may be one of the causative factors in idiopathic oligospermia and azoospermia, resulting in male infertility. (PMID:23732668)
• We conclude that abnormal Pygo2 protein expression may be a marker for advanced non-small cell lung cancer (PMID:23865714)
• Our findings suggest that Pygopus-2 may be an important predictor of poor outcome in HCC patients, and could serve as a novel biomarker for HCC. (PMID:25545771)
• Pygopus-2 over-expression is associated with hepatic carcinoma. (PMID:25871475)
• Pygo2 is a common node downstream of oncogenic Wnt and Akt signaling pathways. (PMID:26170450)
• this study demonstrated that SNPs in the coding region of Pygo2 might be one of the causative factors in idiopathic oligospermia and azoospermia, resulting in male infertility. (PMID:26345837)
• The activation of its expression by ERalpha and/or specificity protein-1 (SP1) suggests hPYGO2 as a theranostic target for hormone therapy responsive and refractory breast cancer. (PMID:26645832)
• We also determined the effect of Pygo2 on the sensitivity of breast tumors resistant to doxorubicin in a mouse model. Finally, RNA samples from 64 paired patient tumors (before and after chemotherapy) highly and significantly overexpressed Pygo2 and/or MDR1 after treatment, thus underlining a pivotal role for the Pygo2-mediated Wnt/b-catenin pathway in the clinical chemoresistance of breast cancer. (PMID:26876203)
• Pygo2 functions as a prognostic factor for glioma due to its up-regulation of H3K4me3 and promotion of MLL1/MLL2 complex recruitment. (PMID:26902498)
• Findings are consistent with a model in which acetylation of Pygo2 by CBP/p300 family members in the active TCF/beta-catenin complex occurs coincident with histone acetylation and may be required for the recycling of Pygo2 away from the complex subsequent to target gene activation. (PMID:27647933)
• Overexpression of Pygo2 facilitated the expression of P-glycoprotein, which acts as a drug efflux pump, by promoting the transcription of MDR1 at the MDR1 promoter loci, resulting in acceleration of the efflux of paclitaxel in human glioma cells. (PMID:28427190)
• Elevated PYGO2 expression in primary prostate adenocarcinoma is a potential risk factor for biochemical recurrence. (PMID:28924059)
• evidence supports a role for Pygo2 as an essential component of MYC oncogenic activity required for mitosis. (PMID:29719262)
• Amplification/overexpression of PYGO2 may serve as a biomarker. (PMID:29769196)
• miR-516a-3p inhibits breast cancer cell growth and EMT by blocking the Pygo2/Wnt signalling pathway. (PMID:31273950)
• The expression pattern of pygopus 2 (PYGO2) was evaluated by immunohistochemistry in colorectal cancer(CRC) tissues. results showed expression was significantly higher in CRC samples than in normal tissues, and there was a significant association between PYGO2 expression in CRC and tumor cell metastasis to the lymph nodes. (PMID:31492088)
• Overexpression of Pygo2 Increases Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Cardiomyocyte-like Cells. (PMID:31749426)
• LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/beta-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes. (PMID:32727463)
• Long non-coding RNA SNHG8 enhances triple-negative breast cancer cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis. (PMID:34362407)
• Pygopus2 ameliorates mesenteric adipocyte poor differentiation to alleviate Crohn’s disease -like colitis via the Axin2/GSK3beta pathway. (PMID:35707871)
• Interference of EFNA4 suppresses cell proliferation, invasion and angiogenesis in hepatocellular carcinoma by downregulating PYGO2. (PMID:36404439)
• Association of Single Nucleotide Polymorphisms in the PYGO2 and PRDM9 Genes with Idiopathic Azoospermia in Iranian Infertile Male Patients. (PMID:36688188)
• Novel biphasic mechanism of the canonical Wnt signalling component PYGO2 promotes cardiomyocyte differentiation from hUC-MSCs. (PMID:37233752)
• Pygo2 activates BRPF1 via Pygo2-H3K4me2/3 interaction to maintain malignant progression in colon cancer. (PMID:37423512)
• PYGO2 increases proliferation and migration capacities through critical signaling pathways in esophageal squamous cell carcinoma. (PMID:38229324)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pygo2	ENSDARG00000036772
mus_musculus	Pygo2	ENSMUSG00000047824
rattus_norvegicus	Pygo2	ENSRNOG00000020663
drosophila_melanogaster	pygo	FBGN0043900
caenorhabditis_elegans		WBGENE00015330

Paralogs (1): PYGO1 (ENSG00000171016)

Protein

Protein identifiers

Pygopus homolog 2 — Q9BRQ0 (reviewed: Q9BRQ0)

All UniProt accessions (3): Q9BRQ0, Q5T170, Q5T171

UniProt curated annotations — full annotation on UniProt →

Function. Involved in signal transduction through the Wnt pathway.

Subunit / interactions. Binds to BCL9 via the PHD-type zinc finger motif, and thereby becomes part of the nuclear beta-catenin/TCF complex.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_612157* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR052475	Wnt_Signal_Transd_Protein	Family

Pfam: PF00628

UniProt features (25 total): compositionally biased region 5, modified residue 3, turn 3, strand 3, helix 3, sequence conflict 2, region of interest 2, initiator methionine 1, chain 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4UP0	X-RAY DIFFRACTION	1.28
4UP5	X-RAY DIFFRACTION	1.65
2XB1	X-RAY DIFFRACTION	1.9
8HIB	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRQ0-F1	56.52	0.13

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): 2, 40, 302

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex

MSigDB gene sets: 107 (showing top): LFA1_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, PATIL_LIVER_CANCER, MODULE_331, GATA1_01, AACTTT_UNKNOWN, FOXJ2_02, MODULE_397, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, chr1q21

GO Biological Process (11): kidney development (GO:0001822), lens development in camera-type eye (GO:0002088), spermatid nucleus differentiation (GO:0007289), brain development (GO:0007420), mammary gland development (GO:0030879), regulation of mammary gland epithelial cell proliferation (GO:0033599), developmental growth (GO:0048589), roof of mouth development (GO:0060021), canonical Wnt signaling pathway (GO:0060070), spermatid development (GO:0007286), Wnt signaling pathway (GO:0016055)

GO Molecular Function (6): chromatin binding (GO:0003682), zinc ion binding (GO:0008270), histone acetyltransferase regulator activity (GO:0035034), histone binding (GO:0042393), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), beta-catenin-TCF complex (GO:1990907), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
anatomical structure development	2
binding	2
renal system development	1
camera-type eye development	1
nucleus organization	1
spermatid development	1
central nervous system development	1
head development	1
gland development	1
mammary gland epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
developmental process	1
growth	1
Wnt signaling pathway	1
germ cell development	1
spermatid differentiation	1
cell surface receptor signaling pathway	1
transition metal ion binding	1
histone acetyltransferase activity	1
enzyme regulator activity	1
histone acetyltransferase binding	1
protein binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
RNA polymerase II transcription regulator complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYGO2	BCL9	O00512	981
PYGO2	CTNNB1	P35222	915
PYGO2	LEF1	Q9UJU2	891
PYGO2	BCL9L	Q86UU0	854
PYGO2	HNF4A	P41235	852
PYGO2	H3-3A	P06351	776
PYGO2	H3C1	P02295	776
PYGO2	H3-4	Q16695	776
PYGO2	H3C14	Q71DI3	775
PYGO2	H3-5	Q6NXT2	775
PYGO2	H3-7	Q5TEC6	775
PYGO2	KAT2B	Q92831	631
PYGO2	KMT2A	Q03164	500
PYGO2	KAT2A	Q92830	499
PYGO2	RBBP5	Q15291	445

IntAct

39 interactions, top by confidence:

A	B	Type	Score
CDC73	CTNNB1	psi-mi:“MI:0914”(association)	0.710
BCL9	PYGO2	psi-mi:“MI:0915”(physical association)	0.690
PYGO2	BCL9	psi-mi:“MI:0914”(association)	0.690
PYGO2	BCL9	psi-mi:“MI:0915”(physical association)	0.690
SORCS3	PYGO2	psi-mi:“MI:0915”(physical association)	0.560
PYGO2	SORCS3	psi-mi:“MI:0915”(physical association)	0.560
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
rep	PYGO2	psi-mi:“MI:0915”(physical association)	0.490
Bcl9l	PYGO2	psi-mi:“MI:0915”(physical association)	0.400
PYGO2	JRK	psi-mi:“MI:0915”(physical association)	0.400
BCL9L	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
gL	PPP1R12B	psi-mi:“MI:0914”(association)	0.350
AR	MED6	psi-mi:“MI:2364”(proximity)	0.270
RAVER1	KDM6A	psi-mi:“MI:2364”(proximity)	0.270
ERG	BCL9	psi-mi:“MI:2364”(proximity)	0.270
ETV4	BCL9	psi-mi:“MI:2364”(proximity)	0.270
IRF4	ARID1A	psi-mi:“MI:2364”(proximity)	0.270
KLF15	TAF4	psi-mi:“MI:2364”(proximity)	0.270
LHX1	ZNF724	psi-mi:“MI:2364”(proximity)	0.270
LHX3	BCL9	psi-mi:“MI:2364”(proximity)	0.270
LHX4	BCL9	psi-mi:“MI:2364”(proximity)	0.270
LHX8	BCL9	psi-mi:“MI:2364”(proximity)	0.270
PAX7	BCL9	psi-mi:“MI:2364”(proximity)	0.270
PAX8	BCL9	psi-mi:“MI:2364”(proximity)	0.270
PAX9	BCL9	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (69): PYGO2 (Affinity Capture-RNA), PYGO2 (Affinity Capture-RNA), CTNNB1 (Affinity Capture-Western), PYGO2 (Co-fractionation), DDB1 (Reconstituted Complex), VPRBP (Reconstituted Complex), DDB1 (Affinity Capture-Western), PYGO2 (Affinity Capture-Western), CUL4A (Affinity Capture-Western), AKT1 (Affinity Capture-Western), PYGO2 (Reconstituted Complex), PYGO2 (Affinity Capture-MS), PYGO2 (Affinity Capture-RNA), PYGO2 (Affinity Capture-MS), PYGO2 (Affinity Capture-MS)

ESM2 similar proteins: A7EYK3, A7SEP9, A8NYM5, A8XW44, C0NN85, C3Z1P5, C5XYW4, C5XZK6, C7YRT4, D0NHA2, D3B3B7, D5GDH4, E0VI98, E3KIY6, E3LAN7, E3X5D6, F4NYQ2, F6HQ26, G3CHK5, O43670, O95104, P90815, Q0P5D2, Q16630, Q16IW3, Q1K7T5, Q298E0, Q4N6K2, Q4UJ14, Q4WQM6, Q56XE4, Q5BBX9, Q5KC16, Q5NVH8, Q5PQQ2, Q5R8K4, Q63627, Q6DDW4, Q6NVF9, Q6NWC6

Diamond homologs: Q9BRQ0, Q9D0P5, Q9V9W8, Q9Y3Y4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Cullin4-RBX1-DDB1	“down-regulates quantity by destabilization”	PYGO2	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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
Deactivation of the beta-catenin transactivating complex	5	46.6×	7e-06
TCF dependent signaling in response to WNT	6	28.3×	7e-06
Signaling by WNT	5	22.4×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	8	15.2×	7e-06
neuron differentiation	5	13.6×	1e-03
chromatin remodeling	5	9.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

270 predictions. Top by Δscore:

Variant	Effect	Δscore
1:154961489:T:TA	donor_gain	1.0000
1:154960991:T:TA	donor_gain	0.9900
1:154961468:GCTCA:G	donor_loss	0.9900
1:154961469:CT:C	donor_loss	0.9900
1:154961470:TCA:T	donor_loss	0.9900
1:154961472:A:AC	donor_gain	0.9900
1:154961473:C:CC	donor_gain	0.9900
1:154961473:CCGG:C	donor_gain	0.9900
1:154961536:C:A	donor_gain	0.9900
1:154959845:CC:C	acceptor_gain	0.9800
1:154959846:CCTAG:C	acceptor_gain	0.9800
1:154961037:G:T	acceptor_gain	0.9800
1:154961472:ACCGG:A	donor_gain	0.9800
1:154961473:CCGGC:C	donor_gain	0.9800
1:154961481:G:A	donor_gain	0.9800
1:154961492:T:TA	donor_gain	0.9800
1:154961493:C:A	donor_gain	0.9800
1:154960966:C:CT	donor_gain	0.9700
1:154960972:TTCA:T	donor_loss	0.9700
1:154960973:TCACC:T	donor_loss	0.9700
1:154960974:CA:C	donor_loss	0.9700
1:154960975:ACC:A	donor_loss	0.9700
1:154960976:C:CT	donor_loss	0.9700
1:154961023:AGACC:A	acceptor_loss	0.9700
1:154961024:GACC:G	acceptor_loss	0.9700
1:154961027:C:CC	acceptor_gain	0.9700
1:154961027:C:CG	acceptor_loss	0.9700
1:154961028:T:A	acceptor_loss	0.9700
1:154961476:G:A	donor_gain	0.9700
1:154961530:C:CT	donor_gain	0.9600

AlphaMissense

2628 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:154958852:A:G	L383P	1.000
1:154958854:G:C	C382W	1.000
1:154958855:C:A	C382F	1.000
1:154958855:C:G	C382S	1.000
1:154958855:C:T	C382Y	1.000
1:154958856:A:C	C382G	1.000
1:154958856:A:G	C382R	1.000
1:154958856:A:T	C382S	1.000
1:154958861:T:A	D380V	1.000
1:154958863:G:C	C379W	1.000
1:154958864:C:A	C379F	1.000
1:154958864:C:G	C379S	1.000
1:154958864:C:T	C379Y	1.000
1:154958865:A:C	C379G	1.000
1:154958865:A:G	C379R	1.000
1:154958865:A:T	C379S	1.000
1:154958867:G:T	A378D	1.000
1:154958868:C:G	A378P	1.000
1:154958869:C:A	W377C	1.000
1:154958869:C:G	W377C	1.000
1:154958870:C:G	W377S	1.000
1:154958871:A:G	W377R	1.000
1:154958871:A:T	W377R	1.000
1:154958873:A:T	V376D	1.000
1:154958876:G:T	A375D	1.000
1:154958877:C:G	A375P	1.000
1:154958884:T:A	E372D	1.000
1:154958884:T:G	E372D	1.000
1:154958894:A:G	L369P	1.000
1:154958894:A:T	L369Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000051262 (1:154963298 T>C), RS1000103307 (1:154963488 C>G), RS1000821281 (1:154956878 A>G), RS1000899186 (1:154961435 C>T), RS1001725976 (1:154962347 G>C), RS1001778390 (1:154962488 G>T), RS1002104060 (1:154961741 C>G,T), RS1002453132 (1:154961792 C>T), RS1002482900 (1:154961981 C>T), RS1002925473 (1:154958416 G>A), RS1003226963 (1:154956928 T>A), RS1003304946 (1:154958123 T>C), RS1003721065 (1:154960076 A>G), RS1003773694 (1:154960417 G>A,T), RS1004459738 (1:154958769 T>C)

Disease associations

OMIM: gene MIM:606903 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001942_19	Prostate cancer	2.000000e-08
GCST003602_3	Inflammatory bowel disease	2.000000e-09
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST008103_81	Bipolar disorder	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3766920	PYGO2, SHC1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	2
Resveratrol	affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases oxidation, increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, increases expression	1
N,N-dimethylaniline	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	increases phosphorylation	1
Indomethacin	affects cotreatment, increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Potassium Dichromate	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW40	K562 eGFP-PYGO2	Cancer cell line	Female

Clinical trials (associated diseases)

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