PYGO1

Summary

PYGO1 (pygopus family PHD finger 1, HGNC:30256) is a protein-coding gene on chromosome 15q21.3, encoding Pygopus homolog 1 (Q9Y3Y4). Involved in signal transduction through the Wnt pathway.

Enables methylated histone binding activity. Predicted to be involved in kidney development and spermatid nucleus differentiation. Predicted to act upstream of or within several processes, including hematopoietic progenitor cell differentiation; positive regulation of transcription by RNA polymerase II; and spermatid development. Predicted to be located in nucleoplasm.

Source: NCBI Gene 26108 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_001367806

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30256
Approved symbol	PYGO1
Name	pygopus family PHD finger 1
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171016
Ensembl biotype	protein_coding
OMIM	606902
Entrez	26108

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000302000, ENST00000563719, ENST00000645724

RefSeq mRNA: 3 — MANE Select: NM_001367806 NM_001330326, NM_001367806, NM_015617

CCDS: CCDS10155, CCDS81885

Canonical transcript exons

ENST00000563719 — 3 exons

Exon	Start	End
ENSE00001163792	55548910	55548995
ENSE00002604692	55587835	55588345
ENSE00002612696	55538884	55547147

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 86.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5378 / max 55.6919, expressed in 1077 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150108	1.2592	797
150107	0.9465	572
150111	0.8372	435
150109	0.4341	271
150110	0.0608	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	86.21	gold quality
ventricular zone	UBERON:0003053	83.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.93	gold quality
ganglionic eminence	UBERON:0004023	82.78	gold quality
gastrocnemius	UBERON:0001388	82.70	gold quality
muscle of leg	UBERON:0001383	82.34	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.56	gold quality
biceps brachii	UBERON:0001507	80.17	gold quality
calcaneal tendon	UBERON:0003701	79.77	gold quality
skeletal muscle organ	UBERON:0014892	79.69	gold quality
muscle organ	UBERON:0001630	79.68	gold quality
stromal cell of endometrium	CL:0002255	78.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.50	gold quality
skeletal muscle tissue	UBERON:0001134	75.24	gold quality
colonic epithelium	UBERON:0000397	72.88	silver quality
left ovary	UBERON:0002119	72.76	gold quality
endometrium epithelium	UBERON:0004811	72.59	gold quality
right ovary	UBERON:0002118	72.51	gold quality
tendon	UBERON:0000043	72.37	gold quality
smooth muscle tissue	UBERON:0001135	72.33	gold quality
body of uterus	UBERON:0009853	72.16	gold quality
cerebellar cortex	UBERON:0002129	71.75	gold quality
cerebellar hemisphere	UBERON:0002245	71.68	gold quality
muscle tissue	UBERON:0002385	71.66	gold quality
quadriceps femoris	UBERON:0001377	71.53	silver quality
lower esophagus muscularis layer	UBERON:0035833	71.46	gold quality
vastus lateralis	UBERON:0001379	71.43	silver quality
lower esophagus	UBERON:0013473	71.41	gold quality
muscle layer of sigmoid colon	UBERON:0035805	71.39	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-89	no	118.34
E-ANND-3	no	5.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

265 targeting PYGO1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170

Literature-anchored findings (GeneRIF, showing 2)

• Data show that human and Drosophila Pygo PHD fingers associate with their cognate HD1 domains from BCL9/Legless to bind specifically to the histone H3 tail methylated at lysine 4 (H3K4me). (PMID:18498752)
• Pygo1 Regulates the Behavior of Human Non-Small-Cell Lung Cancer via the Wnt/beta-Catenin Pathway. (PMID:36398031)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pygo1	ENSDARG00000098687
mus_musculus	Pygo1	ENSMUSG00000034910
rattus_norvegicus	Pygo1	ENSRNOG00000066086
drosophila_melanogaster	pygo	FBGN0043900
caenorhabditis_elegans		WBGENE00015330

Paralogs (1): PYGO2 (ENSG00000163348)

Protein

Protein identifiers

Pygopus homolog 1 — Q9Y3Y4 (reviewed: Q9Y3Y4)

All UniProt accessions (1): Q9Y3Y4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in signal transduction through the Wnt pathway.

Subunit / interactions. Interacts with BCL9 via The PHD-type zinc finger motiv, and thereby becomes part of the nuclear beta-catenin/TCF complex. Identified in a complex with BCL9L, CDC73, CTNNB1 and PYGO1. Interacts with histone H3 mono-, di- or tri-methylated at ‘Lys4’ (H3K4me1, H3K4me2, H3K4me3); the interaction is enhanced by the interaction with BCL9.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y3Y4-1	1	yes
Q9Y3Y4-2	2

RefSeq proteins (3): NP_001317255, NP_001354735, NP_056432 (=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 (31 total): mutagenesis site 8, compositionally biased region 5, region of interest 4, strand 4, helix 3, turn 2, chain 1, zinc finger region 1, splice variant 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2VPB	X-RAY DIFFRACTION	1.59
2VPG	X-RAY DIFFRACTION	1.6
2VP7	X-RAY DIFFRACTION	1.65
2VPE	X-RAY DIFFRACTION	1.7
2VPD	X-RAY DIFFRACTION	2.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3Y4-F1	55.06	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (8):

Position	Phenotype
349	reduces interaction with h3k4me2.
350	almost complete loss of interaction with h3k4me2.
351	reduces interaction with h3k4me2.
354	reduces interaction with h3k4me2.
356	almost complete loss of interaction with h3k4me2.
357	loss of interaction with h3k4me2.
360	loss of interaction with h3k4me2.
366	loss of interaction with h3k4me2.

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: 124 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_MALE_GAMETE_GENERATION, CEBP_Q2, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_NUCLEUS_ORGANIZATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_SPERMATID_NUCLEUS_DIFFERENTIATION, AACTTT_UNKNOWN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_PROTEIN_LOCALIZATION_TO_NUCLEUS, HATADA_METHYLATED_IN_LUNG_CANCER_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, CACBINDINGPROTEIN_Q6, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II

GO Biological Process (9): kidney development (GO:0001822), hematopoietic progenitor cell differentiation (GO:0002244), spermatid nucleus differentiation (GO:0007289), protein localization to nucleus (GO:0034504), positive regulation of transcription by RNA polymerase II (GO:0045944), canonical Wnt signaling pathway (GO:0060070), chromatin organization (GO:0006325), spermatid development (GO:0007286), Wnt signaling pathway (GO:0016055)

GO Molecular Function (4): zinc ion binding (GO:0008270), histone H3K4me3 reader activity (GO:0140002), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleoplasm (GO:0005654), 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	1
renal system development	1
hemopoiesis	1
cell differentiation	1
nucleus organization	1
spermatid development	1
protein localization to organelle	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
Wnt signaling pathway	1
cellular component organization	1
germ cell development	1
spermatid differentiation	1
cell surface receptor signaling pathway	1
transition metal ion binding	1
histone H3 reader activity	1
binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYGO1	BCL9	O00512	984
PYGO1	CTNNB1	P35222	858
PYGO1	LEF1	Q9UJU2	818
PYGO1	HNF4A	P41235	802
PYGO1	BCL9L	Q86UU0	798
PYGO1	H3C1	P02295	636
PYGO1	H3-4	Q16695	635
PYGO1	H3-3A	P06351	634
PYGO1	H3-7	Q5TEC6	634
PYGO1	H3-5	Q6NXT2	634
PYGO1	H3C14	Q71DI3	634
PYGO1	KMT2A	Q03164	517
PYGO1	EP300	Q09472	508
PYGO1	CREBBP	Q92793	479
PYGO1	SRCAP	Q6ZRS2	456

IntAct

31 interactions, top by confidence:

A	B	Type	Score
PYGO1	BCL9	psi-mi:“MI:0914”(association)	0.700
PYGO1	BCL9	psi-mi:“MI:0407”(direct interaction)	0.700
BCL9	PYGO1	psi-mi:“MI:0407”(direct interaction)	0.700
BCL9	PYGO1	psi-mi:“MI:0915”(physical association)	0.700
PYGO1	BCL9	psi-mi:“MI:0915”(physical association)	0.700
B2M	PYGO1	psi-mi:“MI:0915”(physical association)	0.560
CALR	PYGO1	psi-mi:“MI:0915”(physical association)	0.560
DLST	PYGO1	psi-mi:“MI:0915”(physical association)	0.560
TP53BP2	PYGO1	psi-mi:“MI:0915”(physical association)	0.560
PYGO1	NEK7	psi-mi:“MI:0915”(physical association)	0.560
BCL9		psi-mi:“MI:0407”(direct interaction)	0.440
PYGO1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
PYGO1	lgs	psi-mi:“MI:0915”(physical association)	0.400
CARM1	PYGO1	psi-mi:“MI:0915”(physical association)	0.370
PRMT6	PYGO1	psi-mi:“MI:0915”(physical association)	0.370
SP7	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
TLX1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
LENG8	PYGO1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): UBR5 (Affinity Capture-Western), BCL9 (Reconstituted Complex), PYGO1 (Synthetic Lethality), PYGO1 (Affinity Capture-MS), PYGO1 (Affinity Capture-Western), BCL9 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), LDB1 (Affinity Capture-MS), SSBP3 (Affinity Capture-MS), BCL9 (Affinity Capture-MS), SSBP2 (Affinity Capture-MS), PYGO1 (Affinity Capture-MS), ORC6 (Affinity Capture-MS), BCL9L (Affinity Capture-MS), ISL2 (Affinity Capture-MS)

ESM2 similar proteins: A3RK75, A5X7A0, A7XYH5, A7XYH9, A7XYI6, A7XYQ1, E7F888, E9PT37, E9Q2Z1, P0DW16, P48634, P61129, P79522, P98177, Q08D57, Q0P5V2, Q1LY77, Q1RNF8, Q3UQS8, Q4R7I8, Q5F3P8, Q5JSZ5, Q5T481, Q5TM26, Q5VK71, Q63014, Q66J90, Q6MG07, Q6MG48, Q6PJG2, Q75N03, Q767L1, Q7TPM1, Q7TSC1, Q7YR36, Q811B5, Q8BYK8, Q8C208, Q8CFT2, Q96EV2

Diamond homologs: Q9BRQ0, Q9D0P5, Q9V9W8, Q9Y3Y4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BCL9	up-regulates	PYGO1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

504 predictions. Top by Δscore:

Variant	Effect	Δscore
15:55548904:GTTTA:G	donor_loss	1.0000
15:55548905:TTTAC:T	donor_loss	1.0000
15:55548906:TTA:T	donor_loss	1.0000
15:55548907:TAC:T	donor_loss	1.0000
15:55548908:ACCTG:A	donor_loss	1.0000
15:55548909:C:CG	donor_loss	1.0000
15:55548992:CCAC:C	acceptor_gain	1.0000
15:55548993:CACC:C	acceptor_gain	1.0000
15:55548996:C:CA	acceptor_loss	1.0000
15:55548996:C:CC	acceptor_gain	1.0000
15:55548997:T:A	acceptor_loss	1.0000
15:55547146:CC:C	acceptor_gain	0.9900
15:55547147:CC:C	acceptor_gain	0.9900
15:55547148:C:CC	acceptor_gain	0.9900
15:55548993:CAC:C	acceptor_gain	0.9900
15:55587830:GTTA:G	donor_loss	0.9900
15:55587833:ACCT:A	donor_loss	0.9900
15:55587834:CCTCG:C	donor_loss	0.9900
15:55547149:T:A	acceptor_loss	0.9800
15:55548920:G:A	donor_gain	0.9700
15:55548938:T:C	donor_gain	0.9700
15:55548624:TCA:T	donor_gain	0.9600
15:55576816:A:C	donor_gain	0.9600
15:55546595:C:CT	acceptor_gain	0.9500
15:55547143:GGTCC:G	acceptor_gain	0.9500
15:55547145:TCC:T	acceptor_gain	0.9500
15:55547146:CCC:C	acceptor_gain	0.9500
15:55553829:C:CT	donor_gain	0.9500
15:55587836:TCGA:T	donor_gain	0.9500
15:55547159:A:AC	acceptor_gain	0.9400

AlphaMissense

2785 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:55546108:C:G	C392S	1.000
15:55546108:C:T	C392Y	1.000
15:55546109:A:G	C392R	1.000
15:55546109:A:T	C392S	1.000
15:55546113:C:A	W390C	1.000
15:55546113:C:G	W390C	1.000
15:55546115:A:G	W390R	1.000
15:55546115:A:T	W390R	1.000
15:55546138:A:G	L382S	1.000
15:55546141:A:G	L381P	1.000
15:55546150:G:T	A378D	1.000
15:55546162:A:G	M374T	1.000
15:55546170:A:C	C371W	1.000
15:55546171:C:A	C371F	1.000
15:55546171:C:G	C371S	1.000
15:55546171:C:T	C371Y	1.000
15:55546172:A:G	C371R	1.000
15:55546172:A:T	C371S	1.000
15:55546177:C:G	R369P	1.000
15:55546179:A:C	H368Q	1.000
15:55546179:A:T	H368Q	1.000
15:55546181:G:C	H368D	1.000
15:55546181:G:T	H368N	1.000
15:55546182:A:C	F367L	1.000
15:55546182:A:T	F367L	1.000
15:55546183:A:C	F367C	1.000
15:55546183:A:G	F367S	1.000
15:55546184:A:G	F367L	1.000
15:55546185:C:A	W366C	1.000
15:55546185:C:G	W366C	1.000

dbSNP variants (sampled 300 via entrez): RS1000039991 (15:55545578 C>T), RS1000085955 (15:55583856 C>T), RS1000086479 (15:55583126 A>G), RS1000150414 (15:55582550 T>A,C,G), RS1000163234 (15:55565696 AGAGT>A), RS1000187377 (15:55563738 T>A), RS1000203132 (15:55578450 G>A,T), RS1000216865 (15:55540017 A>G), RS1000297408 (15:55551347 T>C), RS1000319618 (15:55578254 A>G), RS1000447613 (15:55572473 A>T), RS1000547033 (15:55579912 A>G), RS1000578151 (15:55579575 G>A), RS1000591537 (15:55559859 C>T), RS1000629263 (15:55567660 T>A,G)

Disease associations

OMIM: gene MIM:606902 | 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
GCST010703_182	Brain morphology (MOSTest)	5.000000e-11
GCST90000025_214	Appendicular lean mass	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	decreases phosphorylation	1
geldanamycin	increases expression	1
sodium arsenite	increases expression, increases abundance	1
butyraldehyde	decreases expression	1
diallyl trisulfide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arsenic	increases abundance, increases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Vanadates	decreases expression	1
Zinc	decreases expression	1
Silver Compounds	increases expression	1
Antirheumatic Agents	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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