PCGF3

Summary

PCGF3 (polycomb group ring finger 3, HGNC:10066) is a protein-coding gene on chromosome 4p16.3, encoding Polycomb group RING finger protein 3 (Q3KNV8). Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.

The protein encoded by this gene contains a C3HC4 type RING finger, which is a motif known to be involved in protein-protein interactions. The specific function of this protein has not yet been determined.

Source: NCBI Gene 10336 — RefSeq curated summary.

At a glance

• GWAS associations: 25 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 41 total
• GTEx eGene: eQTL in 50 tissues, sQTL in 47 (q < 0.05)
• Constraint (gnomAD): pLI 0.97 (loss-of-function intolerant), LOEUF 0.50 (moderately constrained)
• MANE Select transcript: NM_006315

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10066
Approved symbol	PCGF3
Name	polycomb group ring finger 3
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36550, DONG1, RNF3A, MGC40413
Ensembl gene	ENSG00000185619
Ensembl biotype	protein_coding
OMIM	617543
Entrez	10336

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 34 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000362003

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 4, TSL 3: 2, TSL 4: 3, TSL 5: 2

ENST00000362003, ENST00000400151, ENST00000419774, ENST00000427463, ENST00000430644, ENST00000433814, ENST00000440452, ENST00000470161, ENST00000475288, ENST00000482726, ENST00000484141, ENST00000488032, ENST00000620529, ENST00000870362, ENST00000870363, ENST00000870364, ENST00000917776, ENST00000917777, ENST00000954672, ENST00000954673, ENST00000954674, ENST00000954675, ENST00000954676, ENST00000954677, ENST00000954678, ENST00000954679, ENST00000954680, ENST00000954681, ENST00001000514, ENST00001053290, ENST00001053291, ENST00001104883, ENST00001104884, ENST00001104885, ENST00001118725, ENST00001118726, ENST00001118727, ENST00001118728, ENST00001126010, ENST00001126011, ENST00001126012, ENST00001126013, ENST00001138550

RefSeq mRNA: 9 — MANE Select: NM_006315 NM_001317836, NM_001395245, NM_001395246, NM_001395247, NM_001395248, NM_001395249, NM_001395250, NM_001395251, NM_006315

CCDS: CCDS3339

Canonical transcript exons

ENST00000362003 — 11 exons

Exon	Start	End
ENSE00001354120	730970	731110
ENSE00001354124	730630	730668
ENSE00003495438	734931	735027
ENSE00003543410	733672	733789
ENSE00003569995	743474	743584
ENSE00003580193	744600	744688
ENSE00003633495	761279	761416
ENSE00003654200	737466	737521
ENSE00003669111	764984	765064
ENSE00003978152	705832	705970
ENSE00003978153	766032	770089

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6190 / max 137.5056, expressed in 1813 samples.

Highest expression (Bgee): sural nerve, ovary, lower esophagus mucosa, skin of abdomen, skin of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PCGF3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 50 tissues and its splicing (sQTL) in 47 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 97 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	3.7e-130	-0.89	4:732533:G:A
Skin Sun Exposed Lower leg	eqtl	4.6e-115	-0.71	4:732533:G:A
Nerve Tibial	eqtl	1.9e-109	-0.87	4:732533:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.6e-101	-0.67	4:732533:G:A
Lung	eqtl	3.1e-87	-0.70	4:732533:G:A
Skin Sun Exposed Lower leg	sqtl	1.2e-85	+1.02	4:732533:G:A
Breast Mammary Tissue	eqtl	1.2e-81	-0.85	4:732533:G:A
Artery Tibial	eqtl	3.0e-81	-0.60	4:732533:G:A
Whole Blood	eqtl	1.4e-77	-0.48	4:789526:A:G
Adipose Visceral Omentum	eqtl	1.1e-76	-0.82	4:732533:G:A
Muscle Skeletal	eqtl	2.2e-75	-0.56	4:732533:G:A
Thyroid	eqtl	1.3e-73	-0.65	4:732533:G:A
Esophagus Muscularis	eqtl	1.3e-72	-0.68	4:732533:G:A
Skin Not Sun Exposed Suprapubic	sqtl	9.5e-69	+1.01	4:732533:G:A
Artery Aorta	eqtl	4.8e-63	-0.72	4:732533:G:A
Colon Transverse	eqtl	3.7e-62	-0.70	4:732533:G:A
Esophagus Mucosa	eqtl	5.7e-61	-0.68	4:732533:G:A
Esophagus Mucosa	sqtl	1.3e-57	+1.09	4:732533:G:A
Whole Blood	sqtl	1.1e-56	+0.96	4:732533:G:A
Heart Atrial Appendage	eqtl	6.9e-56	-0.68	4:732533:G:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
46515	11.7034	1803
46514	10.2795	1792
46516	0.6173	344
46517	0.0123	5
46518	0.0065	3

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.36	gold quality
left ovary	UBERON:0002119	96.26	gold quality
lower esophagus mucosa	UBERON:0035834	96.02	gold quality
skin of abdomen	UBERON:0001416	95.76	gold quality
skin of leg	UBERON:0001511	95.64	gold quality
right ovary	UBERON:0002118	95.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.55	gold quality
cerebellar hemisphere	UBERON:0002245	95.50	gold quality
cerebellar cortex	UBERON:0002129	95.22	gold quality
granulocyte	CL:0000094	95.21	gold quality
endocervix	UBERON:0000458	95.14	gold quality
body of uterus	UBERON:0009853	95.14	gold quality
right lobe of thyroid gland	UBERON:0001119	95.12	gold quality
right lung	UBERON:0002167	95.06	gold quality
minor salivary gland	UBERON:0001830	94.90	gold quality
cortical plate	UBERON:0005343	94.89	gold quality
right adrenal gland cortex	UBERON:0035827	94.86	gold quality
left lobe of thyroid gland	UBERON:0001120	94.80	gold quality
ganglionic eminence	UBERON:0004023	94.66	gold quality
ectocervix	UBERON:0012249	94.61	gold quality
cerebellum	UBERON:0002037	94.54	gold quality
right uterine tube	UBERON:0001302	94.49	gold quality
tibia	UBERON:0000979	94.48	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.48	gold quality
left uterine tube	UBERON:0001303	94.32	gold quality
ovary	UBERON:0000992	94.30	gold quality
left adrenal gland cortex	UBERON:0035825	94.22	gold quality
tibial nerve	UBERON:0001323	94.21	gold quality
zone of skin	UBERON:0000014	94.18	gold quality
spleen	UBERON:0002106	94.16	gold quality
vagina	UBERON:0000996	94.06	gold quality
adrenal cortex	UBERON:0001235	93.97	gold quality
thyroid gland	UBERON:0002046	93.89	gold quality
transverse colon	UBERON:0001157	93.85	gold quality
left adrenal gland	UBERON:0001234	93.85	gold quality
right adrenal gland	UBERON:0001233	93.83	gold quality
body of stomach	UBERON:0001161	93.71	gold quality
mouth mucosa	UBERON:0003729	93.46	gold quality
adenohypophysis	UBERON:0002196	93.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.41	gold quality
adrenal gland	UBERON:0002369	93.40	gold quality
small intestine	UBERON:0002108	93.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.14	gold quality
omental fat pad	UBERON:0010414	93.08	gold quality
peritoneum	UBERON:0002358	93.07	gold quality
lower esophagus	UBERON:0013473	93.04	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.03	gold quality
esophagus mucosa	UBERON:0002469	93.02	gold quality
fundus of stomach	UBERON:0001160	93.01	gold quality
saliva-secreting gland	UBERON:0001044	92.87	gold quality
esophagus	UBERON:0001043	92.86	gold quality
stomach	UBERON:0000945	92.84	gold quality
apex of heart	UBERON:0002098	92.77	gold quality
upper lobe of left lung	UBERON:0008952	92.71	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.70	gold quality
pituitary gland	UBERON:0000007	92.66	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.57	gold quality
body of pancreas	UBERON:0001150	92.55	gold quality
adrenal tissue	UBERON:0018303	92.29	gold quality
upper lobe of lung	UBERON:0008948	92.15	gold quality
metanephros cortex	UBERON:0010533	92.07	gold quality
mucosa of stomach	UBERON:0001199	92.03	gold quality
upper leg skin	UBERON:0004262	91.95	gold quality
skin of hip	UBERON:0001554	91.80	gold quality
stromal cell of endometrium	CL:0002255	91.57	gold quality
female reproductive system	UBERON:0000474	91.53	gold quality
descending thoracic aorta	UBERON:0002345	91.53	gold quality
ascending aorta	UBERON:0001496	91.51	gold quality
thoracic aorta	UBERON:0001515	91.48	gold quality
right atrium auricular region	UBERON:0006631	91.46	gold quality
intestine	UBERON:0000160	91.41	gold quality
sigmoid colon	UBERON:0001159	91.36	gold quality
myometrium	UBERON:0001296	91.36	gold quality
colon	UBERON:0001155	91.33	gold quality
left coronary artery	UBERON:0001626	91.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.14	gold quality
uterus	UBERON:0000995	91.09	gold quality
prostate gland	UBERON:0002367	91.08	gold quality
cartilage tissue	UBERON:0002418	91.02	gold quality
aorta	UBERON:0000947	90.97	gold quality
large intestine	UBERON:0000059	90.86	gold quality
coronary artery	UBERON:0001621	90.73	gold quality
mucosa of transverse colon	UBERON:0004991	90.67	gold quality
tibial artery	UBERON:0007610	90.64	gold quality
popliteal artery	UBERON:0002250	90.63	gold quality
right lobe of liver	UBERON:0001114	90.41	gold quality
monocyte	CL:0000576	90.34	gold quality
adipose tissue	UBERON:0001013	90.27	gold quality
right coronary artery	UBERON:0001625	90.25	gold quality
mononuclear cell	CL:0000842	90.18	gold quality
right frontal lobe	UBERON:0002810	90.15	gold quality
endometrium	UBERON:0001295	90.12	gold quality
anatomical system	UBERON:0000467	90.09	gold quality
connective tissue	UBERON:0002384	90.06	gold quality
cardiac atrium	UBERON:0002081	89.92	gold quality
multicellular organism	UBERON:0000468	89.91	gold quality
material anatomical entity	UBERON:0000465	89.88	gold quality
leukocyte	CL:0000738	89.85	gold quality
pylorus	UBERON:0001166	89.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.57

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	52.4	high
Prefrontal cortex	tissue	41.6
Cerebral cortex	tissue	41.6	medium
Somatosensory cortex	tissue	41.0
Motor cortex	tissue	39.9
Hippocampal formation	tissue	39.3
Entorhinal cortex	tissue	39.3
Occipital cortex	tissue	38.7
Temporal cortex	tissue	38.6
Vagina	tissue	38.0	high
Nucleus accumbens	tissue	36.8
Insular cortex	tissue	36.7
Retrosplenial and cingulate cortex	tissue	36.5
Hippocampus	tissue	36.2	medium
Choroid plexus	tissue	35.1
Retrosplenial cortex	tissue	34.6
Putamen	tissue	34.1
Amygdala	tissue	33.2
Ventral forebrain	tissue	33.2
Basal ganglia	tissue	32.7	not detected
Pituitary gland	tissue	31.2
Olfactory bulb	tissue	31.0
Locus coeruleus	tissue	30.4
Postcentral gyrus	tissue	30.4
Corpus callosum	tissue	30.0
Thalamus	tissue	29.8
Septum	tissue	29.7
Midbrain	tissue	29.1
Pons	tissue	28.4
Bone marrow	tissue	28.3	not detected
Superior colliculi	tissue	27.9
Hypothalamus	tissue	27.0
Substantia nigra	tissue	26.6
Medulla oblongata	tissue	25.0
Cerebellum	tissue	24.4	low
Spinal cord	tissue	24.3
Periaqueductal gray	tissue	23.8
Adrenal gland	tissue	22.7	high
Duodenum	tissue	21.0	high
Spleen	tissue	20.8	high
Small intestine	tissue	20.2	high
Placenta	tissue	19.2	high
Ovary	tissue	18.4	high
Stomach 1	tissue	18.1	medium
Lymph node	tissue	17.9	high
Endometrium 1	tissue	17.8	high
Thymus	tissue	17.4
Salivary gland	tissue	17.3	high
Prostate	tissue	14.9	high
Esophagus	tissue	14.8	high
Appendix	tissue	14.8	high
Adipose tissue	tissue	14.6	not detected
Gallbladder	tissue	14.1	high
Skeletal muscle	tissue	13.4	high
Retina	tissue	12.8
Breast	tissue	12.7	high
Frontal cortex	tissue	12.7
Urinary bladder	tissue	12.6	high
Colon	tissue	12.5	high
Heart muscle	tissue	12.4	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Flocculonodular lobe (64.5), Vermis (60.9), Cerebellar cortex (60.7), Parieto-temporal junction (white matter) (48.8), Temporal white matter (47.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PCGF3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 231 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
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-574-5P	100.00	66.01	989
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
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-4262	100.00	73.26	3931
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1184	99.99	68.19	1458

Functional genomics

gnomAD constraint: pLI 0.971, LOEUF 0.5, missense Z 1.79 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000362003 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
4:733,681–737,506	53 / 106.5	0.50	no
4:737,507–744,665	95 / 83.0	1.14	no
4:744,666–766,076	63 / 123.8	0.51	no

Literature-anchored findings (GeneRIF, showing 3)

• We demonstrate that promoter binding by TRF2 mediates PCGF3 promoter activity, and both the N-terminal and C-terminal domains of TRF2 are necessary for promoter activity. (PMID:29589913)
• PNPT1 and PCGF3 variants associated with angiotensin-converting enzyme inhibitor-induced cough: a nested case-control genome-wide study. (PMID:32397904)
• PCGF3 promotes the proliferation and migration of non-small cell lung cancer cells via the PI3K/AKT signaling pathway. (PMID:33485844)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pcgf3	ENSMUSG00000033623
rattus_norvegicus	Pcgf3	ENSRNOG00000000062
drosophila_melanogaster	l(3)73Ah	FBGN0002283
caenorhabditis_elegans		WBGENE00008684

Paralogs (7): PCGF1 (ENSG00000115289), RNF2 (ENSG00000121481), PCGF6 (ENSG00000156374), BMI1 (ENSG00000168283), PCGF5 (ENSG00000180628), RING1 (ENSG00000204227), PCGF2 (ENSG00000277258)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1916837) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.

Mouse phenotype (MP)	Records
cleft palate	1
polydactyly	1
syndactyly	1
microphthalmia	1
hyperactivity	1
abnormal embryo size	1
abnormal limb morphology	1
abnormal tail morphology	1
abnormal facial morphology	1
facial cleft	1
decreased prepulse inhibition	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R8L2	100.0%	Diamond
Felis catus	Q9TST0	99.4%	Diamond
Bos taurus	Q32KX7	99.1%	Diamond
Xenopus tropicalis	Q28H21	98.1%	Diamond
Xenopus laevis	Q4QR06	98.1%	Diamond
Gallus gallus	Q5SDR3	88.3%	Diamond
Danio rerio	Q8JIR0	81.8%	Diamond
Arabidopsis thaliana	Q94AY3	67.1%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CTZ8	47.7%	Diamond
Eremothecium gossypii ATCC 10895	Q75EN0	45.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CPLX1-AS1	ncRNA	105374339
CPLX1	protein-coding	10815
PCGF3-AS1	ncRNA	100129917
GAK-AS1	protein-coding	105374341
GAK	protein-coding	2580
TMEM175	protein-coding	84286
SLC49A3-AS1	ncRNA	124900643
PCGF3-AS2	ncRNA	138842257
SLC49A3	protein-coding	84179
MYL5	protein-coding	4636
ATP5ME	protein-coding	521
PDE6B-AS1	ncRNA	101928521
PDE6B	protein-coding	5158

Protein

Protein identifiers

Polycomb group RING finger protein 3 — Q3KNV8 (reviewed: Q3KNV8)

Alternative names: RING finger protein 3A

All UniProt accessions (7): A0A087WVH5, B5MEC4, C9J3G7, C9JGV3, C9JYD0, Q3KNV8, F2Z3P3

UniProt curated annotations — full annotation on UniProt →

Function. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A ‘Lys-119’, rendering chromatin heritably changed in its expressibility. Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity. Plays a redundant role with PCGF5 as part of a PRC1-like complex that mediates monoubiquitination of histone H2A ‘Lys-119’ on the X chromosome and is required for normal silencing of one copy of the X chromosome in XX females.

Subunit / interactions. Component of a PRC1-like complex that contains PCGF3, RNF2 and RYBP. Interacts with CBX6, CBX7 and CBX8. Interacts with BCORL1.

Subcellular location. Nucleus. Nucleoplasm.

Isoforms (2)

UniProt ID	Names	Canonical?
Q3KNV8-1	1	yes
Q3KNV8-2	2

RefSeq proteins (9): NP_001304765, NP_001382174, NP_001382175, NP_001382176, NP_001382177, NP_001382178, NP_001382179, NP_001382180, NP_006306* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR032443	RAWUL	Domain
IPR051507	PCGF	Family

Pfam: PF13923, PF16207

UniProt features (6 total): region of interest 2, chain 1, zinc finger region 1, compositionally biased region 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3KNV8-F1	85.76	0.75

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 197 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, TTTGTAG_MIR520D, TATTATA_MIR374, BROWNE_HCMV_INFECTION_16HR_UP, MODULE_503, CCATCCA_MIR432, LI_WILMS_TUMOR_ANAPLASTIC_UP, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, BROWNE_HCMV_INFECTION_24HR_UP, ONKEN_UVEAL_MELANOMA_UP, MODULE_195, GENTILE_UV_RESPONSE_CLUSTER_D2, GENTILE_UV_HIGH_DOSE_DN, chr4p16, MODULE_147

GO Biological Process (5): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), heterochromatin formation (GO:0031507), positive regulation of DNA-templated transcription (GO:0045893), random inactivation of X chromosome (GO:0060816)

GO Molecular Function (4): zinc ion binding (GO:0008270), histone H2AK119 ubiquitin ligase activity (GO:0140862), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), X chromosome (GO:0000805), nucleus (GO:0005634), nucleoplasm (GO:0005654), PcG protein complex (GO:0031519), PRC1 complex (GO:0035102)

GO top-level categories

23 GO namespaces:

Category	Terms
regulation of DNA-templated transcription	2
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
transcription by RNA polymerase II	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
dosage compensation by inactivation of X chromosome	1
transition metal ion binding	1
histone H2A ubiquitin ligase activity	1
binding	1
cation binding	1
chromosome	1
sex chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
nuclear ubiquitin ligase complex	1
PcG protein complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
PcG protein complex	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 675 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCGF3	ZNRF3	Q9ULT6	962
PCGF3	RING1	Q06587	866
PCGF3	YAF2	Q8IY57	731
PCGF3	RYBP	Q8N488	723
PCGF3	AUTS2	Q8WXX7	702
PCGF3	RNF5	Q99942	629
PCGF3	FBRS	Q9HAH7	628
PCGF3	KDM2B	Q8NHM5	584
PCGF3	HNRNPK	P61978	578
PCGF3	CBX7	O95931	568
PCGF3	CBX2	Q14781	550
PCGF3	PHC1	P78364	548
PCGF3	CBX6	O95503	535
PCGF3	PCGF1	Q9BSM1	518
PCGF3	PCGF5	Q86SE9	517

IntAct

Human interaction partners of PCGF3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

25 partners by confidence:

Partner	Interaction type	MIscore	Records
RING1	physical association	0.720	2
RNF2	physical association	0.720	2
CBX8	physical association	0.690	2
CBX7	physical association	0.660	2
BCOR	physical association	0.560	3
PHC2	physical association	0.560	3
CBX6	physical association	0.540	2
HSP90AB1	physical association	0.400	1
BMI1	physical association	0.370	1
DZIP3	physical association	0.370	1
TRIM9	physical association	0.370	1
UBE2C	physical association	0.370	1
MBL2	association	0.350	1
PFDN6	association	0.350	1
POTEI	association	0.350	1
ARID3A	physical association	0.000	1
CREBBP	physical association	0.000	1
EIF4ENIF1	physical association	0.000	1
FBRS	physical association	0.000	1
HELZ	physical association	0.000	1
MARF1	physical association	0.000	1
NISCH	physical association	0.000	1
PAN2	physical association	0.000	1
RB1	physical association	0.000	1
SOWAHA	physical association	0.000	1

BioGRID (182 interactions; top human partners by supporting records): CSNK2A2 (Affinity Capture-MS; 11 records), RNF2 (Affinity Capture-MS; 11 records), CSNK2A1 (Affinity Capture-MS; 8 records), RYBP (Affinity Capture-MS; 8 records), YAF2 (Affinity Capture-MS; 7 records), RING1 (Affinity Capture-MS; 6 records), BCORL1 (Reconstituted Complex; 5 records), CBX7 (Affinity Capture-MS; 5 records), CBX8 (Affinity Capture-MS; 5 records), CSNK2B (Affinity Capture-MS; 5 records), DCAF7 (Affinity Capture-MS; 5 records), BCOR (Two-hybrid; 4 records), FBRS (Affinity Capture-MS; 4 records), AUTS2 (Affinity Capture-MS; 3 records), BMI1 (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	PCGF3	ubiquitination

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
PRC1.3a complex	10	RING1, CSNK2A1, FBRSL1, RNF2, RYBP, AUTS2, CSNK2A2, CSNK2B, FBRS, PCGF3
PRC1.3b complex	10	AUTS2, FBRS, FBRSL1, RING1, CSNK2A1, CSNK2A2, CSNK2B, PCGF3, RNF2, YAF2
PCGF3-RING1A complex	2	RING1, PCGF3
PCGF3-RING1B complex	2	RNF2, PCGF3

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
SUMOylation of DNA methylation proteins	5	197.6×	2e-09
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	6	106.1×	1e-09
SUMOylation of transcription cofactors	6	85.8×	2e-09
SUMOylation of RNA binding proteins	5	70.0×	2e-07
Regulation of PTEN gene transcription	6	63.0×	1e-08
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	60.3×	1e-09
SUMOylation of chromatin organization proteins	5	46.6×	1e-06
SUMOylation of DNA damage response and repair proteins	5	43.1×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	5	15.9×	2e-03

Disease & clinical

Genetic variants

Variant evidence for PCGF3: 41 ClinVar records (0 pathogenic / likely pathogenic); 25 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 39 predictions of 1,813):

Position(s)	Effect	Δscore	Sites
4:730628–730629	acceptor_loss	1.0000	6
4:730669–730670	donor_loss	1.0000	5
4:733670–733671	acceptor_loss	1.0000	6
4:733817	donor_gain	1.0000
4:744596	acceptor_gain	1.0000
4:744598–744599	acceptor_loss	1.0000	3
4:744689–744690	donor_loss	1.0000	5
4:705971–705972	donor_loss	0.9900	5
4:733937	donor_gain	0.9900
4:735028–735029	donor_loss	0.9900	6

AlphaMissense

1,068 missense substitutions predicted likely pathogenic (of 1,616 scored), across 190 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M74	9	0.890	0.997
H60	8	1.000	1.000
D71	8	1.000	1.000
H35	8	0.999	1.000
D213	8	0.999	1.000
H214	8	0.999	1.000
H149	8	0.996	1.000
F218	8	0.996	1.000
D152	8	0.995	0.999
S62	8	0.992	1.000
D202	8	0.991	0.999
H184	8	0.989	1.000
D76	8	0.988	0.999
H63	8	0.981	1.000
F37	8	0.979	1.000
D26	8	0.978	0.998
F188	8	0.955	1.000
D147	8	0.950	0.990
F96	8	0.945	1.000
N206	8	0.920	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:617543 | disease phenotypes:

GWAS associations

25 associations:

Study	Trait	p-value
GCST90002394_193	Monocyte percentage of white cells	5e-28
GCST90002398_162	Neutrophil count	8e-28
GCST90002407_64	White blood cell count	6e-22
GCST90002399_410	Neutrophil percentage of white cells	4e-17
GCST006979_64	Heel bone mineral density	6e-17
GCST010118_84	Type 2 diabetes	3e-16
GCST009379_176	Type 2 diabetes	4e-14
GCST004629_10	Neutrophil count	1e-11
GCST004608_83	Granulocyte percentage of myeloid white cells	2e-11
GCST004620_80	Sum basophil neutrophil counts	2e-11
GCST004613_97	Sum neutrophil eosinophil counts	4e-11
GCST004614_89	Granulocyte count	7e-11
GCST004609_45	Monocyte percentage of white cells	2e-10
GCST90000025_935	Appendicular lean mass	3e-10
GCST004626_99	Myeloid white cell count	1e-9
GCST011769_6	Schizophrenia	2e-9
GCST004610_139	White blood cell count	5e-9
GCST005316_267	Intelligence (MTAG)	1e-8
GCST90020025_389	Waist-to-hip ratio adjusted for BMI	2e-8
GCST90020027_1636	Waist-hip index	2e-8
GCST006269_602	General cognitive ability	5e-8
GCST009379_177	Type 2 diabetes	4e-7
GCST001378_6	Hemostatic factors and hematological phenotypes	6e-6
GCST004865_73	Itch intensity from mosquito bite adjusted by bite size	7e-6
GCST009379_175	Type 2 diabetes	8e-6

EFO canonical traits (from GWAS)

15 canonical traits:

EFO ID	Trait name
EFO:0004503	hematological measurement
EFO:0004637	protein S measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004337	intelligence
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1044147	enalapril	Toxicity	Allele A is associated with increased likelihood of Cough when treated with enalapril in people with Hypertension as compared to allele G.	PMID:32397904

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation	2
Valproic Acid	decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol A	decreases methylation	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
Bortezomib	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Atrazine	increases expression	1
Folic Acid	increases expression	1
Methapyrilene	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases 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_E2G9	HAP1 PCGF3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.