PCNA

Summary

PCNA (proliferating cell nuclear antigen, HGNC:8729) is a protein-coding gene on chromosome 20p12.3, encoding DNA sliding clamp PCNA (P12004). Confers DNA tethering and processivity to DNA polymerases and other proteins. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome.

Source: NCBI Gene 5111 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ataxia-telangiectasia-like disorder 2 (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 33 total — 1 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_182649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8729
Approved symbol	PCNA
Name	proliferating cell nuclear antigen
Location	20p12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000132646
Ensembl biotype	protein_coding
OMIM	176740
Entrez	5111

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000379143, ENST00000379160, ENST00000875656, ENST00000875657, ENST00000875658, ENST00000875659, ENST00000930445, ENST00000968046, ENST00000968047

RefSeq mRNA: 2 — MANE Select: NM_182649 NM_002592, NM_182649

CCDS: CCDS13087

Canonical transcript exons

ENST00000379143 — 6 exons

Exon	Start	End
ENSE00000906719	5114953	5115362
ENSE00000906720	5115449	5115572
ENSE00000906721	5117470	5117664
ENSE00001479898	5119578	5119958
ENSE00001693283	5118610	5118677
ENSE00001747465	5118769	5118866

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 104.7405 / max 1904.5388, expressed in 1816 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186290	86.6105	1815
186289	13.1631	1516
186291	3.4620	1472
186288	1.2174	630
186287	0.2874	134

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.91	gold quality
secondary oocyte	CL:0000655	99.86	gold quality
ganglionic eminence	UBERON:0004023	98.91	gold quality
ventricular zone	UBERON:0003053	98.87	gold quality
embryo	UBERON:0000922	98.76	gold quality
trabecular bone tissue	UBERON:0002483	98.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.02	gold quality
endometrium epithelium	UBERON:0004811	97.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.58	gold quality
rectum	UBERON:0001052	97.54	gold quality
mucosa of transverse colon	UBERON:0004991	97.48	gold quality
vermiform appendix	UBERON:0001154	97.42	gold quality
colonic mucosa	UBERON:0000317	97.34	gold quality
epithelium of nasopharynx	UBERON:0001951	97.23	gold quality
tongue squamous epithelium	UBERON:0006919	97.19	gold quality
bone marrow	UBERON:0002371	97.00	gold quality
caecum	UBERON:0001153	96.97	gold quality
oral cavity	UBERON:0000167	96.48	gold quality
sperm	CL:0000019	96.39	gold quality
adult organism	UBERON:0007023	96.35	gold quality
gingival epithelium	UBERON:0001949	96.32	gold quality
gingiva	UBERON:0001828	96.24	gold quality
right testis	UBERON:0004534	96.20	gold quality
pigmented layer of retina	UBERON:0001782	96.17	gold quality
esophagus mucosa	UBERON:0002469	96.06	gold quality
left testis	UBERON:0004533	95.84	gold quality
lymph node	UBERON:0000029	95.79	gold quality
palpebral conjunctiva	UBERON:0001812	95.79	gold quality
penis	UBERON:0000989	95.56	gold quality
testis	UBERON:0000473	95.43	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	796.51
E-GEOD-114530	yes	732.22
E-MTAB-9435	yes	720.88
E-ENAD-20	yes	688.70
E-MTAB-10485	yes	617.20
E-MTAB-6075	yes	608.49
E-HCAD-24	yes	573.67
E-CURD-114	yes	542.39
E-GEOD-149689	yes	488.65
E-MTAB-9906	yes	479.91
E-MTAB-10287	yes	475.61
E-HCAD-10	yes	473.60
E-HCAD-32	yes	417.02
E-MTAB-11121	yes	414.43
E-MTAB-10662	yes	395.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, ATF1, ATM, CDX1, CDX2, CEBPA, CREB1, CRX, DNMT1, E2F1, E2F2, E2F4, EMX2, EP300, EZH2, FOSL1, FOXC1, GJA1, GLI2, HDAC1, HMGA1, HMGN1, HOXA1, HOXC8, ING1, JUN, KLF6, KMT2A, KMT2B, MBD2, MEF2A, MYB, MYC, NCOA3, NFE2L2, NFKB, NR4A1, PARP1, PPARG

miRNA regulators (miRDB)

41 targeting PCNA, 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-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-4263	99.18	69.25	2236

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• PCNA physically interacts with and directly binds AP endonuclease 1 (APE1) in whole cell extracts, thus demonstrating involvement of multiprotein reactions during long-patch base excision repair. (PMID:11601988)
• It is hypothesized from these observations that pol epsilon and PCNA have separate but associated functions early in S phase and that pol epsilon participates with PCNA in DNA replication late in S phase. (PMID:11741962)
• Functional interaction of MutY homolog with proliferating cell nuclear antigen in fission yeast (and in human) (PMID:11805113)
• The over-expression of PCNA in the lens epithelium of fetus and children suggests that PCNA might be related to the development of cataract. (PMID:11864421)
• The promoter of the human proliferating cell nuclear antigen gene is not sufficient for cell cycle-dependent regulation in organotypic cultures of keratinocytes (PMID:11877408)
• association with histone deacetylase activity, integrating DNA replication and chromatin modification (PMID:11929879)
• Human cell DNA replication is mediated by a discrete multiprotein complex. The eluted complex contains DNA polymerase delta, proliferating cell nuclear antigen, and replication protein A. (PMID:11968016)
• the interaction of PCNA with DNA polymerase delta is mediated through the small subunit of the enzyme (PMID:11986310)
• Expression of c-erbB-2 in node negative breast cancer does not correlate with estrogen receptor status, predictors of hormone responsiveness, or PCNA expression. (PMID:12088102)
• presence in CNS tumors correlates with histological type and grade (PMID:12125971)
• RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. (PMID:12226657)
• expressive quantity of PCNA was more in hypertrophic scars and less in chronic skin ulcers (PMID:12382578)
• PCNA protein expression may help evaluate the malignancy of hypopharyngeal carcinoma and make prognostic judgement of the patients. (PMID:12390713)
• relationship between the mast cell density and the context of clinicopathological parameters and expression of p185, estrogen receptor, and proliferating cell nuclear antigen in gastric carcinoma (PMID:12439914)
• clinical significance of E-cadherin and proliferating cell nuclear antigen expression in adenoid cystic carcinoma (PMID:12452045)
• abnormal expressions of COX-2, p53, PCNA, and nm23 associate with malignant potential, lymph node metastasis and clinical stage, and they might therefore play a role in development of gastric cancer (PMID:12452062)
• The content variation of Zn, Se, Mo, Cu, Ni could be possessed of certain effect on p53 mutation and PCNA overexpression of esophageal epithelium in the high risk area. (PMID:12479101)
• beta-catenin, p53 and PCNA may play important roles in the carcinogenesis of colorectal adenoma. (PMID:12515622)
• Expression of p57kip2, Rb protein and PCNA and their relationships with clinicopathology in human pancreatic cancer. (PMID:12532471)
• HBV infection may increase expression of PCNA and GST-pi. (PMID:12632497)
• PCNA binds to two distinct functional sites on WRN (PMID:12633936)
• the E2F site in the human PCNA 5’ promoter is a serum-responsive element (PMID:12782299)
• PCNA expression was significantly higher in recurrent aphthous ulcers than in normal oral mucosal tissue. (PMID:12857440)
• Upergulation of PCNA by overexpression of tuberous sclerosis gene products. (PMID:12893285)
• PARP-1 and p21 could cooperate in regulating the functions of PCNA during DNA replication/repair. (PMID:12930846)
• results demonstrate for the first time a novel role for human proliferating cell nuclear antigen(PCNA)in transcriptional repression and in modulating chromatin modification with reciprocal modulation of p300 acetyltransferase and PCNA by each other (PMID:12937166)
• combination of protein p53 induction and ionizing radiation activate the proliferating cell nuclear antigen gene (PMID:12947108)
• The expression of PCNA is associated with the increased malignancy. (PMID:14558955)
• Expression of PCNA was significantly higher than in normal pancreatic tissue. Correlated with the histological grade. Expression rate consistent with exacerbation of cancer. Also correlated significantly with prognosis and p53 expression. (PMID:14612290)
• in hepatocellular carcinoma, PCNA participates both in DNA synthesis and repair and that highly proliferating cancers may display a sustained DNA-repair. (PMID:14642618)
• Detection of PCNA and CD44mRNA expression in colorectal cancer may be useful for evaluating liver metastasis of cancer cells. (PMID:14669354)
• These results suggest that PCNA trimers bound to DNA during the S phase are organized as distinct pools able to bind selectively different partners. Among them, p125-pol delta and DNA ligase I interact with PCNA in a mutually exclusive manner (PMID:14729473)
• The overall expression of PCNA in all stages of fetal testis development was higher than pRb1 expression. (PMID:14871261)
• proliferating cell nuclear antigen is required in different ways in 5’ and 3’ nick-directed excision in human mismatch repair (PMID:14871894)
• PCNA expression in bone marrow plasma cells constitutes a good prognostic indicator of disease activity in patients with multiple myeloma. (PMID:15000866)
• Expression of this apoptosis-related protein may be a useful marker in cervix cancer development. (PMID:15033825)
• XRCC1 co-localizes with proliferating cell nuclear antigen (PCNA) at DNA replication foci, observed exclusively in the S phase of undamaged HeLa cells (PMID:15107487)
• Monoubiquitinated but not unmodified PCNA interacts with polymerase eta, and we found two motifs in poleta involved in this interaction. Our findings provide a mechanism by which monoubiquitination of PCNA might mediate the polymerase switch (PMID:15149598)
• In aids encephalopathy, although virtually all cells positive for HIV-1 p24 were PCNA+, there were many PCNA+ cells where HIV-1 p24 expression was not detected. (PMID:15161643)
• A marker of human esophageal neoplastic progression (PMID:15221970)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcna	ENSDARG00000054155
mus_musculus	Pcna	ENSMUSG00000027342
rattus_norvegicus	Pcna	ENSRNOG00000021264
drosophila_melanogaster	PCNA	FBGN0005655
drosophila_melanogaster	PCNA2	FBGN0032813
caenorhabditis_elegans		WBGENE00003955

Protein

Protein identifiers

DNA sliding clamp PCNA — P12004 (reviewed: P12004)

Alternative names: Cyclin, Proliferating cell nuclear antigen

All UniProt accessions (1): P12004

UniProt curated annotations — full annotation on UniProt →

Function. Confers DNA tethering and processivity to DNA polymerases and other proteins. Auxiliary protein of DNA polymerase delta and epsilon, is involved in the control of DNA replication by increasing the polymerases’ processivity during elongation of the leading strand. Induces a robust stimulatory effect on the 3’-5’ exonuclease and 3’-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while ‘Lys-63’-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.

Subunit / interactions. Homotrimer. Interacts with p300/EP300; the interaction occurs on chromatin in UV-irradiated damaged cells. Interacts with CREBBP (via transactivation domain and C-terminus); the interaction occurs on chromatin in UV-irradiated damaged cells. Directly interacts with POLD1, POLD3 and POLD4 subunits of the DNA polymerase delta complex, POLD3 being the major interacting partner; the interaction with POLD3 is inhibited by CDKN1A/p21(CIP1). Forms a complex with the replication factor C complex in the presence of ATP. Interacts with EXO1, POLH, POLK, DNMT1, ERCC5, FEN1, CDC6 and POLDIP2. Interacts with POLB. Interacts with APEX2; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA. Forms a ternary complex with DNTTIP2 and core histone. Interacts with KCTD10 and PPP1R15A. Interacts with SMARCA5/SNF2H. Interacts with BAZ1B/WSTF; the interaction is direct and is required for BAZ1B/WSTF binding to replication foci during S phase. Interacts with HLTF and SHPRH. Interacts with NUDT15; this interaction is disrupted in response to UV irradiation and acetylation. Interacts with CDKN1A/p21(CIP1) and CDT1; interacts via their PIP-box which also recruits the DCX(DTL) complex. The interaction with CDKN1A inhibits POLD3 binding. Interacts with DDX11. Interacts with EGFR; positively regulates PCNA. Interacts with PARPBP. Interacts (when ubiquitinated) with SPRTN; leading to enhance RAD18-mediated PCNA ubiquitination. Interacts (when polyubiquitinated) with ZRANB3; the interaction stimulates ZRANB3 endonuclease activity and is required for ZRANB3 recruitment to DNA replication sites. Interacts with SMARCAD1. Interacts with CDKN1C. Interacts with PCLAF (via PIP-box). Interacts with RTEL1 (via PIP-box); the interaction is direct and essential for the suppression of telomere fragility. Interacts with FAM111A (via PIP-box); the interaction is direct and required for PCNA loading on chromatin binding. Interacts with LIG1. Interacts with SETMAR. Interacts with ANKRD17. Interacts with FBXO18/FBH1 (via PIP-box); the interaction recruits the DCX(DTL) complex and promotes ubiquitination and degradation of FBXO18/FBH1. Interacts with POLN. Interacts with SDE2 (via PIP-box); the interaction is direct and prevents ultraviolet light induced monoubiquitination. Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR; interaction at least with PCNA occurs during DNA replication. Interacts with MAPK15; the interaction is chromatin binding dependent and prevents MDM2-mediated PCNA destruction by inhibiting the association of PCNA with MDM2. Interacts with PARP10 (via PIP-box). Interacts with DDI2. Interacts with HMCES (via PIP-box). Interacts with TRAIP (via PIP-box). Interacts with UHRF2. Interacts with ALKBH2; this interaction is enhanced during the S-phase of the cell cycle. Interacts with ATAD5; the interaction promotes USP1-mediated PCNA deubiquitination. Interacts with DNA damage up-regulated protein DDUP. Interacts (when phosphorylated) with GRB2. Interacts with ANG. Interacts with nuclear UNG (isoform 2); this interaction mediates UNG recruitment to S-phase replication foci. Interacts with ERCC6L2 (via an atypical PIP-box); this interaction facilitates cenrtomeric localization of ERCC6L2. Interacts with REV1 (via BRCT domain); this interaction is enhanced with a monoubiquitinated form of PCNA and mediates REV1 recruitment to stalled DNA replication. (Microbial infection) Interacts with herpes virus 8 protein LANA1.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA. Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation. Lysine acetylation disrupts association with chromatin, hence promoting PCNA ubiquitination and proteasomal degradation in response to UV damage in a CREBBP- and EP300-dependent manner. Acetylation disrupts interaction with NUDT15 and promotes degradation. Ubiquitinated. Following DNA damage, can be either monoubiquitinated to stimulate direct bypass of DNA lesions by specialized DNA polymerases or polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Following induction of replication stress, monoubiquitinated by the UBE2B-RAD18 complex on Lys-164, leading to recruit translesion (TLS) polymerases, which are able to synthesize across DNA lesions in a potentially error-prone manner. An error-free pathway also exists and requires non-canonical polyubiquitination on Lys-164 through ‘Lys-63’ linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH. This error-free pathway, also known as template switching, employs recombination mechanisms to synthesize across the lesion, using as a template the undamaged, newly synthesized strand of the sister chromatid. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis. Sumoylated during S phase. Methylated on glutamate residues by DCPH1/C6orf211.

Disease relevance. Ataxia-telangiectasia-like disorder 2 (ATLD2) [MIM:615919] A neurodegenerative disorder due to defects in DNA excision repair. ATLD2 is characterized by developmental delay, ataxia, sensorineural hearing loss, short stature, cutaneous and ocular telangiectasia, and photosensitivity. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Antibodies against PCNA are present in sera from patients with systemic lupus erythematosus.

Similarity. Belongs to the PCNA family.

RefSeq proteins (2): NP_002583, NP_872590* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000730	Pr_cel_nuc_antig	Family
IPR022648	Pr_cel_nuc_antig_N	Domain
IPR022649	Pr_cel_nuc_antig_C	Domain
IPR022659	Pr_cel_nuc_antig_CS	Conserved_site
IPR046938	DNA_clamp_sf	Homologous_superfamily

Pfam: PF00705, PF02747

UniProt features (63 total): strand 25, mutagenesis site 17, helix 7, modified residue 5, cross-link 3, chain 1, DNA-binding region 1, sequence variant 1, region of interest 1, turn 1, disulfide bond 1

Structure

Experimental structures (PDB)

102 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1U7B	X-RAY DIFFRACTION	1.88
8F5Q	X-RAY DIFFRACTION	1.9
9N3L	X-RAY DIFFRACTION	1.9
5E0U	X-RAY DIFFRACTION	1.93
5MLO	X-RAY DIFFRACTION	1.96
4RJF	X-RAY DIFFRACTION	2.01
5E0V	X-RAY DIFFRACTION	2.07
3VKX	X-RAY DIFFRACTION	2.1
6HVO	X-RAY DIFFRACTION	2.1
4ZTD	X-RAY DIFFRACTION	2.2
5YCO	X-RAY DIFFRACTION	2.2
5MOM	X-RAY DIFFRACTION	2.27
1VYM	X-RAY DIFFRACTION	2.3
2ZVM	X-RAY DIFFRACTION	2.3
5YD8	X-RAY DIFFRACTION	2.3
6K3A	X-RAY DIFFRACTION	2.3
7KQ0	X-RAY DIFFRACTION	2.4
5MLW	X-RAY DIFFRACTION	2.45
2ZVL	X-RAY DIFFRACTION	2.5
5MAV	X-RAY DIFFRACTION	2.58
1AXC	X-RAY DIFFRACTION	2.6
1U76	X-RAY DIFFRACTION	2.6
4D2G	X-RAY DIFFRACTION	2.65
5E0T	X-RAY DIFFRACTION	2.67
2ZVK	X-RAY DIFFRACTION	2.7
7EFA	X-RAY DIFFRACTION	2.7
9VGW	X-RAY DIFFRACTION	2.7
8COB	X-RAY DIFFRACTION	2.73
6CBI	X-RAY DIFFRACTION	2.75
8UMV	ELECTRON MICROSCOPY	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12004-F1	94.38	0.89

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 (8): 164, 254, 14, 77, 80, 211, 248, 164

Disulfide bonds (1): 135–162

Mutagenesis-validated functional residues (17):

Position	Phenotype
13	inhibits acetylation, recruitment to dna damage sites, inducible ubiquitination and protein degradation, dna replication
14	inhibits acetylation, recruitment to dna damage sites, inducible ubiquitination and protein degradation, dna replication
20	inhibits acetylation, recruitment to dna damage sites, inducible ubiquitination and protein degradation, dna replication
40	complete loss of interaction with uhrf2.
43–45	no effect on pold3-binding. impairs binding to alkbh2.
77	inhibits recruitment to dna damage sites, but nuclear localization is similar as the wild-type; in association with a-80
77	inhibits acetylation, recruitment to dna damage sites, inducible ubiquitination and protein degradation, dna replication
80	inhibits recruitment to dna damage sites, but nuclear localization is similar as the wild-type; in association with a-77
80	inhibits acetylation, recruitment to dna damage sites, inducible ubiquitination and protein degradation, dna replication
125–128	strong decrease in pold3-binding. impairs binding to alkbh2.
128	complete loss of interaction with uhrf2.
164	abolishes ubiquitination. no effect on interaction with shprh.
188–190	no effect on pold3-binding. no effect on alkbh2-binding.
211	alters chromatin-associated pcna stability and its function in dna replication and repair.
250	complete loss of interaction with uhrf2.
251–254	decrease in pold3-binding.
252	complete loss of interaction with uhrf2.

Function

Pathways and Gene Ontology

Reactome pathways

26 pathways

ID	Pathway
R-HSA-110312	Translesion synthesis by REV1
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-110320	Translesion Synthesis by POLH
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-174411	Polymerase switching on the C-strand of the telomere
R-HSA-174414	Processive synthesis on the C-strand of the telomere
R-HSA-174417	Telomere C-strand (Lagging Strand) Synthesis
R-HSA-174437	Removal of the Flap Intermediate from the C-strand
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-5358565	Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5655862	Translesion synthesis by POLK
R-HSA-5656121	Translesion synthesis by POLI
R-HSA-5656169	Termination of translesion DNA synthesis
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6804114	TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-69091	Polymerase switching
R-HSA-69166	Removal of the Flap Intermediate
R-HSA-69183	Processive synthesis on the lagging strand
R-HSA-69205	G1/S-Specific Transcription
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins

MSigDB gene sets: 691 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, KALMA_E2F1_TARGETS, REACTOME_DNA_REPLICATION, MODULE_52, E2F_Q4_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GNF2_MSH2, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, MODULE_451

GO Biological Process (29): negative regulation of transcription by RNA polymerase II (GO:0000122), leading strand elongation (GO:0006272), base-excision repair, gap-filling (GO:0006287), mismatch repair (GO:0006298), chromatin organization (GO:0006325), heart development (GO:0007507), translesion synthesis (GO:0019985), epithelial cell differentiation (GO:0030855), replication fork processing (GO:0031297), response to estradiol (GO:0032355), cellular response to UV (GO:0034644), estrous cycle (GO:0044849), positive regulation of DNA repair (GO:0045739), positive regulation of DNA replication (GO:0045740), response to cadmium ion (GO:0046686), cellular response to hydrogen peroxide (GO:0070301), cellular response to xenobiotic stimulus (GO:0071466), response to dexamethasone (GO:0071548), liver regeneration (GO:0097421), response to L-glutamate (GO:1902065), mitotic telomere maintenance via semi-conservative replication (GO:1902990), DNA replication (GO:0006260), regulation of DNA replication (GO:0006275), DNA repair (GO:0006281), DNA damage response (GO:0006974), response to oxidative stress (GO:0006979), positive regulation of deoxyribonuclease activity (GO:0032077), response to lipid (GO:0033993), positive regulation of DNA-directed DNA polymerase activity (GO:1900264)

GO Molecular Function (15): purine-specific mismatch base pair DNA N-glycosylase activity (GO:0000701), chromatin binding (GO:0003682), damaged DNA binding (GO:0003684), enzyme binding (GO:0019899), nuclear estrogen receptor binding (GO:0030331), DNA polymerase processivity factor activity (GO:0030337), receptor tyrosine kinase binding (GO:0030971), dinucleotide insertion or deletion binding (GO:0032139), MutLalpha complex binding (GO:0032405), histone acetyltransferase binding (GO:0035035), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), DNA polymerase binding (GO:0070182), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (15): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nuclear lamina (GO:0005652), nucleoplasm (GO:0005654), replication fork (GO:0005657), centrosome (GO:0005813), nuclear body (GO:0016604), replisome (GO:0030894), nuclear replication fork (GO:0043596), PCNA complex (GO:0043626), extracellular exosome (GO:0070062), PCNA-p21 complex (GO:0070557)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	5
Telomere C-strand (Lagging Strand) Synthesis	2
Mismatch Repair	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	2
DNA Damage Bypass	1
G0 and Early G1	1
Extension of Telomeres	1
Processive synthesis on the C-strand of the telomere	1
SUMO E3 ligases SUMOylate target proteins	1
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	3
DNA repair	2
response to oxygen-containing compound	2
positive regulation of DNA metabolic process	2
protein binding	2
enzyme binding	2
chromosome	2
replication fork	2
nuclear protein-containing complex	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA replication, synthesis of primer	1
DNA strand elongation involved in DNA replication	1
DNA replication, removal of RNA primer	1
DNA metabolic process	1
base-excision repair	1
cellular component organization	1
animal organ development	1
circulatory system development	1
DNA damage tolerance	1
DNA synthesis involved in DNA replication	1
cell differentiation	1
epithelium development	1
DNA-templated DNA replication maintenance of fidelity	1
response to lipid	1
response to UV	1
cellular response to light stimulus	1
ovulation cycle	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
DNA replication	1
regulation of DNA replication	1
response to metal ion	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to xenobiotic stimulus	1
cellular response to chemical stimulus	1
response to glucocorticoid	1

Protein interactions and networks

STRING

4120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCNA	CDK4	P11802	781
PCNA	CDK1	P06493	595
PCNA	CDK6	Q00534	551
PCNA	POLH	Q9Y253	540
PCNA	FEN1	P39748	505
PCNA	REV1	Q9UBZ9	445
PCNA	LIG1	P18858	432
PCNA	REV3L	O60673	418
PCNA	CCNA1	P78396	417
PCNA	RAD51	Q06609	411
PCNA	CCNA2	P20248	398
PCNA	TOP2A	P11388	394
PCNA	MAD2L2	Q9UI95	393
PCNA	CDK2	P24941	391
PCNA	CDC6	Q99741	384
PCNA	POLL	Q9UGP5	384

IntAct

652 interactions, top by confidence:

A	B	Type	Score
CDKN1A	PCNA	psi-mi:“MI:0915”(physical association)	0.980
PCNA	CDKN1A	psi-mi:“MI:0915”(physical association)	0.980
PCNA	CDKN1A	psi-mi:“MI:0407”(direct interaction)	0.980
PCNA	FEN1	psi-mi:“MI:0407”(direct interaction)	0.960
FEN1	PCNA	psi-mi:“MI:0407”(direct interaction)	0.960
FEN1	PCNA	psi-mi:“MI:0915”(physical association)	0.960
PCNA	FEN1	psi-mi:“MI:0915”(physical association)	0.960
FEN1	PCNA	psi-mi:“MI:2364”(proximity)	0.960
PCNA	PCNA	psi-mi:“MI:0915”(physical association)	0.900
CDKN1A	CDK1	psi-mi:“MI:0914”(association)	0.900
PCNA	PCNA	psi-mi:“MI:0407”(direct interaction)	0.900
PCNA	POLD3	psi-mi:“MI:0407”(direct interaction)	0.870
PCNA	POLD3	psi-mi:“MI:0915”(physical association)	0.870

BioGRID (1307): PCNA (Affinity Capture-Western), DTL (Affinity Capture-Western), PCNA (Affinity Capture-MS), PCNA (Affinity Capture-MS), PCNA (Reconstituted Complex), PCNA (Affinity Capture-MS), PCNA (Biochemical Activity), PCNA (Two-hybrid), PCNA (Two-hybrid), PCNA (Two-hybrid), TMEM218 (Two-hybrid), PCNA (Reconstituted Complex), PCNA (Biochemical Activity), PCNA (Affinity Capture-Western), CDKN1A (Affinity Capture-Western)

ESM2 similar proteins: A2SSW6, A3CVJ2, A7I849, B8GG80, G0SF70, O01377, O02115, O16852, O82134, O82797, P04961, P11038, P12004, P15873, P17070, P17917, P17918, P18248, P22177, P24314, P31008, P43744, P52620, P53358, P57761, P61074, P61258, P78955, Q00265, Q00268, Q03392, Q0W2J4, Q12U18, Q2FNX1, Q3ZBW4, Q43124, Q43266, Q46E39, Q54K47, Q6B6N4

Diamond homologs: A4G0K8, A6UQZ4, A6VHX7, A9A8V2, G0SF70, O01377, O02115, O16852, O82134, O82797, P04961, P11038, P12004, P15873, P17070, P17917, P17918, P18248, P22177, P24314, P31008, P53358, P57761, P61074, P61258, Q00265, Q00268, Q03392, Q3ZBW4, Q43124, Q43266, Q54K47, Q57697, Q6B6N4, Q6KZF1, Q7KQJ9, Q9DDF1, Q9DEA3, Q9M7Q7, Q9MAY3

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
EGFR	up-regulates	PCNA	phosphorylation
RAD18	up-regulates	PCNA	ubiquitination
SHPRH	up-regulates	PCNA	ubiquitination
UBE2A	up-regulates	PCNA	ubiquitination
CDKN1A	down-regulates	PCNA	binding
E2F1	“up-regulates quantity by expression”	PCNA	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	PCNA	“transcriptional regulation”
PCNA	“down-regulates activity”	NCR2	binding
HLTF	“up-regulates activity”	PCNA	ubiquitination
RAD18	“up-regulates activity”	PCNA	ubiquitination
ABL1	“up-regulates activity”	PCNA	phosphorylation
PCNA	“up-regulates activity”	“RNase H2 complex”	binding
“RF-C complex”	“up-regulates activity”	PCNA	binding
PCNA	“up-regulates activity”	“DNA polymerase delta”	binding
PCNA	“up-regulates activity”	“DNA polymerase epsilon”	binding
IGF1R	“up-regulates activity”	PCNA	phosphorylation

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
Removal of the Flap Intermediate from the C-strand	5	36.9×	3e-05
PCNA-Dependent Long Patch Base Excision Repair	5	30.2×	7e-05
Dual Incision in GG-NER	5	15.1×	1e-03
HDR through Homologous Recombination (HRR)	5	11.1×	3e-03
Mitotic G1 phase and G1/S transition	5	10.7×	3e-03
Gap-filling DNA repair synthesis and ligation in TC-NER	5	10.4×	3e-03
Dual incision in TC-NER	5	10.1×	4e-03
SARS-CoV-2 activates/modulates innate and adaptive immune responses	8	8.3×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
DNA replication	8	12.2×	1e-04
DNA repair	14	8.3×	1e-06
DNA damage response	10	5.0×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	11
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
803596	NM_182649.2(PCNA):c.443G>C (p.Cys148Ser)	Likely pathogenic

SpliceAI

675 predictions. Top by Δscore:

Variant	Effect	Δscore
20:5115360:CAA:C	acceptor_gain	1.0000
20:5115363:C:CC	acceptor_gain	1.0000
20:5115443:TCTTA:T	donor_loss	1.0000
20:5115444:CTTA:C	donor_loss	1.0000
20:5115446:TA:T	donor_loss	1.0000
20:5115447:A:AC	donor_gain	1.0000
20:5115447:A:C	donor_loss	1.0000
20:5115448:C:CC	donor_gain	1.0000
20:5115471:A:AC	donor_gain	1.0000
20:5115472:C:CC	donor_gain	1.0000
20:5115568:GTAAC:G	acceptor_gain	1.0000
20:5115569:TAAC:T	acceptor_gain	1.0000
20:5115570:AAC:A	acceptor_gain	1.0000
20:5115571:AC:A	acceptor_gain	1.0000
20:5115572:CC:C	acceptor_gain	1.0000
20:5115573:C:CC	acceptor_gain	1.0000
20:5115576:C:CT	acceptor_gain	1.0000
20:5115577:A:T	acceptor_gain	1.0000
20:5117465:CTT:C	donor_loss	1.0000
20:5117466:TTA:T	donor_loss	1.0000
20:5117468:A:AC	donor_gain	1.0000
20:5117468:ACAG:A	donor_gain	1.0000
20:5117469:C:CT	donor_gain	1.0000
20:5117469:CA:C	donor_gain	1.0000
20:5117469:CAG:C	donor_gain	1.0000
20:5117469:CAGC:C	donor_gain	1.0000
20:5117469:CAGCT:C	donor_gain	1.0000
20:5117474:T:TA	donor_gain	1.0000
20:5117490:CA:C	donor_gain	1.0000
20:5117491:A:AC	donor_gain	1.0000

AlphaMissense

1727 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:5115314:G:T	A252D	1.000
20:5115317:A:C	L251W	1.000
20:5115317:A:G	L251S	1.000
20:5115335:C:T	G245E	1.000
20:5115336:C:G	G245R	1.000
20:5115336:C:T	G245R	1.000
20:5115451:A:G	L235P	1.000
20:5115451:A:T	L235H	1.000
20:5115454:G:T	P234H	1.000
20:5115475:A:G	L227P	1.000
20:5115481:A:T	V225E	1.000
20:5115502:G:T	A218D	1.000
20:5115520:A:G	L212P	1.000
20:5115534:A:C	F207L	1.000
20:5115534:A:T	F207L	1.000
20:5115535:A:G	F207S	1.000
20:5115536:A:G	F207L	1.000
20:5117525:C:T	G176E	1.000
20:5117546:A:G	F169S	1.000
20:5117579:A:T	V158D	1.000
20:5117600:A:G	L151P	1.000
20:5117606:C:G	R149P	1.000
20:5117621:A:G	F144S	1.000
20:5118843:G:T	A82D	1.000
20:5119617:C:G	R61P	1.000
20:5119659:A:G	L47S	1.000
20:5119665:A:T	V45D	1.000
20:5119669:G:C	H44D	1.000
20:5119677:T:A	D41V	1.000
20:5119677:T:G	D41A	1.000

dbSNP variants (sampled 300 via entrez): RS1000006799 (20:5126851 C>G), RS1000464762 (20:5127071 A>G), RS1000473176 (20:5114959 T>C), RS1000498780 (20:5126435 T>C), RS1000651339 (20:5119922 GACA>G), RS1000738869 (20:5120993 AT>A,ATT), RS1000875776 (20:5122772 T>C), RS1001127189 (20:5116584 C>T), RS1001231458 (20:5126815 C>G,T), RS1001234403 (20:5127808 T>G), RS1001340904 (20:5122832 A>C), RS1001902679 (20:5115754 T>A), RS1001933965 (20:5116060 G>C), RS1002016839 (20:5122062 A>G), RS1002181775 (20:5127737 A>C)

Disease associations

OMIM: gene MIM:176740 | disease phenotypes: MIM:615919

GenCC curated gene-disease

Disease	Classification	Inheritance
ataxia-telangiectasia-like disorder 2	Supportive	Autosomal recessive
hereditary ataxia	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary ataxia	Limited	AR

Mondo (2): ataxia-telangiectasia-like disorder 2 (MONDO:0014399), hereditary ataxia (MONDO:0100309)

Orphanet (1): PCNA-related progressive neurodegenerative photosensitivity syndrome (Orphanet:438134)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000524	Conjunctival telangiectasia
HP:0000613	Photophobia
HP:0000776	Congenital diaphragmatic hernia
HP:0000992	Cutaneous photosensitivity
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001324	Muscle weakness
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002180	Neurodegeneration
HP:0002317	Unsteady gait
HP:0002664	Neoplasm
HP:0003323	Progressive muscle weakness
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0004322	Short stature
HP:0005328	Progeroid facial appearance
HP:0007763	Retinal telangiectasia
HP:0010864	Severe intellectual disability
HP:0031087	Absent pubertal growth spurt
HP:0034392	Joint contracture
HP:0034697	Cutaneous telangiectasia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2346488 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 73,155 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1544	LIOTHYRONINE	4	23,700
CHEMBL41632	TIRATRICOL	3	46,632
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL2348292	3,5-DIIODOTHYROPROPIONIC ACID	2	556
CHEMBL291053	THYROPROPIC ACID	2	729

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

ChEMBL bioactivities

107 potent at pChembl≥5 of 119 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	Ki	10	nM	CHEMBL6176775
7.72	Kd	19	nM	MOLIBRESIB
7.40	Ki	40	nM	CHEMBL6167750
7.22	Ki	60	nM	CHEMBL6146344
7.16	Ki	70	nM	CHEMBL2348305
7.10	Ki	80	nM	CHEMBL6167362
7.05	Ki	90	nM	CHEMBL2348291
6.96	Ki	110	nM	CHEMBL6165136
6.96	Ki	110	nM	CHEMBL2348285
6.95	Ki	113	nM	CHEMBL6172421
6.94	Ki	114	nM	CHEMBL6169595
6.92	Ki	120	nM	CHEMBL2348288
6.92	Ki	120	nM	CHEMBL6177399
6.89	Ki	130	nM	CHEMBL6149965
6.89	Ki	130	nM	CHEMBL2348289
6.84	Ki	144	nM	CHEMBL2348287
6.82	Ki	150	nM	CHEMBL6144445
6.79	Ki	163	nM	LIOTHYRONINE
6.77	Ki	170	nM	CHEMBL6169034
6.76	Ki	173	nM	CHEMBL6151510
6.74	Ki	183	nM	CHEMBL2348293
6.64	Ki	231	nM	CHEMBL6164608
6.62	Ki	240	nM	CHEMBL6170243
6.58	Ki	260	nM	CHEMBL2348299
6.57	Ki	270	nM	CHEMBL2348284
6.46	Ki	350	nM	CHEMBL2348306
6.32	IC50	480	nM	CHEMBL6167750
6.30	Kd	502.2	nM	CHEMBL5653589
6.30	ED50	502.2	nM	CHEMBL5653589
6.27	Ki	540	nM	CHEMBL6175576
6.27	Ki	540	nM	CHEMBL6161371
6.24	Ki	570	nM	CHEMBL2348286
6.24	Ki	570	nM	CHEMBL6170864
6.22	IC50	600	nM	CHEMBL6146344
6.22	Ki	600	nM	CHEMBL6167800
6.20	Ki	630	nM	CHEMBL6170325
6.14	Ki	720	nM	CHEMBL6144723
6.11	Ki	780	nM	CHEMBL6163034
6.10	IC50	800	nM	CHEMBL2348305
6.10	IC50	800	nM	CHEMBL6167362
6.06	Ki	870	nM	CHEMBL6167164
6.06	Ki	870	nM	CHEMBL6174767
6.04	Ki	910	nM	CHEMBL6166953
6.03	Ki	930	nM	CHEMBL6151458
6.03	Ki	930	nM	CHEMBL2348303
6.00	IC50	1000	nM	CHEMBL2348291
6.00	IC50	1000	nM	CHEMBL2348305
6.00	IC50	1000	nM	CHEMBL6176775
5.97	Ki	1060	nM	CHEMBL2348302
5.93	IC50	1170	nM	CHEMBL6172421

PubChem BioAssay actives

24 with measured affinity, of 92 total; 23 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179100: Binding affinity against PCNA (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0190	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148948: Binding affinity to human PCNA incubated for 45 mins by Kinobead based pull down assay	kd	0.5022	uM
N-[(2S)-2-amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propyl]methanesulfonamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	1.0000	uM
4-[4-[(2S)-2-amino-3-hydroxypropyl]-2,6-diiodophenoxy]phenol	1315763: Binding affinity to full length human PCNA expressed in Escherichia coli BL21(DE3) assessed as inhibition of interaction with N-terminal 5-carboxyfluorescein-labeled PIP-box sequence peptide after 30 mins by fluorescence polarization assay	ic50	1.0000	uM
1-[(2S)-1-hydroxy-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propan-2-yl]-3-propan-2-ylurea	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	1.2000	uM
N-[(2S)-2-amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propyl]-3-morpholin-4-ylpropanamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	1.2000	uM
1-[(2S)-2-amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propyl]-3-propan-2-ylurea	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	1.3000	uM
N-[(2S)-2-amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propyl]morpholine-4-carboxamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	1.4000	uM
N-[(2S)-2-amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propyl]acetamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	1.5000	uM
2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]-N-methylacetamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	1.9000	uM
2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]-1-morpholin-4-ylethanone	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	2.7000	uM
3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]-N-(oxolan-2-ylmethyl)propanamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	2.9000	uM
methyl N-[(2S)-1-hydroxy-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propan-2-yl]carbamate	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	2.9000	uM
2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]-N,N-dimethylacetamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	3.1000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148948: Binding affinity to human PCNA incubated for 45 mins by Kinobead based pull down assay	kd	3.5119	uM
Liothyronine	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	3.6000	uM
N-[(2S)-1-hydroxy-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propan-2-yl]acetamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	3.7000	uM
N-(2-hydroxyethyl)-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propanamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	6.0000	uM
N-[(2S)-1-hydroxy-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propan-2-yl]methanesulfonamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	6.0000	uM
(2S)-2-amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propanoic acid	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	6.3000	uM
N-(2-ethoxyethyl)-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]propanamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	6.5000	uM
N-(benzenesulfonyl)-2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]acetamide	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	8.6000	uM
3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]-1-morpholin-4-ylpropan-1-one	739861: Inhibition of human recombinant PCNA interaction with PIP box protein N-5-carboxyfluorescein-SAVLQKKITDYFHPKK after 30 mins by fluorescence polarization assay	ic50	9.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, decreases methylation, decreases expression, increases expression (+2 more)	22
sodium arsenite	decreases activity, increases reaction, decreases reaction, affects expression, affects reaction (+6 more)	20
Estradiol	increases expression, increases reaction, decreases expression, decreases response to substance, affects cotreatment (+1 more)	12
Benzo(a)pyrene	affects cotreatment, affects expression, decreases expression, increases expression	6
Cisplatin	affects cotreatment, increases expression, decreases expression, affects reaction, affects response to substance	6
arsenite	affects binding, increases reaction, increases expression, increases methylation, affects reaction	5
Fulvestrant	decreases expression, decreases reaction, increases expression, increases reaction, affects cotreatment (+1 more)	5
Troglitazone	decreases expression	5
Cadmium	affects reaction, decreases reaction, increases abundance, increases expression, increases palmitoylation (+2 more)	5
Curcumin	increases expression, decreases expression, affects cotreatment, decreases reaction	5
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression, increases metabolic processing	5
Aflatoxin B1	affects expression, decreases methylation, increases expression	5
Cadmium Chloride	decreases expression, affects expression, decreases reaction, increases abundance, increases expression (+1 more)	5
Genistein	affects expression, affects reaction, increases abundance, affects cotreatment, decreases expression (+1 more)	5
mono-(2-ethylhexyl)phthalate	affects reaction, increases expression, decreases reaction, decreases expression	4
cobaltous chloride	affects cotreatment, increases expression, decreases expression, decreases reaction	4
Resveratrol	affects cotreatment, increases expression, decreases expression	4
Arsenic Trioxide	decreases expression, increases expression	4
Acetaminophen	affects expression, increases expression	4
Doxorubicin	increases reaction, decreases expression, increases expression, increases response to substance, affects expression (+2 more)	4
Fluorouracil	decreases expression, increases expression	4
Tretinoin	affects binding, affects response to substance, increases reaction, decreases expression	4
Asbestos, Crocidolite	decreases expression, increases expression, decreases reaction	4
methylselenic acid	affects expression, decreases expression	3
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases reaction, decreases expression, increases expression, decreases reaction	3
perfluorooctanoic acid	decreases expression	3
butylbenzyl phthalate	increases expression, affects reaction, decreases reaction	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases abundance, increases expression, decreases expression	3
U 0126	decreases expression, decreases response to substance, affects expression, affects reaction, increases abundance (+2 more)	3
dieckol	decreases expression	3

ChEMBL screening assays

21 unique, capped per target: 21 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2352787	Binding	Inhibition of PCNA in human U2OS cells assessed as cisplatin-induced DNA damage at 25 uM after 22 hrs by comet assay	Small molecule inhibitors of PCNA/PIP-box interaction suppress translesion DNA synthesis. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KT91	HeLa SilenciX PCNA	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT01360164	PHASE1/PHASE2	UNKNOWN	Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Hereditary Ataxia
NCT00004306	Not specified	COMPLETED	Clinical and Molecular Correlations in Spinocerebellar Ataxia Type 10 (SCA10)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04750850	Not specified	COMPLETED	Core Stability Exercises and Hereditary Ataxia
NCT05160870	Not specified	UNKNOWN	Genotype-phenotype Correlation and Pathogenic Mechanism in Hereditary Ataxia
NCT05160883	Not specified	UNKNOWN	Neuroimaging Changes in Hereditary Ataxia
NCT06034886	Not specified	AVAILABLE	Expanded Access Protocol of Troriluzole in Patients With Spinocerebellar Ataxia (SCA)
NCT06152133	Not specified	COMPLETED	Telerehabilitation, Core Stability Exercises and Hereditary Ataxia (TRCore-ataxia)
NCT06267222	Not specified	ENROLLING_BY_INVITATION	Trans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia
NCT07092358	Not specified	RECRUITING	Hereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta
NCT07200505	Not specified	NOT_YET_RECRUITING	Telerehabilitation for Core Stability and Strength in Hereditary Ataxia