PCLAF

Summary

PCLAF (PCNA clamp associated factor, HGNC:28961) is a protein-coding gene on chromosome 15q22.31, encoding PCNA-associated factor (Q15004). PCNA-binding protein that acts as a regulator of DNA repair during DNA replication.

Enables chromatin binding activity and molecular adaptor activity. Involved in several processes, including DNA metabolic process; centrosome cycle; and response to UV. Located in centrosome; nucleus; and perinuclear region of cytoplasm.

Source: NCBI Gene 9768 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 25 total
• Druggable target: yes
• MANE Select transcript: NM_014736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28961
Approved symbol	PCLAF
Name	PCNA clamp associated factor
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	NS5ATP9, OEATC-1, p15(PAF), PAF15
Ensembl gene	ENSG00000166803
Ensembl biotype	protein_coding
OMIM	610696
Entrez	9768

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000300035, ENST00000380258, ENST00000558008, ENST00000558043, ENST00000558250, ENST00000559280, ENST00000559519, ENST00000560234, ENST00000931270, ENST00000931271, ENST00000931272, ENST00000931273, ENST00000931274

RefSeq mRNA: 2 — MANE Select: NM_014736 NM_001029989, NM_014736

CCDS: CCDS10193, CCDS32269

Canonical transcript exons

ENST00000300035 — 4 exons

Exon	Start	End
ENSE00001692288	64364304	64366075
ENSE00002571166	64381326	64381441
ENSE00003784561	64376743	64376905
ENSE00003784878	64380958	64381038

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.4151 / max 920.6677, expressed in 1583 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150474	60.1187	1578
150475	2.0507	830
150473	0.1860	72
150472	0.0596	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	98.76	gold quality
trabecular bone tissue	UBERON:0002483	98.39	gold quality
embryo	UBERON:0000922	97.55	gold quality
ventricular zone	UBERON:0003053	97.38	gold quality
ganglionic eminence	UBERON:0004023	97.12	gold quality
bone marrow	UBERON:0002371	96.79	gold quality
tongue squamous epithelium	UBERON:0006919	96.21	gold quality
gingival epithelium	UBERON:0001949	95.21	gold quality
thymus	UBERON:0002370	95.04	gold quality
cervix squamous epithelium	UBERON:0006922	94.83	gold quality
gingiva	UBERON:0001828	94.24	gold quality
hair follicle	UBERON:0002073	93.74	gold quality
squamous epithelium	UBERON:0006914	93.67	gold quality
bone marrow cell	CL:0002092	93.51	gold quality
oral cavity	UBERON:0000167	93.32	gold quality
buccal mucosa cell	CL:0002336	92.92	gold quality
esophagus squamous epithelium	UBERON:0006920	92.78	gold quality
ileal mucosa	UBERON:0000331	92.44	gold quality
mucosa of transverse colon	UBERON:0004991	92.13	gold quality
epithelium of esophagus	UBERON:0001976	92.05	gold quality
cardia of stomach	UBERON:0001162	91.96	silver quality
pancreatic ductal cell	CL:0002079	91.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.18	gold quality
superior surface of tongue	UBERON:0007371	91.04	gold quality
caecum	UBERON:0001153	90.90	gold quality
vermiform appendix	UBERON:0001154	90.85	gold quality
colonic mucosa	UBERON:0000317	90.80	gold quality
rectum	UBERON:0001052	90.74	gold quality
pylorus	UBERON:0001166	90.74	gold quality
nipple	UBERON:0002030	90.29	gold quality

Single-cell (SCXA)

Detected in 57 experiment(s), a significant marker in 43.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	1300.64
E-MTAB-10485	yes	1299.02
E-MTAB-9906	yes	1203.89
E-HCAD-10	yes	1162.94
E-GEOD-114530	yes	1113.41
E-MTAB-8221	yes	1086.11
E-GEOD-124472	yes	1043.09
E-MTAB-8884	yes	857.96
E-HCAD-4	yes	847.67
E-HCAD-13	yes	744.16
E-MTAB-6653	yes	701.32
E-MTAB-10885	yes	685.60
E-MTAB-9154	yes	671.93
E-HCAD-1	yes	634.46
E-MTAB-6308	yes	599.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

42 targeting PCLAF, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of KIAA0101 is associated with anaplastic thyroid carcinoma (PMID:15789362)
• The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b. (PMID:16288740)
• KIAA0101 protein expression was down-regulated in hepatocellular carcinoma; this gene could inhibit the HCC cell growth in vitro and presumably by its blocking effect on cell cycle (PMID:16646990)
• NS5ATP9 is a NS5A up-regulation gene which may play a role in the pathogenesis of HCV-associated hepatocellular carcinoma. (PMID:18068894)
• p15(PAF) gene is regulated by NF-kappa B signal transduction. (PMID:18727915)
• Interaction between p15(PAF)and Proliferating Cell Nuclear Antigen is required for the DNA repair process. (PMID:19219066)
• KIAA0101 gene may participate in cell cycle regulation of non-small cell lung cancer. (PMID:20118010)
• Data indicate that PAF15 associates with PCNA, and depletion of PAF15 decreases the number of cells in S phase, suggesting a role for it in cell cycle regulation. (PMID:21628590)
• This study identifies KIAA0101 as a protein important for breast tumorigenesis, and as this factor has been reported as a UV repair factor, it may link the UV damage response to centrosome control (PMID:21673012)
• High-level KIAA0101 expression was observed in 33.9% (121 of 357 cases). (PMID:21689861)
• Data supports that KIAA0101 is a marker of cellular proliferation, promotes growth and invasion, and is a good diagnostic marker for distinguishing benign from malignant adrenocortical neoplasm. (PMID:22096502)
• KIAA0101 transcript variant 1 may function as a regulator, promoting cell survival in hepatocellular carcinoma through regulating the function of p53. (PMID:22576474)
• The results uncovered a critical role for PCNA-associated factor PAF15 (p15(PAF)/KIAA0101) ubiquitylation during DNA replication. During unperturbed S phase, chromatin-associated PAF15 is modified by double mono-ubiquitylation of lysine 15 and 24. (PMID:23000965)
• Down-regulation of KIAA0101 expression leads to an inhibition of cell proliferation, cell cycle and cell invasion of gastric carcinoma. (PMID:23157749)
• Low expression of PAF and high expression of TNF-alpha in leukocytospermia affect the sperm motility, which is one of the reasons that leads to infertility. (PMID:23209346)
• GC patients with elevated KIAA0101 expression levels exhibited a high recurrence and subsequently poor prognosis in the survival study (PMID:23240630)
• p15(PAF) is tightly regulated by the Rb/E2F complex. Loss of Rb/E2F-mediated repression during the G1/S transition phase leads to p15(PAF) upregulation, which facilitates DNA synthesis and S-phase progression. (PMID:23593430)
• Data show that hepatitis C virus NS5A-transactivated protein 9 (NS5ATP9) knockdown activated mitogen-activated protein kinase kinase/extracellular signal regulated kinases 1/2 signaling under C virus nonstructural protein 5A (NS5A) expression. (PMID:23698777)
• Data indicate that PAF-EZH2-beta-catenin complex hyperactivates Wnt signaling. (PMID:24055345)
• PAF hyperactivates Wnt signaling by recruiting EZH2 to the beta-catenin transcriptional complex in a PCNA-independent manner, which promotes intestinal tumorigenesis. (PMID:24055345)
• Upregulated expression of KIAA0101 is associated with esophageal cancer progression, resistance to chemotherapy, and poor survival. (PMID:24145239)
• overexpression of KIAA0101 mRNA in peripheral blood mononuclear cells could act as a predictive biomarker for hepatic cancer (PMID:24197986)
• PAF activates MAPK signaling via LAMTOR3 upregulation. (PMID:24209743)
• These results highlight an important potential role for NS5ATP9 in hepatitis C virus NS5A-induced hepatocyte autophagy. (PMID:24750205)
• NS5ATP9 mRNA overexpression in peripheral blood mononuclear cells was significantly associated with poor disease-free survival and overall survival of gastric cancer patients, but not with tumor recurrence. (PMID:24996800)
• Results indicated that the expression of NS5ATP9 was up-regulated by starvation and that Beclin 1 was involved in autophagy induced in hepatoblastoma cells by starvation. (PMID:25649430)
• p15PAF acts as a flexible drag that regulates PCNA sliding along the DNA and facilitates the switch from replicative to translesion synthesis polymerase binding. (PMID:25762514)
• IN PATIENTS WITH HEPATITIS C VIRUS GENOTYPE 1B, TREATMENT RESPONSE WITH DACLATASVIR PLUS ASUNAPREVIR WITHOUT NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms (PMID:26155891)
• High KIAA0101 expression is associated with kidney cancer. (PMID:26575329)
• PAF induced Wnt/beta-catenin signaling-mediated cell plasticity to maintain cancer cell stemness. (PMID:26843124)
• Results unveil an unsuspected role of the PAF-Wnt signalling axis in modulating cell plasticity, which is required for the maintenance of breast cancer cell stemness. (PMID:26843124)
• High KIAA0101 level is associated with metastasis in hepatocellular carcinoma. (PMID:26968109)
• PAF stimulation dose-dependently promoted the invasion, migration and growth of prostate cancer cells in vitro, while knockdow our findings demonstrate that PAFR can activate ERK1/2 pathway, and subsequently increase MMP-3 expression and decrease E-cadherin expression (PMID:27176648)
• Paf15 expression is associated with increased rectal cancer proliferation, decreased patient survival, and a worse radiotherapeutic response (PMID:27246972)
• The complex between p15PAF and trimeric PCNA is of low affinity, forming a transient complex that is difficult to characterize at a structural level due to its inherent polydispersity. We have determined the structure, conformational fluctuations, and relative population of the five species that coexist in solution by combining small-angle X-ray scattering (SAXS) with molecular modelling. (PMID:28180305)
• KIAA0101 tv2 exerts anti-tumor activity in HCC and acts as an endogenous competitor of tumor-associated KIAA0101 tv1. KIAA0101 tv2 has a potential to work as a therapeutic drug targeting the KIAA0101 tv1 in HCC. (PMID:28410205)
• miR-429 mediates deregulation of KIAA0101 by acting as an anti-metastatic miRNA that targets KIAA0101 pro-metastatic gene during metastasis of soft tissue sarcomas (PMID:28432002)
• PAF supports glioma stem cells maintenance, in part, by influencing DNA replication and pyrimidine metabolism pathways.PAF-associated DNA translesion synthesis activity influences glioma stem cell radiation resistance. (PMID:29073105)
• IL-6 could induce autophagy by expressing NS5ATP9, while NS5ATP9 upregulated IL-6 levels in turn, which further induced autophagy. (PMID:29227529)
• PAF-transactivated MYC induces stem and progenitor cell activation for intestinal tissue regeneration and tumorigenesis. (PMID:29533773)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pclaf	ENSDARG00000097691
mus_musculus	Pclaf	ENSMUSG00000040204
rattus_norvegicus	LOC100363428	ENSRNOG00000064722
rattus_norvegicus	Pclaf	ENSRNOG00000067723

Protein

Protein identifiers

PCNA-associated factor — Q15004 (reviewed: Q15004)

Alternative names: Hepatitis C virus NS5A-transactivated protein 9, Overexpressed in anaplastic thyroid carcinoma 1, PCNA-associated factor of 15 kDa, PCNA-clamp-associated factor

All UniProt accessions (3): Q15004, H0YKX3, H0YMA4

UniProt curated annotations — full annotation on UniProt →

Function. PCNA-binding protein that acts as a regulator of DNA repair during DNA replication. Following DNA damage, the interaction with PCNA is disrupted, facilitating the interaction between monoubiquitinated PCNA and the translesion DNA synthesis DNA polymerase eta (POLH) at stalled replisomes, facilitating the bypass of replication-fork-blocking lesions. Also acts as a regulator of centrosome number.

Subunit / interactions. Interacts (when monoubiquitinated at Lys-15 and Lys-24) with PCNA. Interacts with isoform 2/p33ING1b of ING1. Interacts with BRCA1.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed predominantly in liver, pancreas and placenta. Not detected in heart or brain. Highly expressed in a number of tumors, especially esophageal tumors, in anaplastic thyroid carcinomas, adrenocortical carcinomas, and in non-small-cell lung cancer lines.

Post-translational modifications. Monoubiquitinated at Lys-15 and Lys-24 during normal S phase, promoting its association with PCNA. Also diubiquitinated at these 2 sites. Following DNA damage, monoubiquitin chains at Lys-15 and Lys-24 are probably extended, leading to disrupt the interaction with PCNA. Polyubiquitinated by the APC/C complex at the mitotic exit, leading to its degradation by the proteasome.

Domain organisation. The PIP-box mediates the interaction with PCNA. The KEN box is required for the association with the APC/C complex. The D-box (destruction box) mediates the interaction with APC/C proteins, and acts as a recognition signal for degradation via the ubiquitin-proteasome pathway. The initiation motif is required for efficient chain initiation by the APC/C complex E2 ligase UBE2C. It determines the rate of substrate’s degradation without affecting its affinity for the APC/C, a mechanism used by the APC/C to control the timing of substrate proteolysis during the cell cycle.

Induction. By UV irradiation. By ATF3 in response to UV-stress.

Miscellaneous. Overexpression in adrenocortical neoplasms (ACC), may promote growth and invasion in adrenal cancer.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15004-1	1	yes
Q15004-2	2

RefSeq proteins (2): NP_001025160, NP_055551* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031444	PCNA-AF_dom	Domain
IPR040444	PCNA-AF	Family

Pfam: PF15715

UniProt features (26 total): mutagenesis site 8, modified residue 5, short sequence motif 4, cross-link 2, compositionally biased region 2, chain 1, region of interest 1, splice variant 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6IIW	X-RAY DIFFRACTION	1.7
4D2G	X-RAY DIFFRACTION	2.65
6GWS	X-RAY DIFFRACTION	2.9
6EHT	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15004-F1	65.67	0.10

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 (7): 28, 31, 72, 15, 24, 8, 24

Mutagenesis-validated functional residues (8):

Position	Phenotype
15	loss of monoubiquitination; when associated with r-24.
24	loss of monoubiquitination; when associated with r-15.
65	loss of binding to pcna.
68–69	loss of binding to pcna.
68	loss of binding to pcna.
78	stabilizes the protein in g1 by preventing association with the apc/c complex and degradation by the proteasome.
93–97	inhibits chain initiation by apc/c.
93–97	no effect on chain initiation by apc/c.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5656169	Termination of translesion DNA synthesis

MSigDB gene sets: 470 (showing top): E2F_Q4, MODULE_52, E2F_Q4_01, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GNF2_MSH2, HORIUCHI_WTAP_TARGETS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, TSENG_IRS1_TARGETS_UP, GNF2_CENPF, E2F4DP1_01, PAL_PRMT5_TARGETS_UP, CROONQUIST_NRAS_SIGNALING_DN, MORF_RAD21, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_DNA_DAMAGE_TOLERANCE

GO Biological Process (7): DNA replication (GO:0006260), DNA repair (GO:0006281), DNA damage response (GO:0006974), centrosome cycle (GO:0007098), response to UV (GO:0009411), translesion synthesis (GO:0019985), regulation of cell cycle (GO:0051726)

GO Molecular Function (3): chromatin binding (GO:0003682), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
cellular anatomical structure	3
DNA metabolic process	2
DNA biosynthetic process	1
DNA damage response	1
cellular response to stress	1
cell cycle process	1
microtubule organizing center organization	1
response to light stimulus	1
DNA damage tolerance	1
DNA synthesis involved in DNA replication	1
cell cycle	1
regulation of cellular process	1
molecular_function	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCLAF	ING1	Q9UK53	885
PCLAF	CTNNB1	P35222	766
PCLAF	ASPM	Q8IZT6	641
PCLAF	UBE2C	O00762	629
PCLAF	BIRC5	O15392	629
PCLAF	BRCA1	P38398	624
PCLAF	ASF1B	Q9NVP2	621
PCLAF	ZWINT	O95229	615
PCLAF	GSTM2	P28161	609
PCLAF	NUSAP1	Q9BXS6	588
PCLAF	MCM10	Q7L590	578
PCLAF	CCNB1	P14635	574
PCLAF	PTTG1	O95997	573
PCLAF	PHGDH	O43175	571
PCLAF	MAD2L1	Q13257	554

IntAct

18 interactions, top by confidence:

A	B	Type	Score
PCNA	PCLAF	psi-mi:“MI:0915”(physical association)	0.800
CDKN1A	CDK14	psi-mi:“MI:0914”(association)	0.770
TERF1	PCLAF	psi-mi:“MI:0915”(physical association)	0.560
PCNA	POM121C	psi-mi:“MI:0914”(association)	0.550
PCNA	CCNE2	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
Pcna	SIVA1	psi-mi:“MI:0914”(association)	0.350
CDKN1A	CCNE1	psi-mi:“MI:0914”(association)	0.350
FANCM	MOCS2	psi-mi:“MI:0914”(association)	0.350
EPB41L4B	RPSA2	psi-mi:“MI:0914”(association)	0.350
PCLAF	PCNA	psi-mi:“MI:0915”(physical association)	0.000
PCLAF	TERF1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (90): KIAA0101 (Affinity Capture-MS), HARS (Co-fractionation), HSPA14 (Co-fractionation), KIAA0101 (Synthetic Lethality), KIAA0101 (Affinity Capture-MS), KIAA0101 (Affinity Capture-MS), KIAA0101 (Biochemical Activity), PCNA (Reconstituted Complex), PCNA (Affinity Capture-Western), FZR1 (Reconstituted Complex), KIAA0101 (Affinity Capture-MS), KIAA0101 (Affinity Capture-MS), KIAA0101 (Affinity Capture-MS), KIAA0101 (Affinity Capture-MS), KIAA0101 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K0D3, A0A1L8GR68, A0JPP1, B5DF11, D3ZTQ1, O88878, P17095, P17096, P28667, P29536, P35566, P49006, P51608, P52926, P52927, P84798, Q00566, Q0VBZ9, Q15004, Q15054, Q3USH5, Q3UZA1, Q3ZBT0, Q5BK20, Q5EG55, Q5XG50, Q5ZK28, Q60974, Q69Z61, Q6DGQ4, Q6JBY9, Q6PGH2, Q6URC2, Q86XZ4, Q86YP4, Q8BVA4, Q8CHY6, Q8K1N4, Q8K585, Q8N228

Diamond homologs: Q15004, Q5E9B2, Q5HZL4, Q6AZL2, Q6RIA2, Q9CQX4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATF3	“up-regulates quantity by expression”	PCLAF	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

750 predictions. Top by Δscore:

Variant	Effect	Δscore
15:64376741:A:AC	donor_gain	1.0000
15:64376742:C:CA	donor_gain	1.0000
15:64376742:CTTT:C	donor_gain	1.0000
15:64376901:TTCAG:T	acceptor_gain	1.0000
15:64376902:TCAG:T	acceptor_gain	1.0000
15:64376903:CAG:C	acceptor_gain	1.0000
15:64376903:CAGC:C	acceptor_gain	1.0000
15:64376906:C:CC	acceptor_gain	1.0000
15:64381034:CACCA:C	acceptor_gain	1.0000
15:64381035:ACCA:A	acceptor_gain	1.0000
15:64381036:CCA:C	acceptor_gain	1.0000
15:64381036:CCAC:C	acceptor_gain	1.0000
15:64381037:CA:C	acceptor_gain	1.0000
15:64381037:CAC:C	acceptor_gain	1.0000
15:64381037:CACTG:C	acceptor_gain	1.0000
15:64381039:C:CC	acceptor_gain	1.0000
15:64381323:CACCT:C	donor_loss	1.0000
15:64381325:C:CG	donor_loss	1.0000
15:64381325:C:G	donor_loss	1.0000
15:64376736:AACT:A	donor_loss	0.9900
15:64376736:AACTT:A	donor_loss	0.9900
15:64376737:ACTTA:A	donor_loss	0.9900
15:64376738:CT:C	donor_loss	0.9900
15:64376739:T:TC	donor_loss	0.9900
15:64376740:T:TC	donor_loss	0.9900
15:64376741:AC:A	donor_loss	0.9900
15:64376741:ACTTT:A	donor_gain	0.9900
15:64376742:CT:C	donor_gain	0.9900
15:64376742:CTT:C	donor_gain	0.9900
15:64376742:CTTTC:C	donor_gain	0.9900

AlphaMissense

706 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:64376852:A:G	W61R	0.998
15:64376852:A:T	W61R	0.998
15:64376850:C:A	W61C	0.997
15:64376850:C:G	W61C	0.997
15:64376829:G:C	F68L	0.995
15:64376829:G:T	F68L	0.995
15:64376831:A:G	F68L	0.995
15:64376847:T:A	Q62H	0.993
15:64376847:T:G	Q62H	0.993
15:64376851:C:G	W61S	0.990
15:64376830:A:G	F68S	0.988
15:64376851:C:A	W61L	0.986
15:64376857:G:T	P59H	0.978
15:64376875:A:T	V53D	0.977
15:64376848:T:G	Q62P	0.975
15:64381361:G:A	T4I	0.973
15:64376839:A:T	I65N	0.972
15:64376880:G:C	N51K	0.972
15:64376880:G:T	N51K	0.972
15:64376852:A:C	W61G	0.971
15:64376858:G:A	P59S	0.969
15:64376839:A:C	I65S	0.964
15:64381023:G:T	A21D	0.959
15:64376830:A:C	F68C	0.958
15:64381364:C:G	R3P	0.957
15:64376857:G:C	P59R	0.955
15:64376867:G:T	R56S	0.955
15:64376858:G:T	P59T	0.953
15:64381032:G:T	A18D	0.952
15:64381013:C:A	K24N	0.948

dbSNP variants (sampled 300 via entrez): RS1000029826 (15:64383845 C>G), RS1000047199 (15:64377908 C>G,T), RS1000052251 (15:64379350 G>T), RS1000130516 (15:64366703 T>A,C), RS1000220255 (15:64389473 A>G), RS1000417702 (15:64383461 G>A,C), RS1000473132 (15:64388802 C>G,T), RS1000491442 (15:64383754 C>A), RS1000513211 (15:64371665 G>A), RS1000565592 (15:64365930 G>A,C), RS1000710104 (15:64372283 C>G,T), RS1000742450 (15:64365164 G>A,C), RS1000755064 (15:64371902 C>A,G), RS1000998788 (15:64377338 G>A), RS1001002242 (15:64379486 A>G)

Disease associations

OMIM: gene MIM:610696 | 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
GCST005232_36	Neuroticism	3.000000e-07
GCST90002398_284	Neutrophil count	7.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5465218 (PROTEIN-PROTEIN INTERACTION), CHEMBL5574 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.21	Kd	6100	nM	CHEMBL5439922

PubChem BioAssay actives

1 with measured affinity, of 17 total; 1 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
8-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N,N-bis[2-[[(1R,5R,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]ethyl]octanamide	1976061: Binding affinity to PCLAF (unknown origin) assessed as equilibrium dissociation constant by SPR assay	kd	6.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, affects expression, decreases expression, increases expression	5
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	5
sodium arsenite	decreases expression, increases expression	4
Estradiol	decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression	3
Cyclosporine	affects expression, decreases expression	3
Fluorouracil	affects cotreatment, decreases expression	2
Progesterone	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	affects expression, increases expression	2
Genistein	decreases expression, increases expression	2
Particulate Matter	increases abundance, decreases expression	2
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
propionaldehyde	decreases expression	1
arsenite	increases reaction, affects binding	1
afimoxifene	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
gossypol acetic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
diallyl trisulfide	decreases expression	1
phenethyl isothiocyanate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	decreases expression	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5328552	Binding	PROTAC activity at CRBN/PCLAF in human RS4-11 cells assessed as degradation of PCLAF protein at 100 nM incubated for 12 hrs by Western blotting analysis	Facilitated Drug Repurposing with Artemisinin-Derived PROTACs: Unveiling PCLAF as a Therapeutic Target. — J Med Chem

Clinical trials (associated diseases)

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