PWP1

Summary

PWP1 (PWP1 homolog, endonuclein, HGNC:17015) is a protein-coding gene on chromosome 12q23.3, encoding Periodic tryptophan protein 1 homolog (Q13610). Chromatin-associated factor that regulates transcription. It is a selective cancer dependency (DepMap: 83.5% of cell lines).

The protein encoded by this gene contains several WD-40 repeats and is found mostly in the nucleus. The expression and localization of this protein are cell cycle dependent. Expression of this gene is upregulated in pancreatic adenocarcinoma. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 11137 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 70 total
• Cancer dependency (DepMap): dependent in 83.5% of screened cell lines
• MANE Select transcript: NM_007062

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17015
Approved symbol	PWP1
Name	PWP1 homolog, endonuclein
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	IEF-SSP-9502
Ensembl gene	ENSG00000136045
Ensembl biotype	protein_coding
OMIM	620055
Entrez	11137

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000412830, ENST00000541166, ENST00000547120, ENST00000547995, ENST00000552760, ENST00000867450, ENST00000920793, ENST00000920794, ENST00000920795, ENST00000920796, ENST00000945394, ENST00000945395

RefSeq mRNA: 3 — MANE Select: NM_007062 NM_001317962, NM_001317963, NM_007062

CCDS: CCDS81735, CCDS9114

Canonical transcript exons

ENST00000412830 — 15 exons

Exon	Start	End
ENSE00000923100	107692814	107692899
ENSE00000923103	107697467	107697597
ENSE00000923104	107699373	107699434
ENSE00000923105	107702935	107703031
ENSE00000923106	107703685	107703746
ENSE00000923107	107704636	107704747
ENSE00000923108	107708926	107709016
ENSE00000923109	107709111	107709232
ENSE00000923110	107710405	107710510
ENSE00002270920	107712111	107713162
ENSE00002420342	107685799	107685971
ENSE00003471987	107693000	107693096
ENSE00003479325	107688448	107688506
ENSE00003499155	107688615	107688802
ENSE00003564677	107696474	107696584

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.9339 / max 553.9949, expressed in 1829 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127859	55.1330	1829
127860	1.8396	1127
127862	0.8354	464
127861	0.1259	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.86	gold quality
oocyte	CL:0000023	98.74	gold quality
nipple	UBERON:0002030	98.24	gold quality
pylorus	UBERON:0001166	96.85	gold quality
cardia of stomach	UBERON:0001162	96.29	gold quality
tongue squamous epithelium	UBERON:0006919	96.00	gold quality
renal medulla	UBERON:0000362	95.74	gold quality
pericardium	UBERON:0002407	95.25	gold quality
calcaneal tendon	UBERON:0003701	95.14	gold quality
cortical plate	UBERON:0005343	95.06	gold quality
mammalian vulva	UBERON:0000997	95.05	gold quality
pons	UBERON:0000988	95.01	gold quality
parietal pleura	UBERON:0002400	95.01	gold quality
urethra	UBERON:0000057	94.99	gold quality
pharyngeal mucosa	UBERON:0000355	94.95	gold quality
tibia	UBERON:0000979	94.92	gold quality
mammary duct	UBERON:0001765	94.89	gold quality
epithelium of mammary gland	UBERON:0003244	94.86	gold quality
pleura	UBERON:0000977	94.82	gold quality
saphenous vein	UBERON:0007318	94.82	gold quality
cauda epididymis	UBERON:0004360	94.78	gold quality
visceral pleura	UBERON:0002401	94.76	gold quality
ventral tegmental area	UBERON:0002691	94.64	gold quality
adult organism	UBERON:0007023	94.47	gold quality
penis	UBERON:0000989	94.39	gold quality
entorhinal cortex	UBERON:0002728	94.37	gold quality
cranial nerve II	UBERON:0000941	94.32	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.31	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.30	gold quality
superior surface of tongue	UBERON:0007371	94.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

44 targeting PWP1, 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-223-3P	99.99	70.14	1140
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-7977	98.65	66.18	2590

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 83.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Endonuclein interacts with several proteins indicating a broad function including signal transduction and chaperone activity (PMID:20028516)
• High PWP1 expression is associated with head and neck squamous cell carcinoma. (PMID:29065309)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pwp1	ENSDARG00000015921
mus_musculus	Pwp1	ENSMUSG00000001785
rattus_norvegicus	Pwp1	ENSRNOG00000005350
drosophila_melanogaster	nclb	FBGN0263510
caenorhabditis_elegans		WBGENE00021316

Protein

Protein identifiers

Periodic tryptophan protein 1 homolog — Q13610 (reviewed: Q13610)

Alternative names: Keratinocyte protein IEF SSP 9502

All UniProt accessions (3): B4DJV5, Q13610, F8VZ56

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin-associated factor that regulates transcription. Regulates Pol I-mediated rRNA biogenesis and, probably, Pol III-mediated transcription. Regulates the epigenetic status of rDNA.

Subunit / interactions. Associates with the RNA polymerase (Pol I) complex. Interacts with POLR1E.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Tissue specificity. High levels seen in the placenta, skeletal muscle, kidney and pancreas while lower levels were seen in the heart, brain and lung.

Similarity. Belongs to the WD repeat PWP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13610-1	1	yes
Q13610-2	2

RefSeq proteins (3): NP_001304891, NP_001304892, NP_008993* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR044285	PWP1	Family

Pfam: PF00400

UniProt features (21 total): modified residue 8, repeat 7, splice variant 2, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13610-F1	81.45	0.62

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): 21, 50, 55, 57, 59, 86, 485, 494

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 228 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MORF_MTA1, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RIBOSOME_BIOGENESIS, GRUETZMANN_PANCREATIC_CANCER_DN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GCM_NPM1, MORF_CDK2, MORF_HDAC2, GOBP_RRNA_TRANSCRIPTION, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, GCM_PPP1CC, MORF_RAF1, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION

GO Biological Process (8): DNA-templated transcription (GO:0006351), rRNA processing (GO:0006364), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription of nucleolar large rRNA by RNA polymerase I (GO:1901838), positive regulation of stem cell differentiation (GO:2000738), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355), ribosome biogenesis (GO:0042254)

GO Molecular Function (3): histone chaperone activity (GO:0140713), histone H4K20me3 reader activity (GO:1990889), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), chromosome (GO:0005694), nucleolus (GO:0005730), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
intracellular membrane-bounded organelle	2
intracellular membraneless organelle	2
gene expression	1
RNA biosynthetic process	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
nucleolar large rRNA transcription by RNA polymerase I	1
positive regulation of transcription by RNA polymerase I	1
regulation of transcription of nucleolar large rRNA by RNA polymerase I	1
positive regulation of cell differentiation	1
stem cell differentiation	1
regulation of stem cell differentiation	1
cellular component organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
ribonucleoprotein complex biogenesis	1
histone binding	1
protein carrier activity	1
histone H4 reader activity	1
binding	1
nuclear lumen	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

2398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PWP1	EBNA1BP2	Q99848	860
PWP1	TBL3	Q12788	720
PWP1	PDCD11	Q14690	709
PWP1	PWP2	Q15269	678
PWP1	WDR12	Q9GZL7	673
PWP1	NSA2	O95478	663
PWP1	RPF2	Q9H7B2	601
PWP1	WDR3	Q9UNX4	598
PWP1	TYW1	Q9NV66	575
PWP1	GNL2	Q13823	562
PWP1	RRP15	Q9Y3B9	558
PWP1	UTP6	Q9NYH9	550
PWP1	RSL24D1	Q9UHA3	503
PWP1	SDF2L1	Q9HCN8	491
PWP1	BRIX1	Q8TDN6	491

IntAct

103 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
TUBG1	TUBG1	psi-mi:“MI:2364”(proximity)	0.760
PWP1	ANK3	psi-mi:“MI:0914”(association)	0.530
RPL7A	NVL	psi-mi:“MI:0914”(association)	0.530
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
PWP1	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
PWP1	TNS2	psi-mi:“MI:0915”(physical association)	0.370
PIK3R3	PWP1	psi-mi:“MI:0915”(physical association)	0.370
HOXA3	PWP1	psi-mi:“MI:0915”(physical association)	0.370
NFYA	PWP1	psi-mi:“MI:0915”(physical association)	0.370
Srp72		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
C9orf72	CHD2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
NEDD8	DDX3X	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
RPL15	PRMT5	psi-mi:“MI:0914”(association)	0.350
PTPRR	TCP1	psi-mi:“MI:0914”(association)	0.350
TSPYL5	CBX4	psi-mi:“MI:0914”(association)	0.350
rep	NOP56	psi-mi:“MI:0914”(association)	0.350

BioGRID (500): PWP1 (Affinity Capture-MS), PWP1 (Affinity Capture-MS), PWP1 (Affinity Capture-MS), FBL (Co-fractionation), GTPBP4 (Co-fractionation), KIAA0020 (Co-fractionation), PWP1 (Co-fractionation), PWP1 (Co-fractionation), PWP1 (Co-fractionation), PWP1 (Co-fractionation), PWP1 (Co-fractionation), PWP1 (Co-fractionation), PWP1 (Co-fractionation), PWP1 (Co-fractionation), TOP1 (Co-fractionation)

ESM2 similar proteins: A1L112, A4IHS2, A8NZM5, B2ZZS9, O00423, O80775, O95834, P93107, P97452, Q05BC3, Q0DYP5, Q13216, Q13610, Q13685, Q15269, Q1JQD2, Q2HJ56, Q32KQ2, Q32P44, Q3SZK1, Q4V8C3, Q562C2, Q58DT8, Q5BIM8, Q5F3K4, Q5R9T6, Q5RCG7, Q5RFQ3, Q5VU92, Q5XI13, Q5ZK69, Q6DRF9, Q6P6T4, Q6PFM9, Q7TNG5, Q7YR70, Q810D6, Q8BH57, Q8BHB4, Q8BU03

Diamond homologs: A1Z8D0, O17468, Q13610, Q2HJ56, Q54YD8, Q99LL5, Q9P775, P21304, Q5R1S9, A5GFN6, A7EZJ5, O13923, O13985, O14435, O35353, O93277, O94620, P29387, P54311, P62871, P62872, P62873, P62874, P78406, P79959, Q04199, Q13112, Q3MV14, Q3SWS8, Q4IBR4, Q4R6D2, Q5E9A4, Q5FVA9, Q5GIS3, Q5R5W8, Q5RF99, Q6PH57, Q6ZD63, Q7RZI0, Q7ZWF0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
Constitutive Signaling by Aberrant PI3K in Cancer	7	8.8×	6e-03
PIP3 activates AKT signaling	9	6.0×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	5	16.6×	1e-03
cell surface receptor protein tyrosine kinase signaling pathway	10	13.7×	2e-06
regulation of autophagy	5	9.5×	9e-03
neuron differentiation	10	7.9×	1e-04
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	12	7.4×	2e-05
gene expression	9	5.7×	3e-03
protein stabilization	10	5.3×	2e-03
positive regulation of MAPK cascade	8	5.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1809 predictions. Top by Δscore:

Variant	Effect	Δscore
12:107685972:G:GC	donor_loss	1.0000
12:107685973:T:G	donor_loss	1.0000
12:107688445:CA:C	acceptor_loss	1.0000
12:107688446:A:AG	acceptor_gain	1.0000
12:107688447:G:GA	acceptor_gain	1.0000
12:107688447:GGT:G	acceptor_gain	1.0000
12:107688447:GGTA:G	acceptor_gain	1.0000
12:107688502:TTGCA:T	donor_gain	1.0000
12:107688503:TGCA:T	donor_gain	1.0000
12:107688504:GCA:G	donor_gain	1.0000
12:107688504:GCAG:G	donor_gain	1.0000
12:107688505:CA:C	donor_gain	1.0000
12:107688506:AG:A	donor_loss	1.0000
12:107688507:G:C	donor_loss	1.0000
12:107688507:G:GG	donor_gain	1.0000
12:107688508:TAA:T	donor_loss	1.0000
12:107688604:T:A	acceptor_gain	1.0000
12:107688606:T:TA	acceptor_gain	1.0000
12:107688611:A:AG	acceptor_gain	1.0000
12:107688612:T:G	acceptor_gain	1.0000
12:107688613:A:AG	acceptor_gain	1.0000
12:107688614:G:GC	acceptor_gain	1.0000
12:107688614:GA:G	acceptor_gain	1.0000
12:107688614:GAGA:G	acceptor_gain	1.0000
12:107688614:GAGAA:G	acceptor_gain	1.0000
12:107688738:G:GT	donor_gain	1.0000
12:107688759:GGC:G	donor_gain	1.0000
12:107688760:GC:G	donor_gain	1.0000
12:107688761:C:G	donor_gain	1.0000
12:107688765:G:GG	donor_gain	1.0000

AlphaMissense

3322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:107697479:C:A	A209D	1.000
12:107699404:T:A	V259D	1.000
12:107702948:A:C	S274R	1.000
12:107702950:T:A	S274R	1.000
12:107702950:T:G	S274R	1.000
12:107702978:T:A	W284R	1.000
12:107702978:T:C	W284R	1.000
12:107704718:T:A	W350R	1.000
12:107704718:T:C	W350R	1.000
12:107709122:A:C	S394R	1.000
12:107709124:C:A	S394R	1.000
12:107709124:C:G	S394R	1.000
12:107697511:T:A	W220R	0.999
12:107697511:T:C	W220R	0.999
12:107702946:C:A	A273E	0.999
12:107702954:T:C	S276P	0.999
12:107702960:G:C	D278H	0.999
12:107702980:G:C	W284C	0.999
12:107702980:G:T	W284C	0.999
12:107703686:T:A	V302D	0.999
12:107703700:T:C	F307L	0.999
12:107703702:T:A	F307L	0.999
12:107703702:T:G	F307L	0.999
12:107703725:T:C	L315P	0.999
12:107703734:G:A	G318D	0.999
12:107708929:A:C	S361R	0.999
12:107708931:T:A	S361R	0.999
12:107708931:T:G	S361R	0.999
12:107708942:G:A	G365D	0.999
12:107708942:G:T	G365V	0.999

dbSNP variants (sampled 300 via entrez): RS1000061216 (12:107689739 C>G), RS1000076371 (12:107693991 A>G), RS1000112495 (12:107711187 G>A), RS1000156109 (12:107701361 C>T), RS1000194906 (12:107710910 T>A,C), RS1000209346 (12:107701108 G>A), RS1000246255 (12:107695091 T>A), RS1000274163 (12:107695139 G>A), RS1000407001 (12:107695421 A>C), RS1000696119 (12:107684397 G>A,C,T), RS1000725161 (12:107684037 G>C), RS1000784263 (12:107687617 C>A,T), RS1000846879 (12:107691051 A>G), RS1000907280 (12:107706817 T>C), RS1001012369 (12:107697003 G>T)

Disease associations

OMIM: gene MIM:620055 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002481_2	Acne (severe)	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
sodium arsenite	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
geraniol	decreases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diethylstilbestrol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Potassium Dichromate	increases expression	1
Quercetin	decreases expression	1
Selenium	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Vitamin E	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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