PWP2

Summary

PWP2 (PWP2 small subunit processome component, HGNC:9711) is a protein-coding gene on chromosome 21q22.3, encoding Periodic tryptophan protein 2 homolog (Q15269). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. It is a common-essential gene (DepMap: required in 99.2% of cancer cell lines).

Enables RNA binding activity. Involved in ribosomal small subunit biogenesis. Part of small-subunit processome.

Source: NCBI Gene 5822 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 196 total
• Cancer dependency (DepMap): dependent in 99.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_005049

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9711
Approved symbol	PWP2
Name	PWP2 small subunit processome component
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	EHOC-17, UTP1
Ensembl gene	ENSG00000241945
Ensembl biotype	protein_coding
OMIM	601475
Entrez	5822

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000291576, ENST00000456705, ENST00000471490, ENST00000476948, ENST00000486126, ENST00000494310, ENST00000862525, ENST00000862526

RefSeq mRNA: 1 — MANE Select: NM_005049 NM_005049

CCDS: CCDS33579

Canonical transcript exons

ENST00000291576 — 21 exons

Exon	Start	End
ENSE00001050666	44120952	44121102
ENSE00001050669	44119387	44119523
ENSE00001050670	44117820	44117963
ENSE00001050672	44114179	44114278
ENSE00001050675	44124580	44124727
ENSE00001050676	44113753	44113847
ENSE00001050680	44122177	44122357
ENSE00001050681	44118763	44118833
ENSE00001050684	44130597	44131181
ENSE00001177844	44108984	44109096
ENSE00001367795	44107399	44107434
ENSE00003469591	44126900	44126965
ENSE00003545412	44127932	44128150
ENSE00003554676	44128552	44128626
ENSE00003579779	44114625	44114768
ENSE00003592879	44128247	44128397
ENSE00003612411	44120348	44120496
ENSE00003652919	44126011	44126119
ENSE00003660102	44115691	44115920
ENSE00003671210	44120631	44120778
ENSE00003682861	44115264	44115399

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 85.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.5733 / max 56.5763, expressed in 1109 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189425	1.1477	553
189424	1.1175	696
209213	0.3081	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	85.31	gold quality
corpus callosum	UBERON:0002336	84.61	gold quality
mucosa of transverse colon	UBERON:0004991	84.12	gold quality
mucosa of stomach	UBERON:0001199	82.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.37	gold quality
skeletal muscle tissue	UBERON:0001134	79.89	gold quality
sural nerve	UBERON:0015488	79.79	gold quality
prefrontal cortex	UBERON:0000451	78.89	gold quality
right adrenal gland	UBERON:0001233	78.43	gold quality
blood	UBERON:0000178	77.82	gold quality
calcaneal tendon	UBERON:0003701	77.80	gold quality
spleen	UBERON:0002106	77.78	gold quality
tonsil	UBERON:0002372	77.33	gold quality
muscle tissue	UBERON:0002385	77.23	gold quality
endocervix	UBERON:0000458	77.19	gold quality
ectocervix	UBERON:0012249	76.88	gold quality
right ovary	UBERON:0002118	76.87	gold quality
frontal cortex	UBERON:0001870	76.77	gold quality
tibial nerve	UBERON:0001323	76.75	gold quality
muscle organ	UBERON:0001630	76.61	gold quality
skeletal muscle organ	UBERON:0014892	76.61	gold quality
right lobe of thyroid gland	UBERON:0001119	76.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.51	gold quality
right adrenal gland cortex	UBERON:0035827	76.49	gold quality
muscle of leg	UBERON:0001383	76.48	gold quality
omental fat pad	UBERON:0010414	76.45	gold quality
urinary bladder	UBERON:0001255	76.29	gold quality
gastrocnemius	UBERON:0001388	76.26	gold quality
left adrenal gland cortex	UBERON:0035825	76.17	gold quality
left adrenal gland	UBERON:0001234	76.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	120.96
E-CURD-11	no	104.37
E-ANND-3	no	2.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

15 targeting PWP2, 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-1305	99.91	71.43	3443
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-3184-3P	96.96	66.91	845
HSA-MIR-664B-5P	96.74	67.50	509
HSA-MIR-6800-3P	96.15	65.16	461

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.2% of screened cell lines, common-essential.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pwp2h	ENSDARG00000037109
mus_musculus	Pwp2	ENSMUSG00000032834
rattus_norvegicus	Pwp2	ENSRNOG00000001210
drosophila_melanogaster	CG12325	FBGN0033557
caenorhabditis_elegans	F55F8.3	WBGENE00018891

Protein

Protein identifiers

Periodic tryptophan protein 2 homolog — Q15269 (reviewed: Q15269)

All UniProt accessions (2): Q15269, C9J544

UniProt curated annotations — full annotation on UniProt →

Function. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the WD repeat PWP2 family.

RefSeq proteins (1): NP_005040* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR007148	SSU_processome_Utp12	Domain
IPR011047	Quinoprotein_ADH-like_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR027145	PWP2	Family

Pfam: PF00400, PF04003

UniProt features (26 total): repeat 14, compositionally biased region 3, sequence variant 3, region of interest 2, modified residue 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15269-F1	86.48	0.63

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 (2): 898, 902

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 153 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_RIBOSOME_BIOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MATURATION_OF_SSU_RRNA, GOBP_RIBOSOME_ASSEMBLY, RIZKI_TUMOR_INVASIVENESS_3D_DN, NAGASHIMA_NRG1_SIGNALING_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, MODULE_120, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, PETRETTO_HEART_MASS_QTL_CIS_DN, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, MORF_PRKDC, GOBP_ORGANELLE_ASSEMBLY

GO Biological Process (3): ribosomal small subunit assembly (GO:0000028), maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), ribosomal small subunit biogenesis (GO:0042274)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), small-subunit processome (GO:0032040), Pwp2p-containing subcomplex of 90S preribosome (GO:0034388), nucleus (GO:0005634), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
nucleolus	2
nuclear protein-containing complex	2
protein-RNA complex assembly	1
ribosome assembly	1
ribosomal small subunit biogenesis	1
maturation of SSU-rRNA	1
ribonucleoprotein complex biogenesis	1
ribosome biogenesis	1
nucleic acid binding	1
binding	1
cellular anatomical structure	1
preribosome	1
t-UTP complex	1
90S preribosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1855 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PWP2	UTP18	Q9Y5J1	963
PWP2	TBL3	Q12788	949
PWP2	UTP6	Q9NYH9	932
PWP2	TRAPPC10	P48553	924
PWP2	WDR3	Q9UNX4	904
PWP2	WDR36	Q8NI36	887
PWP2	UTP4	Q969X6	852
PWP2	HEATR1	Q9H583	852
PWP2	PDCD11	Q14690	819
PWP2	MPHOSPH10	O00566	817
PWP2	WDR43	Q15061	815
PWP2	PFKL	P17858	803
PWP2	NOP14	P78316	777
PWP2	NOL6	Q9H6R4	773
PWP2	UTP14A	Q9BVJ6	768

IntAct

80 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
EXOSC5	ZFC3H1	psi-mi:“MI:0914”(association)	0.640
PWP2	FBL	psi-mi:“MI:0914”(association)	0.610
UTP18	PWP2	psi-mi:“MI:0915”(physical association)	0.560
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
ZNF71	NVL	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RBM4	NVL	psi-mi:“MI:0914”(association)	0.530
EXOSC4	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
Atrx	ELOC	psi-mi:“MI:0914”(association)	0.350
BAG6	CNOT1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
DDX41	DDX39A	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (199): PWP2 (Affinity Capture-MS), PWP2 (Affinity Capture-MS), PWP2 (Affinity Capture-MS), PWP2 (Affinity Capture-MS), PWP2 (Affinity Capture-MS), MPHOSPH10 (Co-fractionation), PWP2 (Co-fractionation), PWP2 (Co-fractionation), PWP2 (Co-fractionation), PWP2 (Co-fractionation), PWP2 (Co-fractionation), TBL3 (Co-fractionation), WDR36 (Co-fractionation), PWP2 (Affinity Capture-MS), PWP2 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IC37, A0JN52, A1A4K3, E9PY46, O49552, P0CR22, P0CR23, P0DKL4, P0DKL6, P33194, P59015, Q15269, Q15393, Q16531, Q1LVE8, Q21554, Q3U1J4, Q3V3N7, Q4PGM6, Q4WLI5, Q52E49, Q5B1X8, Q5R649, Q5RBI5, Q5RFQ3, Q6AX60, Q6E7D1, Q6L4S0, Q6P6Z0, Q6QNU4, Q7RYR4, Q805F9, Q811G0, Q8BU03, Q8NFJ9, Q8R2N2, Q921M3, Q93VQ0, Q969X6, Q96RY7

Diamond homologs: A0A1L8I2C5, A0A396ISC0, A3LQ86, D3Z3I0, F4K5R6, O13286, O94411, O94423, O94620, P25387, P26309, P53197, P78972, Q09786, Q12834, Q15269, Q3E906, Q4PSE4, Q54KM3, Q54MZ3, Q5H7C0, Q5RFQ3, Q62623, Q86Y33, Q8L3Z8, Q8LPL5, Q8NEZ3, Q8VZS9, Q93134, Q9JJ66, Q9M7I2, Q9P783, Q9R1K5, Q9S7H3, Q9S7I8, Q9SZA4, Q9UM11, A1CF18, A1CUD6, A1DP19

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PWP2	“form complex”	“UTP-B complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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
rRNA modification in the nucleus and cytosol	6	14.0×	9e-04
Major pathway of rRNA processing in the nucleolus and cytosol	14	10.8×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	8	18.4×	4e-06
rRNA processing	11	15.7×	7e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	157
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3952 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44107433:GG:G	donor_gain	1.0000
21:44107434:GG:G	donor_gain	1.0000
21:44108982:A:AG	acceptor_gain	1.0000
21:44108983:G:GA	acceptor_gain	1.0000
21:44108983:GTTTT:G	acceptor_gain	1.0000
21:44109093:AAAAG:A	donor_loss	1.0000
21:44109094:AAA:A	donor_gain	1.0000
21:44109095:AA:A	donor_gain	1.0000
21:44109095:AAG:A	donor_loss	1.0000
21:44109096:AG:A	donor_loss	1.0000
21:44109096:AGT:A	donor_loss	1.0000
21:44109097:G:GG	donor_gain	1.0000
21:44109098:TA:T	donor_loss	1.0000
21:44109099:AAG:A	donor_loss	1.0000
21:44113747:TATCA:T	acceptor_loss	1.0000
21:44113748:A:AG	acceptor_gain	1.0000
21:44113748:ATCAG:A	acceptor_loss	1.0000
21:44113749:TCAGC:T	acceptor_loss	1.0000
21:44113750:CAG:C	acceptor_loss	1.0000
21:44113751:A:AG	acceptor_gain	1.0000
21:44113751:A:C	acceptor_loss	1.0000
21:44113751:AGCAA:A	acceptor_loss	1.0000
21:44113752:G:GA	acceptor_gain	1.0000
21:44113752:GC:G	acceptor_gain	1.0000
21:44113752:GCA:G	acceptor_gain	1.0000
21:44113752:GCAA:G	acceptor_gain	1.0000
21:44113752:GCAAC:G	acceptor_gain	1.0000
21:44113844:GAAG:G	donor_gain	1.0000
21:44113845:AAGG:A	donor_loss	1.0000
21:44113848:G:GG	donor_gain	1.0000

AlphaMissense

6033 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44121018:A:C	S518R	1.000
21:44121020:T:A	S518R	1.000
21:44121020:T:G	S518R	1.000
21:44120478:G:C	R440P	0.999
21:44120481:C:A	A441D	0.999
21:44120496:G:T	R446M	0.999
21:44120636:G:C	R448P	0.999
21:44120641:T:C	F450L	0.999
21:44120643:C:A	F450L	0.999
21:44120643:C:G	F450L	0.999
21:44120645:G:C	R451P	0.999
21:44120749:T:A	W486R	0.999
21:44120749:T:C	W486R	0.999
21:44109056:A:C	S31R	0.998
21:44109058:T:A	S31R	0.998
21:44109058:T:G	S31R	0.998
21:44114752:T:A	W152R	0.998
21:44114752:T:C	W152R	0.998
21:44119399:T:C	L355P	0.998
21:44120357:T:A	W400R	0.998
21:44120357:T:C	W400R	0.998
21:44120459:T:C	S434P	0.998
21:44120496:G:C	R446T	0.998
21:44120642:T:C	F450S	0.998
21:44120711:T:A	V473D	0.998
21:44120717:C:A	A475E	0.998
21:44119407:T:A	W358R	0.997
21:44119407:T:C	W358R	0.997
21:44120460:C:A	S434Y	0.997
21:44120460:C:T	S434F	0.997

dbSNP variants (sampled 300 via entrez): RS1000238161 (21:44129147 TCTC>T), RS1000610771 (21:44107341 G>C), RS1000769465 (21:44119531 C>T), RS1000807591 (21:44116477 CAGACG>C), RS1001398802 (21:44131593 C>T), RS1001469398 (21:44114427 G>A), RS1002122390 (21:44110087 C>G,T), RS1002209759 (21:44106684 C>G), RS1002283319 (21:44106356 T>C), RS1003151000 (21:44113585 C>G), RS1003297313 (21:44117800 CTT>C), RS1003399675 (21:44109196 C>T), RS1003808741 (21:44122159 C>G), RS1004067662 (21:44106942 C>T), RS1004123680 (21:44111822 C>T)

Disease associations

OMIM: gene MIM:601475 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Genistein	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	increases expression	1
coumarin	affects phosphorylation	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Benztropine	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Clozapine	increases expression	1
Copper	affects binding, decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1

Clinical trials (associated diseases)

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