WDR18

Summary

WDR18 (WD repeat domain 18, HGNC:17956) is a protein-coding gene on chromosome 19p13.3, encoding WD repeat-containing protein 18 (Q9BV38). Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. It is a common-essential gene (DepMap: required in 97.6% of cancer cell lines).

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation.

Source: NCBI Gene 57418 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 103 total
• Cancer dependency (DepMap): dependent in 97.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_024100

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17956
Approved symbol	WDR18
Name	WD repeat domain 18
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Ipi3
Ensembl gene	ENSG00000065268
Ensembl biotype	protein_coding
OMIM	620291
Entrez	57418

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000251289, ENST00000585809, ENST00000586317, ENST00000587001, ENST00000590354, ENST00000590397, ENST00000591155, ENST00000591276, ENST00000591985, ENST00000591997, ENST00000607440, ENST00000886861, ENST00000886862, ENST00000886863, ENST00000886864, ENST00000886865, ENST00000886866, ENST00000933665, ENST00000933666, ENST00000966179, ENST00000966180

RefSeq mRNA: 3 — MANE Select: NM_024100 NM_001372085, NM_001372086, NM_024100

CCDS: CCDS12051

Canonical transcript exons

ENST00000585809 — 10 exons

Exon	Start	End
ENSE00000769050	991227	991351
ENSE00003470967	991081	991145
ENSE00003476037	990852	990995
ENSE00003520328	991955	992121
ENSE00003655074	994020	994088
ENSE00003695817	990223	990364
ENSE00003696165	985865	985975
ENSE00003697285	989762	989895
ENSE00003899723	994213	994557
ENSE00003903699	984345	984563

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 94.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.9907 / max 135.4164, expressed in 1795 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172822	21.5278	1794
172823	1.0395	644
172824	0.4234	170

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.51	gold quality
cerebellar hemisphere	UBERON:0002245	93.84	gold quality
cerebellar cortex	UBERON:0002129	93.65	gold quality
right lobe of liver	UBERON:0001114	93.39	gold quality
mucosa of transverse colon	UBERON:0004991	92.77	gold quality
apex of heart	UBERON:0002098	92.45	gold quality
metanephros cortex	UBERON:0010533	92.29	gold quality
adenohypophysis	UBERON:0002196	92.25	gold quality
right adrenal gland cortex	UBERON:0035827	92.20	gold quality
right adrenal gland	UBERON:0001233	91.87	gold quality
right frontal lobe	UBERON:0002810	91.37	gold quality
cerebellum	UBERON:0002037	91.12	gold quality
left adrenal gland	UBERON:0001234	91.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.07	gold quality
left adrenal gland cortex	UBERON:0035825	91.06	gold quality
right lobe of thyroid gland	UBERON:0001119	91.03	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.80	gold quality
ventricular zone	UBERON:0003053	90.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.55	gold quality
pituitary gland	UBERON:0000007	90.39	gold quality
ganglionic eminence	UBERON:0004023	90.22	gold quality
esophagus mucosa	UBERON:0002469	90.03	gold quality
lower esophagus mucosa	UBERON:0035834	89.63	gold quality
granulocyte	CL:0000094	89.54	gold quality
stromal cell of endometrium	CL:0002255	89.50	gold quality
adrenal cortex	UBERON:0001235	89.37	gold quality
skin of abdomen	UBERON:0001416	89.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.08	gold quality
cingulate cortex	UBERON:0003027	89.07	gold quality
left lobe of thyroid gland	UBERON:0001120	89.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.55

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• These data define the PELP1-TEX10-WDR18 complex as a regulator of ribosome biogenesis and suggests that its SUMO-controlled distribution coordinates the rate of ribosome formation. (PMID:21326211)
• Recruitment of the protein complex 5FMC to Zbp-89, a zinc-finger transcription factor, affects its sumoylation status and transactivation potential.[5FMC] (PMID:22872859)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr18	ENSDARG00000041113
mus_musculus	Wdr18	ENSMUSG00000035754
rattus_norvegicus	Wdr18	ENSRNOG00000012379
drosophila_melanogaster	CG14805	FBGN0023514
caenorhabditis_elegans		WBGENE00004185

Protein

Protein identifiers

WD repeat-containing protein 18 — Q9BV38 (reviewed: Q9BV38)

All UniProt accessions (8): Q9BV38, A0A087X237, A0A0A0MQU0, K7EIR0, K7EKX5, K7EML4, U3KQC1, U3KQK3

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit. May play a role during development.

Subunit / interactions. Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148. Interacts with NOL9. Component of the PELP1 complex, composed of at least PELP1, TEX10 and WDR18. The complex interacts with pre-60S ribosome particles.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Cytoplasm. Dynein axonemal particle.

Similarity. Belongs to the WD repeat IPI3/WDR18 family.

RefSeq proteins (3): NP_001359014, NP_001359015, NP_077005* (*=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
IPR026987	WDR18_C	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045227	WDR18/Ipi3/RID3	Family

Pfam: PF00400, PF14077

UniProt features (47 total): strand 27, repeat 6, turn 6, helix 3, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8FL3	ELECTRON MICROSCOPY	2.53
9DUO	ELECTRON MICROSCOPY	2.66
8FL2	ELECTRON MICROSCOPY	2.67
7UWF	ELECTRON MICROSCOPY	2.7
8FL4	ELECTRON MICROSCOPY	2.89
9DUM	ELECTRON MICROSCOPY	3.56

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV38-F1	85.48	0.55

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 119 (showing top): GOBP_RIBOSOME_BIOGENESIS, BASSO_B_LYMPHOCYTE_NETWORK, MATTIOLI_MGUS_VS_PCL, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_MATURATION_OF_LSU_RRNA, MORF_PRKDC, MORF_AATF, GOBP_MATURATION_OF_5_8S_RRNA, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_RIBOSOMAL_LARGE_SUBUNIT_BIOGENESIS, GOBP_DNA_REPLICATION, REACTOME_METABOLISM_OF_RNA, GOCC_PROTEIN_DNA_COMPLEX, GOCC_NUCLEOLUS, chr19p13

GO Biological Process (2): DNA-templated DNA replication (GO:0006261), rRNA processing (GO:0006364)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), nuclear pre-replicative complex (GO:0005656), nucleolus (GO:0005730), dynein axonemal particle (GO:0120293), rixosome complex (GO:0120330), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
DNA replication	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
binding	1
origin recognition complex	1
nucleoplasm	1
pre-replicative complex	1
MCM complex	1
nuclear protein-containing complex	1
cytoplasm	1
endoribonuclease complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR18	TEX10	Q9NXF1	993
WDR18	PELP1	Q8IZL8	943
WDR18	LAS1L	Q9Y4W2	873
WDR18	MDN1	Q9NU22	832
WDR18	NOL9	Q5SY16	744
WDR18	GNL2	Q13823	711
WDR18	SENP3	Q9H4L4	682
WDR18	WDR12	Q9GZL7	673
WDR18	NSA2	O95478	639
WDR18	RPF2	Q9H7B2	630
WDR18	WDR74	Q6RFH5	552
WDR18	INPP4B	O15327	538
WDR18	INPP4A	Q96PE3	535
WDR18	RSL24D1	Q9UHA3	495
WDR18	PIK3C3	Q8NEB9	494

IntAct

97 interactions, top by confidence:

A	B	Type	Score
WDR18	PELP1	psi-mi:“MI:0915”(physical association)	0.900
PELP1	WDR18	psi-mi:“MI:0914”(association)	0.900
PELP1	WDR18	psi-mi:“MI:0915”(physical association)	0.900
PELP1	WDR18	psi-mi:“MI:0407”(direct interaction)	0.900
SENP3	WDR18	psi-mi:“MI:0915”(physical association)	0.780
WDR18	SENP3	psi-mi:“MI:0915”(physical association)	0.780
SENP3	NPM1	psi-mi:“MI:0914”(association)	0.780
BOP1	NPM1	psi-mi:“MI:0403”(colocalization)	0.710
WDR18	TEX10	psi-mi:“MI:0915”(physical association)	0.670
PELP1	ESR1	psi-mi:“MI:0914”(association)	0.600
WDR18	NOL9	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
NOL9	IPO5	psi-mi:“MI:0914”(association)	0.530
ESR1		psi-mi:“MI:0914”(association)	0.460
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
Haus8	MKI67	psi-mi:“MI:0915”(physical association)	0.400
WDR18	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
CSNK2B	WDR18	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (209): WDR18 (Affinity Capture-RNA), WDR18 (Affinity Capture-RNA), WDR18 (Affinity Capture-MS), WDR18 (Affinity Capture-MS), SENP3 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), NOL9 (Affinity Capture-MS), TEX10 (Affinity Capture-MS), ACOT2 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), CHD8 (Co-fractionation), NOL9 (Co-fractionation), PELP1 (Co-fractionation), SENP3 (Co-fractionation), TEX10 (Co-fractionation)

ESM2 similar proteins: A0A1L8HX76, A0JP70, A4IG72, A7E3S5, A7Z052, D3ZW91, E9PY46, P57081, Q05B17, Q0P5H9, Q15061, Q32P44, Q3SZD4, Q3U821, Q499N3, Q4VBE8, Q5BK48, Q5F3K4, Q5RB07, Q5RBH8, Q5RD06, Q5XFW6, Q68EI0, Q6DFC6, Q6KAU8, Q6PFM9, Q6PGF3, Q6ZQL4, Q7ZVF0, Q7ZVR1, Q7ZY78, Q8BH57, Q8C5V5, Q8IWA0, Q8N0Z6, Q8NA23, Q8NAA4, Q8VC03, Q969R8, Q96KV7

Diamond homologs: A0A1L8HX76, A4IHS2, A9UZS7, B3MHX6, B3NLK7, B4GIU9, B4HN85, B4J9K1, B4KQU8, B4MYI5, B4P528, O94411, P97412, P97452, Q14137, Q1DJF7, Q28XF0, Q3SZD4, Q499N3, Q4PHV3, Q4VBE8, Q54MZ3, Q54TD8, Q562C2, Q68EI0, Q7K0Y1, Q7PTC5, Q7T0W1, Q7ZXX9, Q86JF2, Q8C0J2, Q99698, Q9BV38, Q9M3B4, A0JMQ0, A1CQI9, A1D3F5, A2QPZ4, A3LXF0, A4H6F7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WDR18	“form complex”	“Rix1 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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 processing in the nucleus and cytosol	8	19.2×	1e-06
rRNA processing	8	17.5×	2e-06
SARS-CoV-2 modulates host translation machinery	5	16.7×	7e-04
Influenza Viral RNA Transcription and Replication	5	16.1×	8e-04
Influenza Infection	6	15.7×	2e-04
SARS-CoV-1-host interactions	5	13.1×	2e-03
Major pathway of rRNA processing in the nucleolus and cytosol	14	12.9×	1e-09
Signaling by ALK fusions and activated point mutants	5	11.2×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	6	15.3×	7e-04
cytoplasmic translation	6	12.5×	1e-03
rRNA processing	7	11.1×	7e-04
mRNA splicing, via spliceosome	7	7.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1771 predictions. Top by Δscore:

Variant	Effect	Δscore
19:984560:GAAGG:G	donor_loss	1.0000
19:984562:AG:A	donor_loss	1.0000
19:984564:G:GA	donor_loss	1.0000
19:989756:TCACA:T	acceptor_loss	1.0000
19:989759:CAGGT:C	acceptor_loss	1.0000
19:989760:A:AG	acceptor_gain	1.0000
19:989761:G:A	acceptor_loss	1.0000
19:989761:G:GG	acceptor_gain	1.0000
19:989761:GGT:G	acceptor_gain	1.0000
19:989761:GGTCT:G	acceptor_gain	1.0000
19:989860:C:T	donor_gain	1.0000
19:989893:CAG:C	donor_loss	1.0000
19:989894:AGG:A	donor_loss	1.0000
19:989895:GG:G	donor_loss	1.0000
19:989896:G:GA	donor_loss	1.0000
19:989897:T:A	donor_loss	1.0000
19:990994:GG:G	donor_gain	1.0000
19:990995:GG:G	donor_gain	1.0000
19:991224:CA:C	acceptor_loss	1.0000
19:991225:A:AG	acceptor_gain	1.0000
19:991225:A:C	acceptor_loss	1.0000
19:991225:AG:A	acceptor_gain	1.0000
19:991226:G:GG	acceptor_gain	1.0000
19:991226:GG:G	acceptor_gain	1.0000
19:991226:GGAA:G	acceptor_gain	1.0000
19:991347:CAAAG:C	donor_loss	1.0000
19:991348:AAAG:A	donor_loss	1.0000
19:991350:AGG:A	donor_loss	1.0000
19:991353:T:A	donor_loss	1.0000
19:992118:GCAG:G	donor_gain	1.0000

AlphaMissense

2806 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:991306:T:A	W296R	0.999
19:991306:T:C	W296R	0.999
19:984453:T:G	Y34D	0.998
19:984546:T:A	W65R	0.998
19:984546:T:C	W65R	0.998
19:991308:G:C	W296C	0.998
19:991308:G:T	W296C	0.998
19:991961:T:A	V313D	0.998
19:985970:T:A	W106R	0.997
19:985970:T:C	W106R	0.997
19:991280:G:A	G287D	0.997
19:991282:T:C	S288P	0.997
19:991271:T:C	L284P	0.996
19:991274:T:C	L285P	0.996
19:991276:T:C	S286P	0.996
19:991307:G:C	W296S	0.996
19:984548:G:C	W65C	0.995
19:984548:G:T	W65C	0.995
19:985902:T:A	V83D	0.995
19:989882:T:A	W148R	0.995
19:989882:T:C	W148R	0.995
19:984538:T:A	I62N	0.994
19:985972:G:C	W106C	0.994
19:985972:G:T	W106C	0.994
19:989772:G:T	G111V	0.994
19:990952:G:A	G233E	0.994
19:991301:G:C	R294P	0.994
19:991246:T:C	S276P	0.993
19:991279:G:C	G287R	0.993
19:994280:T:C	L412P	0.993

dbSNP variants (sampled 300 via entrez): RS1000117872 (19:982468 AGCTACTCGGGAG>A), RS1000234749 (19:988049 C>T), RS1000343742 (19:983504 C>G), RS1000455136 (19:981078 G>A), RS1000507062 (19:981511 C>T), RS1000525378 (19:986672 T>C,G), RS1000630869 (19:982135 C>A,G), RS1000682975 (19:982347 C>T), RS1000906922 (19:990758 C>G,T), RS1001189352 (19:986378 T>A,G), RS1001420949 (19:993951 G>A,T), RS1001504577 (19:983598 C>T), RS1001558248 (19:983745 T>A), RS1001844597 (19:982414 C>T), RS1002203626 (19:992237 G>A)

Disease associations

OMIM: gene MIM:620291 | 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

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Smoke	decreases expression, increases abundance	2
testosterone enanthate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	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, decreases expression	1
ICG 001	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Atrazine	decreases expression	1
Copper	affects binding, decreases expression	1
Dimethyl Sulfoxide	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Methotrexate	affects response to substance	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Thiram	decreases expression	1

Clinical trials (associated diseases)

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