WDR46

Summary

WDR46 (WD repeat domain 46, HGNC:13923) is a protein-coding gene on chromosome 6p21.32, encoding WD repeat-containing protein 46 (O15213). Scaffold component of the nucleolar structure. It is a common-essential gene (DepMap: required in 90.8% of cancer cell lines).

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

Source: NCBI Gene 9277 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 110 total
• Cancer dependency (DepMap): dependent in 90.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_005452

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13923
Approved symbol	WDR46
Name	WD repeat domain 46
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	BING4, UTP7
Ensembl gene	ENSG00000227057
Ensembl biotype	protein_coding
OMIM	611440
Entrez	9277

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000374617, ENST00000444176, ENST00000461951, ENST00000468157, ENST00000473611, ENST00000477718, ENST00000481025, ENST00000488944, ENST00000489905

RefSeq mRNA: 2 — MANE Select: NM_005452 NM_001164267, NM_005452

CCDS: CCDS4772

Canonical transcript exons

ENST00000374617 — 15 exons

Exon	Start	End
ENSE00001629552	33280674	33280987
ENSE00001721122	33287355	33287505
ENSE00001879074	33289102	33289239
ENSE00003461143	33288804	33289013
ENSE00003490029	33286795	33286894
ENSE00003500190	33279497	33279610
ENSE00003502793	33287965	33288026
ENSE00003575898	33279108	33279374
ENSE00003577831	33288148	33288235
ENSE00003617847	33288358	33288470
ENSE00003645709	33280428	33280522
ENSE00003654706	33288614	33288694
ENSE00003656206	33279764	33279859
ENSE00003666675	33287091	33287226
ENSE00003672336	33287614	33287718

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.8299 / max 199.6434, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73115	28.2995	1818
73114	1.4887	982
73113	0.0417	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	94.55	gold quality
stromal cell of endometrium	CL:0002255	93.96	gold quality
adenohypophysis	UBERON:0002196	93.73	gold quality
pituitary gland	UBERON:0000007	93.51	gold quality
mucosa of transverse colon	UBERON:0004991	93.20	gold quality
spleen	UBERON:0002106	92.49	gold quality
vermiform appendix	UBERON:0001154	92.07	gold quality
left testis	UBERON:0004533	92.06	gold quality
skin of leg	UBERON:0001511	92.02	gold quality
apex of heart	UBERON:0002098	92.02	gold quality
right lobe of thyroid gland	UBERON:0001119	91.99	gold quality
right testis	UBERON:0004534	91.95	gold quality
zone of skin	UBERON:0000014	91.83	gold quality
left uterine tube	UBERON:0001303	91.76	gold quality
body of uterus	UBERON:0009853	91.75	gold quality
metanephros cortex	UBERON:0010533	91.74	gold quality
sural nerve	UBERON:0015488	91.71	gold quality
monocyte	CL:0000576	91.70	gold quality
right adrenal gland	UBERON:0001233	91.69	gold quality
leukocyte	CL:0000738	91.66	gold quality
lymph node	UBERON:0000029	91.65	gold quality
testis	UBERON:0000473	91.62	gold quality
left adrenal gland cortex	UBERON:0035825	91.61	gold quality
skin of abdomen	UBERON:0001416	91.57	gold quality
left adrenal gland	UBERON:0001234	91.52	gold quality
smooth muscle tissue	UBERON:0001135	91.46	gold quality
prostate gland	UBERON:0002367	91.44	gold quality
right adrenal gland cortex	UBERON:0035827	91.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.34	gold quality
body of stomach	UBERON:0001161	91.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting WDR46, 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-2110	99.96	66.68	1930
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-4315	94.78	64.86	112

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• When WDR46 was knocked down, nucleolin and DDX21 were mislocalized from the granular component to the edges of the nucleoli. (PMID:23848194)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr46	ENSDARG00000095879
mus_musculus	Wdr46	ENSMUSG00000024312
rattus_norvegicus	Wdr46	ENSRNOG00000031171
drosophila_melanogaster	CG2260	FBGN0030000
caenorhabditis_elegans		WBGENE00009211

Protein

Protein identifiers

WD repeat-containing protein 46 — O15213 (reviewed: O15213)

Alternative names: WD repeat-containing protein BING4

All UniProt accessions (2): O15213, H0Y6G3

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold component of the nucleolar structure. Required for localization of DDX21 and NCL to the granular compartment of the nucleolus. 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. Interacts with DDX21, NCL, NOP2 and EBNA1BP2.

Subcellular location. Nucleus. Nucleolus.

RefSeq proteins (2): NP_001157739, NP_005443* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR012952	BING4_C_dom	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR040315	WDR46/Utp7	Family

Pfam: PF00400, PF08149

UniProt features (16 total): repeat 6, compositionally biased region 3, sequence variant 3, region of interest 2, chain 1, modified residue 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-O15213-F1	80.98	0.53

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 (1): 41

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: 136 (showing top): GOBP_RIBOSOME_BIOGENESIS, MODULE_255, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_MATURATION_OF_SSU_RRNA, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MODULE_317, FOXO1_01, USF_C, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, ROZANOV_MMP14_TARGETS_UP, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, HFH1_01, FISCHER_DREAM_TARGETS, LIU_CMYB_TARGETS_UP

GO Biological Process (3): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), ribosomal small subunit biogenesis (GO:0042274), rRNA processing (GO:0006364)

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

GO Cellular Component (4): nucleoplasm (GO:0005654), nucleolus (GO:0005730), small-subunit processome (GO:0032040), nucleus (GO:0005634)

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
ribosome biogenesis	2
nuclear lumen	2
maturation of SSU-rRNA	1
ribonucleoprotein complex biogenesis	1
RNA processing	1
rRNA metabolic process	1
nucleic acid binding	1
binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2111 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR46	UTP14A	Q9BVJ6	920
WDR46	TAPBP	O15533	851
WDR46	B3GALT4	O96024	829
WDR46	UTP3	Q9NQZ2	814
WDR46	PFDN6	O15212	789
WDR46	UTP11	Q9Y3A2	785
WDR46	DDX21	Q9NR30	772
WDR46	B3GALNT1	O75752	765
WDR46	RPS18	P25232	765
WDR46	DDX56	Q9NY93	764
WDR46	B3GALT2	O43825	764
WDR46	B3GALT1	Q9Y5Z6	763
WDR46	WDR36	Q8NI36	731
WDR46	DNTTIP2	Q5QJE6	724
WDR46	UTP6	Q9NYH9	689

IntAct

77 interactions, top by confidence:

A	B	Type	Score
SUMO1	CBX4	psi-mi:“MI:0914”(association)	0.600
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RBMX2	WDR46	psi-mi:“MI:0914”(association)	0.530
NPM1	WDR46	psi-mi:“MI:0914”(association)	0.480
WDR46	CANX	psi-mi:“MI:0915”(physical association)	0.400
MARK2	WDR46	psi-mi:“MI:0914”(association)	0.350
MKNK2	WDR46	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
SET	WDR46	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
ZNF677	ZNF320	psi-mi:“MI:0914”(association)	0.350
CTCFL	TARS3	psi-mi:“MI:0914”(association)	0.350
ADARB1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CCT2	WDR91	psi-mi:“MI:0914”(association)	0.350
RPS6	CCDC85C	psi-mi:“MI:0914”(association)	0.350
FGFBP1	ZNF724	psi-mi:“MI:0914”(association)	0.350
SRSF5	FBLL1	psi-mi:“MI:0914”(association)	0.350
FGF13	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
LINC02910	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
SRSF6	U2SURP	psi-mi:“MI:0914”(association)	0.350

BioGRID (259): WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), KIAA0020 (Co-fractionation), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), WDR46 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P2, A6QNR1, A8WY26, D3ZND0, O15213, O59678, P27672, P78316, Q0V8M0, Q15050, Q24K12, Q28IV8, Q2KIH4, Q2KII6, Q3T0Q8, Q3T0Z5, Q3UFY0, Q4KLC4, Q5M985, Q5RAS1, Q5RJT2, Q5TAP6, Q5TJE7, Q5ZKM1, Q640M1, Q6EJB6, Q6P0I6, Q6PFJ1, Q8BK35, Q8IY81, Q8N9T8, Q8NEJ9, Q8R3N1, Q8VDQ9, Q96BZ8, Q96EU6, Q9BRP8, Q9BRR8, Q9BVJ6, Q9C086

Diamond homologs: O15213, P40055, Q0V8F1, Q19873, Q5TJE7, Q9P4X3, Q9Z0H1, A1CF18, A2QP30, A4R3M4, A5DL92, A7RHG8, A8XZJ9, B0R0D7, B0XAF3, B5DG67, B6HP56, B6K1G6, C0NRC6, C0S902, C1GB49, C5FWH1, C5GVJ9, C5JD40, C5PFX0, C6HTE8, C7Z6H2, D4AZ50, D4DG66, D5GBI7, O13982, O35828, O43071, O54927, O54929, O60907, O89053, P31146, P57737, P58404

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
Peptide chain elongation	5	12.4×	3e-03
Viral mRNA Translation	5	12.4×	3e-03
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	5	12.3×	3e-03
Selenocysteine synthesis	5	11.8×	3e-03
Eukaryotic Translation Termination	5	11.8×	3e-03
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	5	11.5×	3e-03
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	5	11.5×	3e-03
Formation of a pool of free 40S subunits	5	11.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	5	15.1×	5e-03
cytoplasmic translation	6	13.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1693 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33279383:C:CT	acceptor_gain	1.0000
6:33279384:G:T	acceptor_gain	1.0000
6:33279493:TTAC:T	donor_loss	1.0000
6:33279494:TAC:T	donor_loss	1.0000
6:33279495:A:AG	donor_loss	1.0000
6:33279495:AC:A	donor_gain	1.0000
6:33279496:C:CA	donor_loss	1.0000
6:33279496:CC:C	donor_gain	1.0000
6:33279504:T:TA	donor_gain	1.0000
6:33279520:T:TA	donor_gain	1.0000
6:33279526:T:TA	donor_gain	1.0000
6:33279606:TAGCC:T	acceptor_gain	1.0000
6:33279609:CC:C	acceptor_gain	1.0000
6:33279610:CC:C	acceptor_gain	1.0000
6:33279610:CCT:C	acceptor_loss	1.0000
6:33279747:AGGGG:A	donor_gain	1.0000
6:33280422:CCTCA:C	donor_loss	1.0000
6:33280423:CTCA:C	donor_loss	1.0000
6:33280425:CACCT:C	donor_loss	1.0000
6:33280427:C:CA	donor_loss	1.0000
6:33280427:CCTT:C	donor_gain	1.0000
6:33280518:GGCCC:G	acceptor_gain	1.0000
6:33280519:GCCC:G	acceptor_gain	1.0000
6:33280520:CCC:C	acceptor_gain	1.0000
6:33280520:CCCC:C	acceptor_gain	1.0000
6:33280521:CC:C	acceptor_gain	1.0000
6:33280521:CCC:C	acceptor_gain	1.0000
6:33280522:CC:C	acceptor_gain	1.0000
6:33280522:CCTGA:C	acceptor_loss	1.0000
6:33280523:C:CC	acceptor_gain	1.0000

AlphaMissense

3944 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:33287385:G:C	F283L	0.994
6:33287385:G:T	F283L	0.994
6:33287387:A:G	F283L	0.994
6:33279285:A:C	F608L	0.993
6:33279285:A:T	F608L	0.993
6:33279287:A:G	F608L	0.993
6:33280687:G:C	S472R	0.993
6:33280687:G:T	S472R	0.993
6:33280689:T:G	S472R	0.993
6:33287479:G:T	A252D	0.990
6:33287684:C:G	A220P	0.990
6:33286880:A:G	W344R	0.989
6:33286880:A:T	W344R	0.989
6:33287128:G:C	N326K	0.989
6:33287128:G:T	N326K	0.989
6:33287205:A:C	Y301D	0.988
6:33287201:A:G	L302P	0.987
6:33286888:A:T	V341E	0.986
6:33286894:C:A	G339V	0.986
6:33287368:A:G	L289P	0.986
6:33287473:G:T	A254D	0.986
6:33287365:A:G	L290P	0.985
6:33287383:A:G	L284P	0.985
6:33287692:C:T	G217D	0.985
6:33280725:C:G	D460H	0.984
6:33287450:A:C	Y262D	0.984
6:33287476:A:T	V253D	0.984
6:33280679:A:T	V475D	0.982
6:33287186:C:A	G307V	0.982
6:33287210:A:G	L299P	0.982

dbSNP variants (sampled 300 via entrez): RS1000544375 (6:33281908 A>G), RS1001113141 (6:33283343 T>C), RS1001217115 (6:33281156 C>G,T), RS1001311651 (6:33281068 C>A,G,T), RS1001362190 (6:33287440 T>C), RS1001461506 (6:33280020 G>A), RS1001895197 (6:33287803 T>C), RS1001922739 (6:33287373 G>A,C), RS1002222812 (6:33279683 C>T), RS1002317453 (6:33279913 C>A,T), RS1002327438 (6:33282853 C>T), RS1002496450 (6:33286252 G>A), RS1003567927 (6:33286186 C>T), RS1004342397 (6:33282175 T>C), RS1004404194 (6:33288908 T>C)

Disease associations

OMIM: gene MIM:611440 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004521_251	Autism spectrum disorder or schizophrenia	6.000000e-12
GCST004521_287	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST005951_153	Body mass index	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	4
Cisplatin	decreases expression, affects response to substance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	decreases expression, affects cotreatment	1
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
nivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
Temozolomide	increases expression	1
Atrazine	decreases expression	1
Benzalkonium Compounds	affects response to substance	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Zinc	decreases expression	1

Clinical trials (associated diseases)

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