WDR33

Summary

WDR33 (WD repeat domain 33, HGNC:25651) is a protein-coding gene on chromosome 2q14.3, encoding pre-mRNA 3’ end processing protein WDR33 (Q9C0J8). Essential for both cleavage and polyadenylation of pre-mRNA 3’ ends. It is a common-essential gene (DepMap: required in 99.3% 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. This gene is highly expressed in testis and the protein is localized to the nucleus. This gene may play important roles in the mechanisms of cytodifferentiation and/or DNA recombination. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 55339 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 160 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_018383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25651
Approved symbol	WDR33
Name	WD repeat domain 33
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11294, WDC146, NET14
Ensembl gene	ENSG00000136709
Ensembl biotype	protein_coding
OMIM	618082
Entrez	55339

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000322313, ENST00000393006, ENST00000408998, ENST00000409658, ENST00000436787, ENST00000855799, ENST00000912950, ENST00000965626

RefSeq mRNA: 3 — MANE Select: NM_018383 NM_001006622, NM_001006623, NM_018383

CCDS: CCDS2150, CCDS42746, CCDS46407

Canonical transcript exons

ENST00000322313 — 22 exons

Exon	Start	End
ENSE00000436145	127765174	127765269
ENSE00000857301	127768189	127768293
ENSE00000857305	127770778	127771004
ENSE00001137725	127708677	127708892
ENSE00001137734	127709490	127709582
ENSE00001137742	127709693	127709856
ENSE00001137749	127713583	127714021
ENSE00001137756	127717155	127717263
ENSE00001137761	127719265	127720353
ENSE00001137767	127721836	127721988
ENSE00001137771	127722591	127722730
ENSE00001137776	127722958	127723044
ENSE00001137782	127723253	127723347
ENSE00001137788	127724333	127724443
ENSE00001137793	127724887	127724965
ENSE00001137797	127725061	127725215
ENSE00001137803	127726651	127726777
ENSE00001137811	127763062	127763159
ENSE00001137816	127764828	127764979
ENSE00001137836	127811012	127811171
ENSE00001224372	127701027	127706552
ENSE00003522260	127768933	127769001

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 95.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.7502 / max 531.8351, expressed in 1812 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30575	33.7502	1812

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	95.00	gold quality
vena cava	UBERON:0004087	94.32	gold quality
gingiva	UBERON:0001828	93.69	gold quality
amniotic fluid	UBERON:0000173	93.25	gold quality
oocyte	CL:0000023	93.11	gold quality
tibia	UBERON:0000979	93.07	gold quality
esophagus squamous epithelium	UBERON:0006920	92.76	gold quality
calcaneal tendon	UBERON:0003701	92.45	gold quality
ganglionic eminence	UBERON:0004023	92.41	gold quality
secondary oocyte	CL:0000655	92.29	gold quality
endothelial cell	CL:0000115	92.08	gold quality
cerebellar hemisphere	UBERON:0002245	92.02	gold quality
parotid gland	UBERON:0001831	91.97	gold quality
cerebellar cortex	UBERON:0002129	91.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.49	gold quality
pericardium	UBERON:0002407	91.35	gold quality
ventricular zone	UBERON:0003053	91.00	gold quality
adrenal tissue	UBERON:0018303	90.93	gold quality
cerebellum	UBERON:0002037	90.67	gold quality
tendon	UBERON:0000043	90.31	gold quality
cartilage tissue	UBERON:0002418	90.22	gold quality
cortical plate	UBERON:0005343	90.21	gold quality
epithelium of nasopharynx	UBERON:0001951	90.09	gold quality
tonsil	UBERON:0002372	89.95	gold quality
sperm	CL:0000019	89.84	gold quality
left ovary	UBERON:0002119	89.62	gold quality
skin of abdomen	UBERON:0001416	89.60	gold quality
oral cavity	UBERON:0000167	89.54	gold quality
skin of leg	UBERON:0001511	89.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting WDR33, 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-6833-3P	100.00	70.63	3197
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-22-3P	99.93	68.13	917

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• unexpectedly found that CPSF subunits CPSF30 and Wdr33 directly contact AAUAAA (PMID:25301780)
• showed that WDR33 binds in and very close to the AAUAAA signal in vivo with high specificity (PMID:25301781)
• The authors define the molecular architecture of the core human CPSF complex comprising CPSF160, WDR33, CPSF30 and Fip1 and identify specific domains involved in inter-subunit interactions. Together, these results shed light on the function of CPSF in mediating polyA signal-dependent RNA cleavage and polyadenylation. (PMID:29274231)
• Non-canonical isoforms of the mRNA polyadenylation factor WDR33 regulate STING-mediated immune responses. (PMID:38430516)
• WDR33 alternative polyadenylation is dependent on stochastic poly(a) site usage and splicing efficiencies. (PMID:39327832)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr33	ENSDARG00000018272
mus_musculus	Wdr33	ENSMUSG00000024400
rattus_norvegicus	Wdr33	ENSRNOG00000011382
drosophila_melanogaster	Wdr33	FBGN0046222
caenorhabditis_elegans		WBGENE00011051

Protein

Protein identifiers

pre-mRNA 3’ end processing protein WDR33 — Q9C0J8 (reviewed: Q9C0J8)

Alternative names: WD repeat-containing protein 33, WD repeat-containing protein of 146 kDa

All UniProt accessions (3): B9A053, C9J8B4, Q9C0J8

UniProt curated annotations — full annotation on UniProt →

Function. Essential for both cleavage and polyadenylation of pre-mRNA 3’ ends.

Subunit / interactions. Component of the cleavage and polyadenylation specificity factor (CPSF) module of the pre-mRNA 3’-end processing complex. Interacts with CPSF3/CPSF73.

Subcellular location. Nucleus.

Tissue specificity. Most highly expressed in testis.

Similarity. Belongs to the WD repeat WDR33 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9C0J8-1	1	yes
Q9C0J8-2	2
Q9C0J8-3	3

RefSeq proteins (3): NP_001006623, NP_001006624, NP_060853* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR008160	Collagen	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045245	Pfs2-like	Family

Pfam: PF00400, PF01391

UniProt features (97 total): strand 34, compositionally biased region 19, modified residue 11, repeat 7, helix 5, splice variant 4, sequence conflict 4, turn 4, cross-link 3, sequence variant 2, initiator methionine 1, chain 1, region of interest 1, domain 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
9T3X	ELECTRON MICROSCOPY	2.1
6F9N	X-RAY DIFFRACTION	2.5
8E3I	ELECTRON MICROSCOPY	2.53
9OXE	ELECTRON MICROSCOPY	2.53
8E3Q	ELECTRON MICROSCOPY	2.68
8R8R	ELECTRON MICROSCOPY	2.79
6URG	ELECTRON MICROSCOPY	3
6FUW	ELECTRON MICROSCOPY	3.07
9OXS	ELECTRON MICROSCOPY	3.07
6BLY	ELECTRON MICROSCOPY	3.36
6DNH	ELECTRON MICROSCOPY	3.4
6URO	ELECTRON MICROSCOPY	3.6
6BM0	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0J8-F1	56.14	0.28

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 (14): 2, 7, 46, 782, 915, 987, 1035, 1210, 1262, 1315, 1315, 526, 530, 560

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77595	Processing of Intronless Pre-mRNAs
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA

MSigDB gene sets: 216 (showing top): WANG_CLIM2_TARGETS_UP, NKX25_02, GOCC_COLLAGEN_TRIMER, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_DNA_DAMAGE_TOLERANCE, GOBP_MALE_GAMETE_GENERATION, KAUFFMANN_DNA_REPAIR_GENES, DOANE_BREAST_CANCER_CLASSES_DN, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, MUELLER_PLURINET, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_MRNA_3_END_PROCESSING, OCT1_06

GO Biological Process (4): DNA damage tolerance (GO:0006301), spermatogenesis (GO:0007283), mRNA 3’-end processing (GO:0031124), mRNA processing (GO:0006397)

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

GO Cellular Component (5): fibrillar center (GO:0001650), collagen trimer (GO:0005581), nucleus (GO:0005634), nucleoplasm (GO:0005654), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	1
Processing of Capped Intron-Containing Pre-mRNA	1
RNA Polymerase II Transcription	1
Processing of Capped Intronless Pre-mRNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
DNA metabolic process	1
DNA replication	1
DNA damage response	1
developmental process involved in reproduction	1
male gamete generation	1
mRNA processing	1
RNA 3’-end processing	1
RNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
nucleolus	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
mRNA cleavage factor complex	1

Protein interactions and networks

STRING

3169 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR33	CPSF1	Q10570	998
WDR33	CPSF3	Q9UKF6	997
WDR33	CPSF4	O95639	997
WDR33	CPSF2	Q9P2I0	997
WDR33	FIP1L1	Q6UN15	982
WDR33	CSTF3	Q12996	915
WDR33	CSTF2	P33240	899
WDR33	SYMPK	Q92797	885
WDR33	PCF11	O94913	854
WDR33	PAPOLA	P51003	806
WDR33	CPSF7	Q8N684	788
WDR33	RBBP6	Q7Z6E9	736
WDR33	PAPOLG	Q9BWT3	721
WDR33	NUDT21	O43809	717
WDR33	PAPOLB	Q9NRJ5	712

IntAct

140 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
P4HA2	P4HB	psi-mi:“MI:0914”(association)	0.740
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
CPSF4	FIP1L1	psi-mi:“MI:0914”(association)	0.660
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
CPSF3	CPSF4	psi-mi:“MI:0914”(association)	0.640
CPSF1	CPSF4	psi-mi:“MI:0915”(physical association)	0.560
SYMPK	CPSF4	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
WDR33	CPSF4	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
CPSF4L	CCNH	psi-mi:“MI:0914”(association)	0.530
WASF3	CYFIP1	psi-mi:“MI:0914”(association)	0.530
SRSF3	CASC3	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
CDK4	WDR33	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
WDR33	SERPINB8	psi-mi:“MI:0915”(physical association)	0.400
WWOX	WDR33	psi-mi:“MI:0915”(physical association)	0.400
Anapc5	MAP3K3	psi-mi:“MI:0914”(association)	0.350
CPSF3	P4HA2	psi-mi:“MI:0914”(association)	0.350
Dtl	C1orf226	psi-mi:“MI:0914”(association)	0.350
CEP170P1	PCYT1A	psi-mi:“MI:0914”(association)	0.350
SEC16A	NCOR2	psi-mi:“MI:0914”(association)	0.350
FIP1L1	WWP2	psi-mi:“MI:0914”(association)	0.350
NS1	HAX1	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (214): WDR33 (Affinity Capture-MS), WDR33 (Affinity Capture-MS), WDR33 (Affinity Capture-MS), CPSF2 (Co-fractionation), PAPOLA (Co-fractionation), WDR33 (Co-fractionation), WDR33 (Co-fractionation), WDR33 (Co-fractionation), WDR33 (Co-fractionation), WDR33 (Co-fractionation), WDR33 (Co-fractionation), WDR33 (Affinity Capture-MS), WDR33 (Proximity Label-MS), WDR33 (Affinity Capture-MS), WDR33 (Affinity Capture-MS)

ESM2 similar proteins: A7EYK3, A7SEP9, A8NYM5, A8XW44, B0JYS7, B7Q2M2, C0NN85, C5XYW4, C5XZK6, C7YRT4, D0NHA2, D3ZCL3, D5GDH4, E0VI98, E1C6F0, E2RGI3, E3X5D6, F6HQ26, F6TFD9, F7ARS3, O43670, P09234, P33240, P90815, Q03369, Q05856, Q15637, Q16IW3, Q1K7T5, Q1RLC9, Q298E0, Q32PA0, Q4WQM6, Q562A2, Q56XE4, Q5BBX9, Q5RDA3, Q62241, Q64213, Q6PCR6

Diamond homologs: A8IR43, A9UP22, B8M0Q1, Q2HBX6, Q4P4R3, Q5RB58, Q8K4P0, Q9C0J8, Q9YGY3, A0A223GEB2, A0DB19, A3LNI7, A4R2Q6, A5DJX5, A5DXE2, A6S0T8, A7ECP3, A7RHG8, B0LSW3, B3S4I5, B4GAJ1, B4KT48, B5X3C4, B5X3Z6, B7PS00, B9WD30, C3XVT5, C4Q0P6, C4R6H3, C4YPI7, C5MJE8, E3LB80, G4MQX3, O54927, O54929, O75530, O88342, P07834, P25382, P38011

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 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
Processing of Intronless Pre-mRNAs	8	39.0×	8e-10
mRNA 3’-end processing	17	28.6×	1e-18
RNA Polymerase II Transcription Termination	14	26.3×	8e-15
Transport of Mature Transcript to Cytoplasm	7	22.8×	1e-06
mRNA Polyadenylation	26	19.5×	5e-24
mRNA Splicing	18	16.9×	1e-15
Processing of Capped Intron-Containing Pre-mRNA	22	15.4×	3e-18
Transport of Mature mRNA Derived from an Intronless Transcript	6	13.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	31.5×	5e-06
mRNA splicing, via spliceosome	22	13.8×	3e-16
regulation of alternative mRNA splicing, via spliceosome	8	13.4×	2e-05
mRNA stabilization	5	12.6×	6e-03
mRNA processing	19	10.2×	1e-11
RNA splicing	16	9.7×	3e-09
regulation of RNA splicing	6	9.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	135
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2422856	NC_000002.11:g.(?127806102)(129076137_?)del	Pathogenic

SpliceAI

3980 predictions. Top by Δscore:

Variant	Effect	Δscore
2:127706386:C:CA	donor_gain	1.0000
2:127708671:TCTTA:T	donor_loss	1.0000
2:127708672:CTTAC:C	donor_loss	1.0000
2:127708673:TTACC:T	donor_loss	1.0000
2:127708674:TACC:T	donor_loss	1.0000
2:127708893:C:CA	acceptor_loss	1.0000
2:127708893:C:CC	acceptor_gain	1.0000
2:127709689:TCACC:T	donor_loss	1.0000
2:127709690:CAC:C	donor_loss	1.0000
2:127709692:CCTCG:C	donor_loss	1.0000
2:127709743:T:TA	donor_gain	1.0000
2:127709852:TGAAA:T	acceptor_gain	1.0000
2:127709853:GAAA:G	acceptor_gain	1.0000
2:127709854:AAA:A	acceptor_gain	1.0000
2:127709855:AA:A	acceptor_gain	1.0000
2:127709857:C:CC	acceptor_gain	1.0000
2:127709859:G:C	acceptor_gain	1.0000
2:127709859:G:GC	acceptor_gain	1.0000
2:127721834:ACCT:A	donor_gain	1.0000
2:127721835:C:CG	donor_loss	1.0000
2:127721835:CCTC:C	donor_gain	1.0000
2:127721837:T:TA	donor_gain	1.0000
2:127721984:CAAGC:C	acceptor_gain	1.0000
2:127721985:AAGC:A	acceptor_gain	1.0000
2:127721986:AGC:A	acceptor_gain	1.0000
2:127721987:GC:G	acceptor_gain	1.0000
2:127721988:CC:C	acceptor_gain	1.0000
2:127721989:C:CC	acceptor_gain	1.0000
2:127721989:C:T	acceptor_gain	1.0000
2:127721990:T:C	acceptor_gain	1.0000

AlphaMissense

8747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:127721983:C:A	W508C	1.000
2:127721983:C:G	W508C	1.000
2:127721984:C:G	W508S	1.000
2:127721985:A:G	W508R	1.000
2:127721985:A:T	W508R	1.000
2:127721988:C:G	A507P	1.000
2:127722597:G:C	F504L	1.000
2:127722597:G:T	F504L	1.000
2:127722598:A:C	F504C	1.000
2:127722598:A:G	F504S	1.000
2:127722599:A:C	F504V	1.000
2:127722599:A:G	F504L	1.000
2:127722599:A:T	F504I	1.000
2:127722610:A:C	I500S	1.000
2:127722610:A:G	I500T	1.000
2:127722610:A:T	I500N	1.000
2:127722615:T:A	K498N	1.000
2:127722615:T:G	K498N	1.000
2:127722617:T:C	K498E	1.000
2:127722623:A:C	Y496D	1.000
2:127722628:A:T	V494D	1.000
2:127722683:A:G	W476R	1.000
2:127722683:A:T	W476R	1.000
2:127722688:A:G	L474S	1.000
2:127722691:C:T	G473D	1.000
2:127722692:C:G	G473R	1.000
2:127722697:A:C	I471S	1.000
2:127722697:A:G	I471T	1.000
2:127722697:A:T	I471N	1.000
2:127723005:A:G	M444T	1.000

dbSNP variants (sampled 300 via entrez): RS1000000667 (2:127783696 C>T), RS1000050018 (2:127793443 C>A), RS1000079653 (2:127778162 G>T), RS1000109771 (2:127734883 A>T), RS1000200698 (2:127785073 G>A,C), RS1000204221 (2:127762568 A>C), RS1000210993 (2:127743500 C>A,T), RS1000247536 (2:127759288 G>A,T), RS1000262978 (2:127778376 G>A,T), RS1000264216 (2:127785548 G>A), RS1000269807 (2:127710996 G>A), RS1000304955 (2:127779444 C>A,T), RS1000356838 (2:127779582 T>A,C), RS1000363822 (2:127772223 G>A), RS1000379565 (2:127808807 G>C)

Disease associations

OMIM: gene MIM:618082 | disease phenotypes: MIM:176860

GenCC curated gene-disease

Mondo (1): thrombophilia due to protein C deficiency, autosomal dominant (MONDO:0008316)

Orphanet (1): Severe hereditary thrombophilia due to congenital protein C deficiency (Orphanet:745)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002097_43	Coronary artery calcification	6.000000e-06
GCST005196_206	Coronary artery disease	4.000000e-06
GCST90002407_63	White blood cell count	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725052 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.47	Kd	33.7	nM	CHEMBL5653589
7.47	ED50	33.7	nM	CHEMBL5653589
5.96	IC50	1090	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149776: Binding affinity to human WDR33 incubated for 45 mins by Kinobead based pull down assay	kd	0.0337	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178948: Inhibition of WDR33 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.0900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	5
sodium arsenite	affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation	2
Doxorubicin	decreases expression, affects phosphorylation, affects response to substance	2
Hydrogen Peroxide	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
quercitrin	decreases expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	decreases expression	1
beta-methylcholine	affects expression	1
pentanal	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
ormosil	affects binding, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Decitabine	affects expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects expression	1
Demecolcine	decreases expression	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652818	Binding	Binding affinity to human WDR33 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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