WTAP

Summary

WTAP (WT1 associated protein, HGNC:16846) is a protein-coding gene on chromosome 6q25.3, encoding Pre-mRNA-splicing regulator WTAP (Q15007). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. It is a selective cancer dependency (DepMap: 66.6% of cell lines).

The Wilms tumor suppressor gene WT1 appears to play a role in both transcriptional and posttranscriptional regulation of certain cellular genes. This gene encodes a WT1-associating protein, which is a ubiquitously expressed nuclear protein. Like WT1 protein, this protein is localized throughout the nucleoplasm as well as in speckles and partially colocalizes with splicing factors. Alternative splicing of this gene results in several transcript variants encoding three different isoforms.

Source: NCBI Gene 9589 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 66.6% of screened cell lines
• MANE Select transcript: NM_001270531

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16846
Approved symbol	WTAP
Name	WT1 associated protein
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0105, MGC3925, Mum2
Ensembl gene	ENSG00000146457
Ensembl biotype	protein_coding
OMIM	605442
Entrez	9589

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000337387, ENST00000358372, ENST00000462110, ENST00000494513, ENST00000614346, ENST00000621533, ENST00000631126, ENST00000650096, ENST00000971718, ENST00000971719, ENST00000971720, ENST00000971721

RefSeq mRNA: 6 — MANE Select: NM_001270531 NM_001270531, NM_001270532, NM_001270533, NM_004906, NM_152857, NM_152858

CCDS: CCDS5266, CCDS5267, CCDS75542

Canonical transcript exons

ENST00000621533 — 8 exons

Exon	Start	End
ENSE00001273785	159753460	159753614
ENSE00003748790	159727506	159727703
ENSE00003888888	159738990	159739045
ENSE00003888972	159736258	159736295
ENSE00003889132	159742088	159742146
ENSE00003889383	159748191	159748369
ENSE00003889497	159743665	159743792
ENSE00003893598	159755028	159756319

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 123.1876 / max 1044.9606, expressed in 1828 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70972	55.7005	1824
70970	38.1788	1825
70973	24.5009	1727
70971	3.4414	1480
204275	0.5778	349
70969	0.2701	109
70974	0.2632	123
70975	0.2549	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.76	gold quality
oocyte	CL:0000023	99.43	gold quality
epithelium of nasopharynx	UBERON:0001951	99.09	gold quality
vena cava	UBERON:0004087	98.89	gold quality
buccal mucosa cell	CL:0002336	98.77	gold quality
cartilage tissue	UBERON:0002418	98.74	gold quality
amniotic fluid	UBERON:0000173	98.08	gold quality
germinal epithelium of ovary	UBERON:0001304	98.07	gold quality
pericardium	UBERON:0002407	98.03	gold quality
parietal pleura	UBERON:0002400	97.87	gold quality
caput epididymis	UBERON:0004358	97.73	gold quality
ganglionic eminence	UBERON:0004023	97.70	gold quality
bone marrow	UBERON:0002371	97.50	gold quality
palpebral conjunctiva	UBERON:0001812	97.49	gold quality
esophagus squamous epithelium	UBERON:0006920	97.49	gold quality
pharyngeal mucosa	UBERON:0000355	97.48	gold quality
thymus	UBERON:0002370	97.46	gold quality
corpus epididymis	UBERON:0004359	97.40	gold quality
cauda epididymis	UBERON:0004360	97.39	gold quality
endometrium	UBERON:0001295	97.34	gold quality
tonsil	UBERON:0002372	97.33	gold quality
lymph node	UBERON:0000029	97.27	gold quality
ventricular zone	UBERON:0003053	97.27	gold quality
pleura	UBERON:0000977	97.22	gold quality
gingival epithelium	UBERON:0001949	97.21	gold quality
saphenous vein	UBERON:0007318	97.11	gold quality
gastrocnemius	UBERON:0001388	97.07	gold quality
tibia	UBERON:0000979	97.05	gold quality
embryo	UBERON:0000922	96.85	gold quality
visceral pleura	UBERON:0002401	96.84	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10137	no	5991.92
E-GEOD-76312	no	2283.28
E-GEOD-124858	no	1705.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, WT1

miRNA regulators (miRDB)

121 targeting WTAP, 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-3120-5P	100.00	65.56	965
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-124-3P	99.89	73.74	3043

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 66.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• WTAP protein involved in the morphogenesis of the genitourinaty tract and in the etiology of isolated hypospadias. (PMID:14675924)
• WTAP and ATF3 Transcription Factor are activated in Wilms’ tumor and accelerate tumorigenesis. (PMID:16912181)
• WTAP as an essential factor for the stabilization of cyclin A2 mRNA, thereby regulating G2/M cell-cycle transition (PMID:17088532)
• WTAP is a novel regulator of the cell cycle and cell survival and implicate a WTAP-WT1 axis as a novel pathway for controlling vascular smooth muscle cell phenotype. (PMID:17095724)
• Nuclear degradation of Wilms tumor 1-associating protein and survivin splice variant switching underlie IGF-1-mediated survival (PMID:19605357)
• WTAP level in poodocytes is a valuable alternative technique in the study of podocyte injury in diabetic nephropathy. (PMID:19969384)
• WTAP overexpression made cancer cells more tumorigenic (PMID:22957919)
• WTAP regulates migration and invasion of cholangiocarcinoma cells. (PMID:23354623)
• the WTAP complex is a novel component of the RNA processing machinery, implying an important role in both posttranscriptional control and cell cycle regulation. (PMID:24100041)
• WTAP as a regulatory subunit is required for formation of a functional m6A methyltransferase complex including METTL3 and METTL14, which play an important role in the regulation of gene expression and alternative splicing. (PMID:24407421)
• WTAP has an important role in abnormal proliferation and arrested differentiation of leukemia cells, and WTAP is a novel client protein of Hsp90 (PMID:24413322)
• WTAP was over-expressed in glioma tissues, and the expression was closely correlated with glioma grade. (PMID:27370540)
• These findings suggest that WTAP may have an oncogenic role in RCC through physically binding to CDK2 transcript and enhancing its transcript stability which might provide new insights into RCC therapy. (PMID:29482572)
• WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL (PMID:30143009)
• Our study is the first to report that WTAP-mediated m6A methylation has a crucial role in HCC oncogenesis, and highlights WTAP as a potential therapeutic target of HCC treatment. (PMID:31438961)
• High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour-associated T lymphocyte infiltration. (PMID:32176425)
• Wilms’ tumour 1-associating protein inhibits endothelial cell angiogenesis by m6A-dependent epigenetic silencing of desmoplakin in brain arteriovenous malformation. (PMID:32281240)
• WTAP and BIRC3 are involved in the posttranscriptional mechanisms that impact on the expression and activity of the human lactonase PON2. (PMID:32382056)
• WTAP gene single nucleotide polymorphism is associated with Wilms tumor susceptibility. (PMID:32504654)
• LncRNA PCGEM1 accelerates non-small cell lung cancer progression via sponging miR-433-3p to upregulate WTAP. (PMID:32787827)
• WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m(6)A-dependent manner. (PMID:32814762)
• Wilms’ tumor 1-associating protein contributes to psoriasis by promoting keratinocytes proliferation via regulating cyclinA2 and CDK2. (PMID:32866786)
• High Wilms’ tumor 1 associating protein expression predicts poor prognosis in acute myeloid leukemia and regulates m(6)A methylation of MYC mRNA. (PMID:32880751)
• Gene Signatures and Prognostic Values of m6A RNA Methylation Regulators in Ovarian Cancer. (PMID:32951457)
• Identification of WTAP-related genes by weighted gene co-expression network analysis in ovarian cancer. (PMID:32998774)
• m6A methyltransferase Wilms’ tumor 1-associated protein facilitates cell proliferation and cisplatin resistance in NK/T cell lymphoma by regulating dual-specificity phosphatases 6 expression via m6A RNA methylation. (PMID:33205540)
• ARRB2 promotes colorectal cancer growth through triggering WTAP. (PMID:33367479)
• N(6)-methyladenosine (m(6)A) methyltransferase WTAP accelerates the Warburg effect of gastric cancer through regulating HK2 stability. (PMID:33378974)
• WTAP facilitates progression of endometrial cancer via CAV-1/NF-kappaB axis. (PMID:33559954)
• Long Noncoding RNA DUXAP8 Promotes Pancreatic Carcinoma Cell Migration and Invasion Via Pathway by miR-448/WTAP/Fak Signaling Axis. (PMID:33625109)
• WTAP promotes myocardial ischemia/reperfusion injury by increasing endoplasmic reticulum stress via regulating m(6)A modification of ATF4 mRNA. (PMID:33819187)
• C5aR1-positive neutrophils promote breast cancer glycolysis through WTAP-dependent m6A methylation of ENO1. (PMID:34312368)
• EBV downregulates the m(6)A ““writer”” WTAP in EBV-associated gastric carcinoma. (PMID:34329695)
• [The Relationship between HIF1alpha and WTAP Expression Level in t(8;21) Acute Myeloid Leukemia]. (PMID:34627420)
• LINC00839/miR-144-3p/WTAP (WT1 Associated protein) axis is involved in regulating hepatocellular carcinoma progression. (PMID:34634995)
• m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK. (PMID:34828353)
• N(6)-methyladenosine (m(6)A)-mediated lncRNA DLGAP1-AS1enhances breast canceradriamycin resistance through miR-299-3p/WTAP feedback loop. (PMID:34866525)
• WTAP-mediated m(6)A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis. (PMID:34999731)
• Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation. (PMID:35143566)
• WTAP-mediated m(6)A modification of lncRNA NORAD promotes intervertebral disc degeneration. (PMID:35304463)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	wtap	ENSDARG00000042642
mus_musculus	Wtap	ENSMUSG00000060475
rattus_norvegicus	Wtap	ENSRNOG00000019091
drosophila_melanogaster	fl(2)d	FBGN0000662

Protein

Protein identifiers

Pre-mRNA-splicing regulator WTAP — Q15007 (reviewed: Q15007)

Alternative names: Female-lethal(2)D homolog, WT1-associated protein, Wilms tumor 1-associating protein

All UniProt accessions (2): Q15007, A0A087X1R4

UniProt curated annotations — full annotation on UniProt →

Function. Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. Required for accumulation of METTL3 and METTL14 to nuclear speckle. Acts as a mRNA splicing regulator. Regulates G2/M cell-cycle transition by binding to the 3’ UTR of CCNA2, which enhances its stability. Impairs WT1 DNA-binding ability and inhibits expression of WT1 target genes.

Subunit / interactions. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of METTL3 and METTL14. The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B). Interacts with WT1. Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3.

Subcellular location. Nucleus speckle. Nucleus. Nucleoplasm. Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Induction. In smooth muscle cells, up-regulated after serum withdrawal, when cells become mature and non proliferative.

Similarity. Belongs to the fl(2)d family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15007-1	1	yes
Q15007-2	2

RefSeq proteins (6): NP_001257460, NP_001257461, NP_001257462, NP_004897, NP_690596, NP_690597 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033757	WTAP	Family

Pfam: PF17098

UniProt features (23 total): modified residue 7, compositionally biased region 6, helix 4, splice variant 2, chain 1, region of interest 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9XOE	X-RAY DIFFRACTION	1.65
7YFJ	X-RAY DIFFRACTION	2.4
9XOF	X-RAY DIFFRACTION	2.79
7VF2	ELECTRON MICROSCOPY	3
7VF5	ELECTRON MICROSCOPY	3
7YG4	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15007-F1	72.41	0.34

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 (7): 305, 306, 341, 350, 388, 1, 14

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA

MSigDB gene sets: 282 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GNF2_BNIP2, PAL_PRMT5_TARGETS_UP, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, TGACCTY_ERR1_Q2, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_DN, GOBP_MRNA_MODIFICATION, PUJANA_CHEK2_PCC_NETWORK, GTGCCTT_MIR506, AGTCTTA_MIR499, chr6q25, CATTTCA_MIR203

GO Biological Process (4): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA processing (GO:0006397), RNA splicing (GO:0008380), mRNA modification (GO:0016556)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607), nuclear membrane (GO:0031965), RNA N6-methyladenosine methyltransferase complex (GO:0036396)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
mRNA metabolic process	2
cellular anatomical structure	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
RNA modification	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
nucleus	1
nuclear envelope	1
organelle membrane	1
methyltransferase complex	1

Protein interactions and networks

STRING

1580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WTAP	METTL3	Q86U44	999
WTAP	METTL14	Q9HCE5	999
WTAP	ZC3H13	Q5T200	998
WTAP	VIRMA	Q69YN4	998
WTAP	RBM15B	Q8NDT2	998
WTAP	RBM15	Q96T37	998
WTAP	METTL16	Q86W50	997
WTAP	CBLL1	Q75N03	997
WTAP	WT1	P19544	995
WTAP	METTL4	Q8N3J2	994
WTAP	SMAD2	Q15796	982
WTAP	ALKBH5	Q6P6C2	935
WTAP	YTHDF1	Q9BYJ9	922
WTAP	YTHDC1	Q96MU7	921
WTAP	YTHDC2	Q9H6S0	917

IntAct

130 interactions, top by confidence:

A	B	Type	Score
VPS52	WTAP	psi-mi:“MI:0915”(physical association)	0.720
WTAP	VPS52	psi-mi:“MI:0915”(physical association)	0.720
IKZF1	WTAP	psi-mi:“MI:0915”(physical association)	0.670
MAGEA11	WTAP	psi-mi:“MI:0915”(physical association)	0.670
WTAP	SLIRP	psi-mi:“MI:0915”(physical association)	0.670
HYPK	NAA10	psi-mi:“MI:0914”(association)	0.640
MAP2K6	MAP2K3	psi-mi:“MI:0914”(association)	0.610
WTAP	TNIP1	psi-mi:“MI:0915”(physical association)	0.560
WTAP	TCF12	psi-mi:“MI:0915”(physical association)	0.560
WTAP	ABHD15	psi-mi:“MI:0915”(physical association)	0.560
PSMA1	WTAP	psi-mi:“MI:0915”(physical association)	0.560
WTAP	ZNF239	psi-mi:“MI:0915”(physical association)	0.560
BYSL	WTAP	psi-mi:“MI:0915”(physical association)	0.560
WT1	WTAP	psi-mi:“MI:0915”(physical association)	0.560
WTAP	WTAP	psi-mi:“MI:0915”(physical association)	0.560
WTAP	ZNF572	psi-mi:“MI:0915”(physical association)	0.560
WTAP	YWHAZ	psi-mi:“MI:0915”(physical association)	0.560
METTL3	WTAP	psi-mi:“MI:0914”(association)	0.530
METTL14	WTAP	psi-mi:“MI:0914”(association)	0.530
ABRAXAS1	LAMC1	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
GRK7	HSP90AA1	psi-mi:“MI:0914”(association)	0.530

BioGRID (255): WTAP (Two-hybrid), IKZF1 (Two-hybrid), WTAP (Affinity Capture-MS), WTAP (Affinity Capture-MS), WTAP (Two-hybrid), KIAA1429 (Co-fractionation), WTAP (Co-fractionation), ZC3H13 (Co-fractionation), WTAP (Affinity Capture-MS), WTAP (Affinity Capture-MS), WTAP (Two-hybrid), WTAP (Affinity Capture-MS), WTAP (Affinity Capture-MS), WTAP (Affinity Capture-MS), WTAP (Affinity Capture-MS)

ESM2 similar proteins: A1Z7Z9, A9UM82, G5EEK3, O14490, P11929, P97836, Q15007, Q2KN93, Q2KN94, Q2KN95, Q2KN96, Q2KN97, Q2KN98, Q2KN99, Q2KNA0, Q2KNA1, Q2TLY1, Q2TLY2, Q2TLZ1, Q2TLZ2, Q2TLZ3, Q2TLZ4, Q2TLZ5, Q3UIJ9, Q4KLT6, Q4V7D3, Q5EB94, Q5M775, Q5NVC2, Q5SXY1, Q60JJ0, Q60MF5, Q69YQ0, Q6P4K5, Q7SXL7, Q7TQE6, Q7YZA2, Q86W92, Q8C8U0, Q8N5G2

Diamond homologs: Q15007, Q28XY0, Q4KLT6, Q6P4K5, Q7SXL7, Q9ER69, Q9Y091, Q9ZSZ8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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
Transport of Mature Transcript to Cytoplasm	5	25.0×	9e-05
mRNA 3’-end processing	8	20.7×	5e-07
RNA Polymerase II Transcription Termination	6	17.3×	8e-05
Processing of Capped Intron-Containing Pre-mRNA	13	14.1×	3e-09
Transport of Mature mRNA derived from an Intron-Containing Transcript	7	14.0×	5e-05
mRNA Splicing	9	13.0×	3e-06
Loss of Nlp from mitotic centrosomes	5	10.4×	3e-03
Loss of proteins required for interphase microtubule organization from the centrosome	5	10.4×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	9	21.3×	6e-08
mRNA export from nucleus	7	20.1×	8e-06
mRNA splicing, via spliceosome	15	13.3×	3e-10
RNA splicing	13	11.1×	4e-08
mRNA processing	14	10.7×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1392 predictions. Top by Δscore:

Variant	Effect	Δscore
6:159736292:GAAG:G	donor_gain	1.0000
6:159736297:T:A	donor_loss	1.0000
6:159738985:TATAG:T	acceptor_loss	1.0000
6:159738987:TAGGT:T	acceptor_loss	1.0000
6:159738988:A:AG	acceptor_gain	1.0000
6:159738988:AGGT:A	acceptor_loss	1.0000
6:159738989:G:GG	acceptor_gain	1.0000
6:159739030:A:G	donor_gain	1.0000
6:159739041:CTAAG:C	donor_loss	1.0000
6:159739042:TAAGG:T	donor_loss	1.0000
6:159739043:AAGGT:A	donor_loss	1.0000
6:159739044:AG:A	donor_loss	1.0000
6:159739045:GG:G	donor_loss	1.0000
6:159739046:GT:G	donor_loss	1.0000
6:159739047:T:A	donor_loss	1.0000
6:159742082:TATTA:T	acceptor_loss	1.0000
6:159742083:ATTAG:A	acceptor_loss	1.0000
6:159742084:TTAGA:T	acceptor_loss	1.0000
6:159742085:TA:T	acceptor_loss	1.0000
6:159742086:A:AG	acceptor_gain	1.0000
6:159742086:AG:A	acceptor_loss	1.0000
6:159742087:G:GG	acceptor_gain	1.0000
6:159742087:G:GT	acceptor_loss	1.0000
6:159742147:G:GG	donor_gain	1.0000
6:159743654:T:TA	acceptor_gain	1.0000
6:159743656:A:AG	acceptor_gain	1.0000
6:159743657:A:AG	acceptor_gain	1.0000
6:159743658:T:G	acceptor_gain	1.0000
6:159743660:A:AG	acceptor_gain	1.0000
6:159743661:T:G	acceptor_gain	1.0000

AlphaMissense

2622 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:159743704:T:C	L62P	1.000
6:159743731:G:C	R71P	1.000
6:159743734:G:C	R72T	1.000
6:159743734:G:T	R72M	1.000
6:159743735:G:C	R72S	1.000
6:159743735:G:T	R72S	1.000
6:159743746:T:C	L76P	1.000
6:159743755:G:C	R79P	1.000
6:159743758:T:C	L80P	1.000
6:159743760:G:C	A81P	1.000
6:159743768:G:C	K83N	1.000
6:159743768:G:T	K83N	1.000
6:159743769:G:A	E84K	1.000
6:159743773:A:C	Q85P	1.000
6:159748300:T:C	L128P	1.000
6:159748321:T:C	L135P	1.000
6:159748329:G:C	A138P	1.000
6:159748342:T:C	L142P	1.000
6:159748347:G:C	A144P	1.000
6:159748348:C:A	A144D	1.000
6:159748350:T:A	W145R	1.000
6:159748350:T:C	W145R	1.000
6:159748353:A:G	K146E	1.000
6:159748356:T:A	F147I	1.000
6:159748356:T:C	F147L	1.000
6:159748356:T:G	F147V	1.000
6:159748357:T:C	F147S	1.000
6:159748357:T:G	F147C	1.000
6:159748358:T:A	F147L	1.000
6:159748358:T:G	F147L	1.000

dbSNP variants (sampled 300 via entrez): RS1000024361 (6:159731391 C>A), RS1000045877 (6:159756818 G>A,T), RS1000138692 (6:159741814 C>A,G,T), RS1000196404 (6:159750763 C>G,T), RS1000389129 (6:159733393 G>A), RS1000389447 (6:159738944 T>C), RS1000443296 (6:159727695 C>T), RS1000599025 (6:159743074 G>T), RS1000631498 (6:159732428 C>T), RS1000791104 (6:159752042 A>T), RS1001000545 (6:159732592 T>A,C), RS1001026959 (6:159755991 C>T), RS1001082583 (6:159748797 C>G), RS1001304526 (6:159728262 T>C), RS1001340026 (6:159742858 C>T)

Disease associations

OMIM: gene MIM:605442 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000301_1	Iron status biomarkers	1.000000e-06
GCST006218_56	Erosive tooth wear (severe vs non-severe)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004461	iron biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523298 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, decreases reaction, increases expression	7
Valproic Acid	affects expression, decreases expression, decreases methylation	5
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
TL8-506	affects cotreatment, increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
nickel sulfate	decreases expression	1
cadmium sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
CC-8490	increases expression	1
abrine	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Acetylcysteine	decreases reaction, increases expression	1
Amiodarone	increases expression	1
Arsenic	increases expression	1
Benzo(a)pyrene	increases expression	1
Cobalt	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4379086	Binding	Binding affinity to WTAP (unknown origin) at protein to compound concentration ratio of 1:20 by differential scanning fluorimetry	Discovery of 4H-Chromen-4-one Derivatives as a New Class of Selective Rho Kinase (ROCK) Inhibitors, which Showed Potent Activity in ex Vivo Diabetic Retinopathy Models. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TY23	HAP1 WTAP (-) 1	Cancer cell line	Male
CVCL_TY24	HAP1 WTAP (-) 2	Cancer cell line	Male
CVCL_TY25	HAP1 WTAP (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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