WTAP

protein-coding

WT1 associated protein, the group of WTAP complex|m6A methyltransferase complex

Gene summary

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. [provided by RefSeq, Jul 2012]

MANE transcript

NM_001270531.2

Inheritance

—

ClinVar variants

U:21B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr6:159,725,585-159,756,319

External References & Databases

Ensembl (ENSG00000146457)

Transcript & Mutation Effects

hg38 • Region Span ~30.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WTAP variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001270531.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			15 clinvar	2 clinvar		17
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	21	2	0	23

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001270531.2	RefSeq	NP_001257460.1	7	MANE Select
ENST00000621533.5	Ensembl	ENSP00000479438.1	7	MANE Select
NM_001270532.2	RefSeq	NP_001257461.1	6	Standard
NM_001270533.2	RefSeq	NP_001257462.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wtap	Danio rerio	Structure: ventricular system Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

wtap

Danio rerio

Structure: ventricular system

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of RNA
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

regulation of alternative mRNA splicing, via spliceosome
mRNA processing
cell cycle
multicellular organism development
RNA splicing

Molecular Function

protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
nuclear speck
nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358372
Coding exons: 7
Length: 30735
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.27	121	215	0.564	0.0000114	2612
Missense (PolyPhen)		24	49.169	0.48811		681
Synonymous	-0.581	88	81.3	1.08	0.00000462	733
Loss of Function	4.44	0	22.9	0.00	0.00000126	236

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000066	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 (PubMed:29507755). Required for accumulation of METTL3 and METTL14 to nuclear speckle (PubMed:24316715, PubMed:24407421, PubMed:24981863). Acts as a mRNA splicing regulator (PubMed:12444081). Regulates G2/M cell-cycle transition by binding to the 3' UTR of CCNA2, which enhances its stability (PubMed:17088532). Impairs WT1 DNA-binding ability and inhibits expression of WT1 target genes (PubMed:17095724). {ECO:0000269|PubMed:12444081, ECO:0000269|PubMed:17088532, ECO:0000269|PubMed:17095724, ECO:0000269|PubMed:24316715, ECO:0000269|PubMed:24407421, ECO:0000269|PubMed:24981863, ECO:0000269|PubMed:29507755}.;

Recessive Scores

pRec: 0.159

Intolerance Scores

LoFtool: 0.345
RVIS EVS: -0.14
RVIS percentile EVS: 43.29

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.942

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium