WNT3A

protein-coding

Wnt family member 3A, the group of Wnt family

Gene summary

The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 96% amino acid identity to mouse Wnt3A protein, and 84% to human WNT3 protein, another WNT gene product. This gene is clustered with WNT14 gene, another family member, in chromosome 1q42 region. [provided by RefSeq, Jul 2008]

MANE transcript

NM_033131.4

Inheritance

—

ClinVar variants

U:113B:48

Top phenotype

WNT3A-related disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr1:228,006,998-228,061,271

External References & Databases

Ensembl (ENSG00000154342)

Transcript & Mutation Effects

hg38 • Region Span ~54.3 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 WNT3A variants in ClinVar

3 Conditions Cataloged

not providedTotal: 152

not specifiedTotal: 56

WNT3A-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033131.4. 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				43 clinvar	3 clinvar	46
missense			108 clinvar		2 clinvar	110
nonsense			2 clinvar			2
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	0	0	113	43	5	161

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033131.4	RefSeq	NP_149122.1	4	MANE Select
ENST00000284523.2	Ensembl	ENSP00000284523.1	4	MANE Select
ENST00000948304.1	Ensembl	ENSP00000618363.1	4	Standard
ENST00001144544.1	Ensembl	ENSP00000804555.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wnt3a	Danio rerio	Structure: aortic arch Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

wnt3a

Danio rerio

Structure: aortic arch

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gastric cancer - Homo sapiens (human)
mTOR signaling pathway - Homo sapiens (human)
Cushing,s syndrome - Homo sapiens (human)
Breast cancer - Homo sapiens (human)
HTLV-I infection - Homo sapiens (human)

Biological Process

osteoblast differentiation
in utero embryonic development
positive regulation of cytokine production
positive regulation of protein phosphorylation
heart looping

Molecular Function

transcription coactivator activity
signaling receptor binding
frizzled binding
protein binding
protein domain specific binding

Cellular Component

extracellular region
extracellular space
endoplasmic reticulum lumen
Golgi lumen
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000284523
Coding exons: 4
Length: 54210
Individuals with no LoFs: 125637
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125640
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.00	160	249	0.643	0.0000170	2275
Missense (PolyPhen)		53	113.54	0.46681		1018
Synonymous	2.41	79	111	0.709	0.00000842	699
Loss of Function	3.33	1	14.8	0.0675	6.35e-7	156

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000020	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (PubMed:20093360, PubMed:21244856, PubMed:24841207, PubMed:26902720). Required for normal embryonic mesoderm development and formation of caudal somites. Required for normal morphogenesis of the developing neural tube (By similarity). Mediates self-renewal of the stem cells at the bottom on intestinal crypts (in vitro) (PubMed:26902720). {ECO:0000250|UniProtKB:P27467, ECO:0000269|PubMed:20093360, ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24841207, ECO:0000269|PubMed:26902720, ECO:0000305}.;

Recessive Scores

pRec: 0.585

Intolerance Scores

LoFtool: 0.276
RVIS EVS: -0.21
RVIS percentile EVS: 38.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.921

Gene Damage Prediction

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