WNT6

protein-coding

Wnt family member 6, 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 is overexpressed in cervical cancer cell line and strongly coexpressed with another family member, WNT10A, in colorectal cancer cell line. The gene overexpression may play key roles in carcinogenesis. This gene and the WNT10A gene are clustered in the chromosome 2q35 region. The protein encoded by this gene is 97% identical to the mouse Wnt6 protein at the amino acid level. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006522.4

Inheritance

—

ClinVar variants

U:48B:4

Top phenotype

Bladder exstrophy-epispadias-cloacal exstrophy complex

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr2:218,859,805-218,874,233

External References & Databases

Ensembl (ENSG00000115596)

Transcript & Mutation Effects

hg38 • Region Span ~14.4 kb

Loading mutation effect viewer...

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 WNT6 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 2

Bladder exstrophy-epispadias-cloacal exstrophy complexTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006522.4. 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				3 clinvar		3
missense			46 clinvar	1 clinvar		47
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	48	4	0	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006522.4	RefSeq	NP_006513.1	4	MANE Select
ENST00000233948.4	Ensembl	ENSP00000233948.3	4	MANE Select
ENST00001140979.1	Ensembl	ENSP00000802098.1	4	Standard

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

branching involved in ureteric bud morphogenesis
axis specification
positive regulation of gene expression
Wnt signaling pathway
neuron differentiation

Molecular Function

frizzled 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: ENST00000233948
Coding exons: 4
Length: 14412
Individuals with no LoFs: 125445
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125449
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.73	136	206	0.661	0.0000108	2235
Missense (PolyPhen)		44	79.591	0.55283		862
Synonymous	0.944	82	93.6	0.876	0.00000492	802
Loss of Function	2.00	5	12.7	0.393	6.10e-7	131

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000019	0.000018	rare
South Asian	0.000066	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters. Together with CAV1 may promote chemoresistance of gastric cancer cells to DNA-damaging anthracycline drugs through the activation of the canonical Wnt receptor signaling pathway. {ECO:0000269|PubMed:22370641}.;

Recessive Scores

pRec: 0.227

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.662

Gene Damage Prediction

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