WNT2B

protein-coding

Wnt family member 2B, the group of Wnt family

Gene summary

This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

Previous symbols:

WNT13

MANE transcript

NM_024494.3

Inheritance

ClinVar variants

P:5U:95B:80

Top phenotype

Diarrhea 9

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr1:112,466,541-112,530,165

External References & Databases

Ensembl (ENSG00000134245)

Transcript & Mutation Effects

hg38 • Region Span ~63.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

diarrhea 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032575

Submitter: PanelApp Australia

diarrhea 9LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032575

Submitter: Ambry Genetics

diarrhea 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032575

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Diarrhea 9AR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: The condition can involve severe and early-onset diarrhea, and awareness may help with management (eg, via parenteral nutrition, which has been described as necessary)

Refs: 29909964

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WNT2B variants in ClinVar

9 Conditions Cataloged

not providedTotal: 160

not specifiedTotal: 59

WNT2B-related disorderTotal: 8

Diarrhea 9Total: 6

Failure to thrive in infancyTotal: 1

Chronic diarrheaTotal: 1

Impaired feeding abilityTotal: 1

DiarrheaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024494.3. 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				74 clinvar	3 clinvar	77
missense		1 clinvar	94 clinvar	1 clinvar	2 clinvar	98
nonsense	2 clinvar	1 clinvar	1 clinvar			4
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)						0
Total	2	3	95	75	5	180

Highest pathogenic variant AF is 0.0000065770437

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024494.3	RefSeq	NP_078613.1	5	MANE Select
ENST00000369684.5	Ensembl	ENSP00000358698.4	5	MANE Select
NM_001291880.1	RefSeq	NP_001278809.1	4	Standard
NM_004185.4	RefSeq	NP_004176.2	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wnt2bb	Danio rerio	Structure: extrahepatic duct Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

wnt2bb

Danio rerio

Structure: extrahepatic duct

Quality: decreased size

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

chondrocyte differentiation
lens development in camera-type eye
male gonad development
cellular response to starvation
Wnt signaling pathway

Molecular Function

frizzled binding

Cellular Component

extracellular region
extracellular space
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369684
Coding exons: 5
Length: 63625
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	198	267	0.741	0.0000185	2492
Missense (PolyPhen)		60	115.19	0.52087		1074
Synonymous	-0.0268	98	97.7	1.00	0.00000529	836
Loss of Function	2.82	6	19.4	0.309	0.00000154	170

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt/beta- catenin signaling pathway. Plays a redundant role in embryonic lung development. {ECO:0000250|UniProtKB:O70283}.;

Recessive Scores

pRec: 0.223

Intolerance Scores

LoFtool: 0.851
RVIS EVS: -0.54
RVIS percentile EVS: 20.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.379

Gene Damage Prediction

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