WNT11

protein-coding

Wnt family member 11, 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 97%, 85%, and 63% amino acid identity with mouse, chicken, and Xenopus Wnt11 protein, respectively. This gene may play roles in the development of skeleton, kidney and lung, and is considered to be a plausible candidate gene for High Bone Mass Syndrome. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004626.3

Inheritance

AD, AR

ClinVar variants

U:56B:7

Top phenotype

osteoporosis

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr11:76,186,325-76,210,736

External References & Databases

Ensembl (ENSG00000085741)

Transcript & Mutation Effects

hg38 • Region Span ~24.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

osteoporosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0005298

Submitter: PanelApp Australia

congenital heart diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005453

Submitter: PanelApp Australia

osteoporosisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005298

Submitter: LiferaOmics

Genetic evidence – Published (AR scope: WNT11-related osteoporosis) No scorable published cases of biallelic (autosomal recessive) WNT11 variants causing a defined osteoporosis / early-onset osteoporosis phenotype were identified in the literature. Published genetic evidence total = 0 / 12 Published (AD context; not scored for AR) PMID: 34875064 – Early-onset osteoporosis / bone fragility with heterozygous WNT11 variants, including a de novo heterozygous loss-of-function variant and additional heterozygous missense variants in adults with bone fragility. Because this is a dominant/heterozygous context, it is not scorable under the autosomal recessive model. AD-context evidence total (not scored for AR) = 0 Genetic evidence – Our case Family 1 – one proband. Case-level (AR homozygous; predicted null frameshift; AR predicted null default = 1.5; consanguineous family; −0.5 consanguinity deduction applied) = (1.5 − 0.5) = 1.0; Segregation = 0; Case-control = 0 Family 1 total = 1.0 Total genetic evidence (Published AR + Our case) 1.0 / 12 Experimental evidence – Published (conservative and phenotype-aligned) PMID: 34875064 – Osteoblast/osteogenic functional studies in engineered cells (WNT11 LoF modeling). Functional alteration (engineered system): heterozygous WNT11 LoF in U2OS cells reduces proliferation and osteoblast differentiation/mineralization and disrupts Wnt pathway gene expression; recombinant WNT11 partially rescues pathway readouts = 2.0. Experimental evidence total = 2.0 / 6 Overall score Genetic evidence = 1.0 Experimental evidence = 2.0 Total = 3.0

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WNT11 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 6

Bladder exstrophy-epispadias-cloacal exstrophy complexTotal: 2

WNT11-related disorderTotal: 2

HypospadiasTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004626.3. 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				1 clinvar	4 clinvar	5
missense			55 clinvar		2 clinvar	57
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	56	1	6	63

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004626.3	RefSeq	NP_004617.2	5	MANE Select
ENST00000322563.8	Ensembl	ENSP00000325526.3	5	MANE Select
ENST00000529461.1	Ensembl	ENSP00000436140.1	1	Standard
ENST00000864022.1	Ensembl	ENSP00000534081.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wnt11	Danio rerio	Structure: cranial neural crest cell Quality: mislocalised ventrally abnormal

Gene / Model

Organism

Observed Phenotype

wnt11

Danio rerio

Structure: cranial neural crest cell

Quality: mislocalised ventrally

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
epithelial to mesenchymal transition
outflow tract morphogenesis
planar cell polarity pathway involved in axis elongation
protein phosphorylation

Molecular Function

GTPase activator activity
frizzled binding
protein binding
protein kinase activator activity
transcription regulatory region DNA binding

Cellular Component

extracellular region
extracellular space
cytoplasm
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322563
Coding exons: 5
Length: 24412
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.41	169	229	0.738	0.0000154	2238
Missense (PolyPhen)		77	113.09	0.68087		1074
Synonymous	0.703	92	101	0.911	0.00000725	718
Loss of Function	2.08	6	14.6	0.412	8.04e-7	161

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	0.00011	0.00011	rare
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000065	0.000065	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.;

Recessive Scores

pRec: 0.232

Intolerance Scores

LoFtool: 0.226
RVIS EVS: -0.09
RVIS percentile EVS: 46.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.532

Gene Damage Prediction

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