WNT10B

Wnt family member 10B, the group of Wnt family

Basic information

Region (hg38): 12:48965340-48971735

Links

ENSG00000169884 ∙ NCBI:7480 ∙ OMIM:601906 ∙ HGNC:12775 ∙ Uniprot:O00744 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• split hand-foot malformation 6 (Definitive), mode of inheritance: AR
• split hand-foot malformation (Supportive), mode of inheritance: AD
• tooth agenesis (Supportive), mode of inheritance: AD
• split hand-foot malformation 6 (Moderate), mode of inheritance: AR
• tooth agenesis, selective, 8 (Moderate), mode of inheritance: AD
• split hand-foot malformation 6 (Strong), mode of inheritance: AR
• tooth agenesis, selective, 8 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tooth agenesis, selective, 8; Split-hand/foot malformation 6	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental; Dermatologic; Musculoskeletal	12072797; 18515319; 20635353; 21554266; 27321946; 29427788

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WNT10B gene.

• Split hand-foot malformation 6 (4 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WNT10B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				9	3	12
missense	1	1	37	3	3	45
nonsense		1				1
start loss						0
frameshift	5		1			6
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				1		1
non coding			2	1	2	5
Total	6	3	40	13	8

Highest pathogenic variant AF is 0.0000131

Variants in WNT10B

This is a list of pathogenic ClinVar variants found in the WNT10B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-48965910-T-C			Benign (Jun 28, 2020)
12-48966108-T-C			Uncertain significance (Oct 27, 2021)
12-48966138-C-T			Uncertain significance (Nov 22, 2022)
12-48966178-G-A			Uncertain significance (Jun 07, 2019)
12-48966178-G-C			Uncertain significance (Sep 26, 2017)
12-48966195-C-T		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
12-48966196-G-A			Uncertain significance (Nov 24, 2023)
12-48966202-C-T			Uncertain significance (Oct 03, 2022)
12-48966203-G-A			Likely benign (Oct 13, 2023)
12-48966206-G-A		not specified • Split hand-foot malformation 6 • Tooth agenesis, selective, 8	Benign (Jan 31, 2024)
12-48966270-C-T		Split hand-foot malformation 6	Uncertain significance (Oct 01, 2017)
12-48966271-G-A		Split hand-foot malformation 6	Pathogenic (Mar 10, 2023)
12-48966295-T-TA			Pathogenic (Jan 09, 2024)
12-48966298-T-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jul 08, 2022)
12-48966316-A-T		Split hand-foot malformation 6	Likely pathogenic (Sep 27, 2018)
12-48966352-A-G		Inborn genetic diseases	Uncertain significance (Dec 06, 2022)
12-48966364-G-A		not specified • WNT10B-related disorder	Benign (Jan 29, 2024)
12-48966368-CAGACGGGGCTGGA-C			Pathogenic (Sep 22, 2022)
12-48966372-C-T			Uncertain significance (Feb 23, 2022)
12-48966373-G-A		Inborn genetic diseases	Uncertain significance (May 04, 2022)
12-48966411-A-G			Conflicting classifications of pathogenicity (Jan 14, 2024)
12-48966416-G-T		Inborn genetic diseases	Likely benign (Oct 27, 2023)
12-48966418-T-C		Inborn genetic diseases	Uncertain significance (Jun 10, 2024)
12-48966424-G-A		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
12-48966429-A-G			Uncertain significance (Oct 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WNT10B	protein_coding	protein_coding	ENST00000301061	4	6424

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000362	0.957	125701	0	45	125746	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	202	249	0.812	0.0000146	2490
Missense in Polyphen		84	102.25	0.82152		1075
Synonymous	0.950	87	99.0	0.879	0.00000495	826
Loss of Function	1.81	8	15.8	0.508	0.00000115	136

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000351	0.000351
Ashkenazi Jewish	0.00	0.00
East Asian	0.000493	0.000489
Finnish	0.00	0.00
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.000493	0.000489
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Member of the Wnt ligand gene family that encodes for secreted proteins, which activate the Wnt signaling cascade. Specifically activates canonical Wnt/beta-catenin signaling and thus triggers beta-catenin/LEF/TCF-mediated transcriptional programs. Involved in signaling networks controlling stemness, pluripotency and cell fate decisions. Acts in the immune system, mammary gland, adipose tissue, bone and skin. {ECO:0000305|PubMed:16477437, ECO:0000305|PubMed:21447090, ECO:0000305|PubMed:27321946}.
• Disease: DISEASE: Split-hand/foot malformation 6 (SHFM6) [MIM:225300]: A limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting. {ECO:0000269|PubMed:18515319}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Tooth agenesis, selective, 8 (STHAG8) [MIM:617073]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG8 inheritance is autosomal dominant. {ECO:0000269|PubMed:27321946}. Note=The disease is caused by mutations affecting the gene represented in this entry. Potential genotype-phenotype correlation between variants and the positions of missing teeth. {ECO:0000269|PubMed:27321946}.
• Pathway: 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);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);WNT-Core;White fat cell differentiation;Adipogenesis;Hair Follicle Development- Induction (Part 1 of 3);ESC Pluripotency Pathways;Wnt Signaling Pathway and Pluripotency;White fat cell differentiation;Wnt Signaling in Kidney Disease;EMT transition in Colorectal Cancer;Wnt Signaling Pathway;DNA Damage Response (only ATM dependent);Signaling by GPCR;Signaling by WNT;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;WNT ligand biogenesis and trafficking;GPCR signaling-G alpha i;Wnt Canonical;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.217

Intolerance Scores

• loftool: 0.764
• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.82

Haploinsufficiency Scores

• pHI: 0.799
• hipred: Y
• hipred_score: 0.517
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.727

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wnt10b
• Phenotype: muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;chondrocyte differentiation;lipid metabolic process;cell cycle arrest;smoothened signaling pathway;positive regulation of cell population proliferation;regulation of signaling receptor activity;positive regulation of G2/M transition of mitotic cell cycle;myoblast differentiation involved in skeletal muscle regeneration;Wnt signaling pathway;neuron differentiation;positive regulation of bone mineralization;positive regulation of epithelial cell differentiation;regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of apoptotic process;cell fate commitment;negative regulation of fat cell differentiation;positive regulation of osteoblast differentiation;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;regulation of skeletal muscle tissue development;skeletal muscle fiber development;negative regulation of epithelial cell proliferation;protein stabilization;sensory perception of taste;positive regulation of DNA-binding transcription factor activity;positive regulation of timing of anagen;canonical Wnt signaling pathway;bone trabecula formation;fungiform papilla development;cellular response to retinoic acid;cellular response to cAMP;cellular response to parathyroid hormone stimulus;hematopoietic stem cell proliferation;positive regulation of canonical Wnt signaling pathway;negative regulation of cold-induced thermogenesis
• Cellular component: extracellular region;extracellular space
• Molecular function: frizzled binding;receptor ligand activity