WNT7A

Wnt family member 7A, the group of Wnt family

Basic information

Region (hg38): 3:13816257-13880071

Links

ENSG00000154764 ∙ NCBI:7476 ∙ OMIM:601570 ∙ HGNC:12786 ∙ Uniprot:O00755 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fuhrmann syndrome (Definitive), mode of inheritance: AR
• phocomelia, Schinzel type (Definitive), mode of inheritance: AR
• Fuhrmann syndrome (Supportive), mode of inheritance: AR
• phocomelia, Schinzel type (Supportive), mode of inheritance: AR
• Fuhrmann syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ulna and fibula, absence of, with severe limb deficiency (Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome); Fuhrmann syndrome	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	Dermatologic; Genitourinary; Musculoskeletal	7363910; 3981578; 3400735; 3066902; 2338339; 1785629; 9128926; 11332978; 12868468; 16826533; 19309796; 20949531; 21271649; 21344627

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WNT7A gene.

• not provided (51 variants)
• Inborn genetic diseases (17 variants)
• not specified (3 variants)
• Fuhrmann syndrome (2 variants)
• Schinzel phocomelia syndrome (2 variants)
• Anophthalmia-microphthalmia syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WNT7A 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				15	5	20
missense		1	17	1		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				12	8	20
Total	0	1	17	28	13

Variants in WNT7A

This is a list of pathogenic ClinVar variants found in the WNT7A region.

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

Position	Type	Phenotype	Significance	ClinVar
3-13818812-G-A			Likely benign (Feb 23, 2020)
3-13818958-A-G		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
3-13818965-C-T			Likely benign (Jun 13, 2022)
3-13818966-G-A			Conflicting classifications of pathogenicity (Aug 18, 2023)
3-13819013-C-G		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
3-13819052-G-A			Likely benign (May 31, 2018)
3-13819057-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 29, 2023)
3-13819075-T-A		Inborn genetic diseases	Uncertain significance (Feb 10, 2023)
3-13819103-C-T		WNT7A-related disorder	Likely benign (Jan 16, 2020)
3-13819110-T-C		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
3-13819120-G-A		Schinzel phocomelia syndrome	Likely pathogenic (Mar 25, 2024)
3-13819133-C-T		not specified	Conflicting classifications of pathogenicity (Nov 27, 2023)
3-13819167-T-A		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
3-13819171-G-A		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
3-13819173-G-C		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
3-13819183-T-C		Inborn genetic diseases	Uncertain significance (May 09, 2022)
3-13819217-C-T			Benign (Feb 03, 2022)
3-13819247-G-T			Likely benign (May 04, 2021)
3-13819261-G-A			Uncertain significance (Sep 16, 2018)
3-13819313-C-T			Benign (Sep 27, 2023)
3-13819329-C-T			Uncertain significance (Sep 16, 2018)
3-13819330-G-A		Schinzel phocomelia syndrome	Pathogenic (Nov 01, 2010)
3-13819370-C-T			Benign/Likely benign (Nov 28, 2022)
3-13819384-C-T		Schinzel phocomelia syndrome	Pathogenic/Likely pathogenic (Mar 25, 2024)
3-13819422-A-G		Inborn genetic diseases	Uncertain significance (Apr 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WNT7A	protein_coding	protein_coding	ENST00000285018	4	63864

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0358	0.957	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.34	186	245	0.758	0.0000180	2282
Missense in Polyphen		39	90.45	0.43118		799
Synonymous	-0.773	115	105	1.10	0.00000863	678
Loss of Function	2.36	5	14.8	0.338	7.25e-7	161

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000532	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt/beta- catenin signaling pathway (By similarity). Plays an important role in embryonic development, including dorsal versus ventral patterning during limb development, skeleton development and urogenital tract development (PubMed:16826533). Required for normal, sexually dimorphic development of the Mullerian ducts, and for normal fertility in both sexes. Required for normal neural stem cell proliferation in the hippocampus dentate gyrus. Required for normal progress through the cell cycle in neural progenitor cells, for self-renewal of neural stem cells, and for normal neuronal differentiation and maturation. Promotes formation of synapses via its interaction with FZD5 (By similarity). {ECO:0000250|UniProtKB:P24383, ECO:0000269|PubMed:16826533}.
• Disease: DISEASE: Limb pelvis hypoplasia aplasia syndrome (LPHAS) [MIM:276820]: A syndrome of severe deficiency of the extremities due to hypo- or aplasia of one or more long bones of one or more limbs. Pelvic manifestations include hip dislocation, hypoplastic iliac bone and aplastic pubic bones. Thoracic deformity, unusual facies and genitourinary anomalies can be present. {ECO:0000269|PubMed:16826533, ECO:0000269|PubMed:17431918, ECO:0000269|PubMed:20949531, ECO:0000269|PubMed:21271649, ECO:0000269|PubMed:27638328}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Fuhrmann syndrome (FUHRS) [MIM:228930]: Distinct limb- malformation disorder characterized also by various degrees of limb aplasia/hypoplasia and joint dysplasia. {ECO:0000269|PubMed:16826533}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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;ESC Pluripotency Pathways;Wnt Signaling Pathway and Pluripotency;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;Wnt Canonical;Wnt signaling network;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.288

Intolerance Scores

• loftool: 0.288
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.62

Haploinsufficiency Scores

• pHI: 0.434
• hipred: Y
• hipred_score: 0.875
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wnt7a
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: embryonic axis specification;cartilage condensation;angiogenesis;chondrocyte differentiation;neurotransmitter secretion;axonogenesis;sex differentiation;dorsal/ventral pattern formation;regulation of signaling receptor activity;positive regulation of endothelial cell migration;skeletal muscle satellite cell activation;skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration;Wnt signaling pathway;cerebellar granule cell differentiation;cell proliferation in forebrain;central nervous system vasculogenesis;establishment of cell polarity;neuron differentiation;regulation of axon diameter;positive regulation of cellular protein metabolic process;response to estradiol;somatic stem cell population maintenance;embryonic forelimb morphogenesis;embryonic hindlimb morphogenesis;wound healing, spreading of epidermal cells;synaptic vesicle recycling;embryonic digit morphogenesis;negative regulation of apoptotic process;response to estrogen;cell fate commitment;asymmetric protein localization involved in cell fate determination;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of JNK cascade;somatic stem cell division;stem cell development;negative regulation of neurogenesis;positive regulation of synapse assembly;positive regulation of epithelial cell proliferation involved in wound healing;oviduct development;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;dendritic spine morphogenesis;uterus morphogenesis;secondary palate development;lens fiber cell development;cellular response to transforming growth factor beta stimulus;presynapse assembly;postsynapse assembly;regulation of postsynapse organization;excitatory synapse assembly;positive regulation of excitatory synapse assembly;positive regulation of protein localization to presynapse;regulation of presynapse assembly;regulation of synaptic vesicle exocytosis;positive regulation of excitatory postsynaptic potential
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi lumen;plasma membrane;cell surface;endocytic vesicle membrane;extracellular matrix;extracellular exosome;Schaffer collateral - CA1 synapse;presynapse;glutamatergic synapse
• Molecular function: signaling receptor binding;frizzled binding;cytokine activity;protein binding;receptor ligand activity