WNT7A

Summary

WNT7A (Wnt family member 7A, HGNC:12786) is a protein-coding gene on chromosome 3p25.1, encoding Protein Wnt-7a (O00755). Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.

This gene is a member of the WNT gene family, which consists of structurally related genes that 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 involved in the development of the anterior-posterior axis in the female reproductive tract, and also plays a critical role in uterine smooth muscle pattering and maintenance of adult uterine function. Mutations in this gene are associated with Fuhrmann and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndromes.

Source: NCBI Gene 7476 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Fuhrmann syndrome (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 98 total — 6 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 101
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004625

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12786
Approved symbol	WNT7A
Name	Wnt family member 7A
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Aliases	Wnt-7a
Ensembl gene	ENSG00000154764
Ensembl biotype	protein_coding
OMIM	601570
Entrez	7476

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000285018, ENST00000489346, ENST00000497808

RefSeq mRNA: 1 — MANE Select: NM_004625 NM_004625

CCDS: CCDS2616

Canonical transcript exons

ENST00000285018 — 4 exons

Exon	Start	End
ENSE00001017561	13854532	13854803
ENSE00001017562	13874947	13875173
ENSE00001132828	13879746	13880071
ENSE00001211668	13816258	13819423

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 80.21.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0675 / max 274.9542, expressed in 361 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41205	1.8257	314
41203	0.5683	218
41206	0.4391	175
41207	0.1219	74
41202	0.0674	40
41204	0.0451	22

Top tissues by expression

269 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	80.21	gold quality
endometrium epithelium	UBERON:0004811	77.76	gold quality
ventricular zone	UBERON:0003053	75.22	gold quality
ganglionic eminence	UBERON:0004023	73.33	gold quality
prefrontal cortex	UBERON:0000451	72.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.36	gold quality
right frontal lobe	UBERON:0002810	68.41	gold quality
cingulate cortex	UBERON:0003027	68.06	gold quality
anterior cingulate cortex	UBERON:0009835	67.91	gold quality
amygdala	UBERON:0001876	67.77	gold quality
frontal lobe	UBERON:0016525	67.61	gold quality
frontal cortex	UBERON:0001870	67.60	gold quality
neocortex	UBERON:0001950	67.45	gold quality
right lung	UBERON:0002167	67.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.53	gold quality
gall bladder	UBERON:0002110	66.47	gold quality
nucleus accumbens	UBERON:0001882	66.30	gold quality
caudate nucleus	UBERON:0001873	66.16	gold quality
placenta	UBERON:0001987	66.09	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.68	gold quality
putamen	UBERON:0001874	65.45	gold quality
Brodmann (1909) area 10	UBERON:0013541	65.18	gold quality
cerebral cortex	UBERON:0000956	64.29	gold quality
telencephalon	UBERON:0001893	64.29	gold quality
frontal pole	UBERON:0002795	64.24	gold quality
embryo	UBERON:0000922	63.81	gold quality
upper lobe of left lung	UBERON:0008952	63.77	gold quality
middle frontal gyrus	UBERON:0002702	63.53	gold quality
tongue squamous epithelium	UBERON:0006919	63.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.07

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SPRY4	Repression

Upstream regulators (CollecTRI, top): EN1, ESR1, LMX1B, MSX2

miRNA regulators (miRDB)

43 targeting WNT7A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• WNT7a gene expression is regulated by TGF-beta1 through the intracellular beta-catenin-TCF pathway (PMID:12893825)
• provides support that E-cadherin induction by WNT/beta-catenin signaling is an evolutionarily conserved pathway operative in lung cancer cells and that loss of expression may be important in lung cancer development or progression (PMID:12937339)
• WNT7A mutations are an unlikely cause of Mullerian duct derivative abnormalities in humans (PMID:14550385)
• Wnt-7a is associated with cartilage destruction by regulating the maintenance of differentiation status and the apoptosis of articular chondrocytes via different mechanisms (PMID:15082716)
• analysis of multiple Wnt mRNAs in non-small cell lung cancer (NSCLC) cell lines and primary lung tumors revealed markedly decreased Wnt-7a expression compared with normal short-term bronchial epithelial cell lines and normal uninvolved lung tissue (PMID:15705594)
• By regulating the proliferation of corneal epithelial cells, Wnt-7a and MMP-12 appear to contribute to corneal wound healing (PMID:15802269)
• Partial loss of WNT7A causes Fuhrmann syndrome, whereas the more severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations. (PMID:16826533)
• ERK5-dependent activation of PPARgamma represents a major effector pathway mediating the anti-tumorigenic effects of Wnt 7a and Fzd 9 in non-small cell lung cancer cells (PMID:16835228)
• the absence of tumour-specific somatic events in WNT7A and HDAC11 suggests that these genes are unlikely to have a classical tumour suppressor gene role in sporadic malignant pancreatic endocrine tumours (PMID:17201809)
• WNT7A plays a role in the pathophysiology of endometriosis. (PMID:17588571)
• These biological tools could help lead to a better understanding of Wnt-Fzd interactions and the identification of new modulators of Wnt signaling. (PMID:18230341)
• WNT7A gene is unlikely to be a major contributor to the aetiology of familial congenital talipes equinovarus (PMID:18538017)
• Based on these results it is unlikely CAND2 and WNT7a are the major genes that causes clubfoot. (PMID:19159115)
• Mutations in the coding sequence of WNT4, WNT5A, WNT7A, and WNT9B are not responsible for the Mayer-Rokitansky-Kuster-Hauser syndrome. (PMID:19171330)
• Female mammals with a deficiency in the product of Wnt7a gene are infertile as a result of abnormal development of the uterus and the oviducts. (PMID:19849868)
• Results suggest that this diminished expression of the WNT7A gene may be related to a supposed protection of fragile X syndrome patients to develop cancer. (PMID:20470940)
• The activity of the Sprouty4 promoter is increased by Wnt7A/Frizzled 9 homolog (Fzd9) signaling through peroxisome proliferator-activated receptor gamma in lung cancer cells. (PMID:20501643)
• Expression levels of Wnt7A, beta-catenin, and FoxA1, along with cell-type specific markers, are observed to vary with differentiation and often also in response to the presence of heparin during the time of exposure to heparin. (PMID:20503388)
• Abnormalities in the Wnt7a pathway (located in the dorsal ectoderm) produce several clinically relevant conditions. (PMID:20709709)
• High Wnt7a expression in ovarian cancer may be associated with poor prognosis. (PMID:20845993)
• A novel homozygous missense mutation in coding exon 4 of the WNT7A was detected in both affected daughters (c.664C > T) leading to an amino acid exchange from arginine to tryptophan (p.Arg222Trp; R222W). (PMID:20949531)
• Partial loss of WNT7A function resulted in Fuhrmann syndrome, while complete loss of WNT7A function resulted in the more severe phenotype of Al-Awadi-Raas-Rothschild syndrome. (PMID:21271649)
• The novel missense homozygous mutation (p.Gly204Ser) in the WNT7A gene is a unique mutation in the degree of loss of function in the upper limb development which ranges from mild to complete absence of both upper limbs (amelia). (PMID:21344627)
• Mutations in the coding sequence of WNT7A are not responsible for mullerian duct abnormalities in the Chinese population. (PMID:22177312)
• Reexpression of WNT7A during malignant transformation of ovarian epithelial cells plays a critical role in ovarian cancer progression mediated by WNT/beta-catenin signaling pathway. (PMID:22232518)
• Wnt7a has a role in postmenstrual regeneration and proliferation of endometrial glands and luminal epithelium in primates (PMID:22294752)
• Wnt7a is lost by methylation in a subset of tumors and that this methylation is maintained by DNMT1 (PMID:22403725)
• Gene expression profiling identifies WNT7A as a key SVZ-glial factor lacking in OB-glia that enhances self-renewal, thereby improving the propagation of OB-NSC cultures. (PMID:22987443)
• WNT7A gene is inactivated by genetic/epigenetic alterations in clear cell RCC and demonstrates tumor suppressor properties (PMID:23056560)
• Overexpression of Wnt7a may contribute to the progression of endometrial cancer and thus may serve as a new biomarker to predict the prognosis of endometrial cancer. (PMID:23321718)
• Novel mutations in the WNT7A gene in two unrelated cases of Al-Awadi Raas-Rothschild syndrome. (PMID:23727605)
• Binding of Wnt7a to Fzd7 leads to an activation of noncanonical Wnt signaling, resulting in directed myogenic stem cell migration and enhanced engraftment. (PMID:24711502)
• findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases (PMID:25030175)
• Prognosis was significantly more favorable for patients with high Wnt7A expression. (PMID:25632963)
• loss of the Wnt7a gene induced by promoter methylation might be a prognostic factor for non-small cell lung carcinoma (PMID:25653486)
• Wnt7a has a role in specifying the fate of neural crest-like cells via suppression of notch in the human skin microenvironment (PMID:25705850)
• identified Iloprost, a prostacyclin analog, which initiates downstream signaling cascades similar to that of Wnt7a, as a novel inducer of cellular senescence, presenting potential future clinical translational strategies (PMID:25728679)
• this is the first study reporting reduced WNT7A levels in cervical cancer -derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration. (PMID:25978974)
• Wnt7a overexpression is associated with an unfavorable prognosis and that positive Wnt7a may be an independent prognosis factor influencing OS and DFS prediction in colorectal cancer patients. (PMID:26055144)
• Wnt7a is involved in the transformation of the retinal pigment epithelium. (PMID:26388562)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt7ab	ENSDARG00000002483
danio_rerio	wnt7aa	ENSDARG00000044827
mus_musculus	Wnt7a	ENSMUSG00000030093
rattus_norvegicus	Wnt7a	ENSRNOG00000048782
drosophila_melanogaster	Wnt2	FBGN0004360
drosophila_melanogaster	Wnt5	FBGN0010194
drosophila_melanogaster	Wnt10	FBGN0031903
caenorhabditis_elegans		WBGENE00000857
caenorhabditis_elegans		WBGENE00000858
caenorhabditis_elegans	lin-44	WBGENE00003029

Paralogs (18): WNT16 (ENSG00000002745), WNT8A (ENSG00000061492), WNT8B (ENSG00000075290), WNT11 (ENSG00000085741), WNT2 (ENSG00000105989), WNT3 (ENSG00000108379), WNT5B (ENSG00000111186), WNT5A (ENSG00000114251), WNT6 (ENSG00000115596), WNT1 (ENSG00000125084), WNT2B (ENSG00000134245), WNT10A (ENSG00000135925), WNT9A (ENSG00000143816), WNT3A (ENSG00000154342), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Protein Wnt-7a — O00755 (reviewed: O00755)

All UniProt accessions (1): O00755

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway. Plays an important role in embryonic development, including dorsal versus ventral patterning during limb development, skeleton development and urogenital tract development. Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation. 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.

Subunit / interactions. Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids. Interacts with PORCN. Interacts (via intrinsically disordered linker region) with RECK; interaction with RECK confers ligand selectivity for Wnt7 in brain endothelial cells and allows these cells to selectively respond to Wnt7. Interacts with FZD5.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expression is restricted to placenta, kidney, testis, uterus, fetal lung, and fetal and adult brain.

Post-translational modifications. Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Fuhrmann syndrome (FUHRS) [MIM:228930] An autosomal recessive disorder characterized by severe bowing of femora, aplasia or hypoplasia of fibulae, hypoplasia of the pelvis, and congenital dislocation of the hip. Patients exhibit absence or coalescence of tarsal bones, absence of various metatarsals, hypoplasia and aplasia of toes, clinodactyly, hypoplasia of fingers and fingernails, and postaxial polydactyly. The disease is caused by variants affecting the gene represented in this entry. Santos syndrome (SS) [MIM:613005] An autosomal recessive syndrome characterized by short stature due to mesomelic shortening of the lower limbs with fibular agenesis or hypoplasia, clubfeet with severe oligodactyly, upper limbs with acromial dimples and variable motion limitation of the forearms and/or hands, and severe nail hypoplasia or anonychia that is associated with brachydactyly in some cases. Pre-axial polydactyly may also be present. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The intrinsically disordered linker region is required for recognition by RECK in brain endothelial cells.

Similarity. Belongs to the Wnt family.

RefSeq proteins (1): NP_004616* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005817	Wnt	Family
IPR013300	Wnt7	Family
IPR018161	Wnt_CS	Conserved_site
IPR043158	Wnt_C	Homologous_superfamily

Pfam: PF00110

UniProt features (66 total): strand 14, disulfide bond 11, sequence conflict 9, helix 9, sequence variant 6, turn 6, mutagenesis site 4, glycosylation site 3, signal peptide 1, chain 1, region of interest 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4UZQ	X-RAY DIFFRACTION	1.5
8TZO	ELECTRON MICROSCOPY	3.1
8TZP	ELECTRON MICROSCOPY	3.23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00755-F1	88.65	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 206

Disulfide bonds (11): 200–214, 202–209, 278–309, 294–304, 308–348, 324–339, 326–336, 331–332, 73–84, 123–131, 133–152

Glycosylation sites (3): 83, 127, 295

Mutagenesis-validated functional residues (4):

Position	Phenotype
206	does not affect interaction with reck.
241	in 4a; abolished interaction with reck; when associated with 251-a-a-252 and a-262.
251–252	in 4a; abolished interaction with reck; when associated with a-241 and a-262.
262	in 4a; abolished interaction with reck; when associated with a-241 and 251-a-a-252.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-373080	Class B/2 (Secretin family receptors)

MSigDB gene sets: 621 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_DENDRITE_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, GOBP_METENCEPHALON_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_AXIS_SPECIFICATION, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CARTILAGE_DEVELOPMENT

GO Biological Process (74): embryonic axis specification (GO:0000578), cartilage condensation (GO:0001502), angiogenesis (GO:0001525), chondrocyte differentiation (GO:0002062), apoptotic process (GO:0006915), neurotransmitter secretion (GO:0007269), axonogenesis (GO:0007409), sex differentiation (GO:0007548), dorsal/ventral pattern formation (GO:0009953), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), skeletal muscle satellite cell activation (GO:0014719), skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration (GO:0014834), cerebellar granule cell differentiation (GO:0021707), cell proliferation in forebrain (GO:0021846), central nervous system vasculogenesis (GO:0022009), establishment of cell polarity (GO:0030010), neuron differentiation (GO:0030182), regulation of axon diameter (GO:0031133), response to estradiol (GO:0032355), somatic stem cell population maintenance (GO:0035019), embryonic forelimb morphogenesis (GO:0035115), embryonic hindlimb morphogenesis (GO:0035116), wound healing, spreading of epidermal cells (GO:0035313), synaptic vesicle recycling (GO:0036465), embryonic digit morphogenesis (GO:0042733), negative regulation of apoptotic process (GO:0043066), response to estrogen (GO:0043627), cell fate commitment (GO:0045165), asymmetric protein localization involved in cell fate determination (GO:0045167), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330), somatic stem cell division (GO:0048103), stem cell development (GO:0048864), negative regulation of neurogenesis (GO:0050768), positive regulation of protein metabolic process (GO:0051247), positive regulation of synapse assembly (GO:0051965), positive regulation of epithelial cell proliferation involved in wound healing (GO:0060054), oviduct development (GO:0060066)

GO Molecular Function (5): signaling receptor binding (GO:0005102), frizzled binding (GO:0005109), cytokine activity (GO:0005125), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (12): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), endocytic vesicle membrane (GO:0030666), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), Schaffer collateral - CA1 synapse (GO:0098685), presynapse (GO:0098793), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by WNT	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	3
cartilage development	2
cell differentiation	2
intracellular organelle lumen	2
axis specification	1
embryonic pattern specification	1
skeletal system morphogenesis	1
cell aggregation	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
neurotransmitter transport	1
chemical synaptic transmission	1
establishment of localization in cell	1
presynapse	1
signal release from synapse	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
developmental process involved in reproduction	1
regionalization	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell activation	1
skeletal muscle tissue regeneration	1
maintenance of cell number	1
cell differentiation in hindbrain	1
cerebellar granular layer formation	1
central nervous system neuron differentiation	1
glutamatergic neuron differentiation	1
forebrain development	1
neural precursor cell proliferation	1
vasculogenesis	1

Protein interactions and networks

STRING

1716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT7A	LRP5	O75197	991
WNT7A	FZD7	O75084	986
WNT7A	FZD5	Q13467	982
WNT7A	FZD4	Q9ULV1	973
WNT7A	LRP6	O75581	963
WNT7A	RYK	P34925	958
WNT7A	FZD9	O00144	955
WNT7A	FZD10	Q9ULW2	954
WNT7A	FZD6	O60353	883
WNT7A	DVL1	O14640	859
WNT7A	FZD3	Q9NPG1	812
WNT7A	FZD2	Q14332	803
WNT7A	FZD1	Q9UP38	769
WNT7A	SFRP1	Q8N474	761
WNT7A	PORCN	Q9H237	759

IntAct

32 interactions, top by confidence:

A	B	Type	Score
WIF1	WNT7A	psi-mi:“MI:0407”(direct interaction)	0.620
WNT7A	Reck	psi-mi:“MI:2364”(proximity)	0.580
WNT7A	Reck	psi-mi:“MI:0915”(physical association)	0.580
Reck	WNT7A	psi-mi:“MI:2364”(proximity)	0.580
WNT7A	Reck	psi-mi:“MI:0407”(direct interaction)	0.580
WNT7A	WLS	psi-mi:“MI:0915”(physical association)	0.560
CASP6	WNT7A	psi-mi:“MI:0915”(physical association)	0.560
WNT7A	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
WNT7A	GSN	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	WNT7A	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	WNT7A	psi-mi:“MI:0915”(physical association)	0.560
WNT7A	LDLR	psi-mi:“MI:0914”(association)	0.530
NOTUM	WNT7A	psi-mi:“MI:0407”(direct interaction)	0.440
WNT7A	AFM	psi-mi:“MI:0915”(physical association)	0.400
DKK3	MYO9A	psi-mi:“MI:0914”(association)	0.350
WNT7A	MGRN1	psi-mi:“MI:0914”(association)	0.350
Fzd5	WNT7A	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (61): WNT7B (Affinity Capture-MS), WNT5A (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), MAPK9 (Affinity Capture-MS), WLS (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), PIK3AP1 (Affinity Capture-MS), SDF2L1 (Affinity Capture-MS)

ESM2 similar proteins: A0M8S1, A0M8T2, A1X153, A4D7S0, O00755, P09544, P21552, P22725, P22726, P28465, P87387, Q07DV4, Q07DW8, Q07DX7, Q07DY7, Q07DZ8, Q07E18, Q07E31, Q07E44, Q09YI4, Q09YJ6, Q09YK7, Q09YN1, Q108U2, Q1KYK4, Q1KYK5, Q1KYK6, Q1KYK7, Q1KYK9, Q1KYL1, Q2IBB0, Q2IBB5, Q2IBE2, Q2IBF4, Q2IBG1, Q2QL76, Q2QL85, Q2QL96, Q2QLA5, Q2QLB6

Diamond homologs: A0M8S1, A0M8T2, A1X153, A4D7S0, B2GUT4, O00755, O13267, O15978, O42122, O70283, P04426, P04628, P09544, P09615, P10108, P17553, P21551, P21552, P22724, P22725, P22726, P22727, P24257, P24383, P27467, P28047, P28465, P31285, P31286, P33945, P34888, P34889, P41221, P43446, P47793, P49337, P49338, P49339, P49340, P49893

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
WNT7A	“up-regulates activity”	FZD3	binding
WNT7A	“up-regulates activity”	LRP5	binding
WNT7A	“up-regulates activity”	LRP6	binding
WNT7A	“up-regulates activity”	PRKACA
WNT7A	“up-regulates activity”	FZD7	binding
WNT7A	“down-regulates quantity by repression”	SPRY4	“transcriptional regulation”
WNT7A	“up-regulates activity”	Frizzled	binding
WNT7A	down-regulates	Proliferation
miR-370-3p	“down-regulates quantity by repression”	WNT7A	“post transcriptional regulation”
WNT7A	“up-regulates quantity by expression”	MMP10	“transcriptional regulation”
WNT7A	“up-regulates quantity by expression”	MMP1	“transcriptional regulation”
WNT7A	down-regulates	Epithelial-mesenchymal_transition
WNT7A	“down-regulates activity”	SKP2	binding
hsa-miR-127-5p	“up-regulates quantity by expression”	WNT7A	“post transcriptional regulation”
WNT7A	“up-regulates activity”	MYOD1
SOSTDC1	“down-regulates activity”	WNT7A
FN1/SDC4	up-regulates	WNT7A

Disease & clinical

Clinical variants and AI predictions

ClinVar

98 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	2
Uncertain significance	40
Likely benign	28
Benign	12

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1338765	NM_004625.4:c.(71+1_72-1)_(298+1_299-1)del	Pathogenic
3393509	NM_004625.4(WNT7A):c.814G>T (p.Glu272Ter)	Pathogenic
3393516	G312S	Pathogenic
40130	NM_004625.4(WNT7A):c.664C>T (p.Arg222Trp)	Pathogenic
40302	NM_004625.4(WNT7A):c.214G>A (p.Glu72Lys)	Pathogenic
4795218	Single allele	Pathogenic
4056356	NM_004625.4(WNT7A):c.71+1G>A	Likely pathogenic
8060	NM_004625.4(WNT7A):c.874C>T (p.Arg292Cys)	Likely pathogenic

SpliceAI

851 predictions. Top by Δscore:

Variant	Effect	Δscore
3:13819420:GGAT:G	acceptor_gain	1.0000
3:13819422:ATCT:A	acceptor_loss	1.0000
3:13819423:TC:T	acceptor_loss	1.0000
3:13819424:C:CC	acceptor_gain	1.0000
3:13819424:C:CG	acceptor_loss	1.0000
3:13819437:C:CT	acceptor_gain	1.0000
3:13854799:GCTCC:G	acceptor_gain	1.0000
3:13854800:CTCC:C	acceptor_gain	1.0000
3:13854800:CTCCC:C	acceptor_gain	1.0000
3:13854801:TCC:T	acceptor_gain	1.0000
3:13854801:TCCCT:T	acceptor_gain	1.0000
3:13854802:CC:C	acceptor_gain	1.0000
3:13854802:CCC:C	acceptor_gain	1.0000
3:13854803:CC:C	acceptor_gain	1.0000
3:13854804:C:CC	acceptor_gain	1.0000
3:13854804:C:CG	acceptor_loss	1.0000
3:13854805:T:C	acceptor_loss	1.0000
3:13854807:C:CT	acceptor_gain	1.0000
3:13854808:G:T	acceptor_gain	1.0000
3:13874945:A:AC	donor_gain	1.0000
3:13874945:AC:A	donor_gain	1.0000
3:13874946:C:CC	donor_gain	1.0000
3:13874946:CC:C	donor_gain	1.0000
3:13874946:CCCA:C	donor_gain	1.0000
3:13874949:A:AC	donor_gain	1.0000
3:13874950:C:CC	donor_gain	1.0000
3:13874962:T:TA	donor_gain	1.0000
3:13874963:C:A	donor_gain	1.0000
3:13875169:AGCCA:A	acceptor_gain	1.0000
3:13875170:GCCA:G	acceptor_gain	1.0000

AlphaMissense

2292 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:13819004:C:A	W330C	1.000
3:13819004:C:G	W330C	1.000
3:13819010:G:C	F328L	1.000
3:13819010:G:T	F328L	1.000
3:13819011:A:C	F328C	1.000
3:13819012:A:G	F328L	1.000
3:13819349:C:A	W215C	1.000
3:13819349:C:G	W215C	1.000
3:13819368:C:G	C209S	1.000
3:13819369:A:T	C209S	1.000
3:13819389:C:G	C202S	1.000
3:13819390:A:T	C202S	1.000
3:13819395:C:G	C200S	1.000
3:13819396:A:T	C200S	1.000
3:13854655:C:A	W149C	1.000
3:13854655:C:G	W149C	1.000
3:13874999:C:A	W82C	1.000
3:13874999:C:G	W82C	1.000
3:13875001:A:G	W82R	1.000
3:13875001:A:T	W82R	1.000
3:13818950:G:C	C348W	0.999
3:13818951:C:T	C348Y	0.999
3:13818952:A:G	C348R	0.999
3:13818987:C:G	C336S	0.999
3:13818988:A:T	C336S	0.999
3:13818999:C:G	C332S	0.999
3:13818999:C:T	C332Y	0.999
3:13819000:A:T	C332S	0.999
3:13819002:C:G	C331S	0.999
3:13819003:A:T	C331S	0.999

dbSNP variants (sampled 300 via entrez): RS1000028799 (3:13845293 C>T), RS1000041914 (3:13842126 T>C), RS1000084339 (3:13881046 G>A), RS1000161480 (3:13839446 C>T), RS1000186070 (3:13868508 G>C), RS1000294852 (3:13833994 G>A), RS1000300314 (3:13826557 A>G), RS1000308996 (3:13818217 C>G,T), RS1000335866 (3:13821220 T>C), RS1000344356 (3:13870976 T>C), RS1000442838 (3:13828120 C>T), RS1000442917 (3:13850979 C>G), RS1000451946 (3:13821002 C>G), RS1000496442 (3:13865319 G>A,C), RS1000513278 (3:13848014 C>G,T)

Disease associations

OMIM: gene MIM:601570 | disease phenotypes: MIM:228930, MIM:276820, MIM:613005

GenCC curated gene-disease

Disease	Classification	Inheritance
Fuhrmann syndrome	Definitive	Autosomal recessive
phocomelia, Schinzel type	Strong	Autosomal recessive
Santos syndrome	Strong	Autosomal recessive

Mondo (6): Fuhrmann syndrome (MONDO:0009232), phocomelia, Schinzel type (MONDO:0010164), Santos syndrome (MONDO:0013077), hypoglycemia (MONDO:0004946), fetal growth restriction (MONDO:0005030), lactic acidosis (MONDO:0006040)

Orphanet (3): Fuhrmann syndrome (Orphanet:2854), Phocomelia, Schinzel type (Orphanet:2879), Microphthalmia-anophthalmia-coloboma (Orphanet:98555)

HPO phenotypes

101 total (30 of 101 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000047	Hypospadias
HP:0000141	Amenorrhea
HP:0000151	Aplasia of the uterus
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000218	High palate
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000475	Broad neck
HP:0000768	Pectus carinatum
HP:0000884	Prominent sternum
HP:0000885	Broad ribs
HP:0000916	Broad clavicles
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001162	Postaxial hand polydactyly
HP:0001171	Split hand
HP:0001362	Calvarial skull defect
HP:0001374	Congenital hip dislocation
HP:0001511	Intrauterine growth retardation

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001737_15	Chronic obstructive pulmonary disease-related biomarkers	9.000000e-06
GCST003372_29	Glomerular filtration rate (creatinine)	3.000000e-08
GCST003469_5	Response to cognitive-behavioural therapy in anxiety disorder	1.000000e-06
GCST005951_48	Body mass index	5.000000e-08
GCST007096_131	Pulse pressure	6.000000e-10
GCST007269_82	Pulse pressure	8.000000e-10
GCST007917_11	Estimated glomerular filtration rate	2.000000e-16
GCST007918_13	Serum uric acid levels	2.000000e-16
GCST007919_20	Creatinine levels	3.000000e-13
GCST008058_35	Estimated glomerular filtration rate	9.000000e-11
GCST90002383_359	Hematocrit	2.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004810	interleukin-6 measurement
EFO:0007820	cognitive behavioural therapy
EFO:0004340	body mass index
EFO:0005763	pulse pressure measurement
EFO:0004761	uric acid measurement
EFO:0004348	hematocrit

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D000140	Acidosis, Lactic	C18.452.076.176.180
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450
D007003	Hypoglycemia	C18.452.394.984
C535612	Al Awadi syndrome (supp.)
C538189	Fuhrmann syndrome (supp.)
C567819	Santos Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression, decreases reaction	2
Smoke	decreases expression, increases abundance, increases expression	2
Genistein	decreases expression	2
pirinixic acid	affects binding, increases activity, increases expression	1
lead acetate	decreases reaction, increases phosphorylation	1
methylselenic acid	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
cypermethrin	increases expression	1
sodium arsenite	increases expression	1
pyrvinium	decreases activity	1
aflatoxin B2	increases methylation	1
cyfluthrin	increases expression	1
CGP 52608	affects binding, increases reaction	1
NSC 668036	decreases activity	1
XAV939	decreases activity	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	decreases expression, decreases reaction	1
Microplastics	increases abundance, increases expression	1
Glyphosate	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Chelating Agents	increases expression, affects binding	1
Copper	affects binding, increases expression	1
Diethylstilbestrol	decreases expression	1
Naled	affects expression	1
Niclosamide	decreases activity, affects reaction, increases cleavage, increases expression, increases response to substance	1
Phthalic Acids	increases methylation	1
Polystyrenes	increases abundance, increases expression	1
Silicon Dioxide	increases expression	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7W6	SEES3-1V human WNT7A, clone1	Embryonic stem cell	Male
CVCL_A7W7	SEES3-1V human WNT7A, clone2	Embryonic stem cell	Male
CVCL_A7W8	SEES3-1V human WNT7A, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00490893	PHASE4	TERMINATED	Hypoglycemia Counterregulation and Symptom Perception With Insulin Detemir
NCT00641407	PHASE4	COMPLETED	Bedtime Insulins and Oral Antihyperglycemic Drugs in Type 2 Diabetes
NCT00766441	PHASE4	TERMINATED	Sitagliptin Versus Sulphonylurea in Type 2 Diabetes During Ramadan
NCT01013402	PHASE4	COMPLETED	Investigating the Accuracy of the Home Glucose Monitors in Hypoglycemia
NCT01147276	PHASE4	COMPLETED	Vildagliptin and the Glucagon Response to Hypoglycemia in Type 1 Diabetes
NCT01387477	PHASE4	WITHDRAWN	Lactate to Treat Hypoglycemia
NCT01841359	PHASE4	COMPLETED	Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery
NCT02007278	PHASE4	COMPLETED	Glycemic Excursions in Type 2 Diabetic Patients With Vildagliptin and Metformin Versus Vildagliptin and Glimepiride
NCT02336438	PHASE4	COMPLETED	The Effect of Glucomannan Soluble Fiber on Glucose Homeostasis in Patients With Roux En Y (RNY) Gastric Bypass Surgery
NCT02527993	PHASE4	COMPLETED	Treatment of Hypoglycemia Following Gastric Bypass Surgery
NCT02578498	PHASE4	COMPLETED	Glucagon Efficiency After High and Low Carbohydrate Diet
NCT02881060	PHASE4	COMPLETED	The Late Effects of Ethanol Intake on the Glucose Response to Subcutaneous Glucagon in Type 1 Diabetes
NCT03429946	PHASE4	COMPLETED	Hypoglycemia and Autonomic Nervous System Function-B
NCT03608163	PHASE4	TERMINATED	Novel Approach for the Prevention of Hypoglycemia Associated Autonomic Failure (HAAF)
NCT04053712	PHASE4	COMPLETED	Dual-hormone Closed-loop Glucose Control in Type 1 Diabetes
NCT06986603	PHASE4	ACTIVE_NOT_RECRUITING	Glucagon Dose-Response in Patients With Post-Bariatric Hypoglycemia
NCT00347867	PHASE4	UNKNOWN	Viagra for the Treatment of IUGR
NCT00909974	PHASE4	COMPLETED	Effect of Prenatal Nutritional Supplementation on Birth Outcome in Hounde District, Burkina Faso
NCT00554281	PHASE3	COMPLETED	Using Glucose Sensors to Prevent Hypoglycemia
NCT00804297	PHASE3	COMPLETED	Octreotide for the Treatment of Sulfonylurea-Associated Hypoglycemia
NCT02171130	PHASE3	COMPLETED	Clinical Usability of Intranasal Glucagon in Treatment of Hypoglycemia
NCT02402933	PHASE3	COMPLETED	Clinical Usability of Nasal Glucagon in Treatment of Hypoglycemia in Children and Adolescents
NCT02656069	PHASE3	COMPLETED	Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics
NCT03216226	PHASE3	COMPLETED	A Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen in Patients With Type 1 Diabetes Mellitus
NCT03378635	PHASE3	COMPLETED	A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects
NCT03439072	PHASE3	COMPLETED	G-Pen™ Compared to Lilly Glucagon for Hypoglycemia Rescue in Adults With Type 1 Diabetes
NCT03667053	PHASE3	COMPLETED	Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in T1DM Children
NCT03688711	PHASE3	COMPLETED	Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Subjects With T1DM
NCT03738865	PHASE3	COMPLETED	G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes
NCT03802942	PHASE3	UNKNOWN	Prevention of Hypoglycemia Among Diabetes Patients Admitted to Internal Medicine Departments With Nutritional Care
NCT03895697	PHASE3	COMPLETED	A Trial to Compare the Efficacy and Safety of 2 Different Batches of Subcutaneous Dasiglucagon in Patients With T1DM
NCT04786262	PHASE3	RECRUITING	A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes
NCT05378672	PHASE3	COMPLETED	A Study to Inv. Safety, Efficacy & PD of Dasiglucagon as Hypoglycemia Rescue Therapy in Children <6 Years With T1D
NCT00434772	PHASE2	COMPLETED	Glucagon in the Treatment of Hypoglycemia in Newborn Infants of Diabetic Mothers
NCT00446264	PHASE2	COMPLETED	Islet Allotransplantation With Steroid Free Immunosuppression
NCT00678145	PHASE2	TERMINATED	Mechanisms of Hypoglycemia Associated Autonomic Failure
NCT00798590	PHASE2	TERMINATED	The Efficacy of Glucagon Like Peptide (GLP) - 1(7-36) Amide for Glycemic Control in Critically Ill Patients
NCT01556594	PHASE2	COMPLETED	Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia
NCT01972152	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of G-Pen(TM) (Glucagon Injection) to Treat Severe Hypoglycemia
NCT02081001	PHASE2	COMPLETED	PK/PD Study With G-Pump (Glucagon Infusion) in T1DM Patients