RSPO3

R-spondin 3, the group of R-spondin family

Basic information

Region (hg38): 6:127118671-127199481

Previous symbols: [ "THSD2" ]

Links

ENSG00000146374

∙ NCBI:84870 ∙ OMIM:610574 ∙ HGNC:20866 ∙ Uniprot:Q9BXY4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RSPO3 gene.

not_specified (27 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RSPO3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032784.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			26 clinvar	1 clinvar		27
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	26	1	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RSPO3	protein_coding	protein_coding	ENST00000356698	5	79162

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0893	0.909	125690	0	18	125708	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	107	141	0.759	0.00000658	1787
Missense in Polyphen		27	48.273	0.55932		615
Synonymous	0.279	46	48.5	0.949	0.00000232	475
Loss of Function	2.75	5	17.4	0.287	0.00000117	188

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000267	0.000267
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000618	0.0000616
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000499	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta- catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway (PubMed:21727895, PubMed:21909076, PubMed:22615920). Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells (By similarity). {ECO:0000250|UniProtKB:Q2TJ95, ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22615920}.;
Pathway: Transcriptional regulation by RUNX1;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Regulation of FZD by ubiquitination;RUNX1 regulates transcription of genes involved in WNT signaling;Transcriptional regulation by RUNX1;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

pRec: 0.115

Intolerance Scores

loftool: 0.464
rvis_EVS: -0.14
rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

pHI: 0.198
hipred: Y
hipred_score: 0.613
ghis: 0.435

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.129

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Rspo3
Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; embryo phenotype; skeleton phenotype; limbs/digits/tail 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); 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype;

Zebrafish Information Network

Gene name: rspo3
Affected structure: posterior lateral line primordium
Phenotype tag: abnormal
Phenotype quality: decreased process quality

Gene ontology

Biological process: blood vessel remodeling;sprouting angiogenesis;Wnt signaling pathway;regulation of Wnt signaling pathway;positive regulation of Wnt signaling pathway;branching involved in labyrinthine layer morphogenesis;positive regulation of canonical Wnt signaling pathway;positive regulation of non-canonical Wnt signaling pathway;positive regulation of Wnt signaling pathway, planar cell polarity pathway
Cellular component: extracellular region;extracellular space
Molecular function: signaling receptor binding;frizzled binding;heparin binding