RSPO3
R-spondin 3, the group of R-spondin family
Basic information
Region (hg38): 6:127118671-127199481
Previous symbols: [ "THSD2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
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.
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 | 0 | |||||
| missense | 10 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 9 | 1 | 0 |
Variants in RSPO3
This is a list of pathogenic ClinVar variants found in the RSPO3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-127119217-C-T | not specified | Likely benign (Apr 07, 2023) | ||
| 6-127119238-A-G | not specified | Uncertain significance (Oct 17, 2023) | ||
| 6-127148653-C-A | not specified | Uncertain significance (Oct 03, 2023) | ||
| 6-127148779-C-G | not specified | Uncertain significance (Apr 17, 2024) | ||
| 6-127148795-G-A | not specified | Uncertain significance (Jul 05, 2023) | ||
| 6-127155351-C-T | not specified | Uncertain significance (Mar 27, 2023) | ||
| 6-127195823-G-C | not specified | Uncertain significance (Dec 21, 2022) | ||
| 6-127195877-A-C | not specified | Uncertain significance (Feb 22, 2023) | ||
| 6-127195942-C-G | not specified | Uncertain significance (Oct 13, 2023) | ||
| 6-127195958-G-A | not specified | Uncertain significance (Jul 06, 2021) | ||
| 6-127195982-C-T | not specified | Uncertain significance (Jan 08, 2024) |
GnomAD
Source:
| 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:
- 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