RSPO1
R-spondin 1, the group of R-spondin family
Basic information
Region (hg38): 1:37611350-37634892
Links
Phenotypes
GenCC
Source:
- palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome (Strong), mode of inheritance: AR
- palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome (Moderate), mode of inheritance: AR
- palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome (Strong), mode of inheritance: AR
- palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and 46,XX sex reversal | AR | Genitourinary; Oncologic | Surveillance/treatment of gonadal tumors and specific malignancies may improve outcome | Audiologic/Otolaryngologic; Dermatologic; Endocrine; Genitourinary; Oncologic; Ophthalmologic | 17041600; 18085567 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (35 variants)
- not_provided (32 variants)
- Palmoplantar_keratoderma-XX_sex_reversal-predisposition_to_squamous_cell_carcinoma_syndrome (4 variants)
- RSPO1-related_disorder (3 variants)
- not_specified (1 variants)
- Palmoplantar_hyperkeratosis_and_true_hermaphroditism (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RSPO1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001242908.2. 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 | 14 | 16 | ||||
| missense | 42 | 46 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 2 | 1 | 45 | 17 | 1 |
Highest pathogenic variant AF is 0.0000013681107
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RSPO1 | protein_coding | protein_coding | ENST00000356545 | 5 | 23645 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00000144 | 0.406 | 124795 | 0 | 22 | 124817 | 0.0000881 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.647 | 138 | 161 | 0.857 | 0.0000109 | 1706 |
| Missense in Polyphen | 36 | 49.682 | 0.72462 | 498 | ||
| Synonymous | -0.473 | 70 | 65.1 | 1.07 | 0.00000426 | 514 |
| Loss of Function | 0.558 | 10 | 12.1 | 0.827 | 5.93e-7 | 146 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000158 | 0.000158 |
| Ashkenazi Jewish | 0.0000993 | 0.0000993 |
| East Asian | 0.0000556 | 0.0000556 |
| Finnish | 0.0000934 | 0.0000928 |
| European (Non-Finnish) | 0.000106 | 0.000106 |
| Middle Eastern | 0.0000556 | 0.0000556 |
| South Asian | 0.0000654 | 0.0000654 |
| Other | 0.000165 | 0.000165 |
dbNSFP
Source:
- Function
- FUNCTION: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. 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. Has a essential roles in ovary determination. Regulates Wnt signaling by antagonizing DKK1/KREM1-mediated internalization of LRP6 through an interaction with KREM1 (PubMed:17804805). {ECO:0000269|PubMed:16109882, ECO:0000269|PubMed:17804805, ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22575959, ECO:0000269|PubMed:22615920, ECO:0000269|PubMed:22815884, ECO:0000269|PubMed:23756652, ECO:0000269|PubMed:23809763}.;
- Disease
- DISEASE: Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal (PKKSCC) [MIM:610644]: A recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. {ECO:0000269|PubMed:17041600}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Signaling by WNT;Signal Transduction;Regulation of FZD by ubiquitination;Wnt;Wnt signaling network;TCF dependent signaling in response to WNT
(Consensus)
Recessive Scores
- pRec
- 0.170
Intolerance Scores
- loftool
- 0.423
- rvis_EVS
- 0.17
- rvis_percentile_EVS
- 65.76
Haploinsufficiency Scores
- pHI
- 0.261
- hipred
- N
- hipred_score
- 0.342
- ghis
- 0.426
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.126
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rspo1
- Phenotype
- homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region 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); 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; skeleton phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- rspo1
- Affected structure
- vascular sprouts
- Phenotype tag
- abnormal
- Phenotype quality
- absent
Gene ontology
- Biological process
- positive regulation of protein phosphorylation;regulation of receptor internalization;Wnt signaling pathway;positive regulation of Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway
- Cellular component
- extracellular region;extracellular space;nucleus
- Molecular function
- G protein-coupled receptor binding;signaling receptor binding;frizzled binding;protein binding;heparin binding