RSPO2

R-spondin 2, the group of R-spondin family

Basic information

Region (hg38): 8:107899316-108083642

Links

ENSG00000147655 ∙ NCBI:340419 ∙ OMIM:610575 ∙ HGNC:28583 ∙ Uniprot:Q6UXX9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• tetraamelia syndrome 2 (Strong), mode of inheritance: AR
• tetraamelia-multiple malformations syndrome (Supportive), mode of inheritance: AR
• tetraamelia syndrome 2 (Strong), mode of inheritance: AR
• tetraamelia syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tetraamelia syndrome 2	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Pulmonary	8030673; 18837045; 29769720

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RSPO2 gene.

• not_provided (62 variants)
• not_specified (27 variants)
• RSPO2-related_disorder (3 variants)
• Tetraamelia-multiple_malformations_syndrome (2 variants)
• Tetraamelia_syndrome_2 (2 variants)
• Humerofemoral_hypoplasia_with_radiotibial_ray_deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RSPO2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000178565.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				25	2	27
missense	1		47	2		50
nonsense	2					2
start loss						0
frameshift		1	1			2
splice donor/acceptor (+/-2bp)		1				1
Total	3	2	48	27	2

Highest pathogenic variant AF is 0.000004342987

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RSPO2	protein_coding	protein_coding	ENST00000276659	5	184370

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.496	121	137	0.881	0.00000709	1613
Missense in Polyphen		46	52.355	0.87862		592
Synonymous	-1.26	55	44.3	1.24	0.00000223	410
Loss of Function	2.19	5	13.8	0.363	8.33e-7	162

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000927	0.0000919
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000560	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.0000560	0.0000544
South Asian	0.000102	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• 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. Probably also acts as a ligand for frizzled and LRP receptors. {ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22615920}.
• Pathway: Signaling by WNT;Signal Transduction;Regulation of FZD by ubiquitination;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.420
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.202

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: rspo2
• Affected structure: pelvic fin lepidotrichium
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: osteoblast differentiation;Wnt signaling pathway;positive regulation of Wnt signaling pathway;bone mineralization;embryonic forelimb morphogenesis;embryonic hindlimb morphogenesis;negative regulation of odontogenesis of dentin-containing tooth;limb development;lung growth;epithelial tube branching involved in lung morphogenesis;trachea cartilage morphogenesis;dopaminergic neuron differentiation;positive regulation of canonical Wnt signaling pathway
• Cellular component: extracellular region;extracellular space;cell surface
• Molecular function: signaling receptor binding;frizzled binding;protein binding;heparin binding