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-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 (58 variants)
not_specified (25 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				24 clinvar	2 clinvar	26
missense	1 clinvar		44 clinvar	2 clinvar		47
nonsense	2 clinvar					2
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	3	2	45	26	2

Highest pathogenic variant AF is 0.000004342987

Loading clinvar variants...

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
0.0246	0.963	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

Haploinsufficiency Scores

pHI: 0.294
hipred: Y
hipred_score: 0.625
ghis: 0.484

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

Mouse Genome Informatics

Gene name: Rspo2
Phenotype: homeostasis/metabolism phenotype; craniofacial 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); endocrine/exocrine gland phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; hearing/vestibular/ear 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); reproductive system phenotype; 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); embryo phenotype;

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