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

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 (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.

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				18	2	20
missense			27	2	1	30
nonsense	1					1
start loss			1			1
frameshift		1				1
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				4	6	10
Total	1	1	30	24	9

Highest pathogenic variant AF is 0.00000658

Variants in RSPO2

This is a list of pathogenic ClinVar variants found in the RSPO2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-107901078-T-C			Likely benign (Aug 16, 2022)
8-107901084-A-G			Likely benign (Aug 20, 2022)
8-107901086-C-T		not specified	Uncertain significance (Dec 27, 2023)
8-107901107-C-T			Uncertain significance (Dec 11, 2023)
8-107901108-G-A		RSPO2-related disorder	Likely benign (Jun 20, 2023)
8-107901109-C-A		not specified	Uncertain significance (Feb 15, 2023)
8-107901110-T-C		not specified	Uncertain significance (Jul 08, 2022)
8-107901114-T-C			Likely benign (Sep 21, 2023)
8-107901124-G-A		not specified	Uncertain significance (May 16, 2022)
8-107901126-C-G		not specified	Uncertain significance (May 28, 2024)
8-107901128-T-C		not specified	Uncertain significance (Sep 29, 2023)
8-107901141-C-T			Likely benign (Oct 03, 2023)
8-107901150-TTTCTTG-T			Uncertain significance (Oct 22, 2022)
8-107901171-C-T			Likely benign (Mar 11, 2022)
8-107901173-CC-TT			Uncertain significance (Oct 22, 2022)
8-107901181-G-A			Uncertain significance (Nov 18, 2023)
8-107901209-A-G			Likely benign (Oct 03, 2023)
8-107901346-GAAT-G			Benign (May 14, 2021)
8-107958036-T-TCA		Humerofemoral hypoplasia with radiotibial ray deficiency • Tetraamelia syndrome 2	Benign (Nov 07, 2021)
8-107958101-T-C			Uncertain significance (May 25, 2022)
8-107958108-G-A			Benign (Jan 14, 2024)
8-107958138-CA-TG			Likely benign (Feb 24, 2023)
8-107958139-A-G		Tetraamelia syndrome 2 • Humerofemoral hypoplasia with radiotibial ray deficiency	Benign (Jan 31, 2024)
8-107958140-GTAT-G			Uncertain significance (Feb 15, 2022)
8-107958143-T-C		not specified	Uncertain significance (May 14, 2024)

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