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UniProtKB/Swiss-Prot Q6UXX9: Variant p.Arg69Cys

R-spondin-2
Gene: RSPO2
Variant information

Variant position:  69
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Arginine (R) to Cysteine (C) at position 69 (R69C, p.Arg69Cys).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from large size and basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In HHRRD; loss of LGR5-, RNF43- and ZNRF3-binding; decreased ability to amplify WNT3A signaling.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  69
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  243
The length of the canonical sequence.

Location on the sequence:   DNGCSRCQQKLFFFLRREGM  R QYGECLHSCPSGYYGHRAPD
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         DNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPD

Mouse                         DNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPD

Xenopus laevis                DNGCLRCQPKLFFFLRREGMRQYGECLQSCPPGYYGVRGPD

Xenopus tropicalis            DNGCLRCQPKLFFYLRREGMRQYGECLQSCPPGYYGVRGPD

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 22 – 243 R-spondin-2
Disulfide bond 55 – 74
Alternative sequence 32 – 95 ASYVSNPICKGCLSCSKDNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPDMNRCAR -> G. In isoform 3.


Literature citations

RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6.
Szenker-Ravi E.; Altunoglu U.; Leushacke M.; Bosso-Lefevre C.; Khatoo M.; Thi Tran H.; Naert T.; Noelanders R.; Hajamohideen A.; Beneteau C.; de Sousa S.B.; Karaman B.; Latypova X.; Basaran S.; Yuecel E.B.; Tan T.T.; Vlaminck L.; Nayak S.S.; Shukla A.; Girisha K.M.; Le Caignec C.; Soshnikova N.; Uyguner Z.O.; Vleminckx K.; Barker N.; Kayserili H.; Reversade B.;
Nature 557:564-569(2018)
Cited for: INVOLVEMENT IN TETAMS2; VARIANTS TETAMS2 70-GLN--GLN-243 DEL AND 137-GLU--GLN-243 DEL; INVOLVEMENT IN HHRRD; VARIANT HHRRD CYS-69; CHARACTERIZATION OF VARIANT TETAMS2 70-GLN--GLN-243; CHARACTERIZATION OF VARIANT HHRRD CYS-69; FUNCTION; INTERACTION WITH LGR5; RNF43 AND ZNRF3; MUTAGENESIS OF PHE-105 AND PHE-109;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.