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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q15465: Variant p.Gly31Arg

Sonic hedgehog protein
Gene: SHH
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Variant information Variant position: help 31 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Glycine (G) to Arginine (R) at position 31 (G31R, p.Gly31Arg). 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: help Change from glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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: help In HPE3; the same mutation in the mouse sequence introduces a cleavage site for a furin-like protease resulting in abnormal protein processing; cleavage at this site removes 11 amino acids from the N-terminal domain and reduces affinity of Shh for Ptch1 and signaling potency in assays using chicken embryo neural plate explants and mouse C3H10T1/2 stem cells. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 31 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 462 The length of the canonical sequence.
Location on the sequence: help VLVSSLLVCSGLACGPGRGF G KRRHPKKLTPLAYKQFIPNV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         VLVSSLLVCSGLACGPGRGFGKRRHPKKLTPLAYKQFIPNV

Mouse                         ILASSLLVCPGLACGPGRGFGKRRHPKKLTPLAYKQFIPNV

Rat                           ALASSLLVCPGLACGPGRGFGKRQHPKKLTPLAYKQFIPNV

Chicken                       GFICALLVSSGLTCGPGRGIGKRRHPKKLTPLAYKQFIPNV

Xenopus laevis                SFICTLVTPPGLACGPGRGIGKRRHPKKLTPLAYKQFIPNV

Zebrafish                     SLLTLSLVVSGLACGPGRGYGRRRHPKKLTPLAYKQFIPNV

Sequence annotation in neighborhood: help 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 24 – 462 Sonic hedgehog protein
Chain 24 – 197 Sonic hedgehog protein N-product
Lipidation 24 – 24 N-palmitoyl cysteine
Mutagenesis 24 – 24 C -> SA. Abolishes palmitoylation.
Beta strand 30 – 32



Literature citations
Mutations in the human Sonic hedgehog gene cause holoprosencephaly.
Roessler E.; Belloni E.; Gaudenz K.; Jay P.; Berta P.; Scherer S.W.; Tsui L.-C.; Muenke M.;
Nat. Genet. 14:357-360(1996)
Cited for: VARIANTS HPE3 ARG-31; GLY-117 AND ARG-117; Mutations in the C-terminal domain of Sonic hedgehog cause holoprosencephaly.
Roessler E.; Belloni E.; Gaudenz K.; Vargas F.; Scherer S.W.; Tsui L.-C.; Muenke M.;
Hum. Mol. Genet. 6:1847-1853(1997)
Cited for: VARIANTS HPE3 ARG-31; GLY-117; ARG-117; GLU-224; THR-226 AND THR-383; Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly.
Maity T.; Fuse N.; Beachy P.A.;
Proc. Natl. Acad. Sci. U.S.A. 102:17026-17031(2005)
Cited for: CHARACTERIZATION OF VARIANTS HPE3 ARG-31; VAL-88; HIS-100; LYS-115; ARG-117; GLY-117 AND GLN-188; The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis.
Roessler E.; El-Jaick K.B.; Dubourg C.; Velez J.I.; Solomon B.D.; Pineda-Alvarez D.E.; Lacbawan F.; Zhou N.; Ouspenskaia M.; Paulussen A.; Smeets H.J.; Hehr U.; Bendavid C.; Bale S.; Odent S.; David V.; Muenke M.;
Hum. Mutat. 30:E921-E935(2009)
Cited for: VARIANTS HPE3 THR-6; PRO-17; LEU-26; ALA-27; ARG-31; PRO-39; LYS-53; VAL-83; PHE-84; VAL-88; HIS-100; ARG-102; TYR-102; 106-LEU-ASN-107 DEL; PHE-109; THR-110; ASP-110; PHE-111; ASN-111; LYS-115; GLY-117; ARG-117; MET-124; LYS-136; PRO-140; GLN-140; ASP-143; PRO-144; ASN-147; ARG-150; LYS-150; ARG-156; CYS-170; HIS-171; 176-GLU--LYS-178 DEL; ARG-183; PHE-183; TYR-183; LEU-184; GLN-188; GLU-196; 196-GLY--PRO-200 DEL; VAL-197; SER-198; PHE-198; PRO-218; ASN-222; GLU-224; THR-226; VAL-231; GLY-232; PRO-234; ARG-236; ASN-236; VAL-241; LEU-241; ASN-255; 263-ARG--ALA-269 DEL; ILE-267; PRO-271; GLU-275; TRP-280; ASP-290; ALA-296; CYS-310; SER-321; ALA-332; VAL-346; ARG-347; GLN-347; LEU-347; THR-354; LEU-362; TYR-363; CYS-364; THR-373; ARG-374; ASP-376; SER-377; 378-ALA--PHE-380 DEL; PRO-381; PRO-382; THR-383; THR-391; 402-GLY--GLY-409 DEL; 405-ASP--GLY-409 DEL; GLY-411 INS; ALA-416; ALA-424; ASN-435; LEU-436 AND ARG-456;
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.