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UniProtKB/Swiss-Prot Q03431: Variant p.His223Arg

Parathyroid hormone/parathyroid hormone-related peptide receptor
Gene: PTH1R
Variant information

Variant position:  223
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 Histidine (H) to Arginine (R) at position 223 (H223R, p.His223Arg).
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 medium size and polar (H) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 MCDJ; constitutively activated; constitutively increases adenylate cyclase-activating G-protein coupled receptor signaling pathway; decreases the degree of N-glycosylation; does not affect homodimerization.
Any additional useful information about the variant.

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



Sequence information

Variant position:  223
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  593
The length of the canonical sequence.

Location on the sequence:   TVAVLILAYFRRLHCTRNYI  H MHLFLSFMLRAVSIFVKDAV
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                         TVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAV

                              TVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAV

Mouse                         TVAVLILAYFRRLHCTRNYIHMHMFLSFMLRAASIFVKDAV

Rat                           TVAVLILAYFRRLHCTRNYIHMHMFLSFMLRAASIFVKDAV

Pig                           TVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAV

Bovine                        TVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAV

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 27 – 593 Parathyroid hormone/parathyroid hormone-related peptide receptor
Transmembrane 220 – 239 Helical; Name=2
Helix 219 – 245


Literature citations

A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia.
Schipani E.; Kruse K.; Jueppner H.;
Science 268:98-100(1995)
Cited for: VARIANT MCDJ ARG-223;

Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia.
Schipani E.; Langman C.B.; Parfitt A.M.; Jensen G.S.; Kikuchi S.; Kooh S.W.; Cole W.G.; Jueppner H.;
N. Engl. J. Med. 335:708-714(1996)
Cited for: VARIANTS MCDJ ARG-223 AND PRO-410;

Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia.
Schipani E.; Jensen G.S.; Pincus J.; Nissenson R.A.; Gardella T.J.; Jueppner H.;
Mol. Endocrinol. 11:851-858(1997)
Cited for: CHARACTERIZATION OF VARIANTS MCDJ ARG-223 AND PRO-410;

Characterization of a PTH1R missense mutation responsible for Jansen type metaphyseal chondrodysplasia.
Shimomura-Kuroki J.; Farooq M.; Sekimoto T.; Amizuka N.; Shimomura Y.;
Odontology 105:150-154(2017)
Cited for: VARIANT MCDJ ARG-223; CHARACTERIZATION OF VARIANT MCDJ ARG-223; GLYCOSYLATION; FUNCTION; SUBUNIT;

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.