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UniProtKB/Swiss-Prot P10912: Variant p.Ile171Thr

Growth hormone receptor
Gene: GHR
Chromosomal location: 5p12-p13
Variant information

Variant position:  171
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Isoleucine (I) to Threonine (T) at position 171 (I171T, p.Ile171Thr).
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 hydrophobic (I) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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

Involvement in disease:  Laron syndrome (LARS) [MIM:262500]: A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone. {ECO:0000269|PubMed:10870033, ECO:0000269|PubMed:14678285, ECO:0000269|PubMed:2779634, ECO:0000269|PubMed:8137822, ECO:0000269|PubMed:8450064, ECO:0000269|PubMed:8504296, ECO:0000269|PubMed:9024232, ECO:0000269|PubMed:9661642, ECO:0000269|PubMed:9851797}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In LARS; almost completely abolishes GH-binding at cell surface: 53% binding to membrane fractions.
Any additional useful information about the variant.

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



Sequence information

Variant position:  171
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  638
The length of the canonical sequence.

Location on the sequence:   PPIALNWTLLNVSLTGIHAD  I QVRWEAPRNADIQKGWMVLE
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                         PPIALNWTLLNVSLTGIHADIQVRWEAPRNADIQKGWMVLE

                              PPVGLNWTLLNISLTEIHADILVKWEPPPNTDVKMGWIILE

                              PPIGLNWTLLNISLTGIHADIQVRWEPPPNADVQKGWIVLK

Rhesus macaque                PPIALNWTLLNVSLTGIHADILVRWEAPPNADIQKGWMVLE

Mouse                         PPIGLNWTLLNISLTGIRGDIQVSWQPPPNADVLKGWIILE

Rat                           PPIGLNWTLLNISLPGIRGDIQVSWQPPPSADVLKGWIILE

Pig                           PPIGLNWTLLNISLTGIHADIQVRWEPPPNADVQKGWIVLE

Bovine                        PPVGLNWTLLNISLTEIHADILVKWEPPPNTDVKMGWIILE

Rabbit                        PPIGLNWTLLNVSLTGIHADIQVRWEPPPNADVQKGWIVLE

Sheep                         PPVGLNWTLLNISLTEIHADILVKWEPPPNTDVKMGWIILE

Chicken                       PPVHLNWTLLNTSQTGIHGDIQVRWDPPPTADVQKGWITLE

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 19 – 638 Growth hormone receptor
Chain 19 – 256 Growth hormone-binding protein
Topological domain 19 – 264 Extracellular
Domain 151 – 254 Fibronectin type-III
Glycosylation 156 – 156 N-linked (GlcNAc...) asparagine
Glycosylation 161 – 161 N-linked (GlcNAc...) asparagine
Beta strand 167 – 176


Literature citations

Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor.
Wojcik J.; Berg M.A.; Esposito N.; Geffner M.E.; Sakati N.; Reiter E.O.; Dower S.; Francke U.; Postel-Vinay M.-C.; Finidori J.;
J. Clin. Endocrinol. Metab. 83:4481-4489(1998)
Cited for: VARIANTS LARS HIS-170; THR-171; PRO-172 AND GLY-173; CHARACTERIZATION OF VARIANTS LARS THR-171; PRO-172 AND GLY-173;

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.