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UniProtKB/Swiss-Prot P10912: Variant p.Ser244Ile

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

Variant position:  244
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 Serine (S) to Isoleucine (I) at position 244 (S244I, p.Ser244Ile).
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 small size and polar (S) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

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.
Any additional useful information about the variant.

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



Sequence information

Variant position:  244
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:   KEYEVRVRSKQRNSGNYGEF  S EVLYVTLPQMSQFTCEEDFY
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                         KEYEVRVRSKQRNSGNYGEFSEVLYVTLPQMS-QFT-CEEDFY

                              KEYEVRVRTRQRNTEKYGKFSEVLLITFPQMN-PSA-CEED

                              KEYEVRVRSRQRNSEKYGEFSEALYVTLPQMS-PFA-CEED

Rhesus macaque                KEYEVLVRSKRRNSRNYGEFSEVLYVTLPQMN-QFT-CEED

Mouse                         KEHEVRVRSRQRSFEKYSEFSEVLRVIFPQTN-ILEACEED

Rat                           KEHEVRVRSRQRSFEKYSEFSEVLRVTFPQMD-TLAACEED

Pig                           KEYEVRVRSRQRNSEKYGEFSEVLYVTLPQMS-PFA-CEED

Bovine                        KEYEVRVRTRQRNTEKYGKFSEVLLITFPQMN-PSA-CEED

Rabbit                        KEYEVRVRSRQRSSEKYGEFSEVLYVTLPQMS-PFT-CEED

Sheep                         KEYEVRVRTRQRNTEKYGKFSEVLLITFPQMN-PSA-CEED

Chicken                       RDYEIRVRSRQRTSEKFGEFSEILYVSFTQAGIEFVHCAEE

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
Motif 240 – 244 WSXWS motif
Mutagenesis 260 – 260 E -> A. No change in shedding activity: No change in hormone binding.
Mutagenesis 261 – 261 E -> A. No change in shedding activity: No change in hormone binding.
Mutagenesis 262 – 262 D -> A. No change in shedding activity: No change in hormone binding.


Literature citations

The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of the GH receptor causing Laron syndrome: suppression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration.
Jorge A.A.L.; Souza S.C.A.L.; Arnhold I.J.P.; Mendonca B.B.;
Clin. Endocrinol. (Oxf.) 60:36-40(2004)
Cited for: VARIANT LARS ILE-244;

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.