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UniProtKB/Swiss-Prot P10912: Variant p.Asp262Asn

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

Variant position:  262
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 Aspartate (D) to Asparagine (N) at position 262 (D262N, p.Asp262Asn).
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 acidic (D) to medium size and polar (N)
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.
Any additional useful information about the variant.



Sequence information

Variant position:  262
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:   EFSEVLYVTLPQMSQFTCEE  D FYFPWLLIIIFGIFGLTVML
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                         EFSEVLYVTLPQMS-QFT-CEEDFYFPWLLIIIFGIFGLTVML

                              KFSEVLLITFPQMN-PSA-CEEDFQFPWFLIIMFGILGLAV

                              EFSEALYVTLPQMS-PFA-CEEDFQFPWFLIIIFGIFGLTM

Rhesus macaque                EFSEVLYVTLPQMN-QFT-CEEDFYFPWLLIIIFGIFGLTV

Mouse                         EFSEVLRVIFPQTN-ILEACEEDIQFPWFLIIIFGIFGVAV

Rat                           EFSEVLRVTFPQMD-TLAACEEDFRFPWFLIIIFGIFGVAV

Pig                           EFSEVLYVTLPQMS-PFA-CEEDFRFPWFLIIIFGIFGLTV

Bovine                        KFSEVLLITFPQMN-PSA-CEEDFQFPWFLIIIFGILGLAV

Rabbit                        EFSEVLYVTLPQMS-PFT-CEEDFRFPWFLIIIFGIFGLTV

Sheep                         KFSEVLLITFPQMN-PSA-CEEDFQFPWFLIIIFGILGLTV

Chicken                       EFSEILYVSFTQAGIEFVHCAEEIEFPWFLVVVFGVCGLAV

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
Topological domain 19 – 264 Extracellular
Region 260 – 262 Required for ADAM17-mediated proteolysis
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

Characterisation of novel missense mutations in the GH receptor gene causing severe growth retardation.
Enberg B.; Luthman H.; Segnestam K.; Ritzen E.M.; Sundstroem M.; Norstedt G.;
Eur. J. Endocrinol. 143:71-76(2000)
Cited for: VARIANTS LARS CYS-226 AND ASN-262;

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.