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UniProtKB/Swiss-Prot P10912: Variant p.Ile544Leu

Growth hormone receptor
Gene: GHR
Variant information

Variant position:  544
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LB/B
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 Isoleucine (I) to Leucine (L) at position 544 (I544L, p.Ile544Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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

Polymorphism:  Genetic variation in GHR may act as phenotype modifier in familial hypercholesterolemia [MIM:143890] patients carrying a mutation in the LDLR gene.
Additional information on the polymorphism described.

Variant description:  Benign variant; associated with lower plasma HDL cholesterol levels in hypercholesterolemia patients that carry a pathogenic variant in LDLR.
Any additional useful information about the variant.

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



Sequence information

Variant position:  544
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:   CQENFLMDNAYFCEADAKKC  I PVAPHIKVESHIQPSLNQED
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                         CQENFLMDNAYFCEADAKKCIPVAPHIKVESHIQPSLNQED

                              CQANFIVDNAYFCEVDAKKYIALAPHVEAESHVEPSFNQED

                              CQANFIMDNAYFCEADAKKCITVAPHVEAESRVEPSFNQED

Rhesus macaque                CQEDFIMDNAYFCEADAKKCIPVAPHIKVESHIEPSFNQED

Mouse                         CQENYSMNSAYFCESDAKKCIAVARRMEATSCIKPSFNQED

Rat                           CQENYSMNSAYFCESDAKKCIAAAPHMEATTCVKPSFNQED

Pig                           CPANFIMDNAYFCEADAKKCIAMAPHVEVESRLAPSFNQED

Bovine                        CQANFIVDNAYFCEVDAKKYIALAPHVEAESHVEPSFNQED

Rabbit                        CQTNFIMDNAYFCEADAKKCIAVAPHVDVESRVEPSFNQED

Sheep                         SQADFIVDSAYFCEVDAKKYIALAPDVEAESHIEPSFNQED

Chicken                       TEQNFTMDNAYFCEADVKKCIAVISQEEDEPRVQEQSCNED

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 289 – 638 Cytoplasmic
Alternative sequence 295 – 638 Missing. In isoform 3.
Alternative sequence 298 – 638 Missing. In isoform 2.


Literature citations

Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism.
Godowski P.J.; Leung D.W.; Meacham L.R.; Galgani J.P.; Hellmiss R.; Keret R.; Rotwein P.S.; Parks J.S.; Laron Z.; Wood W.I.;
Proc. Natl. Acad. Sci. U.S.A. 86:8083-8087(1989)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1); VARIANT LEU-544;

Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS HIS-179; HIS-229; PHE-440; THR-495; LEU-544 AND THR-579;

Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: intra-familial association study in an eight-generation hyperlipidemic kindred.
Takada D.; Ezura Y.; Ono S.; Iino Y.; Katayama Y.; Xin Y.; Wu L.L.; Larringa-Shum S.; Stephenson S.H.; Hunt S.C.; Hopkins P.N.; Emi M.;
Am. J. Med. Genet. A 121:136-140(2003)
Cited for: VARIANT LEU-544;

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.