UniProtKB/Swiss-Prot P55075: Variant p.Pro26Leu

Fibroblast growth factor 8
Gene: FGF8
Chromosomal location: 10q24
Variant information

Variant position:  26
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Proline (P) to Leucine (L) at position 26 (P26L, p.Pro26Leu).
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:  -3
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:  Hypogonadotropic hypogonadism 6 with or without anosmia (HH6) [MIM:612702]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in FGF8 as well as in other HH-associated genes including FGFR1 (PubMed:23643382).
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 HH6; phenotype consistent with Kallmann syndrome.
Any additional useful information about the variant.

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



Sequence information

Variant position:  26
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  233
The length of the canonical sequence.

Location on the sequence:   SALSCLLLHLLVLCLQAQEG  P GRGPALGRELASLFRAGREP
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                         SALSCLLLHLLVLCLQAQ-------EGPGRG---PALG-----RELASLFRAGRE--------P

Mouse                         SALSCLLLHLLVLCLQAQVRSAAQKRGPGAGNPADTLGQGH

Chicken                       SLFSYVFMHLFVLCLQAQVTV----QSP------PNFT---

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 23 – 233 Fibroblast growth factor 8
Alternative sequence 24 – 52 Missing. In isoform FGF-8A.
Alternative sequence 24 – 51 EGPGRGPALGRELASLFRAGREPQGVSQ -> VTVQSSPNFT. In isoform FGF-8B.


Literature citations

Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice.
Falardeau J.; Chung W.C.J.; Beenken A.; Raivio T.; Plummer L.; Sidis Y.; Jacobson-Dickman E.E.; Eliseenkova A.V.; Ma J.; Dwyer A.; Quinton R.; Na S.; Hall J.E.; Huot C.; Alois N.; Pearce S.H.; Cole L.W.; Hughes V.; Mohammadi M.; Tsai P.; Pitteloud N.;
J. Clin. Invest. 118:2822-2831(2008)
Cited for: VARIANTS HH6 ASN-14; LEU-26; LEU-40; GLU-89; GLY-116 AND MET-218;

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.