UniProtKB/SwissProt variant VAR

Variant information

Variant position:

40

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

Type of variant:

LP/P [Disclaimer]

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 Phenylalanine (F) to Leucine (L) at position 40 (F40L, p.Phe40Leu).

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 large size and aromatic (F) to medium size and hydrophobic (L)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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

Variant description:

In HH6; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; some patients also carry mutations in FGFR1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137852661 [ dbSNP | Ensembl ]

Sequence information

Variant position:

40

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:

LQAQEGPGRGPALGRELASL F RAGREPQGVSQQHVREQSLV

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                         LQAQ-------EGPGRG---PALG-----RELASLFRAGRE--------PQG------------VSQQHVREQSLV

Mouse                         LQAQVRSAAQKRGPGAGNPADTLGQGHEDRPFGQRSRAGKN

Chicken                       LQAQVTV----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.

Type	Positions	Description
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.
Alternative sequence	52 – 52	Q -> QVTVQSSPNFTQ. In isoform FGF-8F.

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;

Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.
Miraoui H.; Dwyer A.A.; Sykiotis G.P.; Plummer L.; Chung W.; Feng B.; Beenken A.; Clarke J.; Pers T.H.; Dworzynski P.; Keefe K.; Niedziela M.; Raivio T.; Crowley W.F. Jr.; Seminara S.B.; Quinton R.; Hughes V.A.; Kumanov P.; Young J.; Yialamas M.A.; Hall J.E.; Van Vliet G.; Chanoine J.P.; Rubenstein J.; Mohammadi M.; Tsai P.S.; Sidis Y.; Lage K.; Pitteloud N.;
Am. J. Hum. Genet. 92:725-743(2013)
Cited for: VARIANTS HH6 LEU-40 AND GLU-89;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P55075: Variant p.Phe40Leu