UniProtKB/Swiss-Prot Q9C0B1: Variant p.Ser319Phe

Alpha-ketoglutarate-dependent dioxygenase FTO
Gene: FTO
Chromosomal location: 16q12.2
Variant information

Variant position:  319
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 Phenylalanine (F) at position 319 (S319F, p.Ser319Phe).
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 large size and aromatic (F)
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:  Growth retardation, developmental delay, and facial dysmorphism (GDFD) [MIM:612938]: A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years. {ECO:0000269|PubMed:19559399, ECO:0000269|PubMed:22002720, ECO:0000269|PubMed:26378117, ECO:0000269|PubMed:26697951}. 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 GDFD; reduced enzyme activity.
Any additional useful information about the variant.



Sequence information

Variant position:  319
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  505
The length of the canonical sequence.

Location on the sequence:   DDLNATHQHCVLAGSQPRFS  S THRVAECSTGTLDYILQRCQ
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                         DDLNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILQRCQ

Mouse                         DDLNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILERCQ

Rat                           DDLNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILQRCQ

Xenopus laevis                DDLNKTHQHCVIAGCQPRFSSTHRVAESSTGTLQYIKSQCN

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 1 – 505 Alpha-ketoglutarate-dependent dioxygenase FTO
Region 32 – 327 Fe2OG dioxygenase domain
Metal binding 307 – 307 Iron; catalytic
Binding site 320 – 320 Alpha-ketoglutarate
Binding site 322 – 322 Alpha-ketoglutarate
Alternative sequence 1 – 445 Missing. In isoform 3.
Alternative sequence 1 – 399 Missing. In isoform 4.
Alternative sequence 1 – 378 Missing. In isoform 2.
Beta strand 316 – 322


Literature citations

Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay.
Daoud H.; Zhang D.; McMurray F.; Yu A.; Luco S.M.; Vanstone J.; Jarinova O.; Carson N.; Wickens J.; Shishodia S.; Choi H.; McDonough M.A.; Schofield C.J.; Harper M.E.; Dyment D.A.; Armour C.M.;
J. Med. Genet. 53:200-207(2016)
Cited for: VARIANT GDFD PHE-319; CHARACTERIZATION OF VARIANT GDFD PHE-319;

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.