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UniProtKB/Swiss-Prot P22607: Variant p.Arg621His

Fibroblast growth factor receptor 3
Gene: FGFR3
Variant information

Variant position:  621
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 Arginine (R) to Histidine (H) at position 621 (R621H, p.Arg621His).
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 basic (R) to medium size and polar (H)
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

Involvement in disease:  Camptodactyly, tall stature, and hearing loss syndrome (CATSHLS) [MIM:610474]: An autosomal dominant syndrome characterized by permanent and irreducible flexion of one or more fingers of the hand and/or feet, tall stature, scoliosis and/or a pectus excavatum, and hearing loss. Affected individuals have developmental delay and/or mental retardation, and several of these have microcephaly. Radiographic findings included tall vertebral bodies with irregular borders and broad femoral metaphyses with long tubular shafts. On audiological exam, each tested member have bilateral sensorineural hearing loss and absent otoacoustic emissions. The hearing loss was congenital or developed in early infancy, progressed variably in early childhood, and range from mild to severe. Computed tomography and magnetic resonance imaging reveal that the brain, middle ear, and inner ear are structurally normal. {ECO:0000269|PubMed:17033969}. 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 CATSHLS.
Any additional useful information about the variant.

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



Sequence information

Variant position:  621
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  806
The length of the canonical sequence.

Location on the sequence:   VARGMEYLASQKCIHRDLAA  R NVLVTEDNVMKIADFGLARD
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                         VARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARD

Mouse                         VARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARD

Chicken                       VARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARD

Xenopus laevis                VARGMEYLASQKCIHRDLAARNVLVTDDNVMKIADFGLARD

Zebrafish                     VARGMEYLASKKCIHRDPAARNVLVTEDNVMKIADFGLARD

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 – 806 Fibroblast growth factor receptor 3
Topological domain 397 – 806 Cytoplasmic
Domain 472 – 761 Protein kinase
Active site 617 – 617 Proton acceptor
Helix 620 – 622


Literature citations

A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.
Toydemir R.M.; Brassington A.E.; Bayrak-Toydemir P.; Krakowiak P.A.; Jorde L.B.; Whitby F.G.; Longo N.; Viskochil D.H.; Carey J.C.; Bamshad M.J.;
Am. J. Hum. Genet. 79:935-941(2006)
Cited for: VARIANT CATSHLS HIS-621;

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.