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UniProtKB/Swiss-Prot Q9NUY8: Variant p.Arg518Gln

TBC1 domain family member 23
Gene: TBC1D23
Chromosomal location: 3q12.1-q12.2
Variant information

Variant position:  518
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Glutamine (Q) at position 518 (R518Q, p.Arg518Gln).
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 (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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:  Pontocerebellar hypoplasia 11 (PCH11) [MIM:617695]: A non-degenerative form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH11 features include severely delayed psychomotor development with intellectual disability and poor speech, microcephaly, dysmorphic features, and pontocerebellar hypoplasia. PCH11 inheritance is autosomal recessive. {ECO:0000269|PubMed:28823706, ECO:0000269|PubMed:28823707}. 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 PCH11; unknown pathological significance.
Any additional useful information about the variant.



Sequence information

Variant position:  518
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  699
The length of the canonical sequence.

Location on the sequence:   SVNVREKVISFIENTSTPVD  R MSFNLPWPDRSCTERHVSSS
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                         SVNVREKVISFIENTSTPVDRMSFNLPWPDRSCTERHVSSS

Mouse                         SVTVREKVISFIENSSTPVDR---------------HVSSS

Chicken                       SVNVKEKVISFIENTSTPVDR---------------HVSSS

Xenopus laevis                SVNVKDKVISFIENTATPVDRITFNIPWPERASLERHVSSS

Zebrafish                     SVNVKEKVISFIENTSTPVER---------------HVSSS

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 – 699 TBC1 domain family member 23
Region 514 – 699 May mediate the interaction with WASHC1
Region 514 – 573 May mediate the interaction with C17orf75, FAM91A1 and WDR11
Modified residue 507 – 507 Phosphoserine
Modified residue 514 – 514 Phosphothreonine
Modified residue 520 – 520 Phosphoserine
Alternative sequence 518 – 532 Missing. In isoform 2.


Literature citations

Homozygous mutations in TBC1D23 lead to a non-degenerative form of pontocerebellar hypoplasia.
Marin-Valencia I.; Gerondopoulos A.; Zaki M.S.; Ben-Omran T.; Almureikhi M.; Demir E.; Guemez-Gamboa A.; Gregor A.; Issa M.Y.; Appelhof B.; Roosing S.; Musaev D.; Rosti B.; Wirth S.; Stanley V.; Baas F.; Barr F.A.; Gleeson J.G.;
Am. J. Hum. Genet. 101:441-450(2017)
Cited for: INVOLVEMENT IN PCH11; VARIANT PCH11 GLN-518; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;

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.