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UniProtKB/Swiss-Prot Q9H267: Variant p.Ser243Phe

Vacuolar protein sorting-associated protein 33B
Gene: VPS33B
Variant information

Variant position:  243
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 243 (S243F, p.Ser243Phe).
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:  Arthrogryposis, renal dysfunction and cholestasis syndrome 1 (ARCS1) [MIM:208085]: A multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase activity. Platelet dysfunction is common. {ECO:0000269|PubMed:15052268, ECO:0000269|PubMed:18853461, ECO:0000269|PubMed:20190753, ECO:0000269|PubMed:22753090, ECO:0000269|PubMed:23918659}. 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 ARCS1; no effect on interaction with VIPAS39; impairs localization to VIPAS39-containing endosomal compartment.
Any additional useful information about the variant.

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



Sequence information

Variant position:  243
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  617
The length of the canonical sequence.

Location on the sequence:   PEIGHIFLLDRDVDFVTALC  S QVVYEGLVDDTFRIKCGSVD
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                         PEIGHIFLLDRDVDFVTALCSQVVYEGLVDDTFRIKCGSVD

Mouse                         PEIGHIFLLDRDVDFVTALCSQVVYEGLVDDTFRIKCGSVD

Rat                           PEIGHIFLLDRDVDFVTALCSQVVYEGLVDDTFRIKCGSVD

Bovine                        PEIGHIFLLDRDVDFVTALCSQVVYEGLVDDTFRIKCGSVD

Zebrafish                     PEFAKVFLIDRDVDFVTPLCSQVVYEGLVDDIFRIKCSSVE

Caenorhabditis elegans        P-ISHLFLFDRQLDPVPVLLTGASYEGLLHEFFTIDCGKLA

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 2 – 617 Vacuolar protein sorting-associated protein 33B
Mutagenesis 234 – 234 D -> H. No effect on interaction with VIPAS39; no effect on interaction with STX7 and association with the HOPS complex; impairs localization to VIPAS39-containing endosomal compartment.
Mutagenesis 249 – 249 G -> V. Disrupts interaction with VIPAS39; no effect on interaction with STX7; impairs localization to VIPAS39-containing endosomal compartment.
Mutagenesis 252 – 252 D -> E. No effect on interaction with VIPAS39 and STX7; impairs localization to VIPAS39-containing endosomal compartment.


Literature citations

Vps33b pathogenic mutations preferentially affect VIPAS39/SPE-39-positive endosomes.
Tornieri K.; Zlatic S.A.; Mullin A.P.; Werner E.; Harrison R.; L'hernault S.W.; Faundez V.;
Hum. Mol. Genet. 22:5215-5228(2013)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS ARCS1 PRO-30 AND PHE-243; MUTAGENESIS OF 232-ASP--ASP-234; ASP-234; 235-VAL--PHE-237; GLY-249; 251-VAL--ASP-253 AND ASP-252; INTERACTION WITH VIPAS39; STX7; VPS18 AND VPS41;

Molecular investigations to improve diagnostic accuracy in patients with ARC syndrome.
Cullinane A.R.; Straatman-Iwanowska A.; Seo J.K.; Ko J.S.; Song K.S.; Gizewska M.; Gruszfeld D.; Gliwicz D.; Tuysuz B.; Erdemir G.; Sougrat R.; Wakabayashi Y.; Hinds R.; Barnicoat A.; Mandel H.; Chitayat D.; Fischler B.; Garcia-Cazorla A.; Knisely A.S.; Kelly D.A.; Maher E.R.; Gissen P.;
Hum. Mutat. 30:E330-E337(2009)
Cited for: VARIANT ARCS1 PHE-243;

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.