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UniProtKB/Swiss-Prot Q9H267: Variant p.Leu30Pro

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

Variant position:  30
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 Leucine (L) to Proline (P) at position 30 (L30P, p.Leu30Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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; effect on interaction with VIPAS39 is reported conflictingly but disrupts colocalization with VIPAS39 at cytoplasmic organelle; impairs localization to VIPAS39-containing endosomal compartment; and induces fragmentation of the VIPAS39-containing endosomal compartment; no effect on interaction with STX7 and association with the HOPS complex.
Any additional useful information about the variant.

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



Sequence information

Variant position:  30
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:   PELPDFSMLKRLARDQLIYL  L EQLPGKKDLFIEADLMSPLD
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                         PELPDFSMLKRLARDQLIYLLEQLPGKKDLFIEADLMSPLD

Mouse                         PELPDFSMLKRLARDQLIYLLEQLPGKKDLFIEADLMSPLD

Rat                           PELPDFSMLKRLARDQLIYLLEQLPGKKDLFIEADLMSPLD

Bovine                        PELPDFSMLKRLARDQLIYLLEQLPGKKDLFIEADLMSPLD

Zebrafish                     PELPDFSLLKRLARDQLIFLLEQLPGKKDLFIDADLMSPLD

Caenorhabditis elegans        EIDETLHLLRMVMQREFIHYLETLPGTKELFIDKCLLRPLD

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
Alternative sequence 1 – 91 Missing. In isoform 2.


Literature citations

Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization.
Cullinane A.R.; Straatman-Iwanowska A.; Zaucker A.; Wakabayashi Y.; Bruce C.K.; Luo G.; Rahman F.; Gurakan F.; Utine E.; Ozkan T.B.; Denecke J.; Vukovic J.; Di Rocco M.; Mandel H.; Cangul H.; Matthews R.P.; Thomas S.G.; Rappoport J.Z.; Arias I.M.; Wolburg H.; Knisely A.S.; Kelly D.A.; Muller F.; Maher E.R.; Gissen P.;
Nat. Genet. 42:303-312(2010)
Cited for: FUNCTION; INTERACTION WITH RAB11A AND VIPAS39; CHARACTERIZATION OF VARIANT ARCS1 PRO-30; SUBCELLULAR LOCATION;

Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome.
Smith H.; Galmes R.; Gogolina E.; Straatman-Iwanowska A.; Reay K.; Banushi B.; Bruce C.K.; Cullinane A.R.; Romero R.; Chang R.; Ackermann O.; Baumann C.; Cangul H.; Cakmak Celik F.; Aygun C.; Coward R.; Dionisi-Vici C.; Sibbles B.; Inward C.; Kim C.A.; Klumperman J.; Knisely A.S.; Watson S.P.; Gissen P.;
Hum. Mutat. 33:1656-1664(2012)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT ARCS1 PRO-30;

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;

Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome.
Gissen P.; Johnson C.A.; Morgan N.V.; Stapelbroek J.M.; Forshew T.; Cooper W.N.; McKiernan P.J.; Klomp L.W.J.; Morris A.A.M.; Wraith J.E.; McClean P.; Lynch S.A.; Thompson R.J.; Lo B.; Quarrell O.W.; Di Rocco M.; Trembath R.C.; Mandel H.; Wali S.; Karet F.E.; Knisely A.S.; Houwen R.H.J.; Kelly D.A.; Maher E.R.;
Nat. Genet. 36:400-404(2004)
Cited for: VARIANT ARCS1 PRO-30; SUBCELLULAR LOCATION;

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.