UniProtKB/Swiss-Prot Q9H267 : Variant p.Leu30Pro
Vacuolar protein sorting-associated protein 33B
Gene: VPS33B
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Variant information
Variant position:
30
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LP/P [Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
The variants are classified into three categories: LP/P, LB/B and US.LP/P: likely pathogenic or pathogenic. LB/B: likely benign or benign. US: uncertain significance
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
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 PEL---PDFSMLKRLARDQLIYLL EQLPGKKDLFIEADLMSPLD
Mouse PEL---PDFSMLKRLARDQLIYLL EQLPGKKDLFIEADLMS
Rat PEL---PDFSMLKRLARDQLIYLL EQLPGKKDLFIEADLMS
Bovine PEL---PDFSMLKRLARDQLIYLL EQLPGKKDLFIEADLMS
Zebrafish PEL---PDFSLLKRLARDQLIFLL EQLPGKKDLFIDADLMS
Caenorhabditis elegans AELEIDETLHLLRMVMQREFIHYL ETLPGTKELFIDKCLLR
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.
Type Positions Description
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.