UniProtKB/Swiss-Prot Q9BSA9: Variant p.Gln65Pro

Endosomal/lysosomal proton channel TMEM175
Gene: TMEM175
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Variant information Variant position:

65 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Glutamine (Q) to Proline (P) at position 65 (Q65P, p.Gln65Pro). 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 medium size and polar (Q) to medium size and hydrophobic (P) 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
Variant description:

Associated with decreased risk for Parkinson disease; gain-of-function variant; does not affect lysosomal localization. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs34884217 [ dbSNP | Ensembl ]

Sequence information Variant position:

65 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

504 The length of the canonical sequence.
Location on the sequence:

SIIATVMILPVTHTEISPEQ Q FDRSVQRLLATRIAVYLMTF 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                         SIIATVMILPVTHTEISPEQQFDRSVQRLLATRIAVYLMTF

Mouse                         SIIATVMILPVTHTEISPEQQFDKSIQKLLATRIAVYLMTF

Rat                           SIIATVMILPVTHTEISPEQQFDKSIQKLLATRIAVYLMTF

Bovine                        SIIATVM-------------EFDKSVQRLLATRIAVYLMTF

Chicken                       SIIATVMILPVAHTKIHPDQKLGESVQQLLLTKIAVYLMTF

Zebrafish                     SIIATVMILPVAHTKIQEDEELKQSIQALLTTKIAVYLMTF

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	1 – 504	Endosomal/lysosomal proton channel TMEM175
Topological domain	57 – 77	Lumenal
Region	65 – 71	Short helix H2-1
Site	46 – 46	Hydrophobic filter residue 1-1
Site	50 – 50	Hydrophobic filter residue 2-1
Site	53 – 53	Hydrophobic filter residue 3-1
Alternative sequence	1 – 116	Missing. In isoform 2.
Mutagenesis	45 – 45	S -> A. Reduced potassium channel activity without altering proton channel activity.
Mutagenesis	45 – 45	S -> T. Decreased selectivity for potassium ion.
Mutagenesis	46 – 46	I -> AV. Decreased channel activity.
Mutagenesis	46 – 46	I -> M. Abolished proton and potassium channel activity; when associated with M-271.
Mutagenesis	46 – 46	I -> N. Impaired selectivity; can conduct both K(+) and Na(+); when associated with N-271.
Mutagenesis	49 – 49	T -> A. Decreased selectivity for potassium ion.
Mutagenesis	49 – 49	T -> V. Abolished potassium channel activity and decreased proton channel activity.
Mutagenesis	50 – 50	V -> A. Does not affect selectivity; when associated with A-275.
Mutagenesis	53 – 53	L -> A. Does not affect selectivity; when associated with A-278.
Helix	64 – 66

Literature citations
Genetic, structural, and functional evidence link TMEM175 to synucleinopathies.
Krohn L.; Oeztuerk T.N.; Vanderperre B.; Ouled Amar Bencheikh B.; Ruskey J.A.; Laurent S.B.; Spiegelman D.; Postuma R.B.; Arnulf I.; Hu M.T.M.; Dauvilliers Y.; Hoegl B.; Stefani A.; Monaca C.C.; Plazzi G.; Antelmi E.; Ferini-Strambi L.; Heidbreder A.; Rudakou U.; Cochen De Cock V.; Young P.; Wolf P.; Oliva P.; Zhang X.K.; Greenbaum L.; Liong C.; Gagnon J.F.; Desautels A.; Hassin-Baer S.; Montplaisir J.Y.; Dupre N.; Rouleau G.A.; Fon E.A.; Trempe J.F.; Lamoureux G.; Alcalay R.N.; Gan-Or Z.;
Ann. Neurol. 87:139-153(2020)
Cited for: SUBCELLULAR LOCATION; INVOLVEMENT IN PARK; VARIANTS PRO-65 AND THR-393; CHARACTERIZATION OF VARIANTS PRO-65 AND THR-393; A growth-factor-activated lysosomal K+ channel regulates Parkinson's pathology.
Wie J.; Liu Z.; Song H.; Tropea T.F.; Yang L.; Wang H.; Liang Y.; Cang C.; Aranda K.; Lohmann J.; Yang J.; Lu B.; Chen-Plotkin A.S.; Luk K.C.; Ren D.;
Nature 591:431-437(2021)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; ACTIVITY REGULATION; INTERACTION WITH AKT1; IDENTIFICATION IN THE LYSOK(GF) COMPLEX; INVOLVEMENT IN PARK; CHARACTERIZATION OF VARIANTS PRO-65 AND THR-393; MUTAGENESIS OF SER-241; THR-338 AND MET-393;

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.