UniProtKB/Swiss-Prot Q96S66: Variant p.Trp267Arg

Chloride channel CLIC-like protein 1
Gene: CLCC1
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Variant information Variant position:

267 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 Tryptophan (W) to Arginine (R) at position 267 (W267R, p.Trp267Arg). 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 aromatic (W) to large size and basic (R) 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:

Found in a patient with sporadic ALS; decreases protein stability and expression; decreases protein stability and expression; decreases single channel activity; increases chloride retention in the ER while decreasing ATP-induced Ca(2+) release; in a knockin mouse model causes enhanced ER stress and motor neuron degeneration in compound heterozygosity with a hypomorphic allele; leads to embryonic lethality with a KO allele. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1458236736 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

MEPLNNVCAKKMDWTGSIWE W FRSSWTYKDDPCQKYYELLL 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                         MEPLNNVCA--KKMDWTGSIWEWFRSSWTYKDDPCQKYYELLL

Mouse                         MEPFDNLCA--KKMDWTGSLWEWFTSSWTYKDDPCQKYYEL

Rat                           MAPLNDVCA--KKMDWTENLWEWFRISWTYKDDPCQKYYEL

Bovine                        MEPLNNVCA--EKMNWSGSLWEWLRSSWTYKDDPCQKYYEL

Xenopus laevis                LQDFD-KCS--QKISWSESLFDWMKGAATFQNDPCEDYFKA

Zebrafish                     VESFNAKCTGLKQLNWQDSLSEWYRRTWTLQDDPCKKYYEV

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	19 – 551	Chloride channel CLIC-like protein 1
Topological domain	238 – 329	Lumenal
Alternative sequence	114 – 298	Missing. In isoform 4.

Literature citations
Disruption of ER ion homeostasis maintained by an ER anion channel CLCC1 contributes to ALS-like pathologies.
Guo L.; Mao Q.; He J.; Liu X.; Piao X.; Luo L.; Hao X.; Yu H.; Song Q.; Xiao B.; Fan D.; Gao Z.; Jia Y.;
Cell Res. 33:497-515(2023)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; ACTIVITY REGULATION; SUBCELLULAR LOCATION; SUBUNIT; SITE; CHARACTERIZATION OF VARIANT RP32 GLU-25; MUTAGENESIS OF ASP-152; ASP-153; GLU-175; ASP-176 AND ASP-181; ASSOCIATION WITH AMYOTROPHIC LATERAL SCLEROSIS; CHARACTERIZATION OF VARIANTS TYR-10; THR-29; 239-GLN--GLY-551 DEL; ARG-263; ARG-267; GLY-368 AND SER-515;

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.