Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8NHS3: Variant p.Thr294Lys

Major facilitator superfamily domain-containing protein 8
Gene: MFSD8
Feedback?
Variant information Variant position: help 294 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Threonine (T) to Lysine (K) at position 294 (T294K, p.Thr294Lys). 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: help Change from medium size and polar (T) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In CLN7; endolysosomal localization; decreased chloride channel activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 294 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 518 The length of the canonical sequence.
Location on the sequence: help VLFFVTLFIFALFETIITPL T MDMYAWTQEQAVLYNGIILA 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         VLFFVTLFIFALFETIITPLTMDMYAWTQEQAVLYNGIILA

Mouse                         IVFFVVLFIFAVYETILTPLTLDMYAWTQEQAVLYDGILLV

Xenopus laevis                ILFFVVLFVFAIFETISTPLTMDMYAWTRTQAVFYNGIILA

Zebrafish                     VLFFIILFIFAVFETISTPLSMDMFAWTRKEAVLYNGIILA
Sequence annotation in neighborhood: help 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 1 – 518 Major facilitator superfamily domain-containing protein 8
Topological domain 288 – 304 Extracellular
Alternative sequence 237 – 518 Missing. In isoform 2.
Mutagenesis 287 – 287 E -> A. Decreased chloride channel activity.



Literature citations
CLN7 is an organellar chloride channel regulating lysosomal function.
Wang Y.; Zeng W.; Lin B.; Yao Y.; Li C.; Hu W.; Wu H.; Huang J.; Zhang M.; Xue T.; Ren D.; Qu L.; Cang C.;
Sci. Adv. 7:eabj9608-eabj9608(2021)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; ACTIVITY REGULATION; SUBCELLULAR LOCATION; TOPOLOGY; DILEUCINE MOTIF; MUTAGENESIS OF LEU-13; LEU-14; ARG-153; GLU-287 AND TYR-438; CHARACTERIZATION OF VARIANTS CLN7 PRO-157; LYS-294; GLN-336; GLN-465 AND TRP-465; Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis.
Kousi M.; Siintola E.; Dvorakova L.; Vlaskova H.; Turnbull J.; Topcu M.; Yuksel D.; Gokben S.; Minassian B.A.; Elleder M.; Mole S.E.; Lehesjoki A.-E.;
Brain 132:810-819(2009)
Cited for: VARIANTS CLN7 HIS-139; PRO-157; LYS-294; ASP-310 AND TRP-465; Mutations in MFSD8/CLN7 are a frequent cause of variant-late infantile neuronal ceroid lipofuscinosis.
Aiello C.; Terracciano A.; Simonati A.; Discepoli G.; Cannelli N.; Claps D.; Crow Y.J.; Bianchi M.; Kitzmuller C.; Longo D.; Tavoni A.; Franzoni E.; Tessa A.; Veneselli E.; Boldrini R.; Filocamo M.; Williams R.E.; Bertini E.S.; Biancheri R.; Carrozzo R.; Mole S.E.; Santorelli F.M.;
Hum. Mutat. 30:E530-E540(2009)
Cited for: VARIANTS CLN7 ARG-52; LYS-294; ASP-310 AND LEU-447; Targeted next generation sequencing as a diagnostic tool in epileptic disorders.
Lemke J.R.; Riesch E.; Scheurenbrand T.; Schubach M.; Wilhelm C.; Steiner I.; Hansen J.; Courage C.; Gallati S.; Buerki S.; Strozzi S.; Simonetti B.G.; Grunt S.; Steinlin M.; Alber M.; Wolff M.; Klopstock T.; Prott E.C.; Lorenz R.; Spaich C.; Rona S.; Lakshminarasimhan M.; Kroell J.; Dorn T.; Kraemer G.; Synofzik M.; Becker F.; Weber Y.G.; Lerche H.; Boehm D.; Biskup S.;
Epilepsia 53:1387-1398(2012)
Cited for: VARIANT CLN7 LYS-294;
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.