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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9GZU1: Variant p.Thr232Pro

Mucolipin-1
Gene: MCOLN1
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Variant information Variant position: help 232 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 Proline (P) at position 232 (T232P, p.Thr232Pro). 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 medium size and hydrophobic (P) 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 ML4 and LECD; likely pathogenic; fails to localize to late endosomes; abolishes Fe(2+) permeability; disrupts tetrameric assembly; abolishes lysosomal localization. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 232 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 580 The length of the canonical sequence.
Location on the sequence: help LESSSSYKNLTLKFHKLVNV T IHFRLKTINLQSLINNEIPD 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                         LESSSSYKNLTLKFHKLVNVTIHFRLKTINLQSLINNEIPD

Mouse                         LDGSASYKNLTLKFHKLINVTIHFQLKTINLQSLINNEIPD
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 – 580 Mucolipin-1
Topological domain 87 – 298 Extracellular
Glycosylation 230 – 230 N-linked (GlcNAc...) asparagine
Beta strand 228 – 241



Literature citations
Overexpression of wild-type and mutant mucolipin proteins in mammalian cells: effects on the late endocytic compartment organization.
Manzoni M.; Monti E.; Bresciani R.; Bozzato A.; Barlati S.; Bassi M.T.; Borsani G.;
FEBS Lett. 567:219-224(2004)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS ML4 PRO-232; PHE-408 DEL AND LEU-465; The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel.
Dong X.P.; Cheng X.; Mills E.; Delling M.; Wang F.; Kurz T.; Xu H.;
Nature 455:992-996(2008)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS ML4 PRO-232; TYR-362; CYS-403 AND LEU-446; TRANSPORTER ACTIVITY; Structural basis of dual Ca(2+)/pH regulation of the endolysosomal TRPML1 channel.
Li M.; Zhang W.K.; Benvin N.M.; Zhou X.; Su D.; Li H.; Wang S.; Michailidis I.E.; Tong L.; Li X.; Yang J.;
Nat. Struct. Mol. Biol. 24:205-213(2017)
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 84-296; EXTRACELLULAR/LUMENAL PORE-FORMING DOMAIN; SUBUNIT; ACTIVITY REGULATION; MUTAGENESIS OF SER-110; ASP-111; GLY-112; ALA-113; ASP-114; ASP-115; LEU-144; ARG-146 AND VAL-432; CHARACTERIZATION OF VARIANTS ML4 PRO-106 AND PRO-232; Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population.
Bargal R.; Avidan N.; Olender Z.; Ben-Asher E.; Zeigler M.; Raas-Rothschild A.; Frumkin A.; Ben-Yoseph O.; Friedlender Y.; Lancet D.; Bach G.;
Hum. Mutat. 17:397-402(2001)
Cited for: VARIANTS ML4 PRO-232; PHE-408 DEL AND LEU-465; Mucolipidosis type IV: a subtle pediatric neurodegenerative disorder.
Geer J.S.; Skinner S.A.; Goldin E.; Holden K.R.;
Pediatr. Neurol. 42:223-226(2010)
Cited for: VARIANT ML4 PRO-232; Lisch epithelial corneal dystrophy is caused by heterozygous loss-of-function variants in MCOLN1.
Patterson K.; Chong J.X.; Chung D.D.; Lisch W.; Karp C.L.; Dreisler E.; Lockington D.; Rohrbach J.M.; Garczarczyk-Asim D.; Mueller T.; Tuft S.J.; Skalicka P.; Wilnai Y.; Samra N.N.; Ibrahim A.; Mandel H.; Davidson A.E.; Liskova P.; Aldave A.J.; Bamshad M.J.; Janecke A.R.;
Am. J. Ophthalmol. 258:183-195(2024)
Cited for: VARIANTS LECD 172-ARG--ASN-580 DEL; 192-CYS--ASN-580 DEL; PRO-232; PRO-259; 291-GLN--ASN-580 DEL; 337-GLN--ASN-580 DEL AND 444-TRP--ASN-580 DEL; INVOLVEMENT IN LECD;
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.