UniProtKB/Swiss-Prot O75503: Variant p.Asp230Asn

Bis(monoacylglycero)phosphate synthase CLN5
Gene: CLN5
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Variant information Variant position:

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

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:

From Aspartate (D) to Asparagine (N) at position 230 (D230N, p.Asp230Asn). 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 acidic (D) to medium size and polar (N) 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:

In CLN5; creates a new N-glycosylation site; retained in the endoplasmic reticulum rather than reaching the lysosome; significant decrease in palmitoyl protein thioesterase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs28940280 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

ETWNVKASPEKGAETWFDSY D CSKFVLRTFNKLAEFGAEFK 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                         ETWNVKASPEKGAETWFDSYDCSKFVLRTFNKLAEFGAEFK---

                              ETWTVQASPTKGAETWFESYDCSKFVLRTYKKLAELGAEFK

Mouse                         ETWTVRAGPGQGAQTWFESYDCSNFVLRTYKKLAEFGTEFK

Bovine                        ETWTVQASPERGAERWFESYDCSKFVLRTYEKLAELGADFK

Sheep                         ETWTVQASPKKEAEKWFESYDCSKFVLRTYEKLAELGADFK

Slime mold                    QTWDVWNN--YGQDLFVPSTTCDDFTQQSIEHLGSIGINYN

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 – 358	Bis(monoacylglycero)phosphate synthase CLN5
Chain	44 – 358	Bis(monoacylglycero)phosphate synthase CLN5, secreted form
Topological domain	41 – 358	Lumenal
Active site	231 – 231	Nucleophile; Acyl-thioester intermediate
Mutagenesis	231 – 231	C -> S. Significant decrease in bis(monoacylglycero)phosphate synthase and palmitoyl protein thioesterase activities. No alterations in secondary structure and thermal stability.

Literature citations
CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.
Savukoski M.; Klockars T.; Holmberg V.; Santavuori P.; Lander E.S.; Peltonen L.;
Nat. Genet. 19:286-288(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT CLN5 ASN-230; VARIANT ARG-319; TISSUE SPECIFICITY; Cln5 represents a new type of cysteine-based S-depalmitoylase linked to neurodegeneration.
Luebben A.V.; Bender D.; Becker S.; Crowther L.M.; Erven I.; Hofmann K.; Soeding J.; Klemp H.; Bellotti C.; Staeuble A.; Qiu T.; Kathayat R.S.; Dickinson B.C.; Gaertner J.; Sheldrick G.M.; Kraetzner R.; Steinfeld R.;
Sci. Adv. 8:eabj8633-eabj8633(2022)
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-358; CHARACTERIZATION OF VARIANTS CLN5 ASP-209 AND ASN-230; FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF VAL-101; ILE-115; HIS-117; CYS-231 AND ILE-259; BIOPHYSICOCHEMICAL PROPERTIES; ACTIVITY REGULATION; GLYCOSYLATION AT ASN-130; ASN-143; ASN-203 AND ASN-255; DISULFIDE BONDS; REACTION MECHANISM; ACTIVE SITE; Two novel CLN5 mutations in a Portuguese patient with vLINCL: insights into molecular mechanisms of CLN5 deficiency.
Bessa C.; Teixeira C.A.; Mangas M.; Dias A.; Sa Miranda M.C.; Guimaraes A.; Ferreira J.C.; Canas N.; Cabral P.; Ribeiro M.G.;
Mol. Genet. Metab. 89:245-253(2006)
Cited for: VARIANTS CLN5 PRO-63 AND ASN-230; The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations.
Schmiedt M.L.; Bessa C.; Heine C.; Ribeiro M.G.; Jalanko A.; Kyttaelae A.;
Hum. Mutat. 31:356-365(2010)
Cited for: CHARACTERIZATION OF VARIANTS CLN5 PRO-63; HIS-63 AND ASN-230; PROTEOLYTIC CLEAVAGE; SUBCELLULAR LOCATION (SECRETED FORM); GLYCOSYLATION; Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5.
Larkin H.; Ribeiro M.G.; Lavoie C.;
Hum. Mutat. 34:1688-1697(2013)
Cited for: CHARACTERIZATION OF VARIANT CLN5 ASN-230; SUBCELLULAR LOCATION (MEMBRANE FORM); TOPOLOGY; PROTEOLYTIC CLEAVAGE; GLYCOSYLATION; The role of N-glycosylation in folding, trafficking, and functionality of lysosomal protein CLN5.
Moharir A.; Peck S.H.; Budden T.; Lee S.Y.;
PLoS ONE 8:E74299-E74299(2013)
Cited for: CHARACTERIZATION OF VARIANTS CLN5 SER-143 AND ASN-230; GLYCOSYLATION AT ASN-130; ASN-143; ASN-178; ASN-203; ASN-255; ASN-271; ASN-281 AND ASN-352; MUTAGENESIS OF ASN-130; ASN-143; ASN-178; ASN-203; ASN-255; ASN-271; ASN-281 AND ASN-352; SUBCELLULAR LOCATION (SECRETED FORM); Proteolytic processing of the neuronal ceroid lipofuscinosis related lysosomal protein CLN5.
De Silva B.; Adams J.; Lee S.Y.;
Exp. Cell Res. 338:45-53(2015)
Cited for: CHARACTERIZATION OF VARIANT CLN5 ASN-230; PROTEOLYTIC CLEAVAGE AT C-TERMINUS;

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.