UniProtKB/Swiss-Prot P31327: Variant p.Lys875Glu

Carbamoyl-phosphate synthase [ammonia], mitochondrial
Gene: CPS1
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Variant information Variant position:

875 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 Lysine (K) to Glutamate (E) at position 875 (K875E, p.Lys875Glu). 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 basic (K) to medium size and acidic (E) 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 in cis with S-843 in a patient with carbamoyl-phosphate synthase deficiency; does not affect enzyme activity; significant decrease in protein yield and thermal stability. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs147062907 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1500 The length of the canonical sequence.
Location on the sequence:

AKAIDDNMSLDEIEKLTYID K WFLYKMRDILNMEKTLKGLN 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                         AKAIDDNMSLDEIEKLTYIDKWFLYKMRDILNMEKTLKGLN

Mouse                         AKALENNMSLDEIVRLTSIDKWFLYKMRDILNMDKTLKGLN

Rat                           AKALENNMSLDEIVKLTSIDKWFLYKMRDILNMDKTLKGLN

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	39 – 1500	Carbamoyl-phosphate synthase [ammonia], mitochondrial
Modified residue	856 – 856	N6-acetyllysine; alternate
Modified residue	856 – 856	N6-glutaryllysine; alternate
Modified residue	869 – 869	N6-glutaryllysine
Modified residue	875 – 875	N6-acetyllysine; alternate
Modified residue	875 – 875	N6-glutaryllysine; alternate
Modified residue	875 – 875	N6-succinyllysine; alternate
Modified residue	889 – 889	N6-acetyllysine; alternate
Modified residue	889 – 889	N6-glutaryllysine; alternate
Modified residue	889 – 889	N6-succinyllysine; alternate
Modified residue	892 – 892	N6-acetyllysine; alternate
Modified residue	892 – 892	N6-glutaryllysine; alternate
Modified residue	892 – 892	N6-succinyllysine; alternate
Helix	875 – 892

Literature citations
Gene structure of human carbamylphosphate synthetase 1 and novel mutations in patients with neonatal onset.
Haeberle J.; Schmidt E.; Pauli S.; Rapp B.; Christensen E.; Wermuth B.; Koch H.G.;
Hum. Mutat. 21:444-444(2003)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1); VARIANT CPS1D SER-843; VARIANT GLU-875; Genetic approach to prenatal diagnosis in urea cycle defects.
Haeberle J.; Koch H.G.;
Prenat. Diagn. 24:378-383(2004)
Cited for: VARIANT CPS1D SER-843; VARIANT GLU-875; Understanding carbamoyl phosphate synthetase (CPS1) deficiency by using the recombinantly purified human enzyme: effects of CPS1 mutations that concentrate in a central domain of unknown function.
Diez-Fernandez C.; Hu L.; Cervera J.; Haeberle J.; Rubio V.;
Mol. Genet. Metab. 112:123-132(2014)
Cited for: VARIANTS CPS1D ARG-401; ARG-632; SER-843; CYS-850; HIS-850; PRO-871; VAL-911; GLU-911; LEU-913; HIS-914; GLY-914; PRO-918; THR-932; ASN-937; THR-949; PRO-958; CYS-959; CYS-962; ASP-964; ASP-1194 AND ARG-1462; VARIANT GLU-875; CHARACTERIZATION OF VARIANTS CPS1D SER-843; CYS-850; HIS-850; PRO-871; VAL-911; GLU-911; LEU-913; HIS-914; GLY-914; PRO-918; THR-932; ASN-937; THR-949; PRO-958; CYS-959; CYS-962 AND ASP-964; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT GLU-875; Analysis of protein-coding genetic variation in 60,706 humans.
Lek M.; Karczewski K.J.; Minikel E.V.; Samocha K.E.; Banks E.; Fennell T.; O'Donnell-Luria A.H.; Ware J.S.; Hill A.J.; Cummings B.B.; Tukiainen T.; Birnbaum D.P.; Kosmicki J.A.; Duncan L.E.; Estrada K.; Zhao F.; Zou J.; Pierce-Hoffman E.; Berghout J.; Cooper D.N.; Deflaux N.; DePristo M.; Do R.; Flannick J.; Fromer M.; Gauthier L.; Goldstein J.; Gupta N.; Howrigan D.; Kiezun A.; Kurki M.I.; Moonshine A.L.; Natarajan P.; Orozco L.; Peloso G.M.; Poplin R.; Rivas M.A.; Ruano-Rubio V.; Rose S.A.; Ruderfer D.M.; Shakir K.; Stenson P.D.; Stevens C.; Thomas B.P.; Tiao G.; Tusie-Luna M.T.; Weisburd B.; Won H.H.; Yu D.; Altshuler D.M.; Ardissino D.; Boehnke M.; Danesh J.; Donnelly S.; Elosua R.; Florez J.C.; Gabriel S.B.; Getz G.; Glatt S.J.; Hultman C.M.; Kathiresan S.; Laakso M.; McCarroll S.; McCarthy M.I.; McGovern D.; McPherson R.; Neale B.M.; Palotie A.; Purcell S.M.; Saleheen D.; Scharf J.M.; Sklar P.; Sullivan P.F.; Tuomilehto J.; Tsuang M.T.; Watkins H.C.; Wilson J.G.; Daly M.J.; MacArthur D.G.;
Nature 536:285-291(2016)
Cited for: VARIANT GLU-875;

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.