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UniProtKB/Swiss-Prot Q8NCW5: Variant p.Asp218Val

NAD(P)H-hydrate epimerase
Gene: NAXE
Chromosomal location: 1q21
Variant information

Variant position:  218
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Aspartate (D) to Valine (V) at position 218 (D218V, p.Asp218Val).
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 hydrophobic (V)
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

Involvement in disease:  Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy (PEBEL) [MIM:617186]: An autosomal recessive severe neurometabolic disorder characterized by severe leukoencephalopathy usually associated with a trivial febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures. Disease course is rapidly progressive, leading to coma, global brain atrophy, and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. {ECO:0000269|PubMed:27122014, ECO:0000269|PubMed:27616477}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PEBEL.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  218
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  288
The length of the canonical sequence.

Location on the sequence:   EPFHSILSVLKGLTVPIASI  D IPSGWDVEKGNAGGIQPDLL
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                         EPFHSILS-VLKGLT--VPIASIDIPSGWDVEKG--NAGGI---QPDLL

                              EPFRTILS-VLDGLT--VPIASIDIPSGWDVEKG--NSGGI

Mouse                         EPFHSILS-VLSGLT--VPIASIDIPSGWDVEKG--NPSGI

Rat                           EPFHSILS-VLSGLT--VPIASIDIPSGWDVEKG--NPSGI

Pig                           EPFRSILS-VLNGLT--VPIASIDIPSGWDVERG--NSGGI

Bovine                        EPFRSILS-VLNGLT--VPIASIDIPSGWDVEKG--SSGGI

Xenopus tropicalis            EPFGNILS-TLKRVT--VPIASVDIPSGWDVEKG--NPEGI

Zebrafish                     EPFGEILS-QLKKIT--VPIASVDIPSGWDVEKG--CPDGI

Caenorhabditis elegans        EPFTEMLK-TVRASG--IHVFSIDVPSGWDVELGAPSGNDD

Drosophila                    ADFVAVVE-LMQQTK--LPIASVDIPSGWDVEKGKLTECDV

Slime mold                    SPFDTIIKDSLNNIK--TPIASIDMPSGWDVENG--NIKNL

Baker's yeast                 EPFKGIVE-ELCKVQNIIPIVSVDVPTGWDVDKGPISQPSI

Fission yeast                 DPFGSILA-AIVESK--IKVLSVDAPSSWEIDEGPQKEGPL

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.

TypePositionsDescription
Chain 48 – 288 NAD(P)H-hydrate epimerase
Domain 65 – 275 YjeF N-terminal
Metal binding 221 – 221 Potassium
Binding site 218 – 218 NAD(P)HX


Literature citations

NAXE mutations disrupt the cellular NAD(P)HX repair system and cause a lethal neurometabolic disorder of early childhood.
Kremer L.S.; Danhauser K.; Herebian D.; Petkovic Ramadza D.; Piekutowska-Abramczuk D.; Seibt A.; Mueller-Felber W.; Haack T.B.; Ploski R.; Lohmeier K.; Schneider D.; Klee D.; Rokicki D.; Mayatepek E.; Strom T.M.; Meitinger T.; Klopstock T.; Pronicka E.; Mayr J.A.; Baric I.; Distelmaier F.; Prokisch H.;
Am. J. Hum. Genet. 99:894-902(2016)
Cited for: INVOLVEMENT IN PEBEL; VARIANTS PEBEL VAL-218 AND LYS-270 DEL; FUNCTION;

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.