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UniProtKB/Swiss-Prot Q8IW45: Variant p.Arg326Cys

ATP-dependent (S)-NAD(P)H-hydrate dehydratase
Gene: NAXD
Variant information

Variant position:  326
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 Arginine (R) to Cysteine (C) at position 326 (R326C, p.Arg326Cys).
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 (R) to medium size and polar (C)
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

Variant description:  In PEBEL2; decreased reaction kinetics for ATP-dependent NAD(P)H-hydrate dehydratase activity; decreased affinity for (6S)-NADHX; changed ATP-dependent NAD(P)H-hydrate dehydratase activity; thermostability assays show that activity is lost at temperatures above 30 degrees Celsius.
Any additional useful information about the variant.

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



Sequence information

Variant position:  326
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  347
The length of the canonical sequence.

Location on the sequence:   AFGACSLTRQCNHQAFQKHG  R STTTSDMIAEVGAAFSKLFE
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                         AFGACSLTRQCNHQAFQ----KHGRSTTTSDMIAEVGAAFSKLFE

                              ALGACSLTRQCSLQAFQ----KHGRSTTTTDMIAEIGPAFS

Rhesus macaque                SPGGC-IRRLLSHQAVQPPSLPEARSLHHHLRHDRRGGG--

Mouse                         AWGACTLTRECNRQAFQ----KYGRSTTTTDMITEVGTAFS

Rat                           AWGACTLTRECNHLAFQ----KYGRSTTTTDMIAEVGAAFS

Bovine                        AFGACALTRQCSQQAFQ----KYGRATTTSDMVAEVGPAFR

Zebrafish                     AFGATSLTRQCNRQAFH----KHGRSTTTSDMIQEINSAFK

Caenorhabditis elegans        GIASSWLVRTAGRRAFE----KHGRSMNTPLLLDEIPKLVR

Drosophila                    ACASSYFVKKLNAAAFQ----KFGRSLLASDMVNQIPSVFQ

Slime mold                    AYAACSLLRHCSKKAYQ----ISKRSTVSMDIINQISNGFE

Baker's yeast                 CYAGCTITRECSRLGFK----AKGRAMQTTDLNDRVGEVFA

Fission yeast                 AFGASACTRWCSRLAFK----ECGRATQSTDLVRHVGKAYN

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 1 – 347 ATP-dependent (S)-NAD(P)H-hydrate dehydratase
Domain 53 – 344 YjeF C-terminal
Alternative sequence 299 – 347 SSPLLVAAFGACSLTRQCNHQAFQKHGRSTTTSDMIAEVGAAFSKLFET -> GISDLKLTIWGPEIETGVKTRAQGSCGPRTTTPTSPHLLLSPSPQVQPSPGGRVWRLLSHQAVQPPSLPEARSLHHHLRHDRRGGGRLQQAL. In isoform 2.


Literature citations

NAD(P)HX dehydratase (NAXD) deficiency: a novel neurodegenerative disorder exacerbated by febrile illnesses.
Van Bergen N.J.; Guo Y.; Rankin J.; Paczia N.; Becker-Kettern J.; Kremer L.S.; Pyle A.; Conrotte J.F.; Ellaway C.; Procopis P.; Prelog K.; Homfray T.; Baptista J.; Baple E.; Wakeling M.; Massey S.; Kay D.P.; Shukla A.; Girisha K.M.; Lewis L.E.S.; Santra S.; Power R.; Daubeney P.; Montoya J.; Ruiz-Pesini E.; Kovacs-Nagy R.; Pritsch M.; Ahting U.; Thorburn D.R.; Prokisch H.; Taylor R.W.; Christodoulou J.; Linster C.L.; Ellard S.; Hakonarson H.;
Brain 142:50-58(2019)
Cited for: FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; INVOLVEMENT IN PEBEL2; VARIANTS PEBEL2 SER-81 AND CYS-326; CHARACTERIZATION OF VARIANTS PEBEL2 SER-81 AND CYS-326;

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.