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UniProtKB/Swiss-Prot P00367: Variant p.Arg274Cys

Glutamate dehydrogenase 1, mitochondrial
Gene: GLUD1
Variant information

Variant position:  274
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 274 (R274C, p.Arg274Cys).
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 HHF6; diminished sensitivity to GTP.
Any additional useful information about the variant.

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



Sequence information

Variant position:  274
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  558
The length of the canonical sequence.

Location on the sequence:   CVTGKPISQGGIHGRISATG  R GVFHGIENFINEASYMSILG
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                         CVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILG

Mouse                         CVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILG

Rat                           CVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILG

Pig                           CVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILG

Bovine                        CVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILG

Drosophila                    CVTGKPINQGGIHGRVSATGRGVFHGLENFINEANYMSQIG

Slime mold                    CVTGKPISSGGIRGRTEATGLGVFYGIREFLSYEEVLKKTG

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 54 – 558 Glutamate dehydrogenase 1, mitochondrial
Binding site 266 – 266 GTP
Binding site 270 – 270 GTP
Helix 271 – 284


Literature citations

Novel missense mutations outside the allosteric domain of glutamate dehydrogenase are prevalent in European patients with the congenital hyperinsulinism-hyperammonemia syndrome.
Santer R.; Kinner M.; Passarge M.; Superti-Furga A.; Mayatepek E.; Meissner T.; Schneppenheim R.; Schaub J.;
Hum. Genet. 108:66-71(2001)
Cited for: VARIANTS HHF6 CYS-274 AND HIS-322;

Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase.
MacMullen C.; Fang J.; Hsu B.Y.L.; Kelly A.; de Lonlay-Debeney P.; Saudubray J.-M.; Ganguly A.; Smith T.J.; Stanley C.A.; Brown R.; Buist N.; Dasouki M.; Fefferman R.; Grange D.; Karaviti L.; Luedke C.; Marriage B.; McLaughlin J.; Perlman K.; Seashore M.; van Vliet G.;
J. Clin. Endocrinol. Metab. 86:1782-1787(2001)
Cited for: VARIANTS HHF6 CYS-270; CYS-274; THR-318; CYS-319; CYS-322 AND HIS-322; CHARACTERIZATION OF VARIANTS HHF6 CYS-270; CYS-274; THR-318; CYS-322 AND HIS-322; FUNCTION; ACTIVITY REGULATION;

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.