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UniProtKB/Swiss-Prot Q13423: Variant p.Ala1008Pro

NAD(P) transhydrogenase, mitochondrial
Gene: NNT
Variant information

Variant position:  1008
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 Alanine (A) to Proline (P) at position 1008 (A1008P, p.Ala1008Pro).
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 small size and hydrophobic (A) to medium size and hydrophobic (P)
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

Involvement in disease:  Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) [MIM:614736]: A form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements. {ECO:0000269|PubMed:22634753}. 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 GCCD4.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1008
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1086
The length of the canonical sequence.

Location on the sequence:   LEMDEINHDFPDTDLVLVIG  A NDTVNSAAQEDPNSIIAGMP
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                         LEMDEINHDFPDTDLVLVIGANDTVNSAAQEDPNSIIAGMP

Mouse                         LEMDEINSDFPDTDLVLVIGANDTVNSAAQEDPNSIIAGMP

Bovine                        LEMDEINHDFPDTDLVLVIGANDTVNSAAQEDPNSIIAGMP

Sheep                         LEMDEINHDFPDTDLVLVIGANDTVNSAAQEDPNSIIAGMP

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 44 – 1086 NAD(P) transhydrogenase, mitochondrial
Topological domain 880 – 1086 Mitochondrial matrix
Nucleotide binding 1007 – 1011 NADP


Literature citations

Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency.
Meimaridou E.; Kowalczyk J.; Guasti L.; Hughes C.R.; Wagner F.; Frommolt P.; Nurnberg P.; Mann N.P.; Banerjee R.; Saka H.N.; Chapple J.P.; King P.J.; Clark A.J.; Metherell L.A.;
Nat. Genet. 44:740-742(2012)
Cited for: FUNCTION; TISSUE SPECIFICITY; VARIANTS GCCD4 ASN-193; ALA-357; PRO-365; LEU-437; VAL-533; ARG-664; ARG-678; ASP-862; PRO-977; PRO-1008 AND LYS-1009;

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.