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UniProtKB/Swiss-Prot O43272: Variant p.Ala472Thr

Proline dehydrogenase 1, mitochondrial
Gene: PRODH
Variant information

Variant position:  472
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 Threonine (T) at position 472 (A472T, p.Ala472Thr).
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 polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Hyperprolinemia 1 (HYRPRO1) [MIM:239500]: An inborn error of proline metabolism resulting in elevated levels of proline in the plasma and urine. The disorder is generally benign and most affected individuals are clinically asymptomatic. Some patients, however, have neurologic manifestations, including epilepsy and mental retardation. Association with certain forms of schizophrenia have been reported. {ECO:0000269|PubMed:12217952, ECO:0000269|PubMed:15662599, ECO:0000269|PubMed:17135275}. 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.

Involvement in disease:  Schizophrenia 4 (SCZD4) [MIM:600850]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. Delusions, hallucinations), in mood (e.g. Inappropriate affect), in sense of self and relationship to the external world (e.g. Loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:11891283, ECO:0000269|PubMed:15662599}. Note=Disease susceptibility is associated with variations 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 HYRPRO1 and SCZD4; associated with disease susceptibility; mild decrease of enzymatic activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  472
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  600
The length of the canonical sequence.

Location on the sequence:   ARAAEIGYEDPINPTYEATN  A MYHRCLDYVLEELKHNAKAK
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                         ARAAEIGYEDPINPTYEATNAMYHRCLDYVLEELK-------HNAKAK

Mouse                         VRAAEIGYEDPINPTYEATNAMYHRCLNYVLEELK------

Bovine                        -----VGYEDPINPTYEATSAVYHRCLDYVLEELK------

Caenorhabditis elegans        ARAKAIGYEDPINDNFEATSKMYESCLTRIADEVH-----R

Drosophila                    DRAKSLGYPDPVNPTFEATTDMYHRTLSECLRRIKLMKDCD

Slime mold                    ERSQRLSTENPVLPTIQDTHKSYNTALDFLLNQIK------

Fission yeast                 KAETDKDFDSAVEAIIAAAAKFAPGDPASASDPIA------

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
Modified residue 486 – 486 N6-acetyllysine


Literature citations

Functional consequences of PRODH missense mutations.
Bender H.-U.; Almashanu S.; Steel G.; Hu C.-A.; Lin W.-W.; Willis A.; Pulver A.; Valle D.;
Am. J. Hum. Genet. 76:409-420(2005)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); ENZYME ACTIVITY; COFACTOR; VARIANTS VAL-167 AND ARG-521; CHARACTERIZATION OF VARIANTS HYRPRO1 MET-289; ASN-426; MET-427; HIS-431; PRO-441; CYS-453; SER-455; THR-472 AND ARG-521; CHARACTERIZATION OF VARIANTS SCZD4 LEU-406 AND MET-466; CHARACTERIZATION OF VARIANTS VAL-167; TRP-185; GLN-185 AND GLU-521;

PRODH mutations and hyperprolinemia in a subset of schizophrenic patients.
Jacquet H.; Raux G.; Thibaut F.; Hecketsweiler B.; Houy E.; Demilly C.; Haouzir S.; Allio G.; Fouldrin G.; Drouin V.; Bou J.; Petit M.; Campion D.; Frebourg T.;
Hum. Mol. Genet. 11:2243-2249(2002)
Cited for: VARIANTS HYRPRO1 MET-289; HIS-431; PRO-441; CYS-453; SER-455; THR-472 AND ARG-521; INVOLVEMENT IN HYRPRO1;

Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia.
Liu H.; Heath S.C.; Sobin C.; Roos J.L.; Galke B.L.; Blundell M.L.; Lenane M.; Robertson B.; Wijsman E.M.; Rapoport J.L.; Gogos J.A.; Karayiorgou M.;
Proc. Natl. Acad. Sci. U.S.A. 99:3717-3722(2002)
Cited for: VARIANTS SCZD4 LEU-406; MET-427; PRO-441; CYS-453; MET-466; THR-472 AND ARG-521; INVOLVEMENT IN SCZD4;

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.