UniProtKB/Swiss-Prot P54098: Variant p.Ala467Thr

DNA polymerase subunit gamma-1
Gene: POLG
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Variant information Variant position:

467 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 Alanine (A) to Threonine (T) at position 467 (A467T, p.Ala467Thr). 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
Variant description:

In PEOB1, SANDO, SCAE and MTDPS4A; pathogenic; results in clearly decreased activity, DNA binding and processivity of the polymerase. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs113994095 [ dbSNP | Ensembl ]

Sequence information Variant position:

467 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1239 The length of the canonical sequence.
Location on the sequence:

EAQGTYEELQREMKKSLMDL A NDACQLLSGERYKEDPWLWD 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                         EAQGTYEELQREMKKSLMDLANDACQLLSGERYKEDPWLWD

Mouse                         EAQNTYEELQREMKKSLMDLANDACQLLSGERYKEDPWLWD

Rat                           EAQSTYEELQREMKKSLMELANDACQLLSGERYKEDPWLWD

Xenopus laevis                EAQTSYEELQKEMKKSLMKLANDACQLLTKDAYKEDPWLWD

Drosophila                    EAQLTYEDLSIEAKYHLGRRAEEACSLLLDDQYRQNLWLWD

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.

Type	Positions	Description
Chain	1 – 1239	DNA polymerase subunit gamma-1
Helix	440 – 471

Literature citations
Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions.
Van Goethem G.; Dermaut B.; Loefgren A.; Martin J.-J.; Van Broeckhoven C.;
Nat. Genet. 28:211-212(2001)
Cited for: VARIANTS PEOB1 PRO-3; ARG-304; THR-467 AND CYS-955; POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions.
Di Fonzo A.; Bordoni A.; Crimi M.; Sara G.; Del Bo R.; Bresolin N.; Comi G.P.;
Hum. Mutat. 22:498-499(2003)
Cited for: VARIANTS PEOB1 ILE-251; ALA-268; ARG-312; THR-467; GLN-562; LEU-587; PRO-807 AND TYR-932; VARIANTS GLY-1143 AND HIS-1236; Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).
Agostino A.; Valletta L.; Chinnery P.F.; Ferrari G.; Carrara F.; Taylor R.W.; Schaefer A.M.; Turnbull D.M.; Tiranti V.; Zeviani M.;
Neurology 60:1354-1356(2003)
Cited for: VARIANTS PEOB1 TRP-227; ILE-251; ARG-312; VAL-431; THR-467; GLN-1047; CYS-1096 AND CYS-1104; Patient homozygous for a recessive POLG mutation presents with features of MERRF.
Van Goethem G.; Mercelis R.; Loefgren A.; Seneca S.; Ceuterick C.; Martin J.-J.; Van Broeckhoven C.;
Neurology 61:1811-1813(2003)
Cited for: VARIANT SCAE THR-467; Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.
Van Goethem G.; Martin J.-J.; Dermaut B.; Loefgren A.; Wibail A.; Ververken D.; Tack P.; Dehaene I.; Van Zandijcke M.; Moonen M.; Ceuterick C.; De Jonghe P.; Van Broeckhoven C.;
Neuromuscul. Disord. 13:133-142(2003)
Cited for: VARIANTS SANDO PRO-3; ARG-304; THR-467; TRP-627 AND CYS-955; POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion.
Naviaux R.K.; Nguyen K.V.;
Ann. Neurol. 55:706-712(2004)
Cited for: VARIANT MTDPS4A THR-467; POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.
Van Goethem G.; Luoma P.; Rantamaeki M.; Al-Memar A.; Kaakkola S.; Hackman P.; Krahe R.; Loefgren A.; Martin J.-J.; De Jonghe P.; Suomalainen A.; Udd B.; Van Broeckhoven C.;
Neurology 63:1251-1257(2004)
Cited for: VARIANT PEOB1 THR-467; VARIANT SANDO SER-748; VARIANT GLY-1143; Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA.
Ferrari G.; Lamantea E.; Donati A.; Filosto M.; Briem E.; Carrara F.; Parini R.; Simonati A.; Santer R.; Zeviani M.;
Brain 128:723-731(2005)
Cited for: VARIANTS MTDPS4A GLY-232; PRO-244; ILE-251; THR-467; LEU-587; SER-748; SER-848 AND PRO-957; VARIANT GLY-1143; Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome.
Luoma P.T.; Luo N.; Loescher W.N.; Farr C.L.; Horvath R.; Wanschitz J.; Kiechl S.; Kaguni L.S.; Suomalainen A.;
Hum. Mol. Genet. 14:1907-1920(2005)
Cited for: VARIANT PEOB1 THR-467; VARIANT SANDO GLN-627; VARIANT HIS-1236; CHARACTERIZATION OF VARIANT PEOB1 THR-467; CHARACTERIZATION OF VARIANT SANDO GLN-627; FUNCTION; CATALYTIC ACTIVITY; Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations.
Winterthun S.; Ferrari G.; He L.; Taylor R.W.; Zeviani M.; Turnbull D.M.; Engelsen B.A.; Moen G.; Bindoff L.A.;
Neurology 64:1204-1208(2005)
Cited for: VARIANTS SANDO THR-467; HIS-497 AND SER-748; Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay.
Naiemi M.; Bannwarth S.; Procaccio V.; Pouget J.; Desnuelle C.; Pellissier J.-F.; Roetig A.; Munnich A.; Calvas P.; Richelme C.; Jonveaux P.; Castelnovo G.; Simon M.; Clanet M.; Wallace D.; Paquis-Flucklinger V.;
Eur. J. Hum. Genet. 14:917-922(2006)
Cited for: VARIANTS PEOB1 ARG-304; ASP-380 AND THR-467; VARIANT SANDO SER-748; VARIANT MTDPS4A PRO-914; VARIANTS GLY-1143 AND HIS-1236; Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion.
Taanman J.-W.; Rahman S.; Pagnamenta A.T.; Morris A.A.M.; Bitner-Glindzicz M.; Wolf N.I.; Leonard J.V.; Clayton P.T.; Schapira A.H.V.;
Hum. Mutat. 30:248-254(2009)
Cited for: VARIANTS LS HIS-232 AND SER-848; VARIANTS MTDPS4A ILE-251; THR-467; LEU-587; SER-748; CYS-831; SER-848; PRO-914; TYR-1110; ARG-1134 AND LYS-1136; VARIANTS GLY-1143 AND HIS-1236; Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.
Tzoulis C.; Neckelmann G.; Moerk S.J.; Engelsen B.E.; Viscomi C.; Moen G.; Ersland L.; Zeviani M.; Bindoff L.A.;
Brain 133:1428-1437(2010)
Cited for: VARIANTS SCAE THR-467 AND SER-748; VARIANTS MTDPS4A ARG-303; THR-467 AND SER-848; Alpers syndrome with mutations in POLG: clinical and investigative features.
Hunter M.F.; Peters H.; Salemi R.; Thorburn D.; Mackay M.T.;
Pediatr. Neurol. 45:311-318(2011)
Cited for: VARIANTS MTDPS4A ARG-305; THR-467; SER-748; SER-848; CYS-852 AND ARG-966; PRICKLE2 mutations might not be involved in epilepsy.
Sandford E.; Bird T.D.; Li J.Z.; Burmeister M.;
Am. J. Hum. Genet. 98:588-589(2016)
Cited for: INVOLVEMENT IN SCAE; VARIANTS SCAE THR-467; HIS-497 AND SER-748;

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.