UniProtKB/Swiss-Prot P28340: Variant p.Gln684His

DNA polymerase delta catalytic subunit
Gene: POLD1
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Variant information Variant position:

684 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Glutamine (Q) to Histidine (H) at position 684 (Q684H, p.Gln684His). 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:

Similar physico-chemical property. Both residues are medium size and polar. 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 IMD120; uncertain significance; does not affect interaction with POLD2 and POLD3; does not affect protein stability when tested in a heterologous system; strongly decreased polymerase activity, when tested in transfected HEK293 cells in association with W-939. Any additional useful information about the variant.

Sequence information Variant position:

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

1107 The length of the canonical sequence.
Location on the sequence:

LSARKRAKAELAKETDPLRR Q VLDGRQLALKVSANSVYGFT 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                         LSARKRAKAELAKETDPLRRQVLDGRQLALKVSANSVYGFT

Mouse                         LSARKRAKAELAQETDPLRRQVLDGRQLALKVSANSVYGFT

Rat                           LSARKRAKAELAQETDPLRRQVLDGRQLALKVSPNSVYGFT

Bovine                        LSARKRAKAELAKETDPLRRQVLDGRQLALKVSANSVYGFT

Caenorhabditis elegans        LAARKRAKNDMKNEKDEFKRMVYNGRQLALKISANSVYGFT

Drosophila                    LAARKRAKNDLKVETDPFKRKVLDGRQLALKISANSVYGFT

Slime mold                    LSARKKAKDELKNEKDPFKRAVLDGRQLALKISANSVYGFT

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 – 1107	DNA polymerase delta catalytic subunit
Helix	680 – 704

Literature citations
Polymerase delta deficiency causes syndromic immunodeficiency with replicative stress.
Conde C.D.; Petronczki O.Y.; Baris S.; Willmann K.L.; Girardi E.; Salzer E.; Weitzer S.; Ardy R.C.; Krolo A.; Ijspeert H.; Kiykim A.; Karakoc-Aydiner E.; Foerster-Waldl E.; Kager L.; Pickl W.F.; Superti-Furga G.; Martinez J.; Loizou J.I.; Ozen A.; van der Burg M.; Boztug K.;
J. Clin. Invest. 129:4194-4206(2019)
Cited for: INVOLVEMENT IN IMD120; VARIANTS IMD120 HIS-684; TRP-939 AND TRP-1074; CHARACTERIZATION OF VARIANTS IMD120 HIS-684; TRP-939 AND TRP-1074; FUNCTION; INTERACTION WITH POLD2 AND POLD3; MUTAGENESIS OF ASP-602 AND ASP-757;

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.