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UniProtKB/Swiss-Prot O00329: Variant p.Glu1021Lys

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Gene: PIK3CD
Variant information

Variant position:  1021
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 Glutamate (E) to Lysine (K) at position 1021 (E1021K, p.Glu1021Lys).
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 medium size and acidic (E) to large size and basic (K)
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

Variant description:  In APDS; results in gain of function causing enhanced membrane association and kinase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1021
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1044
The length of the canonical sequence.

Location on the sequence:   SLALGKTEEEALKHFRVKFN  E ALRESWKTKVNWLAHNVSKD
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                         SLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD

Mouse                         SLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD

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 1 – 1044 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Domain 774 – 1041 PI3K/PI4K
Modified residue 1039 – 1039 Phosphoserine; by autocatalysis
Alternative sequence 302 – 1044 Missing. In isoform 2.
Mutagenesis 1039 – 1039 S -> A. Abolishes autophosphorylation, no effect on lipid kinase activity.
Mutagenesis 1039 – 1039 S -> DE. Abolishes autophosphorylation, reduced lipid kinase activity.
Helix 1008 – 1031


Literature citations

Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage.
Angulo I.; Vadas O.; Garcon F.; Banham-Hall E.; Plagnol V.; Leahy T.R.; Baxendale H.; Coulter T.; Curtis J.; Wu C.; Blake-Palmer K.; Perisic O.; Smyth D.; Maes M.; Fiddler C.; Juss J.; Cilliers D.; Markelj G.; Chandra A.; Farmer G.; Kielkowska A.; Clark J.; Kracker S.; Debre M.; Picard C.; Pellier I.; Jabado N.; Morris J.A.; Barcenas-Morales G.; Fischer A.; Stephens L.; Hawkins P.; Barrett J.C.; Abinun M.; Clatworthy M.; Durandy A.; Doffinger R.; Chilvers E.R.; Cant A.J.; Kumararatne D.; Okkenhaug K.; Williams R.L.; Condliffe A.; Nejentsev S.;
Science 342:866-871(2013)
Cited for: VARIANT APDS LYS-1021; CHARACTERIZATION OF VARIANT APDS LYS-1021;

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.