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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14573: Variant p.Ile2506Asn

Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3
Gene: ITPR3
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Variant information Variant position: help 2506 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Isoleucine (I) to Asparagine (N) at position 2506 (I2506N, p.Ile2506Asn). 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: help Change from medium size and hydrophobic (I) to medium size and polar (N) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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: help In IMD133; pathogenic; patients T cells show altered calcium homeostasis; impaired calcium signaling after stimulation; depleted intracellular endoplasmic reticulum calcium stores; dominant-negative effect on channel function by causing channel leakiness and impaired calcium dynamics and signaling in T cells. Any additional useful information about the variant.


Sequence information Variant position: help 2506 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 2671 The length of the canonical sequence.
Location on the sequence: help DESLFPARVVYDLLFFFIVI I IVLNLIFGVIIDTFADLRSE 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         DESLFPARVVYDLLFFFIVIIIVLNLIFGVIIDTFADLRSE

Mouse                         DESLFPARVVYDLLFFFIVIIIVLNLIFGVIIDTFADLRSE

Rat                           DESLFPARVVYDLLFFFIVIIIVLNLIFGVIIDTFADLRSE

Bovine                        DESLFPARVVYDLLFFFIVIIIVLNLIFGVIIDTFADLRSE
Sequence annotation in neighborhood: help 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 – 2671 Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3
Transmembrane 2497 – 2517 Helical
Helix 2501 – 2508



Literature citations
Dominant negative variants in ITPR3 impair T cell Ca2+ dynamics causing combined immunodeficiency.
Blanco E.; Camps C.; Bahal S.; Kerai M.D.; Ferla M.P.; Rochussen A.M.; Handel A.E.; Golwala Z.M.; Spiridou Goncalves H.; Kricke S.; Klein F.; Zhang F.; Zinghirino F.; Evans G.; Keane T.M.; Lizot S.; Kusters M.A.A.; Iro M.A.; Patel S.V.; Morris E.C.; Burns S.O.; Radcliffe R.; Vasudevan P.; Price A.; Gillham O.; Valdebenito G.E.; Stewart G.S.; Worth A.; Adams S.P.; Duchen M.; Andre I.; Adams D.J.; Santili G.; Gilmour K.C.; Hollaender G.A.; Davies E.G.; Taylor J.C.; Griffiths G.M.; Thrasher A.J.; Dhalla F.; Kreins A.Y.;
J. Exp. Med. 222:0-0(2025)
Cited for: VARIANTS IMD133 THR-196; ASN-2506; CYS-2524 AND HIS-2524; CHARACTERIZATION OF VARIANTS IMD133 THR-196; ASN-2506; CYS-2524 AND HIS-2524; VARIANT GLN-1850; INVOLVEMENT IN IMD133; FUNCTION; SUBCELLULAR LOCATION;
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.