UniProtKB/SwissProt variant VAR

Caspase recruitment domain-containing protein 9
Gene: CARD9
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Variant information Variant position:

91 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 Tyrosine (Y) to Histidine (H) at position 91 (Y91H, p.Tyr91His). 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 large size and aromatic (Y) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

2 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 IMD103; does not affect formation of the CBM complex but impairs formation of a complex with RASGRF1. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs921151054 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

TGHKGYVAFLESLELYYPQL Y KKVTGKEPARVFSMIIDASG 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                         TGHKGYVAFLESLELYYPQLYKKVTGKEPARVFSMIIDASG

Mouse                         TGHKGYVAFLESLELYYPQLYRKVTGKEPARVFSMIIDASG

Rat                           TGHKGYVAFLESLELYYPQLYRKVTGKEPARVFSMIIDASG

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 – 536	Caspase recruitment domain-containing protein 9
Domain	6 – 98	CARD
Binding site	73 – 73
Mutagenesis	73 – 73	H -> A. Strongly reduced zinc-binding.
Mutagenesis	101 – 101	R -> Q. Disruption of the linker region, relieving autoinhibition and leading to activation of NF-kappa-B.
Mutagenesis	103 – 103	F -> L. Disruption of the linker region, relieving autoinhibition and leading to activation of NF-kappa-B.
Mutagenesis	107 – 107	I -> E. Disruption of the linker region, relieving autoinhibition and leading to activation of NF-kappa-B. Constitutively forms BCL10-nucleating filaments.
Mutagenesis	111 – 111	G -> S. Disruption of the linker region, relieving autoinhibition and leading to activation of NF-kappa-B.
Helix	88 – 95

Literature citations
CARD9 deficiency and spontaneous central nervous system candidiasis: complete clinical remission with GM-CSF therapy.
Gavino C.; Cotter A.; Lichtenstein D.; Lejtenyi D.; Fortin C.; Legault C.; Alirezaie N.; Majewski J.; Sheppard D.C.; Behr M.A.; Foulkes W.D.; Vinh D.C.;
Clin. Infect. Dis. 59:81-84(2014)
Cited for: VARIANT IMD103 HIS-91; Impaired RASGRF1/ERK-mediated GM-CSF response characterizes CARD9 deficiency in French-Canadians.
Gavino C.; Hamel N.; Zeng J.B.; Legault C.; Guiot M.C.; Chankowsky J.; Lejtenyi D.; Lemire M.; Alarie I.; Dufresne S.; Boursiquot J.N.; McIntosh F.; Langelier M.; Behr M.A.; Sheppard D.C.; Foulkes W.D.; Vinh D.C.;
J. Allergy Clin. Immunol. 137:1178-1188(2016)
Cited for: VARIANT IMD103 HIS-91; CHARACTERIZATION OF VARIANT IMD103 HIS-91; FUNCTION; IDENTIFICATION IN THE CBM COMPLEX; INTERACTION WITH RASGRF1; Novel CARD9 mutation in a patient with chronic invasive dermatophyte infection (tinea profunda).
Nazarian R.M.; Lilly E.; Gavino C.; Hamilos D.L.; Felsenstein D.; Vinh D.C.; Googe P.B.;
J. Cutan. Pathol. 47:166-170(2020)
Cited for: VARIANT IMD103 HIS-91;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9H257: Variant p.Tyr91His