UniProtKB/Swiss-Prot O43918: Variant p.Cys299Trp

Autoimmune regulator
Gene: AIRE
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Variant information Variant position:

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

LB/B 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 Cysteine (C) to Tryptophan (W) at position 299 (C299W, p.Cys299Trp). 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 polar (C) to large size and aromatic (W) 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
Other resources:

Links to websites of interest for the variant.

Variant rs751066946 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

VPAPLALPSDPQLHQKNEDE C AVCRDGGELICCDGCPRAFH 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                         VPAPLALPSDPQLHQKNEDECAVCRDGGELICCDGCPRAFH

Mouse                         VPPLPSLPSEPQVNQKNEDECAVCHDGGELICCDGCPRAFH

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 – 545	Autoimmune regulator
Zinc finger	296 – 343	PHD-type 1
Alternative sequence	293 – 293	Q -> PVCMGVSCLCQ. In isoform 4.
Mutagenesis	295 – 295	N -> A. Abolishes interaction with histone H3.
Mutagenesis	297 – 297	D -> A. Strongly reduces interaction with unmethylated histone H3 and abolishes interaction with histone H3 trimethylated at 'Lys-4'. No effect on doted nuclear localization. Dominant-negative effect on target gene transcription.
Mutagenesis	298 – 298	E -> A. Reduces interaction with histone H3.
Mutagenesis	302 – 302	C -> P. Reduces transcriptional activation.
Mutagenesis	303 – 303	R -> P. Alters protein folding and abolishes interaction with histone H3. No effect on doted nuclear localization. Dominant-negative effect on target gene transcription.
Mutagenesis	304 – 304	D -> A. Strongly reduces interaction with histone H3.
Mutagenesis	307 – 307	E -> A. Reduces interaction with histone H3.
Mutagenesis	312 – 312	D -> A. Abolishes interaction with histone H3.
Mutagenesis	312 – 312	D -> N. No effect on doted nuclear localization. Dominant-negative effect on target gene transcription.
Beta strand	298 – 303

Literature citations
Dominant mutations in the autoimmune regulator AIRE are associated with common organ-specific autoimmune diseases.
Oftedal B.E.; Hellesen A.; Erichsen M.M.; Bratland E.; Vardi A.; Perheentupa J.; Kemp E.H.; Fiskerstrand T.; Viken M.K.; Weetman A.P.; Fleishman S.J.; Banka S.; Newman W.G.; Sewell W.A.; Sozaeva L.S.; Zayats T.; Haugarvoll K.; Orlova E.M.; Haavik J.; Johansson S.; Knappskog P.M.; Loevaas K.; Wolff A.S.; Abramson J.; Husebye E.S.;
Immunity 42:1185-1196(2015)
Cited for: INVOLVEMENT IN APS1; FUNCTION; SUBCELLULAR LOCATION; VARIANTS APS1 PRO-28; CYS-90; MET-301; TYR-311 AND LEU-326; CHARACTERIZATION OF VARIANTS PRO-28; CYS-90; MET-301; TYR-311 AND LEU-326; MUTAGENESIS OF 28-LEU-LEU-29; LEU-97; ASP-297; ARG-303; ASP-312; CYS-446 AND ARG-471; VARIANTS LYS-298; TRP-299; TYR-302; GLN-303; TRP-303; SER-305; ARG-306; MET-309; GLN-316; TRP-316; PRO-319; GLN-328; TRP-328; ARG-332 AND ALA-484; CHARACTERIZATION OF VARIANTS LYS-298; TYR-302; SER-305 AND GLN-328;

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.