UniProtKB/Swiss-Prot Q9H7Z6: Variant p.Arg325Cys

Histone acetyltransferase KAT8
Gene: KAT8
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Variant information Variant position:

325 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 Arginine (R) to Cysteine (C) at position 325 (R325C, p.Arg325Cys). 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 basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-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:

Found in a severe neurodevelopmental disorder similar to Li-Ghorbani-Weisz-Hubshman syndrome with apparently autosomal recessive inheritance; uncertain significance; no effect on protein expression; no effect on localization to the nucleus; no effect on MSL complex assembly; decreased histone acetyltransferase activity. Any additional useful information about the variant.

Sequence information Variant position:

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

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

EKESPDGNNVACILTLPPYQ R RGYGKFLIAFSYELSKLEST 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                         EKESPDGNNVACILTLPPYQRRGYGKFLIAFSYELSKLEST

Mouse                         EKESPDGNNVACILTLPPYQRRGYGKFLIAFSYELSKLEST

Rat                           EKESPDGNNVACILTLPPYQRRGYGKFLIAFSYELSKLEST

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	2 – 458	Histone acetyltransferase KAT8
Domain	174 – 447	MYST-type HAT
Region	174 – 458	Sufficient for interaction with KANSL1
Binding site	317 – 317
Binding site	317 – 317
Binding site	319 – 319
Binding site	319 – 319
Binding site	325 – 325
Binding site	325 – 325
Binding site	326 – 326
Binding site	327 – 327
Binding site	329 – 329
Binding site	329 – 329
Binding site	330 – 330
Binding site	330 – 330
Mutagenesis	316 – 316	C -> S. Strongly reduces histone acetyltransferase activity without abolishing non-enzymatic 'autoacetylation'.
Beta strand	325 – 327

Literature citations
Lysine acetyltransferase 8 is involved in cerebral development and syndromic intellectual disability.
Li L.; Ghorbani M.; Weisz-Hubshman M.; Rousseau J.; Thiffault I.; Schnur R.E.; Breen C.; Oegema R.; Weiss M.M.; Waisfisz Q.; Welner S.; Kingston H.; Hills J.A.; Boon E.M.; Basel-Salmon L.; Konen O.; Goldberg-Stern H.; Bazak L.; Tzur S.; Jin J.; Bi X.; Bruccoleri M.; McWalter K.; Cho M.T.; Scarano M.; Schaefer G.B.; Brooks S.S.; Hughes S.S.; van Gassen K.L.I.; van Hagen J.M.; Pandita T.K.; Agrawal P.B.; Campeau P.M.; Yang X.J.;
J. Clin. Invest. 130:1431-1445(2020)
Cited for: INVOLVEMENT IN LIGOWS; VARIANTS LIGOWS CYS-90; GLN-98; GLN-99; VAL-165; 175-LYS--LYS-458 DEL; GLU-175; ASN-181 AND CYS-325; CHARACTERIZATION OF VARIANTS LIGOWS CYS-90; GLN-98; GLN-99; VAL-165; 175-LYS--LYS-458 DEL; GLU-175; ASN-181 AND CYS-325; FUNCTION; CATALYTIC ACTIVITY; 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.