UniProtKB/Swiss-Prot Q9ULU4: Variant p.Trp291Arg

MYND-type zinc finger-containing chromatin reader ZMYND8
Gene: ZMYND8
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Variant information Variant position:

291 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 Tryptophan (W) to Arginine (R) at position 291 (W291R, p.Trp291Arg). 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 (W) to large size and basic (R) 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 patient with syndromic intellectual disability; uncertain significance; disrupts interaction with DBN1. Any additional useful information about the variant.

Sequence information Variant position:

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

1186 The length of the canonical sequence.
Location on the sequence:

CEPCSNPHPLVWAKLKGFPF W PAKALRDKDGQVDARFFGQH 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                         CEPCSNPHPLVWAKLKGFPFWPAKALRDKDGQ-VDARFFGQH

Drosophila                    VKVCRHPHLLLWAKLKGFPYWPAKAMGSSNSTLVNVRFFGK

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 – 1186	MYND-type zinc finger-containing chromatin reader ZMYND8
Domain	277 – 327	PWWP
Region	1 – 850	Required for interaction with CCNT1
Region	75 – 406	Interaction with histone H3K14ac
Region	88 – 327	Required for interaction with histone H3 and histone H4
Binding site	274 – 274
Alternative sequence	1 – 526	Missing. In isoform 2.
Alternative sequence	1 – 376	Missing. In isoform 4.
Mutagenesis	307 – 307	F -> A. Severely decreases interaction with histone H3.1K36me2.
Mutagenesis	311 – 311	H -> A. Loss of binding to DBN1. Loss of cytoplasmic localization.
Beta strand	291 – 299

Literature citations
De Novo ZMYND8 variants result in an autosomal dominant neurodevelopmental disorder with cardiac malformations.
Dias K.R.; Carlston C.M.; Blok L.E.R.; De Hayr L.; Nawaz U.; Evans C.A.; Bayrak-Toydemir P.; Htun S.; Zhu Y.; Ma A.; Lynch S.A.; Moorwood C.; Stals K.; Ellard S.; Bainbridge M.N.; Friedman J.; Pappas J.G.; Rabin R.; Nowak C.B.; Douglas J.; Wilson T.E.; Guillen Sacoto M.J.; Mullegama S.V.; Palculict T.B.; Kirk E.P.; Pinner J.R.; Edwards M.; Montanari F.; Graziano C.; Pippucci T.; Dingmann B.; Glass I.; Mefford H.C.; Shimoji T.; Suzuki T.; Yamakawa K.; Streff H.; Schaaf C.P.; Slavotinek A.M.; Voineagu I.; Carey J.C.; Buckley M.F.; Schenck A.; Harvey R.J.; Roscioli T.;
Genet. Med. 24:1952-1966(2022)
Cited for: VARIANTS SYNDROMIC INTELLECTUAL DISABILITY GLU-230; ARG-291; LEU-307; GLU-334; LYS-980; SER-1039; ARG-1054 AND ARG-1055; CHARACTERIZATION OF VARIANTS GLU-230; ARG-291; LEU-307; GLU-334; SER-1039; ARG-1054 AND ARG-1055; INVOLVEMENT IN SYNDROMIC INTELLECTUAL DISABILITY; FUNCTION; INTERACTION WITH DBN1 AND GATAD2A; TISSUE SPECIFICITY; DEVELOPMENTAL STAGE;

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.