UniProtKB/SwissProt variant VAR

Variant information

Variant position:

121

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 Arginine (R) to Glutamine (Q) at position 121 (R121Q, p.Arg121Gln).

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 (Q)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

1

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 NSDVS1; gain-of-function, reduced BET proteins stability.

Any additional useful information about the variant.

Sequence information

Variant position:

121

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

374

The length of the canonical sequence.

Location on the sequence:

KFKFSILNAKGEETKAMESQ R AYRFVQGKDWGFKKFIRRDF

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                         KFKFSILNAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDF

Mouse                         KFKFSILNAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDF

Bovine                        KFKFSILNAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDF

Xenopus tropicalis            KFKFSILNAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDF

Zebrafish                     KFKFSILNAKGEETKAMESQRAYRFVQGKDWGFKKFIRRDF

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 – 374	Speckle-type POZ protein
Domain	31 – 161	MATH
Region	71 – 191	Required for nuclear localization
Mutagenesis	123 – 123	Y -> A. Strongly reduced affinity for substrate proteins.
Mutagenesis	130 – 130	D -> A. Strongly reduced affinity for substrate proteins.
Mutagenesis	131 – 131	W -> A. Strongly reduced affinity for substrate proteins.
Mutagenesis	133 – 133	F -> A. Strongly reduced affinity for substrate proteins.

Literature citations

De Novo Variants in SPOP Cause Two Clinically Distinct Neurodevelopmental Disorders.
Nabais Sa M.J.; El Tekle G.; de Brouwer A.P.M.; Sawyer S.L.; Del Gaudio D.; Parker M.J.; Kanani F.; van den Boogaard M.H.; van Gassen K.; Van Allen M.I.; Wierenga K.; Purcarin G.; Elias E.R.; Begtrup A.; Keller-Ramey J.; Bernasocchi T.; van de Wiel L.; Gilissen C.; Venselaar H.; Pfundt R.; Vissers L.E.L.M.; Theurillat J.P.; de Vries B.B.A.;
Am. J. Hum. Genet. 106:405-411(2020)
Cited for: VARIANTS NSDVS2 ALA-25; CYS-83; VAL-132 AND CYS-138; CHARACTERIZATION OF VARIANTS NSDVS2 ALA-25; CYS-83; VAL-132 AND CYS-138; VARIANTS NSDVS1 GLN-121 AND ASN-144; CHARACTERIZATION OF VARIANTS NSDVS1 GLN-121 AND ASN-144; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43791: Variant p.Arg121Gln