UniProtKB/SwissProt variant VAR

Variant information

Variant position:

48

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Cysteine (C) to Phenylalanine (F) at position 48 (C48F, p.Cys48Phe).

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 (F)

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

Involvement in disease:

Intellectual developmental disorder with persistence of fetal hemoglobin (IDPFH) [MIM:617101]: An autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability, variable dysmorphic features, including microcephaly, downslanting palpebral fissures, strabismus, and external ear abnormalities, and asymptomatic persistence of fetal hemoglobin. {ECO:0000269|PubMed:27453576}. Note=The disease is caused by mutations affecting the gene represented in this entry. {ECO:0000269|PubMed:27453576}.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In IDPFH; de novo mutation; loss of function in transactivation of transcription; reduces the interaction between isoform 2 and isoform 3; disrupts the nuclear paraspeckle distribution of isoform 2 and isoform 3.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs886037865 [ dbSNP | Ensembl ]

Sequence information

Variant position:

48

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

Protein sequence length:

835

The length of the canonical sequence.

Location on the sequence:

DDEPDHGPLGAPEGDHDLLT C GQCQMNFPLGDILIFIEHKR

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                         DDEPDHGPLGAPEGDHDLLTCGQCQMNFPLGDILIFIEHKR

Mouse                         DDEPDHGPLGAPEGDHDLLTCGQCQMNFPLGDILIFIEHKR

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 – 835	B-cell lymphoma/leukemia 11A
Region	1 – 210	Required for nuclear body formation and for SUMO1 recruitment

Literature citations

BCL11A haploinsufficiency causes an intellectual disability syndrome and dysregulates transcription.
Dias C.; Estruch S.B.; Grmaham S.A.; McRae J.; Sawiak S.J.; Hurst J.A.; Joss S.K.; Holder S.E.; Morton J.E.; Turner C.; Thevenon J.; Mellul K.; Sanchez-Andrade G.; Ibarra-Soria X.; Deriziotis P.; Santos R.F.; Lee S.C.; Faivre L.; Kleefstra T.; Liu P.; Hurles M.E.; Fisher S.E.; Logan D.W.;
Am. J. Hum. Genet. 99:253-274(2016)
Cited for: INVOLVEMENT IN IDPFH; VARIANTS IDPFH PRO-47; PHE-48 AND GLN-66; CHARACTERIZATION OF VARIANTS IDPFH PRO-47; PHE-48 AND GLN-66; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9H165: Variant p.Cys48Phe