UniProtKB/SwissProt variant VAR

Variant information

Variant position:

313

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 Lysine (K) to Asparagine (N) at position 313 (K313N, p.Lys313Asn).

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 (K) to medium size and polar (N)

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

BLOSUM score:

0

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:

Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD) [MIM:617306]: An autosomal recessive syndrome characterized by severe microphthalmia, profound congenital sensorineural hearing loss, lack of pigment in the hair, skin, and eyes, macrocephaly, facial dysmorphism, and osteopetrosis. {ECO:0000269|PubMed:27889061}. Note=The disease is caused by mutations affecting the gene represented in this entry. An allelic combination involving at least one dominant-negative mutation, inherited in a recessive manner, represents the underlying molecular mechanism leading to COMMAD syndrome. {ECO:0000269|PubMed:27889061}.

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 COMMAD; has both cytoplasmic and nuclear localization; decreased binding to M-box or E-box DNA sequences.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1057519325 [ dbSNP | Ensembl ]

Sequence information

Variant position:

313

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

Protein sequence length:

526

The length of the canonical sequence.

Location on the sequence:

TACIFPTESEARALAKERQK K DNHNLIERRRRFNINDRIKE

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                         TACIFPTESEARALAKERQKKDNHNLIERRRRFNINDRIKE

Mouse                         TACIFPTESEARALAKERQKKDNHNLIERRRRFNINDRIKE

Rat                           TACIFPTESEARALAKERQKKDNHNLIERRRRFNINDRIKE

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 – 526	Microphthalmia-associated transcription factor
Domain	311 – 364	bHLH

Literature citations

Biallelic mutations in MITF cause coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness.
George A.; Zand D.J.; Hufnagel R.B.; Sharma R.; Sergeev Y.V.; Legare J.M.; Rice G.M.; Scott Schwoerer J.A.; Rius M.; Tetri L.; Gamm D.M.; Bharti K.; Brooks B.P.;
Am. J. Hum. Genet. 99:1388-1394(2016)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INVOLVEMENT IN COMMAD; VARIANTS COMMAD ASN-313; ARG-324 DEL AND GLY-324; CHARACTERIZATION OF VARIANTS COMMAD ASN-313 AND ARG-324 DEL;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75030: Variant p.Lys313Asn