UniProtKB/Swiss-Prot O76090: Variant p.Asp312Asn

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 312 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Aspartate (D) to Asparagine (N) at position 312 (D312N, p.Asp312Asn). 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 acidic (D) to medium size and polar (N) 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 VMD2 and ARB; no effect on protein stability; loss of cell membrane localization in transfected MDCK.2 cells; reduced chloride conductance. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs281865277 [ dbSNP | Ensembl ]

Sequence information

Variant position: 312 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 585 The length of the canonical sequence.
Location on the sequence: EQLINPFGEDDDDFETNWIV D RNLQVSLLAVDEMHQDLPRM 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.
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 – 585	Bestrophin-1
Topological domain	289 – 585	Cytoplasmic
Binding site	293 – 293
Binding site	296 – 296
Binding site	301 – 301
Binding site	304 – 304
Alternative sequence	290 – 316	Missing. In isoform 4.
Helix	307 – 323

Literature citations

Biallelic mutation of BEST1 causes a distinct retinopathy in humans.
Burgess R.; Millar I.D.; Leroy B.P.; Urquhart J.E.; Fearon I.M.; De Baere E.; Brown P.D.; Robson A.G.; Wright G.A.; Kestelyn P.; Holder G.E.; Webster A.R.; Manson F.D.C.; Black G.C.M.;
Am. J. Hum. Genet. 82:19-31(2008)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; VARIANTS ARB PRO-41; HIS-141; ALA-152; ASN-312; MET-317 AND THR-325; CHARACTERIZATION OF VARIANTS ARB HIS-141 AND ALA-152; Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa.
Davidson A.E.; Millar I.D.; Urquhart J.E.; Burgess-Mullan R.; Shweikh Y.; Parry N.; O'Sullivan J.; Maher G.J.; McKibbin M.; Downes S.M.; Lotery A.J.; Jacobson S.G.; Brown P.D.; Black G.C.; Manson F.D.;
Am. J. Hum. Genet. 85:581-592(2009)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION; VARIANTS RP50 VAL-140; THR-205; CYS-227 AND ASN-228; CHARACTERIZATION OF VARIANTS RP50 VAL-140; THR-205 AND ASN-228; CHARACTERIZATION OF VARIANT ARB ASN-312; Functional characterization of bestrophin-1 missense mutations associated with autosomal recessive bestrophinopathy.
Davidson A.E.; Millar I.D.; Burgess-Mullan R.; Maher G.J.; Urquhart J.E.; Brown P.D.; Black G.C.; Manson F.D.;
Invest. Ophthalmol. Vis. Sci. 52:3730-3736(2011)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS ARB PRO-41; VAL-140; HIS-141; ALA-152; VAL-195; TRP-202; ASN-312; MET-317 AND THR-325; CHARACTERIZATION OF VARIANTS VMD2 HIS-85 AND ARG-237; Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration.
Kraemer F.; White K.; Pauleikhoff D.; Gehrig A.; Passmore L.; Rivera A.; Rudolph G.; Kellner U.; Andrassi M.; Lorenz B.; Rohrschneider K.; Blankenagel A.; Jurklies B.; Schilling H.; Schuett F.; Holz F.G.; Weber B.H.;
Eur. J. Hum. Genet. 8:286-292(2000)
Cited for: VARIANTS VMD2 PRO-6; MET-9; THR-10; VAL-21; TRP-25; ARG-27; HIS-47; LEU-58; SER-92; LYS-99; ARG-100; ASN-209; SER-218; MET-224; ARG-231; ARG-237; VAL-243; ILE-295 DEL; LYS-300; ASN-301; GLU-301; THR-310; GLY-311 AND ASN-312;