UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1420

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 Arginine (R) to Cysteine (C) at position 1420 (R1420C, p.Arg1420Cys).

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 (C)

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

Involvement in disease:

Familial hyperinsulinemic hypoglycemia 1 (HHF1) [MIM:256450]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. {ECO:0000269|PubMed:10202168, ECO:0000269|PubMed:10334322, ECO:0000269|PubMed:10615958, ECO:0000269|PubMed:11018078, ECO:0000269|PubMed:11226335, ECO:0000269|PubMed:11867634, ECO:0000269|PubMed:12364426, ECO:0000269|PubMed:12941782, ECO:0000269|PubMed:15562009, ECO:0000269|PubMed:15579781, ECO:0000269|PubMed:15807877, ECO:0000269|PubMed:16357843, ECO:0000269|PubMed:16429405, ECO:0000269|PubMed:24814349, ECO:0000269|PubMed:25720052, ECO:0000269|PubMed:8650576, ECO:0000269|PubMed:8751851, ECO:0000269|PubMed:8923011, ECO:0000269|PubMed:9618169, ECO:0000269|PubMed:9648840, ECO:0000269|PubMed:9769320}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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 HHF1; modest impairment of channel function.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28938469 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1420

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

Protein sequence length:

1581

The length of the canonical sequence.

Location on the sequence:

GHIIIDGIDIAKLPLHTLRS R LSIILQDPVLFSGTIRFNLD

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                         GHIIIDGIDIAKLPLHTLRSRLSIILQDPVLFSGTIRFNLD

Rat                           GRIIIDGIDIAKLPLHTLRSRLSIILQDPVLFSGTIRFNLD

Slime mold                    GTIEIDGIDITELGLNPLRSRMAIIPQDPVLFAGSVRYNLD

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 – 1581	ATP-binding cassette sub-family C member 8
Topological domain	1298 – 1581	Cytoplasmic
Domain	1344 – 1578	ABC transporter 2
Alternative sequence	51 – 1581	Missing. In isoform 3.

Literature citations

Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.
Verkarre V.; Fournet J.-C.; de Lonlay P.; Gross-Morand M.-S.; Devillers M.; Rahier J.; Brunelle F.; Robert J.-J.; Nihoul-Fekete C.; Saudubray J.-M.; Junien C.;
J. Clin. Invest. 102:1286-1291(1998)
Cited for: VARIANTS HHF1 PRO-1352; CYS-1420 AND TRP-1493;

Clinical features of 52 neonates with hyperinsulinism.
de Lonlay-Debeney P.; Poggi-Travert F.; Fournet J.-C.; Sempoux C.; Vici C.D.; Brunelle F.; Touati G.; Rahier J.; Junien C.; Nihoul-Fekete C.; Robert J.-J.; Saudubray J.-M.;
N. Engl. J. Med. 340:1169-1175(1999)
Cited for: VARIANTS HHF1 GLY-841; CYS-1420 AND TRP-1493;

Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy: nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to sulfonylurea receptor 1.
Tanizawa Y.; Matsuda K.; Matsuo M.; Ohta Y.; Ochi N.; Adachi M.; Koga M.; Mizuno S.; Kajita M.; Tanaka Y.; Tachibana K.; Inoue H.; Furukawa S.; Amachi T.; Ueda K.; Oka Y.;
Diabetes 49:114-120(2000)
Cited for: CHARACTERIZATION OF VARIANTS HHF1 CYS-1420 AND GLN-1436; VARIANT SER-1369;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q09428: Variant p.Arg1420Cys