UniProtKB/SwissProt variant VAR

Variant information

Variant position:

382

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 Glutamine (Q) at position 382 (R382Q, p.Arg382Gln).

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

Involvement in disease:

Diarrhea 8, secretory sodium, congenital (DIAR8) [MIM:616868]: A disease characterized by watery secretory diarrhea with prenatal onset, prominent abdominal distension after birth due to dilated fluid-filled loops of intestine, elevated fecal sodium concentrations and low urinary sodium concentrations. {ECO:0000269|PubMed:26358773}. 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 DIAR8; decreases cell membrane localization; reduces strongly Na(+)/H(+) exchange activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs766076524 [ dbSNP | Ensembl ]

Sequence information

Variant position:

382

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

Protein sequence length:

834

The length of the canonical sequence.

Location on the sequence:

FIWTWNTAFVLLTLVFISVY R AIGVVLQTWLLNRYRMVQLE

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                         FIWTWNTAFVLLTLVFISVYRAIGVVLQTWLLNRYRMVQLE

Mouse                         DIWTWNTAFVLLTLVFISVYRAIGVVLQTWILNRYRMVQLE

Rat                           VIWTWNTAFVLLTLVFISVYRAIGVVLQTWILNRYRMVQLE

Rabbit                        LIWTWNTAFVLLTLLFVSVFRAIGVVLQTWLLNRYRMVQLE

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 – 834	Sodium/hydrogen exchanger 3
Transmembrane	370 – 390	Helical; Name=K/M9

Literature citations

Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea.
Janecke A.R.; Heinz-Erian P.; Yin J.; Petersen B.S.; Franke A.; Lechner S.; Fuchs I.; Melancon S.; Uhlig H.H.; Travis S.; Marinier E.; Perisic V.; Ristic N.; Gerner P.; Booth I.W.; Wedenoja S.; Baumgartner N.; Vodopiutz J.; Frechette-Duval M.C.; De Lafollie J.; Persad R.; Warner N.; Tse C.M.; Sud K.; Zachos N.C.; Sarker R.; Zhu X.; Muise A.M.; Zimmer K.P.; Witt H.; Zoller H.; Donowitz M.; Mueller T.;
Hum. Mol. Genet. 24:6614-6623(2015)
Cited for: VARIANTS DIAR8 THR-127; THR-269; VAL-311 AND GLN-382; CHARACTERIZATION OF VARIANTS DIAR8 THR-127; THR-269; VAL-311 AND GLN-382; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P48764: Variant p.Arg382Gln