UniProtKB/SwissProt variant VAR

Variant information

Variant position:

337

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

Type of variant:

LP/P [Disclaimer]

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 Arginine (R) to Cysteine (C) at position 337 (R337C, p.Arg337Cys).

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

Variant description:

In AME; decreased half-life from 21 to 4 hours compared to wild-type, probably due to degradation via the proteasomal pathway.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121917781 [ dbSNP | Ensembl ]

Sequence information

Variant position:

337

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

Protein sequence length:

405

The length of the canonical sequence.

Location on the sequence:

DLTPVVDAITDALLAARPRR R YYPGQGLGLMYFIHYYLPEG

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                         DLTPVVDAITDALLAARPRRRYYPGQGLGLMYFIHYYLPEG

Mouse                         DLSPVVDAIIDALLAAQPRSRYYPGRGLGLMYFIHHYLPEG

Rat                           DLSPVVDAIIDALLAAQPRSRYYTGRGLGLMYFIHHYLPGG

Bovine                        DLSPVVDAITDALLAAQPLRRYYPGHGLGLIYFIHYYLPEG

Rabbit                        DLSPVVDAITDALLAARPRPRYYPGRGLGLMYFIHYYLPEG

Sheep                         DLSPVVDAITDALLAAQPRRRYYPGHGLGLIYFIHYYLPEG

Zebrafish                     DLSPVIDTIVEALLSPQPQVRYYAGPGLILMYFICSYLPLS

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 – 405	11-beta-hydroxysteroid dehydrogenase type 2
Region	335 – 339	Essential for protein stability
Mutagenesis	335 – 335	R -> AQ. Reduced enzyme activity.
Mutagenesis	335 – 335	R -> K. No effect on enzyme activity.
Mutagenesis	336 – 336	R -> AQ. Almost complete loss of enzyme activity.
Mutagenesis	336 – 336	R -> K. Reduced enzyme activity.
Mutagenesis	337 – 337	R -> AQ. Almost complete loss of enzyme activity.
Mutagenesis	337 – 337	R -> K. Reduced enzyme activity.
Mutagenesis	338 – 338	Y -> FA. Complete loss of enzyme activity.
Mutagenesis	339 – 339	Y -> AFH. Reduced enzyme activity.

Literature citations

A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess.
Wilson R.C.; Krozowski Z.S.; Li K.; Obeyesekere V.R.; Razzaghy-Azar M.; Harbison M.D.; Wei J.-Q.; Shackleton C.H.L.; Funder J.W.; New M.I.;
J. Clin. Endocrinol. Metab. 80:2263-2266(1995)
Cited for: VARIANT AME CYS-337;

Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess.
Dave-Sharma S.; Wilson R.C.; Harbison M.D.; Newfield R.; Azar M.R.; Krozowski Z.S.; Funder J.W.; Shackleton C.H.L.; Bradlow H.L.; Wei J.-Q.; Hertecant J.; Moran A.; Neiberger R.E.; Balfe J.W.; Fattah A.; Daneman D.; Akkurt H.I.; De Santis C.; New M.I.;
J. Clin. Endocrinol. Metab. 83:2244-2254(1998)
Cited for: VARIANTS AME CYS-186; CYS-208; ASN-244; ARG-250; 250-PRO-SER-251; CYS-337 AND 337-ARG-TYR-338 DELINS HIS;

Impaired protein stability of 11beta-hydroxysteroid dehydrogenase type 2: a novel mechanism of apparent mineralocorticoid excess.
Atanasov A.G.; Ignatova I.D.; Nashev L.G.; Dick B.; Ferrari P.; Frey F.J.; Odermatt A.;
J. Am. Soc. Nephrol. 18:1262-1270(2007)
Cited for: VARIANTS AME CYS-337 AND HIS-338; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; BIOPHYSICOCHEMICAL PROPERTIES; MUTAGENESIS OF ARG-335; ARG-336; ARG-337; TYR-338 AND TYR-339;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P80365: Variant p.Arg337Cys