UniProtKB/SwissProt variant VAR

Variant information

Variant position:

133

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 Glycine (G) to Arginine (R) at position 133 (G133R, p.Gly133Arg).

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 glycine (G) to large size and basic (R)

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

BLOSUM score:

-2

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 MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP(+)) activity; no effect on protein abundance; no effect on endoplasmic reticulum location.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs747724352 [ dbSNP | Ensembl ]

Sequence information

Variant position:

133

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

Protein sequence length:

310

The length of the canonical sequence.

Location on the sequence:

YEHIKEKLAGLEIGILVNNV G MLPNLLPSHFLNAPDEIQSL

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                         YEHIKEKLAGLEIGILVNNVGMLPNLLPSHFLNAPD---EIQSL

Mouse                         YDHIKEHLEGLEIGILVNNVGMLPSFFPSHFLSTSG---ES

Rat                           YDHIEEQLKGLEIGVLVNNVGMLPNLLPSHFLSTSG---ES

Zebrafish                     YGHITENIEGLDIGVLVNNVGILPSQIPCKLLETSDLEERI

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 – 310	17-beta-hydroxysteroid dehydrogenase type 3
Mutagenesis	133 – 133	G -> A. Has 70% of wild-type testosterone 17-beta-dehydrogenase (NADP(+)) activity.
Mutagenesis	133 – 133	G -> F. Almost complete loss of testosterone 17-beta-dehydrogenase (NADP(+)) activity.
Mutagenesis	133 – 133	G -> Q. Almost complete loss of testosterone 17-beta-dehydrogenase (NADP(+)) activity.

Literature citations

Biochemical analyses and molecular modeling explain the functional loss of 17beta-hydroxysteroid dehydrogenase 3 mutant G133R in three Tunisian patients with 46, XY Disorders of Sex Development.
Engeli R.T.; Rhouma B.B.; Sager C.P.; Tsachaki M.; Birk J.; Fakhfakh F.; Keskes L.; Belguith N.; Odermatt A.;
J. Steroid Biochem. Mol. Biol. 155:147-154(2016)
Cited for: VARIANT MPH ARG-133; CHARACTERIZATION OF VARIANT MPH ARG-133; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; MUTAGENESIS OF GLY-133;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P37058: Variant p.Gly133Arg