UniProtKB/SwissProt variant VAR

Variant information

Variant position:

222

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 Proline (P) to Histidine (H) at position 222 (P222H, p.Pro222His).

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 hydrophobic (P) to medium size and polar (H)

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

Involvement in disease:

Adrenal hyperplasia 2 (AH2) [MIM:201810]: A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic). In AH2, virilization is much less marked or does not occur. AH2 is frequently lethal in early life. {ECO:0000269|PubMed:10599696, ECO:0000269|PubMed:10651755, ECO:0000269|PubMed:10843183, ECO:0000269|PubMed:12050213, ECO:0000269|PubMed:18252794, ECO:0000269|PubMed:22579964, ECO:0000269|PubMed:7608265, ECO:0000269|PubMed:7633426, ECO:0000269|PubMed:7633460, ECO:0000269|PubMed:7833923, ECO:0000269|PubMed:7893703, ECO:0000269|PubMed:7962268, ECO:0000269|PubMed:8060486, ECO:0000269|PubMed:8126127, ECO:0000269|PubMed:8185809, ECO:0000269|PubMed:8316254, ECO:0000269|PubMed:9719627}. 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 AH2; nonsalt-wasting form; activity abolished.

Any additional useful information about the variant.

Sequence information

Variant position:

222

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

Protein sequence length:

372

The length of the canonical sequence.

Location on the sequence:

NEALNNNGILSSVGKFSTVN P VYVGNVAWAHILALRALRDP

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                         NEALNNNGILSSVGKFSTVNPVYVGNVAWAHILALRALRDP

Mouse                         IMALKHKGILRSFGKFNTANPVYVGNVAWAHILAARGLRDP

Rat                           IMALKNKGVLNVTGKFSIVNPVYVGNVAWAHILAARGLRDP

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 – 372	3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
Alternative sequence	103 – 222	GTQLLLEACVQASVPVFIYTSSIEVAGPNSYKEIIQNGHEEEPLENTWPTPYPYSKKLAEKAVLAANGWNLKNGDTLYTCALRPTYIYGEGGPFLSASINEALNNNGILSSVGKFSTVNP -> ELQNKIKLTVLEGDILDEPFLKRACQDVSVVIHTACIIDVFGVTHRQSIMNVNVKGRVAWGGDKARWGNEDQKEGQEGKRSLSIEHLLCSGPSDFADHYQLGELKAAIFSFIDEKTRTEQ. In isoform 2.

Literature citations

New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene in eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes.
Moisan A.M.; Ricketts M.L.; Tardy V.; Desrochers M.; Mebarki F.; Chaussain J.-L.; Cabrol S.; Raux-Demay M.C.; Forest M.G.; Sippell W.G.; Peter M.; Morel Y.; Simard J.;
J. Clin. Endocrinol. Metab. 84:4410-4425(1999)
Cited for: VARIANTS AH2 GLU-10; VAL-10; ASP-15; THR-82; SER-100; TRP-108; ARG-129; LYS-142; LEU-155; VAL-167; ARG-173; LEU-186; PRO-205; GLY-213; GLU-216; GLN-222; HIS-222; SER-236; PRO-245; ASN-253; ASP-254; ARG-259; MET-259 AND VAL-294;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P26439: Variant p.Pro222His