UniProtKB/Swiss-Prot P08686: Variant p.Ser269Thr

Steroid 21-hydroxylase
Gene: CYP21A2
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Variant information Variant position:

269 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Serine (S) to Threonine (T) at position 269 (S269T, p.Ser269Thr). 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 small size and polar (S) to medium size and polar (T) 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
Polymorphism:

Several non deleterious alleles have been described including CYP21A2*1A, CYP21A2*1B, CYP21A2*2, CYP21A2*3, CYP21A2*4, CYP21A2*5 and CYP21A2*6. Deleterious alleles are mostly generated by recombinations between CYP21A2 and the pseudogene CYP21A1P through gene conversion. This process consists of recombination events that either delete CYP21A2 or transfer deleterious mutations from CYP21A1P to CYP21A2. Additional information on the polymorphism described.
Variant description:

In allele CYP21A2*5. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs6472 [ dbSNP | Ensembl ]

Sequence information Variant position:

269 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

495 The length of the canonical sequence.
Location on the sequence:

LVAGQWRDMMDYMLQGVAQP S MEEGSGQLLEGHVHMAAVDL 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                         LVAGQWRDMMDYMLQGVAQPSMEEGSGQLLEGHVHMAAVDL

                              MVAGQWRDMTDYMLQRVGRLRAEEGCGQLLEGHVHMSVVDL

Mouse                         LVAGQWKDMIDYMLQGVEKQRDGKDEERLHEGHVHMSVVDL

Rat                           LVAGQWKDMIDYMLQGVEKQRDARDPGQLHERHVHMSVVDL

Pig                           MVAGQWRDMLDYMLQEAGRQRVEEGQGQLLEGHVHMSVVDL

Bovine                        MVAGQWRDMTDYMLQGVGRQRVEEGPGQLLEGHVHMSVVDL

Cat                           MVAGQWRDMTDYMLQGMGKPKVEKGHGRLLEGHVHMSVVDL

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 – 495	Steroid 21-hydroxylase
Mutagenesis	269 – 269	S -> CMT. No effect on progesterone 21-hydroxylase activity.
Mutagenesis	282 – 282	V -> I. Decreased 21-hydroxylase activity. Normal KM but 50% reduced Vmax.
Mutagenesis	282 – 282	V -> T. Decreased 21-hydroxylase activity. Normal KM but 10% reduced Vmax.

Literature citations
Molecular characterization of the HLA-linked steroid 21-hydroxylase B gene from an individual with congenital adrenal hyperplasia.
Rodrigues N.R.; Dunham I.; Yu C.Y.; Carroll M.C.; Porter R.R.; Campbell R.D.;
EMBO J. 6:1653-1661(1987)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT AH3 THR-269; VARIANTS LYS-103 AND ASN-494; INVOLVEMENT IN AH3; A mutation (Pro-30 to Leu) in CYP21 represents a potential nonclassic steroid 21-hydroxylase deficiency allele.
Tusie-Luna M.T.; Speiser P.W.; Dumic M.; New M.I.; White P.C.;
Mol. Endocrinol. 5:685-692(1991)
Cited for: VARIANT AH3 LEU-31; VARIANT THR-269; Molecular analysis of Japanese patients with steroid 21-hydroxylase deficiency.
Asanuma A.; Ohura T.; Ogawa E.; Sato S.; Igarashi Y.; Matsubara Y.; Iinuma K.;
J. Hum. Genet. 44:312-317(1999)
Cited for: VARIANTS AH3 LEU-31; ASN-173; LEU-282 AND TRP-357; VARIANT THR-269; Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS AH3 LEU-282 AND SER-454; VARIANT THR-269;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.