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UniProtKB/Swiss-Prot Q9UBM7: Variant p.Trp248Cys

7-dehydrocholesterol reductase
Gene: DHCR7
Chromosomal location: 11q13.2-q13.5
Variant information

Variant position:  248
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 Tryptophan (W) to Cysteine (C) at position 248 (W248C, p.Trp248Cys).
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 aromatic (W) to medium size and polar (C)
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:  Smith-Lemli-Opitz syndrome (SLOS) [MIM:270400]: An autosomal recessive frequent inborn disorder of sterol metabolism with characteristic congenital malformations and mental retardation. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and low serum cholesterol levels. SLOS occurs in relatively high frequency: approximately 1 in 20,000 to 30,000 births in populations of northern and central European background. Historically, a clinical distinction often was made between classic ('type I') SLOS and the more severely affected ('type II') patients. There is, in reality, a clinical and biochemical continuum from mild to severe SLOS. {ECO:0000269|PubMed:10677299, ECO:0000269|PubMed:10995508, ECO:0000269|PubMed:11175299, ECO:0000269|PubMed:11427181, ECO:0000269|PubMed:12949967, ECO:0000269|PubMed:15954111, ECO:0000269|PubMed:9653161, ECO:0000269|PubMed:9683613}. 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 SLOS.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  248
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  475
The length of the canonical sequence.

Location on the sequence:   RIGKWFDFKLFFNGRPGIVA  W TLINLSFAAKQRELHSHVTN
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                         RIGKWFDFKLFFNGRPGIVAWTLINLSFAAKQRELHSHVTN

Mouse                         RIGKWFDFKLFFNGRPGIVAWTLINLSFAAKQQELYGHVTN

Rat                           RIGKWFDFKLFFNGRPGIVAWTLINLSFAAKQQELYGHVTN

Bovine                        RIGKWFDFKLFFNGRPGIVAWTLINLSFAAKQQELYGHVTN

Xenopus laevis                RIGKWFDFKLFFNGRPGIVAWTLINLSYAAKQQELYGQVTN

Xenopus tropicalis            RIGKWFDFKLFFNGRPGIVAWTLINLSYAAKQQELYGQVTN

Zebrafish                     RIGKWFDFKLFFNGRPGIVAWTLINLSYAAKQQELYGYVTN

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.

TypePositionsDescription
Chain 1 – 475 7-dehydrocholesterol reductase


Literature citations

Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene.
Waterham H.R.; Wijburg F.A.; Hennekam R.C.M.; Vreken P.; Poll-The B.T.; Dorland L.; Duran M.; Jira P.E.; Smeitink J.A.M.; Wevers R.A.; Wanders R.J.A.;
Am. J. Hum. Genet. 63:329-338(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS SLOS LEU-119; ARG-244 AND CYS-248;

Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith-Lemli-Opitz syndrome.
Jira P.E.; Wanders R.J.A.; Smeitink J.A.M.; De Jong J.; Wevers R.A.; Oostheim W.; Tuerlings J.H.A.M.; Hennekam R.C.M.; Sengers R.C.A.; Waterham H.R.;
Ann. Hum. Genet. 65:229-236(2001)
Cited for: VARIANTS SLOS MET-93; PRO-109; LEU-119; MET-154; LEU-182; TYR-183; GLU-198; HIS-242; ARG-244; CYS-248 AND LEU-255;

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.