UniProtKB/Swiss-Prot P19447: Variant p.Phe99Ser

TFIIH basal transcription factor complex helicase XPB subunit
Gene: ERCC3
Chromosomal location: 2q21
Variant information

Variant position:  99
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Phenylalanine (F) to Serine (S) at position 99 (F99S, p.Phe99Ser).
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 (F) to small size and polar (S)
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:  Xeroderma pigmentosum complementation group B (XP-B) [MIM:610651]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-B patients present features of Cockayne syndrome, including cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex. 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 XP-B; combined with features of Cockayne syndrome; mild.
Any additional useful information about the variant.



Sequence information

Variant position:  99
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  782
The length of the canonical sequence.

Location on the sequence:   APDGHIFLEAFSPVYKYAQD  F LVAIAEPVCRPTHVHEYKLT
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                         AP-DGHIFLEAFSPVYKYAQDFLVAIAEPVCRPTHVHEYKLT

Mouse                         AP-DGHIFLEAFSPVYKYAQDFLVAIAEPVCRPTHVHEYKL

Rat                           AP-DGHIFLEAFSPVYKYAQDFLVAIAEPVCRPTHVHEYKL

Bovine                        AP-DGHIFLEAFSPVYKYAQDFLVAIAEPVCRPTHVHEYKL

Chicken                       AP-DGHIFLEAFSPVYKYAQDFLVAIAEPVCRPTHIHEYKL

Zebrafish                     AP-DGHIFLEAFSPVYKYAQDFLVAISEPVCRPTHAHEYKL

Drosophila                    AP-NGHVFLESFSPVYKHAHDFLIAISEPVCRPEHIHEYKL

Slime mold                    CP-DGHIFLETFSAIYKQASDFLVAIAEPVCRPQNIHEYQL

Fission yeast                 NPIDGRIILEAFSPLAEQAIDFLVTISEPVSRPAFIHEYRI

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 – 782 TFIIH basal transcription factor complex helicase XPB subunit


Literature citations

Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3.
Vermeulen W.; Scott R.J.; Rodgers S.; Mueller H.J.; Cole J.; Arlett C.F.; Kleijer W.J.; Bootsma D.; Hoeijmakers J.H.J.; Weeda G.;
Am. J. Hum. Genet. 54:191-200(1994)
Cited for: VARIANT XP-B SER-99;

Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome.
Oh K.-S.; Khan S.G.; Jaspers N.G.J.; Raams A.; Ueda T.; Lehmann A.; Friedmann P.S.; Emmert S.; Gratchev A.; Lachlan K.; Lucassan A.; Baker C.C.; Kraemer K.H.;
Hum. Mutat. 27:1092-1103(2006)
Cited for: VARIANT XP-B SER-99;

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.