UniProtKB/Swiss-Prot P07992: Variant p.Phe231Leu

DNA excision repair protein ERCC-1
Gene: ERCC1
Chromosomal location: 19q13.2-q13.3
Variant information

Variant position:  231
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 Leucine (L) at position 231 (F231L, p.Phe231Leu).
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 medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Cerebro-oculo-facio-skeletal syndrome 4 (COFS4) [MIM:610758]: A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome. 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 COFS4; does not alter interaction with XPF/ERCC4 or GTF2H1.
Any additional useful information about the variant.



Sequence information

Variant position:  231
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  297
The length of the canonical sequence.

Location on the sequence:   TYKAYEQKPADLLMEKLEQD  F VSRVTECLTTVKSVNKTDSQ
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                         TYKAYEQKPADLLMEK---LEQDFVSRVTECLTTVKSVNKTDSQ

Mouse                         TYKAYEQKPADLLMEK---LEQNFLSRATECLTTVKSVNKT

Bovine                        TYKAYEQKPADLLMEK---LEQDFVSRVTECLTTVKSVNKT

Slime mold                    AYKTFNNRAPDPIKARAQPIELGGKSKNEQVLTSIKSVNKT

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 – 297 DNA excision repair protein ERCC-1
Region 220 – 297 HhH2, dimerization with ERCC4


Literature citations

First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure.
Jaspers N.G.J.; Raams A.; Silengo M.C.; Wijgers N.; Niedernhofer L.J.; Robinson A.R.; Giglia-Mari G.; Hoogstraten D.; Kleijer W.J.; Hoeijmakers J.H.J.; Vermeulen W.;
Am. J. Hum. Genet. 80:457-466(2007)
Cited for: VARIANT COFS4 LEU-231;

Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia.
Kashiyama K.; Nakazawa Y.; Pilz D.T.; Guo C.; Shimada M.; Sasaki K.; Fawcett H.; Wing J.F.; Lewin S.O.; Carr L.; Li T.S.; Yoshiura K.; Utani A.; Hirano A.; Yamashita S.; Greenblatt D.; Nardo T.; Stefanini M.; McGibbon D.; Sarkany R.; Fassihi H.; Takahashi Y.; Nagayama Y.; Mitsutake N.; Lehmann A.R.; Ogi T.;
Am. J. Hum. Genet. 92:807-819(2013)
Cited for: VARIANT COFS4 LEU-231; CHARACTERIZATION OF VARIANT COFS4 LEU-231;

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.