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UniProtKB/Swiss-Prot P18074: Variant p.Arg112His

General transcription and DNA repair factor IIH helicase subunit XPD
Gene: ERCC2
Variant information

Variant position:  112
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 Arginine (R) to Histidine (H) at position 112 (R112H, p.Arg112His).
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 basic (R) to medium size and polar (H)
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:  Xeroderma pigmentosum complementation group D (XP-D) [MIM:278730]: 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-D 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. {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:11709541, ECO:0000269|PubMed:15494306, ECO:0000269|PubMed:7585650, ECO:0000269|PubMed:7825573, ECO:0000269|PubMed:7849702, ECO:0000269|PubMed:9101292}. 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.

Involvement in disease:  Trichothiodystrophy 1, photosensitive (TTD1) [MIM:601675]: A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD1 patients manifest cutaneous photosensitivity. {ECO:0000269|PubMed:11242112, ECO:0000269|PubMed:7920640, ECO:0000269|PubMed:8571952, ECO:0000269|PubMed:9195225, ECO:0000269|PubMed:9238033, ECO:0000269|PubMed:9758621}. 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 TTD1 and XP-D.
Any additional useful information about the variant.

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



Sequence information

Variant position:  112
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  760
The length of the canonical sequence.

Location on the sequence:   NFYEKQEGEKLPFLGLALSS  R KNLCIHPEVTPLRFGKDVDG
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                         NFYEKQEGEKLP-FLGLALSSRKNLCIHPEVTPLRFGKDVDG

Mouse                         SFYEQQEGEKLP-FLGLALSSRKNLCIHPEVTPLRFGKDVD

Bovine                        SFYEKQEGEKLP-FLGLALSSRKNLCIHPEVTPLRFGKDVD

Slime mold                    QYRNSEMGEESPKTLCMSMSSRRNLCIQPRVSEERDGKVVD

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 – 760 General transcription and DNA repair factor IIH helicase subunit XPD
Domain 7 – 283 Helicase ATP-binding
Metal binding 116 – 116 Iron-sulfur (4Fe-4S)
Turn 112 – 114


Literature citations

Mutations in the xeroderma pigmentosum group D DNA repair/transcription gene in patients with trichothiodystrophy.
Broughton B.C.; Steingrimsdottir H.; Weber C.A.; Lehmann A.R.;
Nat. Genet. 7:189-194(1994)
Cited for: VARIANTS TTD1 HIS-112; PRO-616; TRP-722 AND 488-VAL--MET-493 DEL;

Analysis of mutations in the XPD gene in Italian patients with trichothiodystrophy: site of mutation correlates with repair deficiency, but gene dosage appears to determine clinical severity.
Botta E.; Nardo T.; Broughton B.C.; Marinoni S.; Lehmann A.R.; Stefanini M.;
Am. J. Hum. Genet. 63:1036-1048(1998)
Cited for: VARIANTS TTD1 HIS-112; TYR-259; VAL-461; THR-482 DEL; GLY-673 AND TRP-722;

Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene.
Broughton B.C.; Berneburg M.; Fawcett H.; Taylor E.M.; Arlett C.F.; Nardo T.; Stefanini M.; Menefee E.; Price V.H.; Queille S.; Sarasin A.; Bohnert E.; Krutmann J.; Davidson R.; Kraemer K.H.; Lehmann A.R.;
Hum. Mol. Genet. 10:2539-2547(2001)
Cited for: VARIANTS XP-D HIS-112; PRO-485 AND 582-GLU-LYS-583 DELINS VAL-SER-GLU; VARIANTS ASN-312 AND GLN-751;

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.