Xeroderma pigmentosum, group D: genes and variants
Xeroderma pigmentosum, group D is linked to 1 analyzed protein (ERCC2). 11 DNA variants are known to cause it; 56 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: xeroderma pigmentosum group D
Genes linked to Xeroderma pigmentosum, group D
ERCC2: General transcription and DNA repair factor IIH helicase subunit XPD
Its XPD helicase activity unwinds damaged DNA during nucleotide-excision repair and also supports transcription initiation within TFIIH. Biallelic pathogenic variants cause xeroderma pigmentosum, trichothiodystrophy, or combined DNA-repair syndromes depending on the functional defect.
11 disease-causing and 56 uncertain variants in ERCC2 are linked to Xeroderma pigmentosum, group D.
Known disease-causing variants in Xeroderma pigmentosum, group D
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ERCC2 R658C | 658 | Disease-causing (★★) | |
| ERCC2 G47R | 47 | Helicase ATP-binding | Disease-causing (★★) |
| ERCC2 R616P | 616 | Mediates interaction with MMS19 | Disease-causing (★★) |
| ERCC2 R616W | 616 | Mediates interaction with MMS19 | Disease-causing (★★) |
| ERCC2 R511Q | 511 | Mediates interaction with MMS19 | Disease-causing (★★) |
| ERCC2 R112H | 112 | Helicase ATP-binding | Disease-causing (★★) |
| ERCC2 C259Y | 259 | Helicase ATP-binding | Disease-causing (★★) |
| ERCC2 T709P | 709 | Disease-causing (★★) | |
| ERCC2 R658G | 658 | Disease-causing (★) | |
| ERCC2 C663R | 663 | Disease-causing (★) | |
| ERCC2 L485P | 485 | Mediates interaction with MMS19 | Disease-causing |
Uncertain variants in Xeroderma pigmentosum, group D that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| ERCC2 R616Q | 616 | Mediates interaction with MMS19 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R616P at the same position is pathogenic; REVEL 0.911 |
Which prediction tools work for Xeroderma pigmentosum, group D
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 94 out of 100
- CADD: 93 out of 100
- phyloP: 83 out of 100
Same protein, different disease
- Cerebrooculofacioskeletal syndrome 2 is also caused by ERCC2 variants; they fall mostly in different places as the Xeroderma pigmentosum, group D variants (15 disease-causing).
- Trichothiodystrophy 1, photosensitive is also caused by ERCC2 variants; they fall mostly in different places as the Xeroderma pigmentosum, group D variants (9 disease-causing).
- Xeroderma pigmentosum is also caused by ERCC2 variants; they fall mostly in different places as the Xeroderma pigmentosum, group D variants (5 disease-causing).
Diseases related to Xeroderma pigmentosum, group D
- Ovarian cancer, also linked to ERCC2
- Xeroderma pigmentosum, also linked to ERCC2
- Cerebrooculofacioskeletal syndrome 2, also linked to ERCC2
- Trichothiodystrophy 1, photosensitive, also linked to ERCC2
Frequently asked questions
Which genes are linked to Xeroderma pigmentosum, group D?
In CATVariant, Xeroderma pigmentosum, group D is linked to 1 analyzed protein: ERCC2 (General transcription and DNA repair factor IIH helicase subunit XPD).
How many genetic variants are linked to Xeroderma pigmentosum, group D?
83 variants: 11 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 56 are of uncertain significance or have conflicting reports.
Which uncertain variants in Xeroderma pigmentosum, group D look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ERCC2 R616Q. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Xeroderma pigmentosum, group D?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.94, based on 11 disease-causing and 9 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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