Cerebrooculofacioskeletal syndrome 2: genes and variants
Cerebrooculofacioskeletal syndrome 2 is linked to 2 analyzed proteins (ERCC2 and ERCC5). 16 DNA variants are known to cause it; 58 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Cerebrooculofacioskeletal syndrome 3
Genes linked to Cerebrooculofacioskeletal syndrome 2
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.
15 disease-causing and 28 uncertain variants in ERCC2 are linked to Cerebrooculofacioskeletal syndrome 2.
ERCC5: DNA excision repair protein ERCC-5
It makes one of the two strand incisions required to remove bulky DNA lesions during nucleotide-excision repair and also supports repair-associated transcriptional responses. Biallelic pathogenic variants can cause xeroderma pigmentosum group G, Cockayne syndrome, or combined phenotypes.
1 disease-causing and 30 uncertain variants in ERCC5 are linked to Cerebrooculofacioskeletal syndrome 2.
Known disease-causing variants in Cerebrooculofacioskeletal syndrome 2
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ERCC2 R658H | 658 | Disease-causing (★★) | |
| ERCC2 R658C | 658 | Disease-causing (★★) | |
| ERCC2 G47R | 47 | Helicase ATP-binding | Disease-causing (★★) |
| ERCC2 S541R | 541 | Mediates interaction with MMS19 | Disease-causing (★★) |
| ERCC2 A725P | 725 | Disease-causing (★★) | |
| ERCC2 A725T | 725 | Disease-causing (★★) | |
| ERCC2 R511Q | 511 | Mediates interaction with MMS19 | Disease-causing (★★) |
| ERCC2 G675R | 675 | Disease-causing (★★) | |
| ERCC2 R112H | 112 | Helicase ATP-binding | Disease-causing (★★) |
| ERCC2 C259Y | 259 | Helicase ATP-binding | Disease-causing (★★) |
| ERCC2 R601L | 601 | Mediates interaction with MMS19 | Disease-causing (★★) |
| ERCC2 R616W | 616 | Mediates interaction with MMS19 | Disease-causing (★★) |
| ERCC2 R666W | 666 | Disease-causing (★★) | |
| ERCC2 T709P | 709 | Disease-causing (★★) | |
| ERCC5 A792V | 792 | I-domain | Disease-causing (★★) |
| ERCC2 C663R | 663 | Disease-causing (★) |
Which prediction tools work for Cerebrooculofacioskeletal syndrome 2
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 95 out of 100
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 90 out of 100
- SIFT: 90 out of 100
Same protein, different disease
- Xeroderma pigmentosum, group D is also caused by ERCC2 variants; they fall partly in the same places as the Cerebrooculofacioskeletal syndrome 2 variants (11 disease-causing).
- Xeroderma pigmentosum, group G is also caused by ERCC5 variants; they fall mostly in different places as the Cerebrooculofacioskeletal syndrome 2 variants (4 disease-causing).
- Xeroderma pigmentosum is also caused by ERCC5 variants; they fall mostly in different places as the Cerebrooculofacioskeletal syndrome 2 variants (4 disease-causing).
Diseases related to Cerebrooculofacioskeletal syndrome 2
- Ovarian cancer, also linked to ERCC2 and ERCC5
- Xeroderma pigmentosum, also linked to ERCC2 and ERCC5
- Xeroderma pigmentosum, group D, also linked to ERCC2
- Trichothiodystrophy 1, photosensitive, also linked to ERCC2
- Xeroderma pigmentosum, group G, also linked to ERCC5
Frequently asked questions
Which genes are linked to Cerebrooculofacioskeletal syndrome 2?
In CATVariant, Cerebrooculofacioskeletal syndrome 2 is linked to 2 analyzed proteins: ERCC2 (General transcription and DNA repair factor IIH helicase subunit XPD) and ERCC5 (DNA excision repair protein ERCC-5).
How many genetic variants are linked to Cerebrooculofacioskeletal syndrome 2?
109 variants: 16 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 58 are of uncertain significance or have conflicting reports.
Which uncertain variants in Cerebrooculofacioskeletal syndrome 2 look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Cerebrooculofacioskeletal syndrome 2?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.95, based on 15 disease-causing and 30 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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