xeroderma pigmentosum group E

Summary

xeroderma pigmentosum group E (MONDO:0010213) is a disease caused by DDB2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: DDB2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 52

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	xeroderma pigmentosum group E
Mondo ID	MONDO:0010213
MeSH	C564732
OMIM	278740
Orphanet	276261
DOID	DOID:0110846
NCIT	C114771
SNOMED CT	56048001
UMLS	C1848411
MedGen	341219
GARD	0005627
Is cancer (heuristic)	no

Also known as: xeroderma pigmentosum group E · xeroderma pigmentosum group type E · xeroderma pigmentosum, complementation group type E · xeroderma pigmentosum, group E, DDB-negative subtype · xeroderma pigmentosum, type 5 · XP-E · XP5 · XPE

Data availability: 52 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary skin disorder › hereditary photodermatosis › xeroderma pigmentosum › xeroderma pigmentosum group E

Related subtypes (9): xeroderma pigmentosum, autosomal dominant, mild, xeroderma pigmentosum group A, xeroderma pigmentosum group C, xeroderma pigmentosum group D, xeroderma pigmentosum variant type, xeroderma pigmentosum group F, xeroderma pigmentosum group G, xeroderma pigmentosum group B, xeroderma pigmentosum, complementation group J

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

52 retrieved; paginated sample, class counts are floors:

27 uncertain significance, 9 conflicting classifications of pathogenicity, 4 benign, 4 pathogenic, 3 likely pathogenic, 3 benign/likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333388	NM_000107.3(DDB2):c.1187C>A (p.Ser396Ter)	DDB2	Pathogenic	criteria provided, single submitter
635330	NM_000107.3(DDB2):c.730_733del (p.Lys243_Lys244insTer)	DDB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8787	NM_000107.3(DDB2):c.730A>G (p.Lys244Glu)	DDB2	Pathogenic	no assertion criteria provided
8788	NM_000107.3(DDB2):c.818G>A (p.Arg273His)	DDB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8789	NM_000107.3(DDB2):c.937C>T (p.Arg313Ter)	DDB2	Pathogenic	criteria provided, single submitter
8790	NM_000107.3(DDB2):c.919G>T (p.Asp307Tyr)	DDB2	Pathogenic	no assertion criteria provided
2431840	NM_000107.3(DDB2):c.85dup (p.Glu29fs)	DDB2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3599767	NM_000107.3(DDB2):c.970dup (p.Leu324fs)	DDB2	Likely pathogenic	criteria provided, single submitter
4081306	NM_000107.3(DDB2):c.880+1G>T	DDB2	Likely pathogenic	criteria provided, single submitter
133961	NM_000107.3(DDB2):c.1228G>A (p.Ala410Thr)	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304916	NM_000107.3(DDB2):c.264+8A>G	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304918	NM_000107.3(DDB2):c.702+12G>A	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304923	NM_000107.3(DDB2):c.930C>T (p.Ser310=)	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
304925	NM_000107.3(DDB2):c.984G>A (p.Pro328=)	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
695307	NM_000107.3(DDB2):c.127+5T>G	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
771441	NM_000107.3(DDB2):c.511C>G (p.Gln171Glu)	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
777199	NM_000107.3(DDB2):c.1053T>C (p.Ile351=)	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
878228	NM_000107.3(DDB2):c.59G>A (p.Arg20Lys)	DDB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1327105	NM_000107.3(DDB2):c.52C>T (p.Arg18Cys)	DDB2	Uncertain significance	criteria provided, single submitter
1333415	NM_000107.3(DDB2):c.985C>T (p.His329Tyr)	DDB2	Uncertain significance	criteria provided, single submitter
2369982	NM_000107.3(DDB2):c.281T>G (p.Phe94Cys)	DDB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2572600	NM_000107.3(DDB2):c.1234+1del	DDB2	Uncertain significance	criteria provided, single submitter
2584821	NM_000107.3(DDB2):c.727_732del (p.Lys243_Lys244del)	DDB2	Uncertain significance	criteria provided, single submitter
304912	NM_000107.3(DDB2):c.-123T>G	DDB2	Uncertain significance	criteria provided, single submitter
304914	NM_000107.3(DDB2):c.-56A>G	DDB2	Uncertain significance	criteria provided, single submitter
304920	NM_000107.3(DDB2):c.876C>T (p.Asn292=)	DDB2	Uncertain significance	criteria provided, single submitter
304921	NM_000107.3(DDB2):c.905G>A (p.Arg302Gln)	DDB2	Uncertain significance	criteria provided, single submitter
304924	NM_000107.3(DDB2):c.979A>T (p.Ile327Phe)	DDB2	Uncertain significance	criteria provided, single submitter
304926	NM_000107.3(DDB2):c.1023+9C>T	DDB2	Uncertain significance	criteria provided, single submitter
304927	NM_000107.3(DDB2):c.1070C>T (p.Pro357Leu)	DDB2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DDB2	Definitive	Autosomal recessive	xeroderma pigmentosum group E	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DDB2	Orphanet:910	Xeroderma pigmentosum

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DDB2	HGNC:2718	ENSG00000134574	Q92466	DNA damage-binding protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DDB2	DNA damage-binding protein 2	Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DDB2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	1
skin of abdomen	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DDB2	235	ubiquitous	marker	skin of abdomen, skin of leg, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDB2	2,628

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DDB2	Q92466	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
DNA Damage Recognition in GG-NER	1	285.5×	0.008	DDB2
Dual Incision in GG-NER	1	259.6×	0.008	DDB2
Formation of Incision Complex in GG-NER	1	253.8×	0.008	DDB2
TP53 Regulates Transcription of DNA Repair Genes	1	181.3×	0.008	DDB2
Ub-specific processing proteases	1	53.1×	0.021	DDB2
Neddylation	1	47.4×	0.021	DDB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pyrimidine dimer repair	1	4213.0×	0.002	DDB2
UV-damage excision repair	1	1296.3×	0.003	DDB2
nucleotide-excision repair	1	383.0×	0.006	DDB2
response to UV	1	366.4×	0.006	DDB2
cellular response to UV	1	295.6×	0.006	DDB2
protein autoubiquitination	1	234.1×	0.006	DDB2
protein polyubiquitination	1	115.4×	0.011	DDB2
DNA repair	1	63.8×	0.018	DDB2
DNA damage response	1	53.5×	0.019	DDB2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DDB2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DDB2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DDB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.