xeroderma pigmentosum group C

Summary

xeroderma pigmentosum group C (MONDO:0010211) is a disease caused by XPC (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: XPC (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 308

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	xeroderma pigmentosum group C
Mondo ID	MONDO:0010211
MeSH	C567886
OMIM	278720
Orphanet	276255
DOID	DOID:0110844
NCIT	C114770
SNOMED CT	25784009
UMLS	C2752147
MedGen	416702
GARD	0005626
Is cancer (heuristic)	no

Also known as: xeroderma pigmentosum group C · xeroderma pigmentosum group type C · xeroderma pigmentosum, complementation group C · xeroderma pigmentosum, complementation group type C · xeroderma pigmentosum, group C · xeroderma pigmentosum, type 3 · XP-C · XP3 · XPC · XPCC

Data availability: 308 ClinVar variants · 6 GenCC gene-disease records · 194 cell lines.

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 C

Related subtypes (9): xeroderma pigmentosum, autosomal dominant, mild, xeroderma pigmentosum group A, xeroderma pigmentosum group D, xeroderma pigmentosum group E, 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

308 retrieved; paginated sample, class counts are floors:

92 uncertain significance, 60 likely pathogenic, 58 pathogenic, 27 conflicting classifications of pathogenicity, 25 pathogenic/likely pathogenic, 21 benign/likely benign, 20 benign, 5 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
255	Multiple alleles		Pathogenic	no assertion criteria provided
551359	NM_004628.5(XPC):c.55C>T (p.Gln19Ter)	LOC129936244	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
553460	NM_004628.5(XPC):c.103+1G>A	LOC129936244	Pathogenic	criteria provided, multiple submitters, no conflicts
554399	NM_004628.5(XPC):c.103+2T>G	LOC129936244	Pathogenic	criteria provided, single submitter
555303	NM_004628.5(XPC):c.1A>T (p.Met1Leu)	LOC129936244	Pathogenic	criteria provided, single submitter
1071266	NM_004628.5(XPC):c.2263G>T (p.Glu755Ter)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072652	NM_004628.5(XPC):c.2050_2051del (p.Leu684fs)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073314	NM_004628.5(XPC):c.1266del (p.Arg423fs)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075325	NM_004628.5(XPC):c.2544G>A (p.Trp848Ter)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342722	NM_004628.5(XPC):c.2250+1G>A	XPC	Pathogenic	criteria provided, single submitter
1438933	NM_004628.5(XPC):c.1306del (p.Ser436fs)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454617	NM_004628.5(XPC):c.2010T>A (p.Cys670Ter)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459990	NM_004628.5(XPC):c.1898del (p.Pro633fs)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1701453	NM_004628.5(XPC):c.2451_2461delinsT (p.Lys818fs)	XPC	Pathogenic	criteria provided, multiple submitters, no conflicts
190208	NM_004628.5(XPC):c.2262del (p.Asn754fs)	XPC	Pathogenic	criteria provided, single submitter
190209	NM_004628.5(XPC):c.622-2A>C	XPC	Pathogenic	criteria provided, multiple submitters, no conflicts
190211	NM_004628.5(XPC):c.1677C>A (p.Tyr559Ter)	XPC	Pathogenic	criteria provided, multiple submitters, no conflicts
190213	NM_004628.5(XPC):c.2251-1G>C	XPC	Pathogenic	criteria provided, multiple submitters, no conflicts
1947826	NM_004628.5(XPC):c.2020_2029del (p.Ala674fs)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2124748	NM_004628.5(XPC):c.2226del (p.Gln742fs)	XPC	Pathogenic	criteria provided, multiple submitters, no conflicts
2139390	NM_004628.5(XPC):c.525_526del (p.Glu177fs)	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254	NM_004628.4(XPC):c.621_622ins83 (p.?)	XPC	Pathogenic	no assertion criteria provided
256	NM_004628.5(XPC):c.1292_1293del (p.Lys431fs)	XPC	Pathogenic	criteria provided, single submitter
257	NM_004628.5(XPC):c.2033+2T>G	XPC	Pathogenic	no assertion criteria provided
258	NM_004628.5(XPC):c.566_567del (p.Tyr189fs)	XPC	Pathogenic	criteria provided, multiple submitters, no conflicts
2581102	NM_004628.5(XPC):c.218_219insT (p.Lys73fs)	XPC	Pathogenic	criteria provided, single submitter
259	NM_004628.5(XPC):c.1735C>T (p.Arg579Ter)	XPC	Pathogenic	criteria provided, multiple submitters, no conflicts
260	NM_004628.5(XPC):c.413-9T>A	XPC	Pathogenic	no assertion criteria provided
261	NM_004628.5(XPC):c.413-24A>G	XPC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
262	NM_004628.5(XPC):c.1643_1644del (p.Val548fs)	XPC	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 5 · 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
XPC	Definitive	Autosomal recessive	xeroderma pigmentosum group C	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
XPC	Orphanet:910	Xeroderma pigmentosum
ERCC2	Orphanet:1466	COFS syndrome
ERCC2	Orphanet:220295	Xeroderma pigmentosum-Cockayne syndrome complex
ERCC2	Orphanet:33364	Trichothiodystrophy
ERCC2	Orphanet:910	Xeroderma pigmentosum

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
XPC	HGNC:12816	ENSG00000154767	Q01831	DNA repair protein complementing XP-C cells	gencc,clinvar
ERCC2	HGNC:3434	ENSG00000104884	P18074	General transcription and DNA repair factor IIH helicase subunit XPD	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XPC	DNA repair protein complementing XP-C cells	Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex.
ERCC2	General transcription and DNA repair factor IIH helicase subunit XPD	ATP-dependent 5’-3’ DNA helicase.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
XPC	Other/Unknown	no		DNA_repair_Rad4, DNA_repair_Rad4-like, Rad4/PNGase_transGLS-fold
ERCC2	Enzyme (other)	yes	3.6.4.12	RAD3/XPD, DNA/RNA_helicase_DEAH_CS, Helicase-like_DEXD_c2

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
mucosa of stomach	1
sural nerve	1
left adrenal gland	1
right adrenal gland	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XPC	295	ubiquitous	marker	sural nerve, calcaneal tendon, mucosa of stomach
ERCC2	184	ubiquitous	marker	stromal cell of endometrium, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERCC2	2,746
XPC	1,916

Intra-cohort edges

A	B	Sources
ERCC2	XPC	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ERCC2	P18074	51
XPC	Q01831	18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of Incision Complex in GG-NER	2	253.8×	5e-04	XPC, ERCC2
Cytosolic iron-sulfur cluster assembly	1	380.7×	0.013	ERCC2
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	1	203.9×	0.013	ERCC2
RNA Pol II CTD phosphorylation and interaction with CE	1	203.9×	0.013	ERCC2
mRNA Capping	1	190.3×	0.013	ERCC2
Formation of the Early Elongation Complex	1	167.9×	0.013	ERCC2
Formation of the HIV-1 Early Elongation Complex	1	167.9×	0.013	ERCC2
RNA Polymerase I Transcription Termination	1	163.1×	0.013	ERCC2
DNA Damage Recognition in GG-NER	1	142.8×	0.013	XPC
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1	132.8×	0.013	ERCC2
Formation of HIV-1 elongation complex containing HIV-1 Tat	1	129.8×	0.013	ERCC2
Tat-mediated elongation of the HIV-1 transcript	1	129.8×	0.013	ERCC2
Dual Incision in GG-NER	1	129.8×	0.013	ERCC2
Formation of HIV elongation complex in the absence of HIV Tat	1	124.1×	0.013	ERCC2
HIV Transcription Initiation	1	116.5×	0.013	ERCC2
RNA Polymerase II HIV Promoter Escape	1	116.5×	0.013	ERCC2
RNA Polymerase II Promoter Escape	1	116.5×	0.013	ERCC2
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	1	116.5×	0.013	ERCC2
RNA Polymerase II Transcription Initiation	1	116.5×	0.013	ERCC2
RNA Polymerase II Transcription Initiation And Promoter Clearance	1	116.5×	0.013	ERCC2
RNA Polymerase I Transcription Initiation	1	112.0×	0.013	ERCC2
Formation of TC-NER Pre-Incision Complex	1	105.7×	0.013	ERCC2
Formation of RNA Pol II elongation complex	1	96.8×	0.013	ERCC2
RNA Polymerase II Transcription Elongation	1	96.8×	0.013	ERCC2
TP53 Regulates Transcription of DNA Repair Genes	1	90.6×	0.013	ERCC2
Gap-filling DNA repair synthesis and ligation in TC-NER	1	89.2×	0.013	ERCC2
Transcription of the HIV genome	1	86.5×	0.013	ERCC2
Dual incision in TC-NER	1	86.5×	0.013	ERCC2
SUMOylation of DNA damage response and repair proteins	1	73.2×	0.015	XPC
RNA Polymerase II Pre-transcription Events	1	68.8×	0.015	ERCC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of mitotic cell cycle phase transition	2	1685.2×	1e-05	XPC, ERCC2
nucleotide-excision repair	2	383.0×	1e-04	XPC, ERCC2
positive regulation of mitotic recombination	1	4213.0×	0.003	ERCC2
pyrimidine dimer repair by nucleotide-excision repair	1	2106.5×	0.005	XPC
central nervous system myelin formation	1	1203.7×	0.005	ERCC2
transcription elongation by RNA polymerase I	1	1053.2×	0.005	ERCC2
hair cell differentiation	1	1053.2×	0.005	ERCC2
hair follicle maturation	1	1053.2×	0.005	ERCC2
response to UV-B	1	936.2×	0.005	XPC
embryonic cleavage	1	842.6×	0.005	ERCC2
UV-damage excision repair	1	648.1×	0.005	XPC
transcription-coupled nucleotide-excision repair	1	601.9×	0.005	ERCC2
UV protection	1	601.9×	0.005	ERCC2
mitotic intra-S DNA damage checkpoint signaling	1	468.1×	0.006	XPC
erythrocyte maturation	1	421.3×	0.006	ERCC2
hematopoietic stem cell differentiation	1	383.0×	0.006	ERCC2
response to auditory stimulus	1	366.4×	0.006	XPC
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	337.0×	0.006	ERCC2
mismatch repair	1	324.1×	0.006	XPC
hematopoietic stem cell proliferation	1	324.1×	0.006	ERCC2
intrinsic apoptotic signaling pathway by p53 class mediator	1	290.6×	0.007	ERCC2
spinal cord development	1	255.3×	0.007	ERCC2
insulin-like growth factor receptor signaling pathway	1	247.8×	0.007	ERCC2
embryonic organ development	1	240.7×	0.007	ERCC2
determination of adult lifespan	1	216.1×	0.007	ERCC2
transcription initiation at RNA polymerase II promoter	1	187.2×	0.008	ERCC2
bone mineralization	1	135.9×	0.011	ERCC2
post-embryonic development	1	102.8×	0.014	ERCC2
chromosome segregation	1	86.9×	0.016	ERCC2
multicellular organism growth	1	68.5×	0.019	ERCC2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ERCC2	SUNITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERCC2	16	4
XPC	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SUNITINIB	4	ERCC2
DINACICLIB	3	ERCC2
DEFACTINIB	3	ERCC2
ALVOCIDIB	3	ERCC2
SELICICLIB	2	ERCC2
ZOTIRACICLIB	2	ERCC2
DANUSERTIB	2	ERCC2
MILCICLIB	2	ERCC2
PF-00562271	1	ERCC2
PHA-793887	1	ERCC2
KW-2449	1	ERCC2
BMS-387032	1	ERCC2
PF-03758309	1	ERCC2
TAK-901	1	ERCC2
RGB-286638	1	ERCC2
XL-228	1	ERCC2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ERCC2	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERCC2	3.6.4.12	DNA helicase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

16 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.

Compound	Max phase	Cohort target (bioactivity)
SUNITINIB	4	ERCC2
DINACICLIB	3	ERCC2
DEFACTINIB	3	ERCC2
ALVOCIDIB	3	ERCC2
SELICICLIB	2	ERCC2
ZOTIRACICLIB	2	ERCC2
DANUSERTIB	2	ERCC2
MILCICLIB	2	ERCC2
PF-00562271	1	ERCC2
PHA-793887	1	ERCC2
KW-2449	1	ERCC2
BMS-387032	1	ERCC2
PF-03758309	1	ERCC2
TAK-901	1	ERCC2
RGB-286638	1	ERCC2
XL-228	1	ERCC2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ERCC2
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	XPC

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)
XPC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.