xeroderma pigmentosum, type F/Cockayne syndrome

Summary

xeroderma pigmentosum, type F/Cockayne syndrome (MONDO:0800313) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	xeroderma pigmentosum, type F/Cockayne syndrome
Mondo ID	MONDO:0800313
UMLS	C3806565
MedGen	812895
GARD	0026496
Is cancer (heuristic)	no

Also known as: XPF/CS

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › xeroderma pigmentosum-Cockayne syndrome complex › xeroderma pigmentosum, type F/Cockayne syndrome

Related subtypes (5): xeroderma pigmentosum group D, xeroderma pigmentosum group F, xeroderma pigmentosum group G, xeroderma pigmentosum group B, xeroderma pigmentosum, type G/Cockayne syndrome

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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
55827	NM_005236.3(ERCC4):c.706T>C (p.Cys236Arg)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
55828	NM_005236.3(ERCC4):c.1730dup (p.Tyr577Ter)	ERCC4	Pathogenic	criteria provided, multiple submitters, no conflicts
55829	NM_005236.3(ERCC4):c.1765C>T (p.Arg589Trp)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ERCC4	Orphanet:220295	Xeroderma pigmentosum-Cockayne syndrome complex
ERCC4	Orphanet:84	Fanconi anemia
ERCC4	Orphanet:90321	Cockayne syndrome type 1
ERCC4	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
ERCC4	HGNC:3436	ENSG00000175595	Q92889	DNA repair endonuclease XPF	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ERCC4	DNA repair endonuclease XPF	Catalytic component of a structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair, and which is essential for nucleotide excision repair (NER) and interstrand cross-link (ICL) repair.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ERCC4	Other/Unknown	no		ERCC4_domain, XPF, RuvA_2-like

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
adrenal tissue	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ERCC4	242	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERCC4	2,102

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ERCC4	Q92889	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
HDR through Single Strand Annealing (SSA)	1	292.8×	0.005	ERCC4
Fanconi Anemia Pathway	1	278.5×	0.005	ERCC4
Dual Incision in GG-NER	1	259.6×	0.005	ERCC4
Formation of Incision Complex in GG-NER	1	253.8×	0.005	ERCC4
Dual incision in TC-NER	1	173.0×	0.006	ERCC4

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
nucleotide-excision repair involved in interstrand cross-link repair	1	5617.3×	0.001	ERCC4
telomeric DNA-containing double minutes formation	1	4213.0×	0.001	ERCC4
negative regulation of protection from non-homologous end joining at telomere	1	4213.0×	0.001	ERCC4
negative regulation of telomere maintenance	1	2808.7×	0.001	ERCC4
negative regulation of telomere maintenance via telomere lengthening	1	1404.3×	0.002	ERCC4
UV protection	1	1203.7×	0.002	ERCC4
resolution of meiotic recombination intermediates	1	936.2×	0.002	ERCC4
double-strand break repair via nonhomologous end joining	1	421.3×	0.004	ERCC4
nucleotide-excision repair	1	383.0×	0.004	ERCC4
response to UV	1	366.4×	0.004	ERCC4
cellular response to UV	1	295.6×	0.005	ERCC4
telomere maintenance	1	267.5×	0.005	ERCC4
regulation of autophagy	1	240.7×	0.005	ERCC4
double-strand break repair via homologous recombination	1	156.0×	0.007	ERCC4
DNA repair	1	63.8×	0.016	ERCC4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERCC4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ERCC4	28	Binding:28

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	ERCC4

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)
ERCC4	28	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.