Fanconi anemia complementation group Q

disease

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Also known as ERCC4 Fanconi anaemiaERCC4 Fanconi anemiaFanconi anaemia caused by mutation in ERCC4Fanconi anaemia complementation group type QFanconi anemia caused by mutation in ERCC4Fanconi anemia complementation group type QFanconi anemia, complementation group QFanconi Anemia, complementation group type QFANCQ

Summary

Fanconi anemia complementation group Q (MONDO:0014108) is a disease caused by ERCC4 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: ERCC4 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 744

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group Q
Mondo ID	MONDO:0014108
OMIM	615272
DOID	DOID:0111093
UMLS	C3808988
MedGen	815318
GARD	0015934
Is cancer (heuristic)	no

Also known as: ERCC4 Fanconi anaemia · ERCC4 Fanconi anemia · Fanconi anaemia caused by mutation in ERCC4 · Fanconi anaemia complementation group type Q · Fanconi anemia caused by mutation in ERCC4 · Fanconi anemia complementation group type Q · Fanconi anemia, complementation group Q · Fanconi Anemia, complementation group type Q · FANCQ

Data availability: 744 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › congenital anemia › Fanconi anemia › Fanconi anemia complementation group Q

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

600 retrieved; paginated sample, class counts are floors:

299 uncertain significance, 208 likely benign, 34 conflicting classifications of pathogenicity, 18 pathogenic, 12 benign, 10 likely pathogenic, 10 benign/likely benign, 9 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1075759	NM_005236.3(ERCC4):c.22C>T (p.Arg8Ter)	ERCC4	Pathogenic	criteria provided, single submitter
1324343	NM_005236.3(ERCC4):c.1197_1198insCA (p.Ala400fs)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1338473	NM_005236.3(ERCC4):c.579G>A (p.Trp193Ter)	ERCC4	Pathogenic	criteria provided, multiple submitters, no conflicts
1400031	NM_005236.3(ERCC4):c.557_558del (p.Phe186fs)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1422307	NM_005236.3(ERCC4):c.1251T>A (p.Cys417Ter)	ERCC4	Pathogenic	criteria provided, single submitter
1452810	NM_005236.3(ERCC4):c.58C>T (p.Arg20Ter)	ERCC4	Pathogenic	criteria provided, single submitter
2048716	NM_005236.3(ERCC4):c.1447_1450del (p.Arg483fs)	ERCC4	Pathogenic	criteria provided, single submitter
2151562	NM_005236.3(ERCC4):c.68del (p.Val23fs)	ERCC4	Pathogenic	criteria provided, single submitter
2181510	NM_005236.3(ERCC4):c.872T>A (p.Leu291Ter)	ERCC4	Pathogenic	criteria provided, single submitter
2425327	NC_000016.9:g.(?14038570)(14038702_?)del	ERCC4	Pathogenic	criteria provided, single submitter
2425329	NC_000016.9:g.(?14020398)(14022112_?)del	ERCC4	Pathogenic	criteria provided, single submitter
288748	NM_005236.3(ERCC4):c.915del (p.Asn308fs)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2923026	NM_005236.3(ERCC4):c.663dup (p.Met222fs)	ERCC4	Pathogenic	criteria provided, single submitter
2927079	NM_005236.3(ERCC4):c.856C>T (p.Gln286Ter)	ERCC4	Pathogenic	criteria provided, single submitter
2928951	NM_005236.3(ERCC4):c.1376C>A (p.Ser459Ter)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2931256	NM_005236.3(ERCC4):c.938dup (p.Arg314fs)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2931654	NM_005236.3(ERCC4):c.886C>T (p.Gln296Ter)	ERCC4	Pathogenic	criteria provided, single submitter
2931871	NM_005236.3(ERCC4):c.849_856del (p.Leu284fs)	ERCC4	Pathogenic	criteria provided, single submitter
2932701	NM_005236.3(ERCC4):c.148C>T (p.Gln50Ter)	ERCC4	Pathogenic	criteria provided, single submitter
2952742	NM_005236.3(ERCC4):c.1402del (p.Arg468fs)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3243523	NC_000016.9:g.(?14028029)(14031735_?)del	ERCC4	Pathogenic	criteria provided, single submitter
3578438	NM_005236.3(ERCC4):c.1349G>A (p.Trp450Ter)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3602651	NM_005236.3(ERCC4):c.1417dup (p.Gln473fs)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3748773	NM_005236.3(ERCC4):c.891T>G (p.Tyr297Ter)	ERCC4	Pathogenic	criteria provided, single submitter
4783059	NM_005236.3(ERCC4):c.2314C>T (p.Arg772Ter)	ERCC4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4783221	NM_005236.3(ERCC4):c.2074C>T (p.Arg692Ter)	ERCC4	Pathogenic	criteria provided, single submitter
4788501	NM_005236.3(ERCC4):c.2241dup (p.Met748fs)	ERCC4	Pathogenic	criteria provided, single submitter
1066740	NM_005236.3(ERCC4):c.1102+1G>T	ERCC4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1192511	NM_005236.3(ERCC4):c.616C>T (p.Gln206Ter)	ERCC4	Likely pathogenic	criteria provided, single submitter
135534	NM_005236.3(ERCC4):c.2017+1G>A	ERCC4	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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
ERCC4	Strong	Autosomal recessive	Fanconi anemia complementation group Q	11

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	gencc,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

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.

Cohort genes: ERCC4