Fanconi anemia complementation group U

Summary

Fanconi anemia complementation group U (MONDO:0014987) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group U
Mondo ID	MONDO:0014987
OMIM	617247
DOID	DOID:0111085
UMLS	C4310651
MedGen	934618
GARD	0016215
Is cancer (heuristic)	no

Also known as: Fanconi anaemia caused by mutation in XRCC2 · Fanconi anaemia complementation group type U · Fanconi anemia caused by mutation in XRCC2 · Fanconi anemia complementation group type U · Fanconi Anemia, complementation group type U · Fanconi Anemia, complementation group U · FANCU · XRCC2 Fanconi anaemia · XRCC2 Fanconi anemia

Data availability: 35 ClinVar variants · 4 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 U

Related subtypes (21): Fanconi anemia complementation group C, Fanconi anemia complementation group D2, Fanconi anemia complementation group A, Fanconi anemia complementation group B, Fanconi anemia complementation group E, Fanconi anemia complementation group F, Fanconi anemia complementation group D1, Fanconi anemia complementation group I, Fanconi anemia complementation group J, Fanconi anemia complementation group N, Fanconi anemia complementation group O, Fanconi anemia complementation group P, Fanconi anemia complementation group G, Fanconi anemia complementation group L, Fanconi anemia complementation group Q, Fanconi anemia complementation group T, Fanconi anemia complementation group V, Fanconi anemia complementation group R, Fanconi anemia, complementation group W, Fanconi anemia, complementation group S, fanconi anemia, complementation group 10

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

35 retrieved; paginated sample, class counts are floors:

14 conflicting classifications of pathogenicity, 14 uncertain significance, 4 benign/likely benign, 2 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4845630	NM_005431.2(XRCC2):c.678T>A (p.Tyr226Ter)	XRCC2	Likely pathogenic	criteria provided, single submitter
127954	NM_005431.2(XRCC2):c.283A>G (p.Ile95Val)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127960	NM_005431.2(XRCC2):c.620A>G (p.Glu207Gly)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127963	NM_005431.2(XRCC2):c.773G>A (p.Arg258His)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
182996	NM_005431.2(XRCC2):c.596T>C (p.Met199Thr)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
182997	NM_005431.2(XRCC2):c.613T>G (p.Ser205Ala)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
245958	NM_005431.2(XRCC2):c.181C>A (p.Leu61Ile)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
246108	NM_005431.2(XRCC2):c.644G>A (p.Arg215Gln)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30063	NM_005431.2(XRCC2):c.643C>T (p.Arg215Ter)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
409968	NM_005431.2(XRCC2):c.662T>C (p.Ile221Thr)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420029	NM_005431.2(XRCC2):c.651_652del (p.Cys217_Asp218delinsTer)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420244	NM_005431.2(XRCC2):c.350dup (p.Leu117fs)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420463	NM_005431.2(XRCC2):c.378_381del (p.Leu126fs)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
486729	NM_005431.2(XRCC2):c.190C>T (p.Arg64Ter)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
584725	NM_005431.2(XRCC2):c.581C>T (p.Thr194Met)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127962	NM_005431.2(XRCC2):c.667T>C (p.Tyr223His)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
182994	NM_005431.2(XRCC2):c.271C>T (p.Arg91Trp)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
240162	NM_005431.2(XRCC2):c.608C>T (p.Ser203Leu)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
240163	NM_005431.2(XRCC2):c.714G>C (p.Arg238Ser)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431667	NM_005431.2(XRCC2):c.756_758del (p.Gln252_Phe253delinsHis)	XRCC2	Uncertain significance	criteria provided, single submitter
3594438	NM_005431.2(XRCC2):c.563G>T (p.Arg188Leu)	XRCC2	Uncertain significance	criteria provided, single submitter
409962	NM_005431.2(XRCC2):c.97G>C (p.Ala33Pro)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
486726	NM_005431.2(XRCC2):c.272G>A (p.Arg91Gln)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
486728	NM_005431.2(XRCC2):c.659A>T (p.Asp220Val)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
584722	NM_005431.2(XRCC2):c.794T>C (p.Leu265Ser)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
584723	NM_005431.2(XRCC2):c.698A>T (p.Gln233Leu)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
584727	NM_005431.2(XRCC2):c.229G>C (p.Glu77Gln)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
824871	NM_005431.2(XRCC2):c.440T>A (p.Ile147Asn)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
827540	NM_005431.2(XRCC2):c.825T>G (p.Ser275Arg)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
127965	NM_005431.2(XRCC2):c.808T>G (p.Phe270Val)	XRCC2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · 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
XRCC2	Moderate	Autosomal recessive	Fanconi anemia complementation group U	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
XRCC2	Orphanet:227535	Hereditary breast cancer
XRCC2	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
XRCC2	Orphanet:84	Fanconi anemia

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
XRCC2	HGNC:12829	ENSG00000196584	O43543	DNA repair protein XRCC2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XRCC2	DNA repair protein XRCC2	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions.

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)
XRCC2	Other/Unknown	no		Rad51_C, RecA_ATP-bd, P-loop_NTPase

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
buccal mucosa cell	1
lateral globus pallidus	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XRCC2	283	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
XRCC2	1,314

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XRCC2	O43543	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Impaired BRCA2 binding to PALB2	1	456.8×	0.004	XRCC2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.004	XRCC2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.004	XRCC2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.004	XRCC2
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.004	XRCC2
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.004	XRCC2
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.004	XRCC2
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.004	XRCC2
HDR through Homologous Recombination (HRR)	1	190.3×	0.005	XRCC2

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
regulation of fibroblast apoptotic process	1	5617.3×	0.002	XRCC2
DNA strand invasion	1	4213.0×	0.002	XRCC2
response to X-ray	1	887.0×	0.005	XRCC2
response to gamma radiation	1	581.1×	0.005	XRCC2
positive regulation of neurogenesis	1	581.1×	0.005	XRCC2
somitogenesis	1	374.5×	0.006	XRCC2
centrosome cycle	1	337.0×	0.006	XRCC2
meiotic cell cycle	1	244.2×	0.008	XRCC2
neurogenesis	1	208.1×	0.008	XRCC2
double-strand break repair via homologous recombination	1	156.0×	0.009	XRCC2
multicellular organism growth	1	137.0×	0.009	XRCC2
mitotic cell cycle	1	133.8×	0.009	XRCC2
negative regulation of neuron apoptotic process	1	110.9×	0.010	XRCC2
in utero embryonic development	1	72.0×	0.015	XRCC2
DNA repair	1	63.8×	0.016	XRCC2

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
XRCC2	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	XRCC2

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)
XRCC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.