DNA repair disease

Summary

DNA repair disease (MONDO:0021190) is a disease (an umbrella term covering 16 Mondo subtypes) with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include atezolizumab, leucovorin, and tilarginine.

At a glance

• Umbrella term: 16 Mondo subtypes
• Cohort genes: 1
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	DNA repair disease
Mondo ID	MONDO:0021190
EFO	EFO:0008499
MeSH	D049914
NCIT	C7757
UMLS	C0268134
MedGen	82774
GARD	0025299
Is cancer (heuristic)	no

Also known as: chromosome instability syndrome · chromosome instability syndromes · deficiency of DNA repair · deficient DNA repair · deficient DNA Repairs · disorder of DNA repair · disorder, DNA repair-deficiency · disorders, DNA repair-deficiency · DNA repair deficiency · DNA repair deficiency disorders · DNA repair disorder · DNA repair, deficient · DNA repair-deficiencies · DNA repair-deficiency · DNA repair-deficiency disorder · DNA Repairs, deficient · repair, deficient DNA · Repairs, deficient DNA · syndrome, chromosome instability · syndromes, chromosome instability

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 16 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › DNA repair disease

Related subtypes (92): thiopurine metabolic disease, hypercalcemia, infantile, hypermanganesemia with dystonia, abdominal obesity-metabolic syndrome, plasma protein metabolism disease, inherited lipid metabolism disorder, lysosomal storage disease, striatonigral degeneration, inborn metal metabolism disorder, inborn vitamin metabolic disorder, chondrocalcinosis 2, Ehlers-Danlos syndrome, spondylodysplastic type, fish eye disease, aromatase excess syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, hypertriglyceridemia 1, autosomal dominant myoglobinuria, diastrophic dysplasia, hemolytic anemia due to diphosphoglycerate mutase deficiency, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, inherited threoninemia, inborn glycerol kinase deficiency, achondrogenesis type IB, diabetes mellitus, noninsulin-dependent, 1, diabetes mellitus, noninsulin-dependent, 2, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, diabetes mellitus, noninsulin-dependent, 3, hypercholesterolemia, familial, 4, hypoalphalipoproteinemia, primary, 1, autosomal recessive proximal renal tubular acidosis, diabetes mellitus, noninsulin-dependent, 4, normophosphatemic familial tumoral calcinosis, apolipoprotein c-III deficiency, hypotonia-failure to thrive-microcephaly syndrome, chondrodysplasia with joint dislocations, gPAPP type, gluthathione peroxidase deficiency, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diabetes mellitus, noninsulin-dependent, 5, congenital disorder of glycosylation, monogenic diabetes, 2-hydroxyglutaric aciduria, familial hypoparathyroidism, familial intrahepatic cholestasis, inborn aminoacylase deficiency, disorder of lysosomal-related organelles, inborn disorder of porphyrin metabolism, disorder of metabolite absorption and transport, autosomal dominant proximal renal tubular acidosis, neurodegeneration with brain iron accumulation, ferro-cerebro-cutaneous syndrome, familial hypocalciuric hypercalcemia, hypophosphatasia, hereditary amyloidosis, peroxisomal disease, inborn disorder of amino acid and other organic acid metabolism, inborn carbohydrate metabolic disorder, inborn disorder of energy metabolism, inborn disorder of biogenic amine metabolism and transport, inborn disorder of purine or pyrimidine metabolism, spondyloepimetaphyseal dysplasia, PAPSS2 type, hereditary lipodystrophy, hereditary recurrent myoglobinuria, 4-hydroxyphenylacetic aciduria, 5-nucleotidase syndrome, antigen-peptide-transporter 2 deficiency, APO A-i deficiency, cardiomyopathy hypogonadism metabolic anomalies, deficiency of coenzyme q cytochrome c reductase, defective apolipoprotein b-100, sulfide quinone oxidoreductase deficiency, congenital disorder of deglycosylation, hypoalphalipoproteinemia, primary, 2, uridine-cytidineuria, NAD(P)HX dehydratase deficiency, inborn disorder of aspartate family metabolism, weinstein kliman scully syndrome, glycoprotein metabolism disease, inherited thyroid metabolism disease, tumoral calcinosis, hyperphosphatemic, familial, 2, tumoral calcinosis, hyperphosphatemic, familial, 3, combined ApoA-I and ApoC-III deficiency, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, tumoral calcinosis, hyperphosphatemic, familial, 1, Waldenstrom macroglobulinemia, mucopolysaccharidosis or mucopolysaccharidosis-like disorder, disorder of peptide and amine metabolism, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis, Lane Hamilton syndrome, SQSTM1-related multisystem proteinopathy, hypertriglyceridemia 2, autosomal dominant dopa-responsive dystonia

Subtypes (16): photosensitive trichothiodystrophy, ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, COFS syndrome, Nijmegen breakage syndrome, ataxia and polyneuropathy, adult-onset, severe combined immunodeficiency due to DCLRE1C deficiency, Nijmegen breakage syndrome-like disorder, karyomegalic interstitial nephritis, ataxia-telangiectasia-like disorder 2, UV-sensitive syndrome, Cockayne syndrome, Fanconi anemia, xeroderma pigmentosum, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy, ataxia-telangiectasia-like disorder 1, mismatch repair cancer 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
UHRF1	Moderate	Autosomal recessive	DNA repair disease	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UHRF1	Orphanet:2268	ICF syndrome

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
UHRF1	HGNC:12556	ENSG00000276043	Q96T88	E3 ubiquitin-protein ligase UHRF1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UHRF1	E3 ubiquitin-protein ligase UHRF1	E3 ubiquitin-protein ligase that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UHRF1	Transcription factor	no		Ubiquitin-like_dom, Znf_RING, Znf_PHD

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
oocyte	1
secondary oocyte	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UHRF1	198	ubiquitous	marker	oocyte, secondary oocyte, thymus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UHRF1	3,009

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UHRF1	Q96T88	45

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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 methylation	1	178.4×	0.006	UHRF1
Chromatin modifications during the maternal to zygotic transition (MZT)	1	163.1×	0.006	UHRF1

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
chromosomal DNA methylation maintenance following DNA replication	1	4213.0×	0.003	UHRF1
homologous recombination	1	1404.3×	0.003	UHRF1
negative regulation of gene expression via chromosomal CpG island methylation	1	1053.2×	0.003	UHRF1
positive regulation of protein metabolic process	1	991.3×	0.003	UHRF1
regulation of epithelial cell proliferation	1	936.2×	0.003	UHRF1
protein localization to chromatin	1	581.1×	0.005	UHRF1
epigenetic regulation of gene expression	1	383.0×	0.006	UHRF1
mitotic spindle assembly	1	343.9×	0.006	UHRF1
heterochromatin formation	1	255.3×	0.007	UHRF1
protein autoubiquitination	1	234.1×	0.007	UHRF1
double-strand break repair via homologous recombination	1	156.0×	0.009	UHRF1
ubiquitin-dependent protein catabolic process	1	74.2×	0.018	UHRF1
DNA damage response	1	53.5×	0.023	UHRF1
protein ubiquitination	1	41.4×	0.028	UHRF1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	UHRF1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	UHRF1

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
UHRF1	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
UHRF1	36	Binding:36

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	UHRF1

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)
UHRF1	36	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	1
PHASE1/PHASE2	1
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02912559	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair
NCT07408583	PHASE1/PHASE2	NOT_YET_RECRUITING	Prenatal Transplantation for Fetuses With Fanconi Anemia
NCT03236935	PHASE1	COMPLETED	Phase Ib of L-NMMA and Pembrolizumab
NCT05484570	Not specified	RECRUITING	Natural History Study for DNA Repair Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ATEZOLIZUMAB	4	1
LEUCOVORIN	4	1
TILARGININE	3	1
CHEMBL5412235	0	1