Ataxia-telangiectasia-like disorder

Summary

Ataxia-telangiectasia-like disorder (MONDO:0011457) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 2
• ClinVar variants: 1,075
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ataxia-telangiectasia-like disorder
Mondo ID	MONDO:0011457
MeSH	C565779
OMIM	604391
ICD-11	242329289
SNOMED CT	700058006
UMLS	C1858391
MedGen	348929
GARD	0024799
Is cancer (heuristic)	no

Also known as: ataxia - telangiectasia-like disorder · ataxia-telangiectasia-like disorder 1 · ataxia-telangiectasia-like disorder type 1 · ATLD · ATLD1

Data availability: 1,075 ClinVar variants · 2 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › ataxia-telangiectasia-like disorder

Related subtypes (81): Huntington disease and related disorders, agenesis of the corpus callosum with peripheral neuropathy, striatonigral degeneration, angioid streaks of choroid, amyotrophic lateral sclerosis-parkinsonism-dementia complex, inherited Creutzfeldt-Jakob disease, mitochondrial DNA depletion syndrome 4a, cerebellar ataxia-hypogonadism syndrome, myoclonic cerebellar dyssynergia, cerebral sclerosis similar to Pelizaeus-Merzbacher disease, Chediak-Higashi syndrome, encephalopathy due to beta-mercaptolactate-cysteine disulfiduria, PEHO syndrome, deafness dystonia syndrome, Kennedy disease, fatal familial insomnia, Huntington disease-like 1, neuronal intranuclear inclusion disease, radiation sensitivity/chromosome instability syndrome, autosomal dominant, Huntington disease-like 2, microphthalmia-brain atrophy syndrome, neurodegenerative syndrome due to cerebral folate transport deficiency, hereditary sensory neuropathy-deafness-dementia syndrome, infantile cerebellar-retinal degeneration, Alzheimer disease 17, hypotonia, infantile, with psychomotor retardation and characteristic facies, Alzheimer disease 18, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, severe neurodegenerative syndrome with lipodystrophy, developmental and epileptic encephalopathy, 35, combined oxidative phosphorylation deficiency 29, neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, neuronal ceroid lipofuscinosis, frontotemporal dementia with motor neuron disease, frontotemporal dementia, GM2 gangliosidosis, attenuated Chédiak-Higashi syndrome, autosomal recessive cerebral atrophy, neurodegeneration with brain iron accumulation, fatal post-viral neurodegenerative disorder, ferro-cerebro-cutaneous syndrome, PRKAR1B-related neurodegenerative dementia with intermediate filaments, ITM2B amyloidosis, corticobasal syndrome, infantile-onset axonal motor and sensory neuropathy-optic atrophy-neurodegenerative syndrome, recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome, posterior cortical atrophy, progressive supranuclear palsy, leukodystrophy, hereditary spastic paraplegia, facial onset sensory and motor neuronopathy, X-linked neurodegenerative syndrome, Bertini type, X-linked neurodegenerative syndrome, Hamel type, boylan dew greco syndrome, hereditary motor neuron disease, neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, frontotemporal dementia and/or amyotrophic lateral sclerosis, neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities, neurodegeneration with ataxia and late-onset optic atrophy, neurodegeneration, childhood-onset, with cerebellar atrophy, neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, neurodegeneration, infantile-onset, biotin-responsive, hereditary optic atrophy, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome, familial Alzheimer disease, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, hereditary cerebellar ataxia, DCTN1-related neurodegeneration, early-childhood-onset neurodegeneration with retinitis pigmentosa, sensorineural hearing loss, and demyelinating peripheral neuropathy, TUBB4A-related neurologic disorder, neurodegeneration, childhood-onset, with progressive microcephaly, neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, neurodegeneration and seizures due to copper transport defect, neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, neurodegenerative disorder, X-linked, female-restricted, with parkinsonism and cognitive impairment, neurodegenerative disorder with cerebellar and caudate atrophy, APP-related brain and vascular amyloidosis

Subtypes (3): ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, ataxia-telangiectasia-like disorder 2, ataxia-telangiectasia-like disorder 1

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:

257 uncertain significance, 210 likely benign, 61 conflicting classifications of pathogenicity, 23 pathogenic/likely pathogenic, 15 pathogenic, 15 benign/likely benign, 10 benign, 9 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073861	NM_005591.4(MRE11):c.1280dup (p.Leu427fs)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076039	NC_000011.9:g.(?94180375)(94180614_?)del	MRE11	Pathogenic	criteria provided, single submitter
1076040	NC_000011.9:g.(?94168988)(94170411_?)del	MRE11	Pathogenic	criteria provided, single submitter
1260482	NM_005591.4(MRE11):c.1100_1131del (p.Val367fs)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140936	NM_005591.4(MRE11):c.845+2T>A	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140941	NM_005591.4(MRE11):c.1516G>T (p.Glu506Ter)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140953	NM_005591.4(MRE11):c.1090C>T (p.Arg364Ter)	MRE11	Pathogenic	criteria provided, multiple submitters, no conflicts
141533	NM_005591.4(MRE11):c.1927-2A>G	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1681442	NC_000011.9:g.(?94153291)(94225967_?)del	MRE11	Pathogenic	criteria provided, single submitter
1681551	NM_005591.4(MRE11):c.1979C>A (p.Ser660Ter)	MRE11	Pathogenic	criteria provided, single submitter
1681558	NM_005591.4(MRE11):c.1888C>T (p.Gln630Ter)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1681596	NM_005591.4(MRE11):c.1096C>T (p.Arg366Ter)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1681628	NM_005591.4(MRE11):c.422dup (p.Leu141fs)	MRE11	Pathogenic	criteria provided, single submitter
1799665	NM_005591.4(MRE11):c.1532dup (p.Asn511fs)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1800352	NM_005591.4(MRE11):c.1378G>T (p.Glu460Ter)	MRE11	Pathogenic	criteria provided, multiple submitters, no conflicts
1800442	NM_005591.4(MRE11):c.939del (p.Val313_Leu314insTer)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
184445	NM_005591.4(MRE11):c.1726C>T (p.Arg576Ter)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
184556	NM_005591.4(MRE11):c.1222dup (p.Thr408fs)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
185530	NM_005591.4(MRE11):c.504_511del (p.Leu169fs)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
187174	NM_005591.4(MRE11):c.1867+2T>C	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
187699	NM_005591.4(MRE11):c.739dup (p.His247fs)	MRE11	Pathogenic	criteria provided, multiple submitters, no conflicts
2002130	NM_005591.4(MRE11):c.-4_13A[5]TGAGTACTGCAGGCCGGTCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAATGAGTACTGCAG[1] (p.Asp5delinsGlyArgSerArgTrpLeuThrProValIleProAlaLeuTrpGluAlaGluAlaGlyGlySerArgXaaXaaXaaXaaLysLysLysLysLysLysLysLysTer)	MRE11	Pathogenic	criteria provided, single submitter
2011918	NM_005591.4(MRE11):c.1477del (p.Leu493fs)	MRE11	Pathogenic	criteria provided, single submitter
2038927	NM_005591.4(MRE11):c.1005_1006del (p.Phe335fs)	MRE11	Pathogenic	criteria provided, single submitter
2041094	NM_005591.4(MRE11):c.1920T>A (p.Tyr640Ter)	MRE11	Pathogenic	criteria provided, single submitter
216094	NM_005591.4(MRE11):c.1143del (p.Phe381fs)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216095	NM_005591.4(MRE11):c.1441del (p.Thr481fs)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
224574	NM_005591.4(MRE11):c.229G>T (p.Glu77Ter)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
230014	NM_005591.4(MRE11):c.659+1G>A	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
231449	NM_005591.4(MRE11):c.1447C>T (p.Arg483Ter)	MRE11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MRE11	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
MRE11	Orphanet:240760	Nijmegen breakage syndrome-like disorder
MRE11	Orphanet:251347	Ataxia-telangiectasia-like disorder

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MIR548L	HGNC:35292	ENSG00000221230		microRNA 548l	clinvar
MRE11	HGNC:7230	ENSG00000020922	P49959	Double-strand break repair protein MRE11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MRE11	Double-strand break repair protein MRE11	Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MIR548L	Other/Unknown	no
MRE11	Other/Unknown	no		Mre11, Calcineurin-like_PHP, Mre11_DNA-bd

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
bone marrow	1
primordial germ cell in gonad	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MIR548L	93		yes	primordial germ cell in gonad, bone marrow, calcaneal tendon
MRE11	254	ubiquitous	marker	calcaneal tendon, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MRE11	3,932
MIR548L	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MRE11	P49959	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. Enrichment computed across 2 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
Sensing of DNA Double Strand Breaks	1	1903.3×	0.007	MRE11
STING mediated induction of host immune responses	1	1038.2×	0.007	MRE11
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	951.7×	0.007	MRE11
HDR through MMEJ (alt-NHEJ)	1	878.5×	0.007	MRE11
IRF3-mediated induction of type I IFN	1	815.7×	0.007	MRE11
Diseases of DNA Double-Strand Break Repair	1	815.7×	0.007	MRE11
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	815.7×	0.007	MRE11
Resolution of D-Loop Structures	1	634.4×	0.007	MRE11
Diseases of DNA repair	1	571.0×	0.007	MRE11
DNA Double Strand Break Response	1	475.8×	0.007	MRE11
Impaired BRCA2 binding to PALB2	1	456.8×	0.007	MRE11
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.007	MRE11
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.007	MRE11
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.007	MRE11
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.007	MRE11
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.007	MRE11
Homology Directed Repair	1	308.6×	0.007	MRE11
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	308.6×	0.007	MRE11
Impaired BRCA2 binding to RAD51	1	308.6×	0.007	MRE11
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.007	MRE11
HDR through Single Strand Annealing (SSA)	1	292.8×	0.007	MRE11
Meiosis	1	285.5×	0.007	MRE11
Cytosolic sensors of pathogen-associated DNA	1	285.5×	0.007	MRE11
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.008	MRE11
DNA Double-Strand Break Repair	1	248.3×	0.008	MRE11
Reproduction	1	190.3×	0.010	MRE11
HDR through Homologous Recombination (HRR)	1	190.3×	0.010	MRE11
Nonhomologous End-Joining (NHEJ)	1	167.9×	0.010	MRE11
DNA Damage/Telomere Stress Induced Senescence	1	163.1×	0.010	MRE11
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	146.4×	0.011	MRE11

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
mitochondrial double-strand break repair via homologous recombination	1	16852.0×	0.002	MRE11
regulation of mitotic recombination	1	8426.0×	0.002	MRE11
telomeric 3’ overhang formation	1	4213.0×	0.002	MRE11
meiotic DNA double-strand break formation	1	2407.4×	0.002	MRE11
DNA strand resection involved in replication fork processing	1	2106.5×	0.002	MRE11
negative regulation of double-strand break repair via nonhomologous end joining	1	2106.5×	0.002	MRE11
R-loop processing	1	1685.2×	0.002	MRE11
DNA double-strand break processing	1	1532.0×	0.002	MRE11
homologous recombination	1	1404.3×	0.002	MRE11
mitotic intra-S DNA damage checkpoint signaling	1	936.2×	0.003	MRE11
mitotic G2/M transition checkpoint	1	802.5×	0.003	MRE11
sister chromatid cohesion	1	766.0×	0.003	MRE11
telomere maintenance via telomerase	1	732.7×	0.003	MRE11
homologous chromosome pairing at meiosis	1	601.9×	0.003	MRE11
reciprocal meiotic recombination	1	561.7×	0.003	MRE11
positive regulation of telomere maintenance	1	510.7×	0.003	MRE11
mitotic G2 DNA damage checkpoint signaling	1	443.5×	0.004	MRE11
double-strand break repair via nonhomologous end joining	1	421.3×	0.004	MRE11
positive regulation of double-strand break repair	1	343.9×	0.004	MRE11
DNA recombination	1	337.0×	0.004	MRE11
telomere maintenance	1	267.5×	0.005	MRE11
double-strand break repair	1	203.0×	0.006	MRE11
double-strand break repair via homologous recombination	1	156.0×	0.008	MRE11
cell population proliferation	1	102.8×	0.011	MRE11
DNA repair	1	63.8×	0.017	MRE11
DNA damage response	1	53.5×	0.019	MRE11
negative regulation of apoptotic process	1	34.8×	0.029	MRE11

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MIR548L	0	0
MRE11	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
MRE11	36	Binding:36

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

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	2	MIR548L, MRE11

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MIR548L	0	—
MRE11	36	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford