Acatalasia

Summary

Acatalasia (MONDO:0013571) is a disease caused by CAT (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: CAT (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	3.2	Europe	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0012517	Reduced catalase activity	Very frequent (80-99%)
HP:0000155	Oral ulcer	Frequent (30-79%)
HP:0000166	Severe periodontitis	Occasional (5-29%)
HP:0000225	Gingival bleeding	Occasional (5-29%)
HP:0000230	Gingivitis	Occasional (5-29%)
HP:0001935	Microcytic anemia	Occasional (5-29%)
HP:0005978	Type II diabetes mellitus	Occasional (5-29%)
HP:0040113	Old-aged sensorineural hearing impairment	Occasional (5-29%)
HP:0100758	Gangrene	Occasional (5-29%)
HP:0001045	Vitiligo	Very rare (<1-4%)
HP:0001300	Parkinsonism	Very rare (<1-4%)
HP:0002634	Arteriosclerosis	Very rare (<1-4%)
HP:0006357	Premature loss of permanent teeth	Very rare (<1-4%)
HP:0012531	Pain	Very rare (<1-4%)
HP:0100605	Neoplasm of the larynx	Very rare (<1-4%)
HP:0100651	Type I diabetes mellitus	Very rare (<1-4%)
HP:0100753	Schizophrenia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	acatalasia
Mondo ID	MONDO:0013571
EFO	EFO:0004144
MeSH	D020642
OMIM	614097
Orphanet	926
DOID	DOID:2582
NCIT	C84526
SNOMED CT	124202004
UMLS	C0268419
MedGen	75679
GARD	0000363
Is cancer (heuristic)	no

Also known as: acatalasemia · acatalasia · catalase deficiency

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › peroxisomal disease › peroxisomal single enzyme/protein defect › disorder of defective peroxisome oxidative status › acatalasia

Related subtypes (2): mulibrey nanism, Mitchell 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

5 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity, 1 uncertain significance, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
29622	NM_001752.4(CAT):c.203_204dup (p.Ile69fs)	CAT	Pathogenic	no assertion criteria provided
4845759	NM_001752.4(CAT):c.196C>T (p.Arg66Ter)	CAT	Likely pathogenic	criteria provided, single submitter
2438860	NM_001752.4(CAT):c.1056+1G>C	CAT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
773245	NM_001752.4(CAT):c.903+5G>T	CAT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1692993	NC_000011.10:g.34438684C>G	CAT	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
CAT	Strong	Autosomal recessive	acatalasia	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CAT	Orphanet:926	Acatalasemia

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
CAT	HGNC:1516	ENSG00000121691	P04040	Catalase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CAT	Catalase	Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CAT	Enzyme (other)	yes	1.11.1.6	Catalase_haem_BS, Catalase_immune_responsive, Catalase_core

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
nephron tubule	1
renal medulla	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CAT	296	ubiquitous	marker	trabecular bone tissue, nephron tubule, renal medulla

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAT	3,713

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CAT	P04040	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Mitochondrial unfolded protein response (UPRmt)	1	601.0×	0.012	CAT
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	380.7×	0.012	CAT
FOXO-mediated transcription	1	335.9×	0.012	CAT
Detoxification of Reactive Oxygen Species	1	300.5×	0.012	CAT
Protein localization	1	190.3×	0.014	CAT
Peroxisomal protein import	1	173.0×	0.014	CAT
Cellular response to chemical stress	1	142.8×	0.015	CAT
Cellular responses to stress	1	36.8×	0.051	CAT
Cellular responses to stimuli	1	31.5×	0.053	CAT
Innate Immune System	1	25.5×	0.055	CAT
Neutrophil degranulation	1	23.1×	0.055	CAT
RNA Polymerase II Transcription	1	22.5×	0.055	CAT
Gene expression (Transcription)	1	17.8×	0.065	CAT
Generic Transcription Pathway	1	15.1×	0.071	CAT
Immune System	1	13.0×	0.077	CAT

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
response to amitrole	1	16852.0×	0.001	CAT
cellular detoxification of hydrogen peroxide	1	8426.0×	0.001	CAT
response to phenylpropanoid	1	8426.0×	0.001	CAT
response to inactivity	1	5617.3×	0.001	CAT
hemoglobin metabolic process	1	4213.0×	0.001	CAT
response to L-ascorbic acid	1	4213.0×	0.001	CAT
response to ozone	1	3370.4×	0.001	CAT
response to vitamin E	1	2808.7×	0.001	CAT
response to light intensity	1	2106.5×	0.002	CAT
UV protection	1	1203.7×	0.002	CAT
response to hyperoxia	1	1123.5×	0.002	CAT
response to reactive oxygen species	1	1053.2×	0.002	CAT
response to vitamin A	1	1053.2×	0.002	CAT
response to fatty acid	1	1053.2×	0.002	CAT
response to lead ion	1	936.2×	0.002	CAT
response to cadmium ion	1	732.7×	0.003	CAT
hydrogen peroxide catabolic process	1	674.1×	0.003	CAT
response to hydrogen peroxide	1	468.1×	0.004	CAT
ureteric bud development	1	455.5×	0.004	CAT
triglyceride metabolic process	1	443.5×	0.004	CAT
positive regulation of cell division	1	337.0×	0.005	CAT
response to activity	1	324.1×	0.005	CAT
cellular response to growth factor stimulus	1	318.0×	0.005	CAT
aerobic respiration	1	247.8×	0.006	CAT
response to insulin	1	230.8×	0.006	CAT
response to estradiol	1	198.3×	0.006	CAT
cholesterol metabolic process	1	195.9×	0.006	CAT
response to ethanol	1	146.5×	0.008	CAT
osteoblast differentiation	1	121.2×	0.009	CAT
response to hypoxia	1	95.8×	0.011	CAT

Therapeutics

Drug target analysis

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

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
CAT	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	CAT
XERUBORBACTAM	1	CAT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CAT	12	Binding:11, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAT	1.11.1.6	catalase

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	CAT
XERUBORBACTAM	1	CAT

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	1	CAT
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.