CAT

protein-coding

catalase

Gene summary

This gene encodes catalase, a key antioxidant enzyme in the bodies defense against oxidative stress. Catalase is a heme enzyme that is present in the peroxisome of nearly all aerobic cells. Catalase converts the reactive oxygen species hydrogen peroxide to water and oxygen and thereby mitigates the toxic effects of hydrogen peroxide. Oxidative stress is hypothesized to play a role in the development of many chronic or late-onset diseases such as diabetes, asthma, Alzheimer's disease, systemic lupus erythematosus, rheumatoid arthritis, and cancers. Polymorphisms in this gene have been associated with decreases in catalase activity but, to date, acatalasemia is the only disease known to be caused by this gene. [provided by RefSeq, Oct 2009]

MANE transcript

NM_001752.4

Inheritance

ClinVar variants

P:5U:42B:23

Top phenotype

Acatalasemia

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr11:34,438,934-34,472,060

External References & Databases

Ensembl (ENSG00000121691)

Transcript & Mutation Effects

hg38 • Region Span ~33.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

acatalasiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013571

Submitter: Labcorp Genetics (formerly Invitae)

acatalasiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013571

Submitter: ClinGen

The relationship between CAT and Acatalasemia (also known as acatalasia), an autosomal recessive disorder, was evaluated using the ClinGen Clinical Validity Framework as of October, 2019 and reevaluated in September, 2022. No new evidence was has emerged that changes the overall score or classification of the curation. CAT encodes catalase, a peroxisomal antioxidant enzyme present in all aerobic cells. Acatalasemia is associated with absent or reduced catalase activity; however, patients exhibit no significant phenotypes. Since oxidative stress may have a role in the development of many chronic illnesses, acatalasemia is reported to be a risk factor for many diseases including type II diabetes mellitus, schizophrenia, cancer, arithritis and microcytic anemia. This curation considers acatalasemia as the disease entity, with the phenotype being reduced levels of catalase activity. CAT was first reported in relation to autosomal recessive Acatalasemia in 1990 (Wen et al, PMID: 2308162). Variants in this gene include missense, splice region and frameshift variants. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Summary of Case Level Data (5.5 points): At least 3 patients from 3 publications have been reported with homozygous variants in CAT (PMIDs: 2308162, 11001624). Several individuals carrying the same variants in the Japanese and Hungarian populations are reported, which may be due to a founder effect. The mechanism of disease is expected to be homozygous loss of function. Heterozygous individuals show intermediate levels of catalase activity. Summary of experimental data (3 points): This gene-disease association is supported by mouse and fly models (PMID: 15178682, 8349109). In summary, the evidence to support the gene-disease relationship of CAT and Acatalasemia is moderate. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was originally approved by the ClinGen Peroxisomal GCEP on Oct 20, 2022. This gene-disease relationship was re-evaluated on February 7, 2025, and as a result of this re-evaluation, the classification did not change.

acatalasiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013571

Submitter: Orphanet

Clinical Genomic Database (CGD)

AcatalasemiaAR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious; Pharmacogenomic

Rationale: Individuals may be prone to manifestations such as oral ulcers and gangrene, and prompt treatment of infections may be beneficial; Pharmacogenomically, variants may be related to adverse reactions with treatment with medications such as uric acid oxidase

Refs: 12991731; 13904105; 2308162; 1999334; 1591863; 1551654; 8673475; 11117918; 11001624; 11197178; 11603354; 11500062; 15771551; 15800961; 17729111

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CAT variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 28

CAT-related disorderTotal: 7

AcatalasiaTotal: 6

Acatalasemia, japanese typeTotal: 2

Intellectual disabilityTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001752.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	11 clinvar	3 clinvar	17
missense			36 clinvar	8 clinvar	1 clinvar	45
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)		2 clinvar	2 clinvar			4
Total	2	3	42	19	4	70

Highest pathogenic variant AF is 0.000030356385

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001752.4	RefSeq	NP_001743.1	13	MANE Select
ENST00000241052.5	Ensembl	ENSP00000241052.4	13	MANE Select
ENST00000650153.1	Ensembl	ENSP00000497751.1	2	Standard
ENST00000856101.1	Ensembl	ENSP00000526160.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tryptophan metabolism - Homo sapiens (human)
Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
Longevity regulating pathway - multiple species - Homo sapiens (human)
Peroxisome - Homo sapiens (human)
Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)

Biological Process

response to reactive oxygen species
osteoblast differentiation
ureteric bud development
response to hypoxia
protein targeting to peroxisome

Molecular Function

aminoacylase activity
catalase activity
signaling receptor binding
antioxidant activity
oxidoreductase activity, acting on peroxide as acceptor

Cellular Component

extracellular region
mitochondrial intermembrane space
lysosome
peroxisome
peroxisomal membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000241052
Coding exons: 13
Length: 33138
Individuals with no LoFs: 125671
Homozygous LoFs: 0
Heterozygous LoFs: 77
Defined: 125748
p: 0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0780	316	312	1.01	0.0000188	3515
Missense (PolyPhen)		151	154.42	0.97784		1785
Synonymous	-0.346	112	107	1.04	0.00000624	982
Loss of Function	1.34	19	26.4	0.719	0.00000130	301

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00086	0.00086	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00014	rare
South Asian	0.00088	0.00085	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide. Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells. {ECO:0000269|PubMed:7882369}.;
Disease: DISEASE: Acatalasemia (ACATLAS) [MIM:614097]: A metabolic disorder characterized by a total or near total loss of catalase activity in red cells. It is often associated with ulcerating oral lesions. Acatalasemia is inherited as an autosomal recessive trait. {ECO:0000269|PubMed:2308162}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.950

Intolerance Scores

LoFtool: 0.221
RVIS EVS: -0.31
RVIS percentile EVS: 32.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium