CAT

Chr 11

catalase

NCBI Gene: 847 ENSG00000121691 UniProt: P04040 OMIM: 115500

Catalase is a key antioxidant enzyme that converts hydrogen peroxide to water and oxygen, protecting cells against oxidative damage in peroxisomes. Mutations cause acatalasemia, which follows autosomal recessive inheritance. This gene is not highly constrained against loss-of-function variants, consistent with acatalasemia typically being a mild condition.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

AcatalasemiaMIM #614097

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · acatalasia · AR · ClinGen 2025

Active trials

13959

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

Mechanism· predicted

📖

GeneReview available — CAT

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.34

OE 0.72 (0.50–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.08Z-score

OE missense 1.01 (0.92–1.11)

316 obs / 312.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.72 (0.50–1.05)

0≤0.351.4

Missense OE?1.01 (0.92–1.11)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 19 / 26.4Missense obs/exp: 316 / 312.1Syn Z: -0.35

Background carrier burden — how many people carry a rare variant somewhere in CAT?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

705 rare PASS variants

Rare truncating (LoF)

1 in 1,400

99 rare PASS variants

Rare synonymous (reference)

1 in 190

234 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CAT. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,400
South Asian	~43k	1 in 91	1 in 600
Remaining (unassigned)	~30k	1 in 90	1 in 1,300
European (Finnish)	~27k	1 in 420	none seen
Admixed American	~22k	1 in 77	1 in 1,100
African / African American	~21k	1 in 63	1 in 740
East Asian	~20k	1 in 100	1 in 1,400
Ashkenazi Jewish	~13k	1 in 310	none seen
Middle Eastern	~2,884	1 in 69	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 13 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 13.? see exons ↓