CASP4

Chr 11

caspase 4

Also known as: CASP-4, ICE(rel)II, ICEREL-II, ICH-2, Mih1, Mih1/TX, TX

NCBI Gene: 837 ENSG00000196954 UniProt: P49662 OMIM: 602664

This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain and a large and small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This caspase is able to cleave and activate its own precursor protein, as well as caspase 1 precursor. When overexpressed, this gene induces cell apoptosis. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.17

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.17LOEUF

pLI 0.000

Z-score 1.01

OE 0.75 (0.49–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.97 (0.86–1.08)

201 obs / 208.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.49–1.17)

0≤0.351.4

Missense OE?0.97 (0.86–1.08)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 14 / 18.7Missense obs/exp: 201 / 208.2Syn Z: -1.32

Background carrier burden — how many people carry a rare variant somewhere in CASP4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

502 rare PASS variants

Rare truncating (LoF)

1 in 370

95 rare PASS variants

Rare synonymous (reference)

1 in 170

201 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CASP4; this gene does not show strong loss-of-function constraint by this measure. 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 130	1 in 610
South Asian	~43k	1 in 130	1 in 830
Remaining (unassigned)	~30k	1 in 92	1 in 380
European (Finnish)	~27k	1 in 580	1 in 3,600
Admixed American	~22k	1 in 79	1 in 440
African / African American	~21k	1 in 97	1 in 800
East Asian	~20k	1 in 140	1 in 790
Ashkenazi Jewish	~13k	1 in 970	1 in 2,200
Middle Eastern	~2,884	1 in 80	≈ 1 in 2,900

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): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓