CARD18

Chr 11

caspase recruitment domain family member 18

Also known as: ICEBERG, UNQ5804, pseudo-ICE

NCBI Gene: 59082 ENSG00000255501 UniProt: P57730 OMIM: 605354

Enables CARD domain binding activity and caspase binding activity. Involved in negative regulation of interleukin-1 beta production. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.85

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.85LOEUF

pLI 0.001

Z-score -0.09

OE 1.05 (0.50–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.52Z-score

OE missense 1.21 (0.98–1.51)

57 obs / 46.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.05 (0.50–1.85)

0≤0.351.4

Missense OE?1.21 (0.98–1.51)

0≤0.61.4

Synonymous OE?0.51

0≤1.21.6

LoF obs/exp: 4 / 3.8Missense obs/exp: 57 / 46.9Syn Z: 1.51

Background carrier burden — how many people carry a rare variant somewhere in CARD18?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

137 rare PASS variants

Rare truncating (LoF)

1 in 1,700

27 rare PASS variants

Rare synonymous (reference)

1 in 2,700

38 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CARD18. 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 670	1 in 7,000
South Asian	~43k	1 in 430	1 in 2,200
Remaining (unassigned)	~30k	1 in 240	1 in 1,700
European (Finnish)	~27k	1 in 560	none seen
Admixed American	~22k	1 in 420	≈ 1 in 7,400
African / African American	~21k	1 in 520	1 in 1,500
East Asian	~20k	1 in 830	≈ 1 in 6,600
Ashkenazi Jewish	~13k	≈ 1 in 13,000	≈ 1 in 4,400
Middle Eastern	~2,884	≈ 1 in 960	none seen

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓