CASP10

Chr 2AD

caspase 10

Also known as: ALPS2, FLICE-2, FLICE2, MCH4

NCBI Gene: 843 ENSG00000003400 UniProt: Q92851

This gene encodes a protein which 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 which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with type IIA autoimmune lymphoproliferative syndrome, non-Hodgkin lymphoma and gastric cancer. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

Primary Disease Associations & Inheritance

Autoimmune lymphoproliferative syndrome, type IIMIM #603909

Gastric cancer, somaticMIM #613659

Lymphoma, non-Hodgkin, somaticMIM #605027

UniProtFamilial non-Hodgkin lymphoma

579

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— CASP10

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Gene-Disease Validity (ClinGen)

autoimmune lymphoproliferative syndrome type 2A · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

29 Pathogenic / Likely Pathogenic· 335 VUS of 579 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.29LOEUF

pLI 0.000

Z-score 0.53

OE 0.88 (0.61–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.03Z-score

OE missense 1.00 (0.90–1.10)

271 obs / 272.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.88 (0.61–1.29)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.90–1.10)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03

0≤1.21.6

LoF obs/exp: 19 / 21.7Missense obs/exp: 271 / 272.2Syn Z: -0.23