PIDD1

Chr 11AR

p53-induced death domain protein 1

Also known as: LRDD, MRT75, PIDD, altPIDD1

NCBI Gene: 55367 ENSG00000177595 UniProt: C0HMD6

The protein encoded by this gene contains a leucine-rich repeat and a death domain. This protein has been shown to interact with other death domain proteins, such as Fas (TNFRSF6)-associated via death domain (FADD) and MAP-kinase activating death domain-containing protein (MADD), and thus may function as an adaptor protein in cell death-related signaling processes. The expression of the mouse counterpart of this gene has been found to be positively regulated by the tumor suppressor p53 and to induce cell apoptosis in response to DNA damage, which suggests a role for this gene as an effector of p53-dependent apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephalyMIM #619827

347

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— PIDD1

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Gene-Disease Validity (ClinGen)

intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

42 Pathogenic / Likely Pathogenic· 236 VUS of 347 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.

1.10LOEUF

pLI 0.000

Z-score 1.07

OE 0.81 (0.60–1.10)

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.

-0.84Z-score

OE missense 1.10 (1.03–1.17)

634 obs / 577.3 exp

Tolerant

Tolerant to missense variation

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.0.81 (0.60–1.10)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (1.03–1.17)

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.1.14

0≤1.21.6

LoF obs/exp: 29 / 35.9Missense obs/exp: 634 / 577.3Syn Z: -1.74