PIDD1

Chr 11AR

p53-induced death domain protein 1

Also known as: LRDD, MRT75, PIDD, altPIDD1

NCBI Gene: 55367ENSG00000177595UniProt: C0HMD6OMIM: 605247

PIDD1 encodes a protein containing leucine-rich repeats and a death domain that functions as an adaptor protein in cell death signaling pathways and serves as an effector of p53-dependent apoptosis in response to DNA damage. Mutations cause autosomal recessive intellectual developmental disorder with neuropsychiatric features and variant lissencephaly, indicating early neurodevelopmental involvement. This condition follows an autosomal recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM
LOFmechanismARLOEUF 1.101 OMIM phenotype
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 unique Pathogenic / Likely Pathogenic· 236 VUS of 376 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
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
-0.84Z-score
OE missense 1.10 (1.03–1.17)
634 obs / 577.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.81 (0.60–1.10)
0≤0.351.4
Missense OE1.10 (1.03–1.17)
0≤0.61.4
Synonymous OE1.14
0≤1.21.6
LoF obs/exp: 29 / 35.9Missense obs/exp: 634 / 577.3Syn Z: -1.74
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPIDD1-related neurodevelopmental disorderLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6064th %ile
GOF
0.72top 25%
LOF
0.3065th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

376 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic5
VUS236
Likely Benign52
Benign13
Conflicting7
37
Pathogenic
5
Likely Pathogenic
236
VUS
52
Likely Benign
13
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
27
0
37
Likely Pathogenic
5
0
0
0
5
VUS
0
221
14
1
236
Likely Benign
0
21
7
24
52
Benign
0
4
3
6
13
Conflicting
—7
Total132485131350

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PIDD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients