PIDD1

p53-induced death domain protein 1

Basic information

Region (hg38): 11:799179-809753

Previous symbols: [ "LRDD", "PIDD" ]

Links

ENSG00000177595 ∙ NCBI:55367 ∙ OMIM:605247 ∙ HGNC:16491 ∙ Uniprot:Q9HB75 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly (Strong), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIDD1 gene.

• Inborn_genetic_diseases (206 variants)
• not_provided (43 variants)
• Intellectual_developmental_disorder,_autosomal_recessive_75,_with_neuropsychiatric_features_and_variant_lissencephaly (26 variants)
• PIDD1-related_disorder (21 variants)
• not_specified (10 variants)
• PIDD1-associated_neurodevelopmental_disorder (2 variants)
• Intellectual_disability (2 variants)
• Developmental_and_epileptic_encephalopathy,_3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIDD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000145886.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	19	6	26
missense	2		203	22	4	231
nonsense	1	1				2
start loss						0
frameshift	5	3				8
splice donor/acceptor (+/-2bp)	2	3				5
Total	10	7	204	41	10

Highest pathogenic variant AF is 0.0000882716

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIDD1	protein_coding	protein_coding	ENST00000347755	15	10575

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.44e-17	0.0986	125445	0	108	125553	0.000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.838	634	577	1.10	0.0000396	5617
Missense in Polyphen		223	210.35	1.0601		2282
Synonymous	-1.74	287	252	1.14	0.0000158	2098
Loss of Function	1.07	29	35.9	0.807	0.00000190	362

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000956	0.000862
Ashkenazi Jewish	0.00172	0.00169
East Asian	0.000771	0.000762
Finnish	0.000250	0.000231
European (Non-Finnish)	0.000355	0.000335
Middle Eastern	0.000771	0.000762
South Asian	0.000629	0.000588
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes apoptosis downstream of the tumor suppressor as component of the DNA damage/stress response pathway that connects p53/TP53 to apoptosis. Associates with NEMO/IKBKG and RIP1 and enhances sumoylation and ubiquitination of NEMO/IKBKG which is important for activation of the transcription factor NF-kappa-B. Associates with CASP2/caspase-2 and CRADD/RAIDD, and induces activation of CASP2 which an important regulator in apoptotic pathways. {ECO:0000269|PubMed:10973264, ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:16360037}.
• Pathway: p53 signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);miRNA Regulation of DNA Damage Response;Apoptosis Modulation and Signaling;ATM Signaling Pathway;TP53 Regulates Transcription of Cell Death Genes;DNA Damage Response;Gene expression (Transcription);Generic Transcription Pathway;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;TP53 Regulates Transcription of Caspase Activators and Caspases;Transcriptional Regulation by TP53;Direct p53 effectors;Caspase Cascade in Apoptosis (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• rvis_EVS: -1.38
• rvis_percentile_EVS: 4.36

Haploinsufficiency Scores

• pHI: 0.121
• hipred: N
• hipred_score: 0.454
• ghis: 0.578

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Pidd1
• Phenotype: normal phenotype

Gene ontology

• Biological process: apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;cellular response to DNA damage stimulus;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;signal transduction;inorganic anion transport;protein autoprocessing;regulation of apoptotic process;positive regulation of apoptotic process;negative regulation of apoptotic process;regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of NF-kappaB transcription factor activity;anion transmembrane transport;positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
• Cellular component: nucleus;nucleoplasm;cytoplasm;Golgi apparatus;cytosol;ion channel complex
• Molecular function: endopeptidase activity;death receptor binding;volume-sensitive anion channel activity;protein binding