PDZD8

PDZ domain containing 8, the group of PDZ domain containing

Basic information

Region (hg38): 10:117277273-117375440

Previous symbols: [ "PDZK8" ]

Links

ENSG00000165650 ∙ NCBI:118987 ∙ OMIM:614235 ∙ HGNC:26974 ∙ Uniprot:Q8NEN9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with autism and dysmorphic facies (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with autism and dysmorphic facies	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	35227461

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDZD8 gene.

• Inborn genetic diseases (37 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDZD8 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			39	1		40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	39	2	2

Variants in PDZD8

This is a list of pathogenic ClinVar variants found in the PDZD8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-117277498-A-C			Benign (May 14, 2021)
10-117283344-T-C		not specified	Uncertain significance (Aug 28, 2023)
10-117283416-C-G		not specified	Uncertain significance (May 05, 2023)
10-117283542-G-A		not specified	Uncertain significance (Feb 12, 2024)
10-117283567-A-C		not specified	Uncertain significance (Feb 21, 2024)
10-117283718-C-A		not specified	Uncertain significance (Jan 23, 2024)
10-117283843-C-T		not specified	Uncertain significance (Apr 25, 2023)
10-117283849-C-A		not specified	Uncertain significance (Feb 06, 2023)
10-117283947-T-C		not specified	Uncertain significance (Jan 29, 2024)
10-117283960-T-C		not specified	Uncertain significance (Mar 31, 2023)
10-117284044-G-C		not specified	Uncertain significance (May 27, 2022)
10-117284287-G-A		not specified	Uncertain significance (Aug 08, 2023)
10-117284322-T-C			Uncertain significance (Aug 01, 2023)
10-117284366-A-C		not specified	Uncertain significance (May 26, 2022)
10-117284376-T-C		not specified	Uncertain significance (Oct 06, 2021)
10-117284418-C-T		not specified	Uncertain significance (Sep 06, 2022)
10-117284458-C-G		not specified	Uncertain significance (Aug 23, 2021)
10-117284487-G-A		not specified	Likely benign (Jan 23, 2024)
10-117284527-G-A		not specified	Uncertain significance (Apr 05, 2023)
10-117284532-AAACT-A		Intellectual developmental disorder with autism and dysmorphic facies	Pathogenic (Aug 31, 2022)
10-117284536-T-G		not specified	Uncertain significance (Feb 02, 2024)
10-117284623-T-C		not specified	Uncertain significance (Sep 13, 2023)
10-117284715-G-A		not specified	Uncertain significance (Dec 07, 2023)
10-117284722-C-A		not specified	Uncertain significance (Apr 12, 2023)
10-117284799-G-A		not specified	Uncertain significance (Feb 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDZD8	protein_coding	protein_coding	ENST00000334464	5	94979

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000160	125731	0	9	125740	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	512	622	0.823	0.0000323	7439
Missense in Polyphen		126	217.27	0.57991		2664
Synonymous	-0.613	266	254	1.05	0.0000135	2359
Loss of Function	5.27	3	38.2	0.0786	0.00000196	505

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Molecular tethering protein that connects endoplasmic reticulum and mitochondria membranes (PubMed:29097544). PDZD8- dependent endoplasmic reticulum-mitochondria membrane tethering is essential for endoplasmic reticulum-mitochondria Ca(2+) transfer (PubMed:29097544). In neurons, involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons (PubMed:29097544). Plays an indirect role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987). May inhibit herpes simplex virus 1 infection at an early stage (PubMed:21549406). {ECO:0000269|PubMed:21549406, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29097544}.

Recessive Scores

• pRec: 0.100

Intolerance Scores

• loftool: 0.0101
• rvis_EVS: 0.29
• rvis_percentile_EVS: 71.6

Haploinsufficiency Scores

• pHI: 0.515
• hipred: Y
• hipred_score: 0.673
• ghis: 0.394

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.214

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pdzd8

Gene ontology

• Biological process: lipid transport;cytoskeleton organization;viral process;regulation of cell morphogenesis;intracellular signal transduction;mitochondrial calcium ion homeostasis;mitochondrion-endoplasmic reticulum membrane tethering
• Cellular component: mitochondrion;endoplasmic reticulum membrane;membrane;integral component of membrane;mitochondria-associated endoplasmic reticulum membrane
• Molecular function: lipid binding;metal ion binding