PDZD8

protein-coding

PDZ domain containing 8, the group of PDZ domain containing

Gene summary

Predicted to enable lipid binding activity and zinc ion binding activity. Involved in mitochondrial calcium ion homeostasis and mitochondrion-endoplasmic reticulum membrane tethering. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane contact site. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

PDZK8

MANE transcript

NM_173791.5

Inheritance

ClinVar variants

P:2U:147B:24

Top phenotype

Intellectual developmental disorder with autism and dysmorphic facies

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr10:117,277,274-117,375,440

External References & Databases

Ensembl (ENSG00000165650)

Transcript & Mutation Effects

hg38 • Region Span ~98.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with autism and dysmorphic faciesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859281

Submitter: PanelApp Australia

intellectual developmental disorder with autism and dysmorphic faciesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859281

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder with autism and dysmorphic faciesAR

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: 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

Refs: 35227461

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDZD8 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 148

not providedTotal: 19

Intellectual developmental disorder with autism and dysmorphic faciesTotal: 6

PDZD8-related conditionTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173791.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				9 clinvar	1 clinvar	10
missense			145 clinvar	14 clinvar		159
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	0	147	23	1	173

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173791.5	RefSeq	NP_776152.1	5	MANE Select
ENST00000334464.7	Ensembl	ENSP00000334642.5	5	MANE Select
ENST00000868795.1	Ensembl	ENSP00000538854.1	4	Standard
ENST00000868795.2	Ensembl	ENSP00000538854.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

lipid transport
cytoskeleton organization
viral process
regulation of cell morphogenesis
intracellular signal transduction

Molecular Function

lipid binding
metal ion binding

Cellular Component

mitochondrion
endoplasmic reticulum membrane
membrane
integral component of membrane
mitochondria-associated endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334464
Coding exons: 5
Length: 94979
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125740
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.57	512	622	0.823	0.0000323	7439
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.214

Gene Damage Prediction

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