PDZD8: PDZ Domain Containing 8
A scaffold protein involved in mitochondrial-endoplasmic reticulum contact sites and calcium homeostasis.
Gene Information Card
| Symbol | PDZD8 |
|---|---|
| Full Name | PDZ domain containing 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q25.3-q26.11 |
| NCBI Gene ID | 118987 ncbi.nlm.nih.gov/gene/118987 |
| Ensembl ID | ENSG00000165804 |
| UniProt ID | Q8NEN9 |
| OMIM ID | 617113 |
| HGNC ID | 26970 |
| Aliases | FLJ11273, MGC12972, PDZ domain protein 8 |
Description
PDZD8 encodes a scaffold protein containing a PDZ domain. It localizes to the endoplasmic reticulum (ER) and is critical for tethering mitochondria to the ER, thereby regulating calcium transfer between these organelles. This function is essential for mitochondrial calcium uptake, lipid metabolism, and cellular stress responses. PDZD8 is also implicated in neuronal development and synaptic function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly and seizures | Loss of PDZD8 disrupts ER-mitochondria calcium transfer, impairing neuronal development and function. | ClinVar, OMIM |
| Hepatocellular carcinoma | Altered PDZD8 expression may affect calcium signaling and mitochondrial dynamics, promoting tumorigenesis. | COSMIC, NCBI |
| Breast cancer | PDZD8 overexpression correlates with poor prognosis; potential role in calcium-dependent cell proliferation. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Heart | 6.1 | Low |
| Kidney | 5.4 | Low |
| Testis | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression in kidney-derived cells |
| HeLa | 7.8 | Moderate expression in cervical cancer cells |
| SH-SY5Y | 9.5 | High expression in neuroblastoma cells |
| HepG2 | 6.3 | Moderate expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Ter) | Nonsense | Rare | Loss of function; truncation of PDZ domain |
| c.1456G>A (p.Gly486Arg) | Missense | Rare | Impaired ER-mitochondria tethering |
| c.2017_2018del (p.Leu673fs) | Frameshift | Rare | Loss of function; protein truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg375Ter, p.Leu673fs) lead to truncated, non-functional PDZD8 protein, disrupting ER-mitochondria contact sites.
Gain of Function (GOF)
No gain-of-function mutations reported in PDZD8.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly486Arg) may produce a dominant-negative effect by interfering with normal PDZD8 tethering function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mitochondrial calcium homeostasis
• ER-mitochondria contact site formation
• Unfolded protein response (UPR)
Protein Summary
PDZD8 is a 1,098-amino-acid scaffold protein with a single N-terminal PDZ domain. It is anchored to the ER membrane and interacts with mitochondrial proteins to form contact sites. These contacts facilitate calcium transfer from the ER to mitochondria, which is critical for ATP production, apoptosis, and cellular signaling. PDZD8 is highly expressed in the brain and is essential for neuronal development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDZD8 Knockout HEK293 Cell Line | EDJ-KQ7635 | Human | 118987 | Details Get a Quote |
| PDZD8 Knockout A-549 Cell Line | EDJ-KQ32988 | Human | 118987 | Details Get a Quote |
| PDZD8 Knockout HCT 116 Cell Line | EDJ-KQ32989 | Human | 118987 | Details Get a Quote |
| PDZD8 Knockout HeLa Cell Line | EDJ-KQ32990 | Human | 118987 | Details Get a Quote |
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