PSD4
protein-codingpleckstrin and Sec7 domain containing 4, the group of Pleckstrin homology domain containing|Pleckstrin and Sec7 domain containing
Gene summary
Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Located in ruffle membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~52.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PSD4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012455.3. 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 | 3 | 3 | ||||
| missense | 128 | 10 | 138 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 133 | 10 | 0 | 143 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036587.2 | 16 | MANE Select | |
| Ensembl | ENSP00000245796.6 | 16 | MANE Select | |
| Ensembl | ENSP00000386606.1 | 5 | Standard | |
| Ensembl | ENSP00000386373.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
Biological Process
- regulation of ARF protein signal transduction
Molecular Function
- ARF guanyl-nucleotide exchange factor activity
- phospholipid binding
Cellular Component
- membrane
- cleavage furrow
- ruffle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000245796
- Coding exons
- 16
- Length
- 52072
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125748
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.965 | 539 | 606 | 0.890 | 0.0000338 | 6824 |
| Missense (PolyPhen) | 160 | 222.98 | 0.71754 | 2501 | ||
| Synonymous | 0.0593 | 251 | 252 | 0.995 | 0.0000151 | 2148 |
| Loss of Function | 5.05 | 11 | 49.2 | 0.223 | 0.00000236 | 546 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide exchange factor for ARF6 and ARL14/ARF7. Through ARL14 activation, controls the movement of MHC class II-containing vesicles along the actin cytoskeleton in dendritic cells. Involved in membrane recycling. Interacts with several phosphatidylinositol phosphate species, including phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 3,5- bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:12082148, ECO:0000269|PubMed:21458045}.;
Recessive Scores
- pRec
- 0.0778
Intolerance Scores
- LoFtool
- 0.553
- RVIS EVS
- 1.41
- RVIS percentile EVS
- 94.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.656
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |