PSD3

Chr 8

pleckstrin and Sec7 domain containing 3

Also known as: EFA6D, EFA6R, HCA67

NCBI Gene: 23362ENSG00000156011UniProt: Q9NYI0

PSD3 encodes a guanine nucleotide exchange factor that activates ARF6 protein and is predicted to function at glutamatergic synapses. The gene is highly constrained against loss-of-function variants (LOEUF 0.445), suggesting mutations would likely cause severe developmental disorders. However, no specific human disease has been definitively associated with PSD3 mutations to date.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
80
P/LP submissions
0%
P/LP missense
0.45
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— PSD3
🧬
Gene-Disease Validity (ClinGen)
antecubital pterygium syndrome · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
80 unique Pathogenic / Likely Pathogenic· 121 VUS of 249 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.009
Z-score 4.55
OE 0.28 (0.18–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-1.50Z-score
OE missense 1.18 (1.10–1.25)
666 obs / 565.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.28 (0.18–0.45)
0≤0.351.4
Missense OE1.18 (1.10–1.25)
0≤0.61.4
Synonymous OE1.31
0≤1.21.6
LoF obs/exp: 13 / 46.4Missense obs/exp: 666 / 565.9Syn Z: -3.57
DN
0.6939th %ile
GOF
0.7029th %ile
LOF
0.3940th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

249 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic76
Likely Pathogenic4
VUS121
Likely Benign11
Benign11
76
Pathogenic
4
Likely Pathogenic
121
VUS
11
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
76
0
76
Likely Pathogenic
0
0
4
0
4
VUS
0
93
28
0
121
Likely Benign
0
4
4
3
11
Benign
0
7
1
3
11
Total01041136223

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PSD3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients