PACSIN1

Chr 6

protein kinase C and casein kinase substrate in neurons 1

Also known as: SDPI

NCBI Gene: 29993ENSG00000124507UniProt: Q9BY11

Enables phospholipid binding activity. Involved in plasma membrane tubulation. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

50
ClinVar variants
5
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PACSIN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 45 VUS of 50 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.20LOEUF
pLI 0.999
Z-score 4.36
OE 0.04 (0.01–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.63Z-score
OE missense 0.54 (0.47–0.62)
140 obs / 259.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.47–0.62)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 1 / 24.1Missense obs/exp: 140 / 259.2Syn Z: 1.10

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
VUS45
5
Pathogenic
45
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
0
0
0
VUS
0
39
6
0
45
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03911050

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

View in ClinVar →

Protein Context — Lollipop Plot

PACSIN1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De Novo PACSIN1 Gene Variant Found in Childhood Lupus and a Role for PACSIN1/TRAF4 Complex in Toll-like Receptor 7 Activation.
Xie C et al.·Arthritis Rheumatol
2023
Axon-derived PACSIN1 binds to the Schwann cell survival receptor, LRP1, and transactivates TrkC to promote gliatrophic activities.
Martellucci S et al.·Glia
2024
GATA2 downregulation contributes to pro-inflammatory phenotype and defective phagocytosis of pulmonary macrophages in chronic obstructive pulmonary disease.
Shen S et al.·Aging (Albany NY)
2024
ANKK1, ANKRD50, GRK5, PACSIN1 and VPS8 are novel candidate genes associated with late onset Parkinson's disease: Definition of a novel predictive protocol based on polygenic model of inheritance.
Carrillo F et al.·Neurobiol Dis
2025Functional
Identification of methylation sites and signature genes with prognostic value for luminal breast cancer.
Xiao B et al.·BMC Cancer
2018
Suppressing aberrant GluN3A expression rescues synaptic and behavioral impairments in Huntington's disease models.
Marco S et al.·Nat Med
2013Functional
A Novel Glycine Receptor Variant with Startle Disease Affects Syndapin I and Glycinergic Inhibition.
Langlhofer G et al.·J Neurosci
2020
Insights into transcriptomic changes in blood of a mouse model of LPS-induced peritonitis.
Li H et al.·Toxicol Appl Pharmacol
2026Functional
Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin.
Caron NS et al.·Proc Natl Acad Sci U S A
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools