PLXNA4

Chr 7

plexin A4

Also known as: FAYV2820, PLEXA4, PLXNA4A, PLXNA4B, PRO34003

NCBI Gene: 91584ENSG00000221866UniProt: Q9HCM2

Predicted to enable semaphorin receptor activity. Predicted to be involved in nervous system development; regulation of cell migration; and semaphorin-plexin signaling pathway. Predicted to act upstream of or within nervous system development; regulation of axon extension involved in axon guidance; and regulation of negative chemotaxis. Predicted to be located in membrane. Predicted to be part of semaphorin receptor complex. Predicted to be active in cerebellar climbing fiber to Purkinje cell synapse and plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]

472
ClinVar variants
1
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PLXNA4
⚡
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
1 Pathogenic / Likely Pathogenic· 220 VUS of 472 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.23LOEUF
pLI 1.000
Z-score 7.32
OE 0.14 (0.09–0.23)
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.
3.80Z-score
OE missense 0.68 (0.65–0.73)
788 obs / 1150.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.14 (0.09–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.65–0.73)
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.1.17
0≤1.21.6
LoF obs/exp: 12 / 84.8Missense obs/exp: 788 / 1150.7Syn Z: -2.89

ClinVar Variant Classifications

472 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS220
Likely Benign248
Benign3
1
Pathogenic
220
VUS
248
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
2
209
7
2
220
Likely Benign
0
12
38
198
248
Benign
0
2
0
1
3
Total222346201472

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

View in ClinVar →

Protein Context — Lollipop Plot

PLXNA4 · 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
PLEXIN A4; PLXNA4
MIM #604280 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of plexin A4 as a novel clusterin receptor links two Alzheimer's disease risk genes.
Kang SS et al.·Hum Mol Genet
2016
Common Variants in PLXNA4 and Correlation to Neuroimaging Phenotypes in Healthy, Mild Cognitive Impairment, and Alzheimer's Disease Cohorts.
Yang X et al.·Mol Neurobiol
2025Cohort
Rare variants in PLXNA4 and Parkinson's disease.
Schulte EC et al.·PLoS One
2013Clinical trial
Identification of prognostic biomarkers and development of a prediction model for prostate cancer.
Chen D et al.·Front Immunol
2026Functional
Host genetic polymorphisms involved in long-term symptoms of COVID-19.
Udomsinprasert W et al.·Emerg Microbes Infect
2023
PLXNA4 is associated with Alzheimer disease and modulates tau phosphorylation.
Jun G et al.·Ann Neurol
2014
Rare gene variants and weight loss at 10 years after sleeve gastrectomy and gastric bypass - a randomized clinical trial.
Loid P et al.·Surg Obes Relat Dis
2025
Integrated analysis of tumor mutation burden and immune infiltrates in endometrial cancer.
Zhou H et al.·Curr Probl Cancer
2021
Analysis of immune-related genes in idiopathic pulmonary fibrosis based on bioinformatics and experimental verification.
Li X et al.·Ann Palliat Med
2021
Cumulative Effects of Genetic Variants Detected in a Child with Early-Onset Non-Syndromic Obesity Due to SIM-1 Gene Mutation.
Luppino G et al.·Genes (Basel)
2025Case report
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