GeneBe

PLAA

protein-coding

phospholipase A2 activating protein, the group of WD repeat domain containing|Armadillo like helical domain containing

Gene summary

Enables phospholipase A2 activator activity. Involved in cellular response to lipopolysaccharide and macroautophagy. Located in several cellular components, including cytosol; extracellular exosome; and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001031689.3

Inheritance

AR

ClinVar variants

P:14U:270B:180

Top phenotype

Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr9:26,903,372-26,947,242

External References & Databases

Ensembl (ENSG00000137055)NCBI Gene (9373)OMIM (603873)HGNC:9043GenCCUniProt (Q9Y263)AlphaFoldClinVar (PLAA)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~43.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060502

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060502

Submitter: G2P

neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060502

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28007986; 28413018Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLAA variants in ClinVar

5 Conditions Cataloged
not providedTotal: 523
Inborn genetic diseasesTotal: 105
not specifiedTotal: 29
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesTotal: 27
PLAA-related disorderTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001031689.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
167
clinvar
2
clinvar
 171
missense
5
clinvar
253
clinvar
11
clinvar
 269
nonsense
2
clinvar
2
clinvar
4
clinvar
 8
start loss
0
frameshift
1
clinvar
2
clinvar
9
clinvar
 12
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
 4
Total952701782464

Highest pathogenic variant AF is 0.0000034380423

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001031689.3RefSeqNP_001026859.114MANE Select
ENST00000397292.8EnsemblENSP00000380460.314MANE Select
NM_001321546.2RefSeqNP_001308475.113Standard
ENST00000487173.5EnsemblENSP00000430734.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Protein processing in endoplasmic reticulum - Homo sapiens (human)

Biological Process

  • phospholipid metabolic process
  • prostaglandin metabolic process
  • inflammatory response
  • signal transduction
  • ubiquitin recycling

Molecular Function

  • protein binding
  • phospholipase A2 activator activity
  • ubiquitin binding

Cellular Component

  • nucleus
  • cytoplasm
  • cell junction
  • synapse
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000397292
Coding exons
14
Length
43381
Individuals with no LoFs
125728
Homozygous LoFs
0
Heterozygous LoFs
19
Defined
125747
p
0.0000756
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.103534160.8480.00001975198
Missense (PolyPhen)92146.650.627361866
Synonymous-1.501731501.160.000007321535
Loss of Function4.37836.50.2190.00000179457

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish00.0absent
European (Non-Finnish)0.0000360.000035rare
South Asian0.000170.00016rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (PubMed:27753622). Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling (By similarity). May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (PubMed:27753622). Plays a role in cerebellar Purkinje cell development (By similarity). Positively regulates cytosolic and calcium-independent phospholipase A2 activities in a tumor necrosis factor alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner, and hence prostaglandin E2 biosynthesis (PubMed:18291623, PubMed:28007986). {ECO:0000250|UniProtKB:P27612, ECO:0000269|PubMed:18291623, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:28007986}.;
Disease
DISEASE: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA) [MIM:617527]: An autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, spastic quadriparesis, global developmental delay, profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. {ECO:0000269|PubMed:28007986, ECO:0000269|PubMed:28413018}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.121

Intolerance Scores

LoFtool
0.468
RVIS EVS
-0.93
RVIS percentile EVS
9.55

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.768

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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