PLAA

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

Basic information

Region (hg38): 9:26903372-26947242

Links

ENSG00000137055 ∙ NCBI:9373 ∙ OMIM:603873 ∙ HGNC:9043 ∙ Uniprot:Q9Y263 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies	AR	General	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	28007986; 28413018

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLAA gene.

• Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLAA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	132	2	135
missense	1		203	2		206
nonsense	1	2	3			6
start loss						0
frameshift		2	9			11
inframe indel			3			3
splice donor/acceptor (+/-2bp)			3			3
splice region			11	23	3	37
non coding			3	68	6	77
Total	2	4	225	202	8

Variants in PLAA

This is a list of pathogenic ClinVar variants found in the PLAA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-26905512-T-A			Uncertain significance (May 28, 2022)
9-26905514-C-A			Likely benign (May 30, 2023)
9-26905523-T-A			Likely benign (Jun 27, 2023)
9-26905525-G-T			Uncertain significance (Apr 24, 2022)
9-26905528-T-G			Uncertain significance (Feb 10, 2021)
9-26905544-A-G			Likely benign (Feb 09, 2021)
9-26905548-AC-A		Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies	Likely pathogenic (Sep 20, 2019)
9-26905573-A-T			Uncertain significance (May 25, 2022)
9-26905576-A-G		Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies	Uncertain significance (Feb 08, 2022)
9-26905578-T-G			Uncertain significance (Aug 17, 2022)
9-26905580-TTTTA-T			Uncertain significance (Jul 15, 2021)
9-26905588-G-A			Uncertain significance (Aug 23, 2022)
9-26905592-A-G			Likely benign (Nov 24, 2023)
9-26905604-A-C			Likely benign (Sep 01, 2024)
9-26905605-G-T		Inborn genetic diseases	Uncertain significance (Sep 22, 2022)
9-26905618-G-C			Uncertain significance (Jul 24, 2019)
9-26905623-G-A			Uncertain significance (Feb 08, 2022)
9-26905626-T-C			Uncertain significance (Mar 04, 2022)
9-26905635-T-C		Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies • PLAA-related disorder	Likely benign (Jan 22, 2024)
9-26905638-C-T			Uncertain significance (Sep 27, 2022)
9-26905645-G-A		Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies	Pathogenic (Jun 21, 2017)
9-26905649-T-C			Likely benign (Oct 09, 2021)
9-26905661-A-G			Likely benign (Nov 15, 2022)
9-26905674-G-C			Uncertain significance (Aug 22, 2022)
9-26905685-G-A			Likely benign (Jun 19, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLAA	protein_coding	protein_coding	ENST00000397292	14	43381

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.469	0.531	125728	0	19	125747	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	353	416	0.848	0.0000197	5198
Missense in Polyphen		92	146.65	0.62736		1866
Synonymous	-1.50	173	150	1.16	0.00000732	1535
Loss of Function	4.37	8	36.5	0.219	0.00000179	457

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000358	0.0000352
Middle Eastern	0.000109	0.000109
South Asian	0.000168	0.000163
Other	0.000327	0.000326

dbNSFP

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.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.468
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.55

Haploinsufficiency Scores

• pHI: 0.151
• hipred: Y
• hipred_score: 0.756
• ghis: 0.615

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.768

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Plaa
• Phenotype: growth/size/body region phenotype; cellular phenotype; muscle phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: phospholipid metabolic process;prostaglandin metabolic process;inflammatory response;signal transduction;ubiquitin recycling;macroautophagy;positive regulation of phospholipase A2 activity;proteasome-mediated ubiquitin-dependent protein catabolic process;ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway;cellular response to lipopolysaccharide;negative regulation of protein K63-linked ubiquitination;positive regulation of synaptic vesicle recycling;positive regulation of dendrite extension;positive regulation of neuron migration
• Cellular component: nucleus;cytoplasm;cell junction;synapse;extracellular exosome
• Molecular function: protein binding;phospholipase A2 activator activity;ubiquitin binding