PNPLA8

patatin like phospholipase domain containing 8, the group of Patatin like phospholipase domain containing

Basic information

Region (hg38): 7:108470417-108569666

Links

ENSG00000135241 ∙ NCBI:50640 ∙ OMIM:612123 ∙ HGNC:28900 ∙ Uniprot:Q9NP80 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial myopathy-lactic acidosis-deafness syndrome (Strong), mode of inheritance: AR
• mitochondrial myopathy-lactic acidosis-deafness syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial myopathy with lactic acidosis	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	Biochemical; Musculoskeletal; Neurologic	25512002

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNPLA8 gene.

• not_provided (256 variants)
• Inborn_genetic_diseases (124 variants)
• Mitochondrial_myopathy-lactic_acidosis-deafness_syndrome (29 variants)
• PNPLA8-related_disorder (10 variants)
• not_specified (3 variants)
• Abnormality_of_the_musculature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNPLA8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001256007.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	82	7	91
missense	1	1	196	13		211
nonsense	5	4	1			10
start loss						0
frameshift	9	6				15
splice donor/acceptor (+/-2bp)		1				1
Total	15	12	199	95	7

Highest pathogenic variant AF is 0.00002052581

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PNPLA8	protein_coding	protein_coding	ENST00000422087	9	99245

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0110	0.989	125717	0	23	125740	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0949	395	400	0.987	0.0000199	5127
Missense in Polyphen		69	82.715	0.83419		1135
Synonymous	0.574	128	137	0.938	0.00000647	1461
Loss of Function	3.77	10	33.6	0.297	0.00000182	456

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000504	0.000491
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000627	0.0000615
Middle Eastern	0.000164	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-independent phospholipase A2, which catalyzes the hydrolysis of the sn-2 position of glycerophospholipids, PtdSer and to a lower extent PtdCho. Cleaves membrane phospholipids. {ECO:0000269|PubMed:10744668, ECO:0000269|PubMed:15695510}.
• Pathway: Eicosanoid Synthesis;Metabolism of lipids;Metabolism;phospholipases;Acyl chain remodelling of PC;Glycerophospholipid biosynthesis;Phospholipid metabolism;Acyl chain remodelling of PE (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.279
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.79

Haploinsufficiency Scores

• pHI: 0.221
• hipred: N
• hipred_score: 0.492
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.632

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pnpla8
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: prostaglandin biosynthetic process;fatty acid metabolic process;cell death;arachidonic acid metabolic process;phosphatidylcholine catabolic process;phosphatidylcholine acyl-chain remodeling;phosphatidylethanolamine acyl-chain remodeling;linoleic acid metabolic process;phosphatidylethanolamine catabolic process;arachidonic acid secretion
• Cellular component: Golgi membrane;peroxisome;peroxisomal membrane;endoplasmic reticulum membrane;membrane;integral component of membrane;perinuclear region of cytoplasm
• Molecular function: lysophospholipase activity;phospholipase A2 activity;ATP binding;calcium-independent phospholipase A2 activity