PNPLA8

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

Basic information

Region (hg38): 7:108470416-108569666

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 (Moderate), 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 (193 variants)
• Inborn genetic diseases (62 variants)
• Mitochondrial myopathy-lactic acidosis-deafness syndrome (18 variants)
• not specified (3 variants)
• PNPLA8-related condition (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.

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				49	7	56
missense			139	4		143
nonsense	3	1	1			5
start loss						0
frameshift	5	4				9
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding			4	20	4	28
Total	8	5	145	73	11

Highest pathogenic variant AF is 0.0000263

Variants in PNPLA8

This is a list of pathogenic ClinVar variants found in the PNPLA8 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-108472444-T-C			Uncertain significance (Oct 17, 2022)
7-108472458-A-G			Benign/Likely benign (Jan 29, 2024)
7-108472473-CAG-C		Mitochondrial myopathy-lactic acidosis-deafness syndrome • not specified	Conflicting classifications of pathogenicity (Jul 12, 2022)
7-108472481-T-A			Uncertain significance (Jun 07, 2022)
7-108472486-TCTTGA-T			Pathogenic (Mar 21, 2023)
7-108472494-T-C			Likely benign (Sep 01, 2023)
7-108472523-G-A		Inborn genetic diseases	Likely pathogenic (Dec 14, 2023)
7-108472538-T-G			Uncertain significance (Aug 09, 2022)
7-108472551-T-C			Likely benign (Dec 08, 2021)
7-108472557-C-A			Uncertain significance (Jul 12, 2022)
7-108472583-G-A			Pathogenic (Jul 07, 2023)
7-108472589-C-T		Mitochondrial myopathy-lactic acidosis-deafness syndrome	Uncertain significance (Dec 17, 2018)
7-108472616-C-T			Uncertain significance (Jun 27, 2022)
7-108472618-G-A			Uncertain significance (Jul 19, 2022)
7-108472629-A-G			Likely benign (Aug 28, 2023)
7-108472633-T-C		Inborn genetic diseases	Uncertain significance (Dec 14, 2021)
7-108472640-C-T		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
7-108472653-G-T			Likely benign (Oct 07, 2022)
7-108472680-T-C			Likely benign (Jun 15, 2023)
7-108472684-G-C			Likely benign (Oct 17, 2022)
7-108472689-A-G			Likely benign (Nov 13, 2023)
7-108472689-A-T			Likely benign (Jul 18, 2022)
7-108479166-G-A			Likely benign (Aug 29, 2023)
7-108479173-A-G			Likely benign (Aug 07, 2023)
7-108479196-T-C			Uncertain significance (May 13, 2022)

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