PNPLA4

protein-coding

patatin like phospholipase domain containing 4, the group of Patatin like phospholipase domain containing

Gene summary

This gene encodes a member of the patatin-like family of phospholipases. The encoded enzyme has both triacylglycerol lipase and transacylase activities and may be involved in adipocyte triglyceride homeostasis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome Y. [provided by RefSeq, Feb 2010]

MANE transcript

NM_004650.3

Inheritance

ClinVar variants

U:87B:8

Top phenotype

PNPLA4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chrX:7,898,247-7,927,739

External References & Databases

Ensembl (ENSG00000006757)

Transcript & Mutation Effects

hg38 • Region Span ~29.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial diseaseLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0044970

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PNPLA4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 36

not providedTotal: 10

PNPLA4-related disorderTotal: 1

Abnormality of neuronal migrationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004650.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			10 clinvar	3 clinvar	1 clinvar	14
missense			65 clinvar	2 clinvar	2 clinvar	69
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	87	5	3	95

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004650.3	RefSeq	NP_004641.1	6	MANE Select
ENST00000381042.9	Ensembl	ENSP00000370430.4	6	MANE Select
NM_001142389.2	RefSeq	NP_001135861.1	6	Standard
NM_001172672.2	RefSeq	NP_001166143.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinol metabolism - Homo sapiens (human)
Vitamin A Deficiency
Retinol Metabolism
Metabolism of lipids
Metabolism

Biological Process

biological_process
triglyceride catabolic process
retinol metabolic process

Molecular Function

triglyceride lipase activity
retinyl-palmitate esterase activity

Cellular Component

mitochondrion
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381042
Coding exons: 6
Length: 29493
Individuals with no LoFs: 125699
Homozygous LoFs: 9
Heterozygous LoFs: 11
Defined: 125719
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.146	101	97.0	1.04	0.00000748	1632
Missense (PolyPhen)		42	40.263	1.0431		605
Synonymous	-0.0410	45	44.7	1.01	0.00000400	520
Loss of Function	1.05	5	8.25	0.606	7.51e-7	120

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00025	rare
Latino/Admixed American	0.00015	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000073	0.000054	rare
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000061	0.000044	rare
South Asian	0.00021	0.00013	rare
Other	0.00023	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lipid hydrolase.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.629
RVIS EVS: -0.43
RVIS percentile EVS: 25.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.317

Gene Damage Prediction

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