PNPLA1

patatin like phospholipase domain containing 1, the group of Patatin like phospholipase domain containing

Basic information

Region (hg38): 6:36243202-36313955

Links

ENSG00000180316 ∙ NCBI:285848 ∙ OMIM:612121 ∙ HGNC:21246 ∙ Uniprot:Q8N8W4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive congenital ichthyosis 10 (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 10 (Moderate), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 10 (Strong), mode of inheritance: AR
• autosomal recessive congenital ichthyosis 10 (Strong), mode of inheritance: AR
• congenital non-bullous ichthyosiform erythroderma (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, congenital, autosomal recessive 10	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	Dermatologic	22246504; 24344921; 26691440; 28403545

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNPLA1 gene.

• Autosomal recessive congenital ichthyosis 10 (80 variants)
• not provided (75 variants)
• Inborn genetic diseases (18 variants)
• Congenital ichthyosiform erythroderma (11 variants)
• not specified (10 variants)
• Lamellar ichthyosis (2 variants)
• PNPLA1-related condition (1 variants)
• Abnormality of the skin (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNPLA1 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			7	7	3	17
missense	2	10	35	4	8	59
nonsense	1	1	1	1		4
start loss						0
frameshift	3	2				5
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)						0
splice region			4	2		6
non coding			13	3	27	43
Total	7	13	57	15	38

Highest pathogenic variant AF is 0.0000263

Variants in PNPLA1

This is a list of pathogenic ClinVar variants found in the PNPLA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-36270493-AC-A		Lamellar ichthyosis	Likely pathogenic (Dec 06, 2022)
6-36270515-C-G		Autosomal recessive congenital ichthyosis 10	Likely pathogenic (Jun 08, 2018)
6-36270545-C-T		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
6-36270546-G-A		Autosomal recessive congenital ichthyosis 10 • PNPLA1-related disorder	Conflicting classifications of pathogenicity (Mar 23, 2020)
6-36270551-C-A		Congenital ichthyosiform erythroderma	Pathogenic (Jun 07, 2017)
6-36270551-C-T		Autosomal recessive congenital ichthyosis 10	Uncertain significance (Jan 13, 2018)
6-36270559-G-A		Autosomal recessive congenital ichthyosis 10 • Congenital ichthyosiform erythroderma	Pathogenic (Jun 10, 2019)
6-36270559-G-C		Autosomal recessive congenital ichthyosis 10	Likely pathogenic (Mar 28, 2022)
6-36270578-C-T			Uncertain significance (Aug 03, 2023)
6-36270601-C-T		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
6-36270608-C-A		Autosomal recessive congenital ichthyosis 10	Likely pathogenic (Jun 08, 2018)
6-36270616-T-C		Congenital ichthyosiform erythroderma	Pathogenic (Jun 07, 2017)
6-36270617-C-G		Congenital ichthyosiform erythroderma • Autosomal recessive congenital ichthyosis 10	Pathogenic/Likely pathogenic (Sep 08, 2023)
6-36270618-G-A		Autosomal recessive congenital ichthyosis 10	Conflicting classifications of pathogenicity (Dec 31, 2019)
6-36270620-C-A			Uncertain significance (Aug 08, 2023)
6-36270628-G-T			Uncertain significance (Aug 08, 2023)
6-36270634-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
6-36270635-C-T		Autosomal recessive congenital ichthyosis 10	Pathogenic (Jan 15, 2012)
6-36270637-G-A		Autosomal recessive congenital ichthyosis 10	Likely pathogenic (Sep 01, 2022)
6-36270669-G-A		Autosomal recessive congenital ichthyosis 10 • Lamellar ichthyosis	Conflicting classifications of pathogenicity (Jan 12, 2024)
6-36270874-G-A			Benign (Nov 12, 2018)
6-36291158-T-G			Benign (Jun 19, 2021)
6-36291342-C-T		Autosomal recessive congenital ichthyosis 10	Uncertain significance (Jan 13, 2018)
6-36291345-G-C		Autosomal recessive congenital ichthyosis 10	Uncertain significance (Jan 15, 2018)
6-36291347-G-T		Inborn genetic diseases	Uncertain significance (Nov 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PNPLA1	protein_coding	protein_coding	ENST00000394571	8	65393

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000185	0.995	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.734	283	320	0.884	0.0000189	3395
Missense in Polyphen		88	114.93	0.76565		1123
Synonymous	-0.815	153	141	1.09	0.00000947	1142
Loss of Function	2.47	10	22.7	0.441	0.00000130	237

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000370	0.000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000333	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Lipid hydrolase. Important in the formation of the epidermal lipid barrier. Plays a role in glycerophospholipid metabolism. {ECO:0000269|PubMed:22246504}.

Intolerance Scores

• loftool: 0.745
• rvis_EVS: 1.27
• rvis_percentile_EVS: 93.63

Haploinsufficiency Scores

• pHI: 0.132
• hipred: N
• hipred_score: 0.210
• ghis: 0.407

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0685

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pnpla1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); limbs/digits/tail phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: triglyceride catabolic process;lipid homeostasis
• Cellular component: cytoplasm;lipid droplet;membrane
• Molecular function: triglyceride lipase activity