PNPLA1

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

Basic information

Region (hg38): 6:36243203-36313955

Links

ENSG00000180316NCBI:285848OMIM:612121HGNC:21246Uniprot:Q8N8W4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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
  • autosomal recessive congenital ichthyosis 10 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ichthyosis, congenital, autosomal recessive 10ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic22246504; 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 (96 variants)
  • Inborn_genetic_diseases (71 variants)
  • not_provided (61 variants)
  • Congenital_ichthyosiform_erythroderma (19 variants)
  • Lamellar_ichthyosis (10 variants)
  • not_specified (9 variants)
  • PNPLA1-related_disorder (8 variants)
  • EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
  • Autosomal_recessive_congenital_ichthyosis (1 variants)
  • Abnormality_of_the_skin (1 variants)
  • Ichthyosis (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. These statistics are base on transcript: NM_001374623.1. 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.

EffectPLPVUSLBBSum
synonymous
7
clinvar
16
clinvar
2
clinvar
25
missense
9
clinvar
21
clinvar
92
clinvar
12
clinvar
5
clinvar
139
nonsense
2
clinvar
3
clinvar
1
clinvar
1
clinvar
7
start loss
0
frameshift
3
clinvar
5
clinvar
2
clinvar
10
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
4
Total 15 32 102 29 7

Highest pathogenic variant AF is 0.0000412602

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PNPLA1protein_codingprotein_codingENST00000394571 865393
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0001850.9951257190291257480.000115
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.7342833200.8840.00001893395
Missense in Polyphen88114.930.765651123
Synonymous-0.8151531411.090.000009471142
Loss of Function2.471022.70.4410.00000130237

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003700.000369
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.0001670.000167
Middle Eastern0.000.00
South Asian0.00006530.0000653
Other0.0003330.000326

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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