PNPLA1

Protein identityUniProt · HPA

UniProt accession

Q8N8W4

Gene

PNPLA1

Ensembl

ENSG00000180316

Chromosome

6

Canonical length

532 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

OverviewNCBI Gene

The protein encoded by this gene belongs to the patatin-like phospholipase (PNPLA) family, which is characterized by the presence of a highly conserved patatin domain. PNPLA family members have diverse lipolytic and acyltransferase activities, and are key elements in lipid metabolism. While other members of this family have been well characterized, the function of this gene remained an enigma. However, recent studies show that this gene is expressed in the skin epidermal keratinocytes, and has a role in glycerophospholipid metabolism in the cutaneous barrier. Consistent with these observations, mutations in this gene are associated with ichthyosis in human (autosomal recessive congenital ichthyoses, ARCI) and dog. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

Canonical amino-acid sequenceUniProt

532 residues, UniProt reviewed canonical sequence.

>Q8N8W4|PNPLA1
     1  MEEQVFKGDP DTPHSISFSG SGFLSFYQAG AVDALRDLAP RMLETAHRFA GTSAGAVIAA
    61  LAICGIEMDE YLRVLNVGVA EVKKSFLGPL SPSCKMVQMM RQFLYRVLPE DSYKVTTGKL
   121  HVSLTRLTDG ENVVVSEFTS KEELIEALYC SCFVPVYCGL IPPTYRGVRY IDGGFTGMQP
   181  CAFWTDAITI STFSGQQDIC PRDCPAIFHD FRMFNCSFQF SLENIARMTH ALFPPDLVIL
   241  HDYYYRGYED AVLYLRRLNA VYLNSSSKRV IFPRVEVYCQ IELALGNECP ERSQPSLRAR
   301  QASLEGATQP HKEWVPKGDG RGSHGPPVSQ PVQTLEFTCE SPVSAPVSPL EQPPAQPLAS
   361  STPLSLSGMP PVSFPAVHKP PSSTPGSSLP TPPPGLSPLS PQQQVQPSGS PARSLHSQAP
   421  TSPRPSLGPS TVGAPQTLPR SSLSAFPAQP PVEELGQEQP QAVALLVSSK PKSAVPLVHV
   481  KETVSKPYVT ESPAEDSNWV NKVFKKNKQK TSGTRKGFPR HSGSKKPSSK VQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PNPLA1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.46

Highest tissue expression

23 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PNPLA1.

Disease | AllUniProt

Conditions PNPLA1 is implicated in, by any mechanism.

• Ichthyosis, congenital, autosomal recessive 10 (ARCI10) MIM:615024

Disease | GeneticClinVar

50 pathogenic / likely-pathogenic of 276 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive congenital ichthyosis 10
• Congenital ichthyosiform erythroderma
• Lamellar ichthyosis
• Ichthyosis
• Autosomal recessive congenital ichthyosis

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.75

gnomAD pLI

0

gnomAD missense Z

0.73

DepMap mean gene effect

-0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ceramide biosynthetic process
• lipid homeostasis
• triglyceride catabolic process
• omega-hydroxyceramide biosynthetic process

Molecular functions

• acyltransferase activity, transferring groups other than amino-acyl groups
• structural constituent of skin epidermis
• triacylglycerol lipase activity
• omega-hydroxyceramide transacylase activity

Cellular components

• cytoplasm
• lipid droplet
• membrane

Protein domainsUniProt · Pfam · InterPro

• Patatin-like phospholipase domain
• Acyl transferase/acyl hydrolase/lysophospholipase
• Patatin-like phospholipase domain-containing protein
• Patatin-like phospholipase
• Omega-hydroxyceramide transacylase PNPLA1

KeywordsUniProt

• Cytoplasm
• Ichthyosis
• Lipid biosynthesis
• Lipid metabolism
• Transferase