PNPLA1 (patatin like domain 1, omega-hydroxyceramide transacylase)

Gene

• Entrez ID: 285848
• Gene name: Patatin like domain 1, omega-hydroxyceramide transacylase
• Gene symbol: PNPLA1
• Synonyms (NCBI Gene): ARCI10, dJ50J22.1
• Chromosome: 6
• Chromosome location: 6p21.31
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs140585347	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, upstream transcript variant, coding sequence variant, genic upstream transcript variant
rs200806519	C>A,T	Pathogenic	Genic upstream transcript variant, coding sequence variant, upstream transcript variant, synonymous variant, missense variant
rs369445146	C>A	Pathogenic, likely-pathogenic	Genic upstream transcript variant, missense variant, coding sequence variant, upstream transcript variant
rs371307766	C>G,T	Likely-pathogenic	Genic upstream transcript variant, missense variant, coding sequence variant, upstream transcript variant
rs373148099	G>A	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs376245108	C>A,T	Pathogenic	Missense variant, coding sequence variant
rs533584507	C>A,T	Likely-pathogenic	Missense variant, coding sequence variant, intron variant, genic upstream transcript variant
rs746575171	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant
rs753687060	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs766188849	C>T	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs766215523	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs767462752	->GTACGAGGATGCAGTTTTGT	Likely-pathogenic	Coding sequence variant, frameshift variant
rs781053760	T>C	Pathogenic-likely-pathogenic, pathogenic	Genic upstream transcript variant, missense variant, coding sequence variant, upstream transcript variant
rs922934422	C>T	Likely-pathogenic	Upstream transcript variant, missense variant, coding sequence variant, genic upstream transcript variant, 5 prime UTR variant
rs938583000	C>-	Likely-pathogenic	Coding sequence variant, intron variant, genic upstream transcript variant, frameshift variant
rs1170446813	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1182312612	G>A,C	Pathogenic	Coding sequence variant, intron variant, genic upstream transcript variant, missense variant
rs1207879599	C>G,T	Pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant, intron variant
rs1231123861	C>A,T	Pathogenic	Coding sequence variant, intron variant, missense variant, genic upstream transcript variant
rs1373230987	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant, genic upstream transcript variant, intron variant
rs1407871103	A>C,G	Pathogenic	Upstream transcript variant, coding sequence variant, genic upstream transcript variant, missense variant
rs1554138062	T>C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs1554139129	->GTCA	Pathogenic	Coding sequence variant, frameshift variant
rs1561853847	C>T	Pathogenic	Genic upstream transcript variant, missense variant, coding sequence variant, intron variant
rs1561864453	G>T	Pathogenic	Upstream transcript variant, coding sequence variant, stop gained, genic upstream transcript variant
rs1582046125	T>C	Pathogenic	Genic upstream transcript variant, missense variant, coding sequence variant, intron variant
rs1582078740	A>G	Pathogenic	Genic upstream transcript variant, upstream transcript variant, coding sequence variant, missense variant
rs1582081682	T>C	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs1582086407	TAC>-	Pathogenic	Coding sequence variant, inframe deletion

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1245377	hsa-miR-1266	CLIP-seq
MIRT1245378	hsa-miR-1273f	CLIP-seq
MIRT1245379	hsa-miR-197	CLIP-seq
MIRT1245380	hsa-miR-24	CLIP-seq
MIRT1245381	hsa-miR-2467-5p	CLIP-seq
MIRT1245382	hsa-miR-3612	CLIP-seq
MIRT1245383	hsa-miR-411	CLIP-seq
MIRT1245384	hsa-miR-4270	CLIP-seq
MIRT1245385	hsa-miR-4441	CLIP-seq
MIRT1245386	hsa-miR-4443	CLIP-seq
MIRT1245387	hsa-miR-4518	CLIP-seq
MIRT1245388	hsa-miR-4534	CLIP-seq
MIRT1245389	hsa-miR-4653-3p	CLIP-seq
MIRT1245390	hsa-miR-4694-3p	CLIP-seq
MIRT1245391	hsa-miR-4700-3p	CLIP-seq
MIRT1245392	hsa-miR-4716-5p	CLIP-seq
MIRT1245393	hsa-miR-4781-3p	CLIP-seq
MIRT1245394	hsa-miR-4802-5p	CLIP-seq
MIRT1245395	hsa-miR-5095	CLIP-seq
MIRT1245396	hsa-miR-5096	CLIP-seq
MIRT1245397	hsa-miR-650	CLIP-seq
MIRT1245398	hsa-miR-1254	CLIP-seq
MIRT1245399	hsa-miR-1343	CLIP-seq
MIRT1245379	hsa-miR-197	CLIP-seq
MIRT1245400	hsa-miR-198	CLIP-seq
MIRT1245401	hsa-miR-2116	CLIP-seq
MIRT1245402	hsa-miR-3116	CLIP-seq
MIRT1245403	hsa-miR-3152-5p	CLIP-seq
MIRT1245404	hsa-miR-3155	CLIP-seq
MIRT1245405	hsa-miR-3155b	CLIP-seq
MIRT1245406	hsa-miR-3176	CLIP-seq
MIRT1245407	hsa-miR-3922-3p	CLIP-seq
MIRT1245408	hsa-miR-4438	CLIP-seq
MIRT1245388	hsa-miR-4534	CLIP-seq
MIRT1245389	hsa-miR-4653-3p	CLIP-seq
MIRT1245409	hsa-miR-4677-5p	CLIP-seq
MIRT1245410	hsa-miR-4687-3p	CLIP-seq
MIRT1245392	hsa-miR-4716-5p	CLIP-seq
MIRT1245411	hsa-miR-4740-3p	CLIP-seq
MIRT1245412	hsa-miR-4753-3p	CLIP-seq
MIRT1245413	hsa-miR-4772-3p	CLIP-seq
MIRT1245393	hsa-miR-4781-3p	CLIP-seq
MIRT1245414	hsa-miR-484	CLIP-seq
MIRT1245415	hsa-miR-498	CLIP-seq
MIRT1245395	hsa-miR-5095	CLIP-seq
MIRT1245396	hsa-miR-5096	CLIP-seq
MIRT1245416	hsa-miR-661	CLIP-seq
MIRT2299723	hsa-miR-122	CLIP-seq
MIRT1245378	hsa-miR-1273f	CLIP-seq
MIRT2299724	hsa-miR-130a	CLIP-seq
MIRT2299725	hsa-miR-130b	CLIP-seq
MIRT1245379	hsa-miR-197	CLIP-seq
MIRT2299726	hsa-miR-301a	CLIP-seq
MIRT2299727	hsa-miR-301b	CLIP-seq
MIRT2299728	hsa-miR-3135b	CLIP-seq
MIRT2299729	hsa-miR-3149	CLIP-seq
MIRT1245403	hsa-miR-3152-5p	CLIP-seq
MIRT2299730	hsa-miR-3605-3p	CLIP-seq
MIRT2299731	hsa-miR-3652	CLIP-seq
MIRT2299732	hsa-miR-3666	CLIP-seq
MIRT2299733	hsa-miR-3907	CLIP-seq
MIRT1245383	hsa-miR-411	CLIP-seq
MIRT2299734	hsa-miR-4295	CLIP-seq
MIRT2299735	hsa-miR-4423-5p	CLIP-seq
MIRT2299736	hsa-miR-4430	CLIP-seq
MIRT2299737	hsa-miR-4492	CLIP-seq
MIRT2299738	hsa-miR-4498	CLIP-seq
MIRT1245388	hsa-miR-4534	CLIP-seq
MIRT2299739	hsa-miR-454	CLIP-seq
MIRT1245389	hsa-miR-4653-3p	CLIP-seq
MIRT2299740	hsa-miR-4654	CLIP-seq
MIRT1245392	hsa-miR-4716-5p	CLIP-seq
MIRT1245411	hsa-miR-4740-3p	CLIP-seq
MIRT2299741	hsa-miR-4769-5p	CLIP-seq
MIRT2299742	hsa-miR-4775	CLIP-seq
MIRT1245393	hsa-miR-4781-3p	CLIP-seq
MIRT1245396	hsa-miR-5096	CLIP-seq
MIRT2299743	hsa-miR-590-3p	CLIP-seq
MIRT2299744	hsa-miR-595	CLIP-seq
MIRT2299745	hsa-miR-652	CLIP-seq
MIRT2299746	hsa-miR-762	CLIP-seq
MIRT1245378	hsa-miR-1273f	CLIP-seq
MIRT2456792	hsa-miR-3170	CLIP-seq
MIRT2299735	hsa-miR-4423-5p	CLIP-seq
MIRT2299737	hsa-miR-4492	CLIP-seq
MIRT2299738	hsa-miR-4498	CLIP-seq
MIRT1245395	hsa-miR-5095	CLIP-seq
MIRT2456793	hsa-miR-552	CLIP-seq
MIRT2299746	hsa-miR-762	CLIP-seq
MIRT2456794	hsa-miR-764	CLIP-seq
MIRT1245399	hsa-miR-1343	CLIP-seq
MIRT1245403	hsa-miR-3152-5p	CLIP-seq
MIRT1245411	hsa-miR-4740-3p	CLIP-seq
MIRT1245412	hsa-miR-4753-3p	CLIP-seq
MIRT1245415	hsa-miR-498	CLIP-seq
MIRT2299733	hsa-miR-3907	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004806	Function	Triacylglycerol lipase activity	IBA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	22246504
GO:0005737	Component	Cytoplasm	IEA
GO:0005811	Component	Lipid droplet	IBA
GO:0006629	Process	Lipid metabolic process	IEA
GO:0016020	Component	Membrane	IBA
GO:0016042	Process	Lipid catabolic process	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016747	Function	Acyltransferase activity, transferring groups other than amino-acyl groups	IMP	27751867
GO:0016787	Function	Hydrolase activity	IEA
GO:0019433	Process	Triglyceride catabolic process	IBA
GO:0030280	Function	Structural constituent of skin epidermis	IC	28248318
GO:0030280	Function	Structural constituent of skin epidermis	IEA
GO:0046513	Process	Ceramide biosynthetic process	IMP	27751867
GO:0055088	Process	Lipid homeostasis	IBA
GO:0106341	Function	Omega-hydroxyceramide transacylase activity	IDA	28248318
GO:0106341	Function	Omega-hydroxyceramide transacylase activity	IEA
GO:0106342	Process	Omega-hydroxyceramide biosynthetic process	IEA
GO:0106342	Process	Omega-hydroxyceramide biosynthetic process	IMP	28248318

Other IDs

• MIM: 612121
• HGNC: 21246
• e!Ensembl: ENSG00000180316

Protein

• UniProt ID: Q8N8W4
• Protein name: Omega-hydroxyceramide transacylase (EC 2.3.1.296) (Patatin-like phospholipase domain-containing protein 1)
• Protein function: Omega-hydroxyceramide transacylase involved in the synthesis of omega-O-acylceramides (esterified omega-hydroxyacyl-sphingosine; EOS), which are extremely hydrophobic lipids involved in skin barrier formation (PubMed:27751867, PubMed:28248318).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01734	Patatin	16 → 84	Patatin-like phospholipase	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the digestive system. Expressed in the epidermis of skin keratinocytes. Strongly expressed in the granular layer. Expressed in the upper epidermis and eccrine sweat glands of the dermis and in the region of keratin filamen
• Sequence:

  MEEQVFKGDPDTPHSISFSGSGFLSFYQAGAVDALRDLAPRMLETAHRFAGTSAGAVIAA
  LAICGIEMDEYLRVLNVGVAEVKKSFLGPLSPSCKMVQMMRQFLYRVLPEDSYKVTTGKL
  HVSLTRLTDGENVVVSEFTSKEELIEALYCSCFVPVYCGLIPPTYRGVRYIDGGFTGMQP
  CAFWTDAITISTFSGQQDICPRDCPAIFHDFRMFNCSFQFSLENIARMTHALFPPDLVIL
  HDYYYRGYEDAVLYLRRLNAVYLNSSSKRVIFPRVEVYCQIELALGNECPERSQPSLRAR
  QASLEGATQPHKEWVPKGDGRGSHGPPVSQPVQTLEFTCESPVSAPVSPLEQPPAQPLAS
  STPLSLSGMPPVSFPAVHKPPSSTPGSSLPTPPPGLSPLSPQQQVQPSGSPARSLHSQAP
  TSPRPSLGPSTVGAPQTLPRSSLSAFPAQPPVEELGQEQPQAVALLVSSKPKSAVPLVHV
  KETVSKPYVTESPAEDSNWVNKVFKKNKQKTSGTRKGFPRHSGSKKPSSKVQ

• Sequence length: 532

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the skin	Likely pathogenic	rs2127346823	RCV001814537	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Autosomal recessive congenital ichthyosis	Likely pathogenic; Pathogenic	rs200806519	RCV001729697	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Autosomal recessive congenital ichthyosis 10	Likely pathogenic; Pathogenic	rs1182312612, rs777268917, rs777658285, rs1170446813, rs781053760, rs369445146, rs922934422, rs1554138062, rs1561864453, rs1561853847, rs200806519, rs1373230987, rs533584507, rs1582086407, rs746575171, rs1207879599, rs1582078740, rs766188849, rs753687060	RCV002254388 RCV003327596 RCV003328085 RCV000504562 RCV000504558 RCV000504569 RCV000504559 RCV000782288 RCV000032761 RCV000032762 RCV000767380 RCV000767379 RCV000782381 RCV000782382 RCV000782404 RCV000782384 RCV003388599 RCV003327469 RCV004720283 RCV003448353	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Congenital ichthyosiform erythroderma	Likely pathogenic; Pathogenic	rs781053760, rs369445146, rs1554138062, rs1182312612, rs1231123861, rs1582046125, rs1207879599, rs1407871103, rs1582078740, rs1582081682, rs766188849, rs373148099, rs753687060	RCV000845143 RCV000845139 RCV000845147 RCV000845142 RCV000845141 RCV000845153 RCV000845154 RCV000845148 RCV000845152 RCV000845145 RCV000845140 RCV000845144 RCV000845146	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ichthyosis	Likely pathogenic; Pathogenic	rs200806519	RCV000755140	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lamellar ichthyosis	Likely pathogenic; Pathogenic	rs1182312612, rs777268917, rs781053760, rs938583000, rs1554138062, rs766188849, rs373148099	RCV005930089 RCV003155798 RCV004689731 RCV002509420 RCV004782423 RCV005432462 RCV005432463	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CONGENITAL NON-BULLOUS ICHTHYOSIFORM ERYTHRODERMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL NONBULLOUS ICHTHYOSIFORM ERYTHRODERMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EBV-positive nodal T- and NK-cell lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ICHTHYOSES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PNPLA1-related disorder	Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSYCHIATRIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
XERODERMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alopecia	Alopecia	HPO_DG			★☆☆☆☆ Found in Text Mining only
cervical cancer	Cervical Cancer	BEFREE	24057234		★☆☆☆☆ Found in Text Mining only
Cervix carcinoma	Cervix carcinoma	BEFREE	24057234		★☆☆☆☆ Found in Text Mining only
Congenital ichthyosis	Congenital Ichthyosis	BEFREE	22246504, 27751867, 27884779, 28248318, 28369476, 30290227, 30361410, 30527376, 30655104, 31120544, 31833240		★☆☆☆☆ Found in Text Mining only
Congenital ichthyosis	Congenital Ichthyosis	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Congenital non-bullous ichthyosiform erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Nonbullous Ichthyosiform Erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	BEFREE	22246504, 27751867, 27884779, 28369476, 30290227, 30655104, 31120544, 31833240		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Nonbullous Ichthyosiform Erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	ORPHANET_DG	22246504		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Nonbullous Ichthyosiform Erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Corneal erosion	Corneal erosion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ectropion	Ectropion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	35789548	Associate	★☆☆☆☆ Found in Text Mining only
Exfoliative dermatitis	Exfoliative Dermatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypohidrosis	Hypohidrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	35789548	Associate	★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	CTD_human_DG	22246504		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ichthyoses	Ichthyosis	BEFREE	27751867, 28248318, 30361410, 30527376		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ichthyoses	Ichthyosis	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ichthyoses	Ichthyosis	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ichthyosiform Erythroderma Congenital	Congenital ichthyosiform erythroderma	Pubtator	27025581	Associate	★☆☆☆☆ Found in Text Mining only
Ichthyosiform Erythroderma, Congenital	Ichthyosis Congenita	BEFREE	22246504, 27751867, 27884779, 28369476, 30290227, 30655104, 31120544, 31833240		★☆☆☆☆ Found in Text Mining only
Ichthyosiform Erythroderma, Congenital	Ichthyosis Congenita	CLINVAR_DG	28403545		★☆☆☆☆ Found in Text Mining only
Ichthyosiform Erythroderma, Congenital	Ichthyosis Congenita	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Ichthyosiform Erythroderma, Congenital	Ichthyosis Congenita	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ichthyosis	Ichthyosis	Pubtator	27025581, 28248318	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 10	Ichthyosis with hypotrichosis	UNIPROT_DG	22246504		★☆☆☆☆ Found in Text Mining only
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 10	Ichthyosis with hypotrichosis	GENOMICS_ENGLAND_DG	26778108		★☆☆☆☆ Found in Text Mining only
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 10	Ichthyosis with hypotrichosis	CLINVAR_DG	28369476		★☆☆☆☆ Found in Text Mining only
ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 10	Ichthyosis with hypotrichosis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Keratitis	Keratitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keratoderma, Palmoplantar	Palmoplantar keratoderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lamellar ichthyosis type 3	Lamellar ichthyosis	Pubtator	27025581, 27884779, 29624231, 30978464, 31120544, 31833240, 36980989	Associate	★☆☆☆☆ Found in Text Mining only
Malignant tumor of cervix	Cervical Tumor	BEFREE	24057234		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	19390624		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	19390624	Associate	★☆☆☆☆ Found in Text Mining only
Triglyceride storage disease with ichthyosis	Triglyceride Storage Disease With Ichthyosis	BEFREE	30527376		★☆☆☆☆ Found in Text Mining only
Xeroderma	Xeroderma	CTD_human_DG	22246504		★★☆☆☆ Found in Text Mining + Unknown/Other Associations