PIGL (phosphatidylinositol glycan anchor biosynthesis class L)

Gene

• Entrez ID: 9487
• Gene name: Phosphatidylinositol glycan anchor biosynthesis class L
• Gene symbol: PIGL
• Synonyms (NCBI Gene): CHIME
• Chromosome: 17
• Chromosome location: 17p11.2
• Summary: This gene encodes an enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). Study of a similar rat enzyme suggests that this protein

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs139004722	C>A,G,T	Pathogenic, uncertain-significance	3 prime UTR variant, stop gained, coding sequence variant, downstream transcript variant, genic downstream transcript variant, missense variant
rs145303331	T>C	Pathogenic, pathogenic-likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, intron variant, genic downstream transcript variant
rs758633805	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs768198327	G>A,T	Likely-pathogenic	Genic downstream transcript variant, splice donor variant, downstream transcript variant
rs770084126	G>A	Pathogenic	Splice acceptor variant
rs1064794861	C>-	Likely-pathogenic	3 prime UTR variant, frameshift variant, coding sequence variant, genic downstream transcript variant
rs1064795400	C>T	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2295753	hsa-miR-2467-3p	CLIP-seq
MIRT2295754	hsa-miR-3678-3p	CLIP-seq
MIRT2295755	hsa-miR-450b-5p	CLIP-seq
MIRT2295756	hsa-miR-4738-5p	CLIP-seq
MIRT2295757	hsa-miR-4781-5p	CLIP-seq
MIRT2295758	hsa-miR-485-5p	CLIP-seq
MIRT2295759	hsa-miR-507	CLIP-seq
MIRT2295760	hsa-miR-557	CLIP-seq
MIRT2295761	hsa-miR-766	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000225	Function	N-acetylglucosaminylphosphatidylinositol deacetylase activity	IBA
GO:0000225	Function	N-acetylglucosaminylphosphatidylinositol deacetylase activity	IEA
GO:0000225	Function	N-acetylglucosaminylphosphatidylinositol deacetylase activity	ISS
GO:0000225	Function	N-acetylglucosaminylphosphatidylinositol deacetylase activity	NAS	10085243
GO:0000225	Function	N-acetylglucosaminylphosphatidylinositol deacetylase activity	TAS
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	14742432
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0006506	Process	GPI anchor biosynthetic process	IEA
GO:0006506	Process	GPI anchor biosynthetic process	IMP	10085243
GO:0006506	Process	GPI anchor biosynthetic process	NAS	10085243
GO:0006506	Process	GPI anchor biosynthetic process	TAS
GO:0006629	Process	Lipid metabolic process	IEA
GO:0016020	Component	Membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA

Other IDs

• MIM: 605947
• HGNC: 8966
• e!Ensembl: ENSG00000108474

Protein

• UniProt ID: Q9Y2B2
• Protein name: N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase (EC 3.5.1.89) (Phosphatidylinositol-glycan biosynthesis class L protein) (PIG-L)
• Protein function: Catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02585	PIG-L	44 → 168	GlcNAc-PI de-N-acetylase	Family

• Sequence:

  MEAMWLLCVALAVLAWGFLWVWDSSERMKSREQGGRLGAESRTLLVIAHPDDEAMFFAPT
  VLGLARLRHWVYLLCFSAGNYYNQGETRKKELLQSCDVLGIPLSSVMIIDNRDFPDDPGM
  QWDTEHVARVLLQHIEVNGINLVVTFDAGGVSGHSNHIALYAAVRALHSEGKLPKGCSVL
  TLQSVNVLRKYISLLDLPLSLLHTQDVLFVLNSKEVAQAKKAMSCHRSQLLWFRRLYIIF
  SRYMRINSLSFL

• Sequence length: 252

Pathways

KEGG:

Glycosylphosphatidylinositol (GPI)-anchor biosynthesis
Metabolic pathways

Reactome:

Synthesis of glycosylphosphatidylinositol (GPI)

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
CHIME syndrome	Likely pathogenic; Pathogenic	rs2142864883, rs768198327, rs773591135, rs2142610073, rs145303331, rs758633805, rs139004722, rs770084126	RCV001782627 RCV001823085 RCV002274225 RCV002052272 RCV000023501 RCV000023502 RCV000023503 RCV000023504	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperphosphatasia with intellectual disability syndrome 1	Likely pathogenic	rs773591135	RCV002274225	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability	Pathogenic	rs145303331	RCV005624705	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PIGL-related disorder	Likely pathogenic; Pathogenic	rs773591135, rs145303331	RCV002508967 RCV002508918	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Syndromic intellectual disability	Pathogenic	rs770084126	RCV005627336	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AMYOTROPHIC LATERAL SCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLEFT PALATE AND BILATERAL CLEFT LIP	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOBOMA, CONGENITAL HEART DISEASE, ICHTHYOSIFORM DERMATOSIS, IMPAIRED INTELLECTUAL DEVELOPMENT, AND EAR ANOMALIES SYNDROME	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERPHOSPHATASEMIA WITH INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERPHOSPHATASIA WITH IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERPHOSPHATASIA-INTELLECTUAL DISABILITY SYNDROME	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ULNAR POLYDACTYLY OF FINGERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ZUNICH NEUROECTODERMAL SYNDROME	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Abnormal dermatoglyphic pattern	Abnormal dermatoglyphic pattern	HPO_DG			★☆☆☆☆ Found in Text Mining only
Accessory nipple	Accessory Nipple	HPO_DG			★☆☆☆☆ Found in Text Mining only
Acute leukemia	Leukemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	9295069		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	GWASDB_DG	22959728		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	GWASCAT_DG	22959728, 24931836		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachycephaly	Brachycephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Burkitt Lymphoma	Burkitt lymphoma	Pubtator	19302917	Associate	★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	37280393	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral cortical atrophy	Cerebral cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
CHIME syndrome	CHIME Syndrome	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Class III malocclusion	Malocclusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly	Clinodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly of fingers	Clinodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Coloboma	Coloboma	Pubtator	35258128	Associate	★☆☆☆☆ Found in Text Mining only
Coloboma of the Retina	Retinal coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital atresia of pulmonary valve	Congenital Atresia Of Pulmonary Valve	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	BEFREE	18271001		★☆☆☆☆ Found in Text Mining only
Congenital pectus excavatum	Congenital Pectus Excavatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	28327575	Associate	★☆☆☆☆ Found in Text Mining only
Esotropia	Esotropia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Frontal bossing	Frontal bossing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fundus coloboma	Fundus Coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hirschsprung Disease	Hirschsprung Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydronephrosis	Hydronephrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperkeratosis	Hyperkeratosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperopia	Hyperopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperphosphatasia with Mental Retardation	Hyperphosphatasia With Mental Retardation	ORPHANET_DG	25706356		★☆☆☆☆ Found in Text Mining only
Hyperphosphatasia with Mental Retardation	Hyperphosphatasia with intellectual disability syndrome	Pubtator	30813920	Associate	★☆☆☆☆ Found in Text Mining only
Hyperphosphatasia-intellectual disability syndrome	Hyperphosphatasia With Mental Retardation	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypodontia	Hypodontia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of nipple	Hypoplasia Of Nipple	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypotrichosis	Hypotrichosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	22444671, 23561847, 30813920, 35258128	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Macrostomia	Macrostomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	BEFREE	31438913		★☆☆☆☆ Found in Text Mining only
Microdontia (disorder)	Microdontia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neck webbing	Neck Webbing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neurocutaneous Syndromes	Neurocutaneous Syndromes	BEFREE	9295069		★☆☆☆☆ Found in Text Mining only
Oculomotor apraxia	Oculomotor apraxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oculovestibuloauditory syndrome	Oculovestibuloauditory Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Palmoplantar Keratosis	Palmoplantar Keratosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral pulmonary artery stenosis	Peripheral pulmonary artery stenosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Plagiocephaly	Plagiocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	BEFREE	9295069		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	23561847	Associate	★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skin Diseases	Skin disease	Pubtator	35258128	Associate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tonic - clonic seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Transposition of Great Vessels	Transposition Of Great Vessels	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Zunich neuroectodermal syndrome	CHIME syndrome	BEFREE	22444671, 28371479, 29473937		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Zunich neuroectodermal syndrome	CHIME syndrome	ORPHANET_DG	22444671		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Zunich neuroectodermal syndrome	CHIME syndrome	CLINVAR_DG	22444671		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Zunich neuroectodermal syndrome	CHIME syndrome	UNIPROT_DG	22444671		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Zunich neuroectodermal syndrome	CHIME syndrome	GENOMICS_ENGLAND_DG	22444671, 27604308, 28371479		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Zunich neuroectodermal syndrome	Zunich neuroectodermal syndrome	Pubtator	22444671, 35258128	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Zunich neuroectodermal syndrome	CHIME syndrome	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations