PIGL

phosphatidylinositol glycan anchor biosynthesis class L, the group of MicroRNA protein coding host genes|Phosphatidylinositol glycan anchor biosynthesis

Basic information

Region (hg38): 17:16217190-16351797

Links

ENSG00000108474 ∙ NCBI:9487 ∙ OMIM:605947 ∙ HGNC:8966 ∙ Uniprot:Q9Y2B2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• CHIME syndrome (Definitive), mode of inheritance: AR
• CHIME syndrome (Strong), mode of inheritance: AR
• CHIME syndrome (Strong), mode of inheritance: AR
• CHIME syndrome (Limited), mode of inheritance: AR
• CHIME syndrome (Strong), mode of inheritance: AR
• CHIME syndrome (Supportive), mode of inheritance: AR
• hyperphosphatasia-intellectual disability syndrome (Supportive), mode of inheritance: AR
• syndromic intellectual disability (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
CHIME syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Neurologic; Ophthalmologic	22444671
The condition can involve multiple congenital anomalies

ClinVar

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

• not provided (81 variants)
• CHIME syndrome (46 variants)
• Coloboma, Congenital Heart Disease, Ichthyosiform Dermatosis, Intellectual Disability, and Ear Anomalies (CHIME) Syndrome (14 variants)
• Inborn genetic diseases (9 variants)
• PIGL-Related Disorder (2 variants)
• 8 conditions (2 variants)
• not specified (1 variants)
• CHIME syndrome;Hyperphosphatasia with intellectual disability syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGL 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			6	11		17
missense		3	37	3		43
nonsense	1					1
start loss			1			1
frameshift	1	2	1			4
inframe indel						0
splice donor/acceptor (+/-2bp)	1	3				4
splice region			3	4		7
non coding			5	9	10	24
Total	3	8	50	23	10

Highest pathogenic variant AF is 0.0000460

Variants in PIGL

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

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

Position	Type	Phenotype	Significance	ClinVar
17-16217230-G-A		CHIME syndrome	Uncertain significance (Aug 31, 2022)
17-16217232-A-C			Uncertain significance (Oct 18, 2022)
17-16217243-T-G			Uncertain significance (Aug 20, 2021)
17-16217245-C-T			Likely benign (Aug 11, 2023)
17-16217247-G-A			Likely benign (May 16, 2022)
17-16217250-T-G			Uncertain significance (Apr 29, 2020)
17-16217251-G-T			Uncertain significance (Jan 19, 2022)
17-16217256-G-T		CHIME syndrome	Uncertain significance (Feb 08, 2013)
17-16217261-C-A		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
17-16217286-G-A			Pathogenic (Mar 24, 2020)
17-16217305-C-A			Likely benign (Jan 15, 2024)
17-16217315-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jul 10, 2023)
17-16217356-C-T		CHIME syndrome	Uncertain significance (Jan 13, 2018)
17-16217358-G-C			Likely benign (Oct 07, 2022)
17-16217370-G-A			Likely benign (Jun 10, 2022)
17-16217375-C-T		Inborn genetic diseases	Uncertain significance (Mar 11, 2024)
17-16217378-ACGATGAAG-A		CHIME syndrome	Likely pathogenic (Mar 22, 2022)
17-16217380-G-A			Likely pathogenic (Jun 17, 2019)
17-16217387-C-T			Uncertain significance (Mar 28, 2022)
17-16217389-A-G		Inborn genetic diseases	Uncertain significance (Oct 09, 2023)
17-16217395-T-C		CHIME syndrome	Uncertain significance (Feb 08, 2013)
17-16217402-C-A		8 conditions • CHIME syndrome	Uncertain significance (Jan 01, 2016)
17-16217444-T-C			Uncertain significance (Jul 25, 2022)
17-16217461-G-GGTAGGAGGCC			Likely benign (Jan 02, 2024)
17-16233930-TA-T			Benign (May 24, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGL	protein_coding	protein_coding	ENST00000225609	7	131611

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.18e-9	0.136	125694	0	54	125748	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0451	146	148	0.990	0.00000780	1644
Missense in Polyphen		36	45.676	0.78816		510
Synonymous	-0.278	58	55.4	1.05	0.00000281	499
Loss of Function	0.167	13	13.7	0.951	5.90e-7	150

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000738	0.000738
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.000345	0.000323
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.000272	0.000272
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the second step of GPI biosynthesis. De-N- acetylation of N-acetylglucosaminyl-phosphatidylinositol.
• Disease: DISEASE: Coloboma, congenital heart disease, ichthyosiform dermatosis, mental retardation and ear anomalies syndrome (CHIME) [MIM:280000]: An extremely rare autosomal recessive multisystem disorder clinically characterized by colobomas, congenital heart defects, migratory ichthyosiform dermatosis, mental retardation, and ear anomalies including conductive hearing loss. Other clinical features include distinctive facial features, abnormal growth, genitourinary abnormalities, seizures, and feeding difficulties. {ECO:0000269|PubMed:22444671}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human);Synthesis of glycosylphosphatidylinositol (GPI);Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins;Phosphatidylinositol phosphate metabolism (Consensus)

Recessive Scores

• pRec: 0.0718

Intolerance Scores

• loftool: 0.558
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.0722
• hipred: N
• hipred_score: 0.197
• ghis: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigl
• Phenotype: 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: GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: N-acetylglucosaminylphosphatidylinositol deacetylase activity