PIGN

phosphatidylinositol glycan anchor biosynthesis class N, the group of Phosphatidylinositol glycan anchor biosynthesis

Basic information

Region (hg38): 18:61905254-62187118

Links

ENSG00000197563 ∙ NCBI:23556 ∙ OMIM:606097 ∙ HGNC:8967 ∙ Uniprot:O95427 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple congenital anomalies-hypotonia-seizures syndrome 1 (Strong), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 1 (Strong), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 1 (Moderate), mode of inheritance: AR
• Fryns syndrome (Supportive), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 1 (Supportive), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 1 (Strong), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple congenital anomalies-hypotonia-seizures syndrome 1	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Renal	21493957; 24253414
The condition can involve multiple congenital anomalies

ClinVar

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

• Multiple congenital anomalies-hypotonia-seizures syndrome 1 (855 variants)
• not provided (253 variants)
• Inborn genetic diseases (104 variants)
• not specified (18 variants)
• PIGN-related condition (3 variants)
• Multiple congenital anomalies-hypotonia-seizures syndrome (2 variants)
• - (2 variants)
• Abnormal brain morphology (1 variants)
• History of neurodevelopmental disorder (1 variants)
• Neurodevelopmental delay (1 variants)
• Seizure;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGN 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			1	185	10	196
missense	3	5	342	5	6	361
nonsense	20	6	1			27
start loss						0
frameshift	24	5	5			34
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)	3	32			1	36
splice region	2	3	28	50	3	86
non coding			9	144	75	228
Total	50	49	362	334	92

Highest pathogenic variant AF is 0.0000723

Variants in PIGN

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

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

Position	Type	Phenotype	Significance	ClinVar
18-62045677-G-GA			Benign (Jul 05, 2018)
18-62045731-T-C			Likely benign (Jul 14, 2018)
18-62045869-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 1 • Inborn genetic diseases • PIGN-related disorder	Conflicting classifications of pathogenicity (Jan 30, 2024)
18-62045876-G-T		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Uncertain significance (Jun 10, 2022)
18-62045880-GC-G		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Uncertain significance (Aug 04, 2023)
18-62045882-C-T		Inborn genetic diseases	Uncertain significance (Jan 05, 2022)
18-62045884-C-G		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Uncertain significance (Jun 01, 2023)
18-62045886-T-C		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Sep 10, 2023)
18-62045888-G-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Dec 18, 2023)
18-62045889-T-C		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Sep 21, 2023)
18-62045890-C-CT		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Uncertain significance (Jul 12, 2022)
18-62045901-C-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1 • Inborn genetic diseases • PIGN-related disorder	Benign/Likely benign (Jan 31, 2024)
18-62045901-C-T		Inborn genetic diseases • Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Jan 22, 2024)
18-62045902-G-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1 • Inborn genetic diseases • not specified	Uncertain significance (Sep 01, 2023)
18-62045905-G-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1 • Inborn genetic diseases	Uncertain significance (Aug 10, 2022)
18-62045906-T-C		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Uncertain significance (Aug 22, 2022)
18-62045907-G-C		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Jan 23, 2023)
18-62045910-C-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Jun 23, 2023)
18-62045912-G-A		Inborn genetic diseases	Likely benign (Jan 25, 2017)
18-62045915-G-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Uncertain significance (Oct 07, 2020)
18-62045916-G-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Mar 27, 2022)
18-62045916-G-C		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Oct 15, 2023)
18-62045919-C-G		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Dec 02, 2023)
18-62045922-G-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Sep 22, 2023)
18-62045928-G-A		Multiple congenital anomalies-hypotonia-seizures syndrome 1	Likely benign (Jan 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGN	protein_coding	protein_coding	ENST00000357637	28	143552

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.29e-21	0.0867	124536	0	116	124652	0.000465

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.416	412	436	0.944	0.0000210	6036
Missense in Polyphen		124	141.69	0.87516		1931
Synonymous	-0.352	162	156	1.04	0.00000788	1727
Loss of Function	1.41	38	48.6	0.782	0.00000234	657

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000730	0.000723
Ashkenazi Jewish	0.000199	0.000199
East Asian	0.000790	0.000556
Finnish	0.000144	0.000139
European (Non-Finnish)	0.000604	0.000593
Middle Eastern	0.000790	0.000556
South Asian	0.000468	0.000458
Other	0.000667	0.000661

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers ethanolamine phosphate to the first alpha-1,4-linked mannose of the glycosylphosphatidylinositol precursor of GPI-anchor (By similarity). May act as suppressor of replication stress and chromosome missegregation. {ECO:0000250, ECO:0000269|PubMed:23446422}.
• Disease: DISEASE: Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1) [MIM:614080]: An autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary, and gastrointestinal systems. Most affected individuals die before 3 years of age. {ECO:0000269|PubMed:21493957}. 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 (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• rvis_EVS: -0.57
• rvis_percentile_EVS: 19.01

Haploinsufficiency Scores

• pHI: 0.218
• hipred: N
• hipred_score: 0.251
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pign
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo phenotype; vision/eye phenotype

Gene ontology

• Biological process: GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane
• Cellular component: endoplasmic reticulum membrane;cytosol;plasma membrane;membrane;integral component of membrane
• Molecular function: mannose-ethanolamine phosphotransferase activity