PIGM

phosphatidylinositol glycan anchor biosynthesis class M, the group of Dolichyl D-mannosyl phosphate dependent mannosyltransferases|Phosphatidylinositol glycan anchor biosynthesis

Basic information

Region (hg38): 1:160024953-160031990

Links

ENSG00000143315 ∙ NCBI:93183 ∙ OMIM:610273 ∙ HGNC:18858 ∙ Uniprot:Q9H3S5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (Limited), mode of inheritance: AR
• hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (Moderate), mode of inheritance: AR
• hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (Supportive), mode of inheritance: AR
• hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycosylphosphatidylinositol biosynthesis defect 1	AR	Biochemical; Hematologic; Neurologic; Pharmacogenomic	Medical treatment may be beneficial (eg, prophylactic oral anticoagulants to prevent thrombosis; sodium phenylbutyrate for seizure control); Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Hepatic-metabolized agents should be avoided	Biochemical; Hematologic; Neurologic	16767100; 17442906; 19168132; 31445883

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGM 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				16	2	18
missense			64		3	67
nonsense		1				1
start loss		1				1
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	2	66	16	6

Variants in PIGM

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

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

Position	Type	Phenotype	Significance	ClinVar
1-160030471-G-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Jun 25, 2023)
1-160030482-TTCTC-T		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • not specified • PIGM-related disorder	Uncertain significance (Feb 22, 2024)
1-160030523-T-G		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Nov 15, 2022)
1-160030541-T-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Jul 12, 2022)
1-160030547-A-G		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Jun 23, 2023)
1-160030548-G-C		not specified	Uncertain significance (Mar 06, 2023)
1-160030590-T-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • PIGM-related disorder	Benign (Jan 24, 2024)
1-160030597-T-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Likely benign (Oct 14, 2023)
1-160030640-C-A		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Feb 28, 2022)
1-160030645-A-T		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Benign (Jan 30, 2024)
1-160030647-A-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Sep 01, 2022)
1-160030650-A-G		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Feb 22, 2024)
1-160030698-G-A		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Benign (Apr 01, 2023)
1-160030698-G-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • not specified	Uncertain significance (Oct 27, 2023)
1-160030723-G-A		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Likely benign (Jul 07, 2020)
1-160030739-T-G		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Uncertain significance (Jun 30, 2022)
1-160030741-G-A		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • PIGM-related disorder	Benign/Likely benign (Aug 30, 2023)
1-160030758-T-A		not specified	Uncertain significance (Aug 13, 2021)
1-160030778-G-T		PIGM-related disorder	Uncertain significance (Aug 18, 2022)
1-160030779-T-C		not specified	Uncertain significance (Dec 19, 2023)
1-160030781-T-C		PIGM-related disorder	Uncertain significance (Dec 02, 2023)
1-160030790-C-T		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency • not specified	Uncertain significance (May 10, 2024)
1-160030802-AGGTCTCTGT-A		See cases	Uncertain significance (May 10, 2021)
1-160030873-G-C		Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	Likely benign (Aug 16, 2022)
1-160030877-A-G		not specified	Uncertain significance (Jun 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGM	protein_coding	protein_coding	ENST00000368090	1	4322

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000539	0.699	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0811	215	212	1.02	0.0000103	2735
Missense in Polyphen		72	79.781	0.90247		1063
Synonymous	0.0922	90	91.1	0.988	0.00000463	893
Loss of Function	0.957	8	11.5	0.695	5.05e-7	146

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly. {ECO:0000269|PubMed:11226175}.
• Disease: DISEASE: Glycosylphosphatidylinositol deficiency (GPID) [MIM:610293]: Autosomal recessive trait that results in a propensity to venous thrombosis and seizures. Deficiency is due to a point mutation in the regulatory sequences of PIGM that disrupts binding of the transcription factor SP1 to its cognate promoter motif, leading to a strong reduction of expression. {ECO:0000269|PubMed:16767100}. 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: 0.102

Intolerance Scores

• loftool: 0.675
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

• pHI: 0.0995
• hipred: N
• hipred_score: 0.239
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.371

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigm
• 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
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: transferase activity, transferring hexosyl groups