PIGH

phosphatidylinositol glycan anchor biosynthesis class H, the group of Phosphatidylinositol glycan anchor biosynthesis|Glycosylphosphatidylinositol-N-acetylglucosaminyltransferase complex

Basic information

Region (hg38): 14:67581954-67600286

Links

ENSG00000100564 ∙ NCBI:5283 ∙ OMIM:600154 ∙ HGNC:8964 ∙ Uniprot:Q14442 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycosylphosphatidylinositol biosynthesis defect 17 (Strong), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 17 (Strong), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 17 (Limited), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 17 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycosylphosphatidylinositol biosynthesis defect 17	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal; Neurologic	29573052; 29603516; 33156547; 35445667

ClinVar

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

• Inborn genetic diseases (10 variants)
• not provided (3 variants)
• Glycosylphosphatidylinositol biosynthesis defect 17 (2 variants)
• PIGH-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGH 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		1
missense	1		9			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	1	0	9	1	0

Highest pathogenic variant AF is 0.00000657

Variants in PIGH

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

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

Position	Type	Phenotype	Significance	ClinVar
14-67582088-G-A		not specified	Uncertain significance (Apr 06, 2022)
14-67582134-C-G		not specified	Uncertain significance (Dec 27, 2022)
14-67583792-T-A		not specified	Uncertain significance (Jan 02, 2024)
14-67583850-G-A		not specified	Uncertain significance (Jul 14, 2021)
14-67584062-C-T		not specified	Uncertain significance (Jan 04, 2024)
14-67585647-A-C		not specified	Uncertain significance (Jun 23, 2023)
14-67585650-C-T		not specified	Uncertain significance (Jun 29, 2023)
14-67585988-C-T		not specified	Uncertain significance (Nov 29, 2021)
14-67586013-C-A		not specified	Uncertain significance (Nov 12, 2021)
14-67587171-A-G		not specified	Uncertain significance (Nov 07, 2022)
14-67587182-C-T			Benign (Dec 31, 2019)
14-67590123-T-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
14-67590144-A-G		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
14-67590151-A-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2023)
14-67590160-G-A		Glycosylphosphatidylinositol biosynthesis defect 17 • Inborn genetic diseases • PIGH-related disorder	Conflicting classifications of pathogenicity (Aug 25, 2023)
14-67592638-G-C		Malignant tumor of prostate	Uncertain significance (-)
14-67592688-A-G		PIGH-related disorder	Likely benign (May 01, 2023)
14-67593759-T-C		Inborn genetic diseases	Uncertain significance (May 17, 2023)
14-67593826-A-G		Glycosylphosphatidylinositol biosynthesis defect 17	Pathogenic (-)
14-67593857-G-A		PIGH-related disorder	Benign (Oct 24, 2019)
14-67593897-T-C		Inborn genetic diseases	Uncertain significance (Apr 26, 2023)
14-67593904-G-A		Inborn genetic diseases	Uncertain significance (Feb 09, 2022)
14-67593945-A-G		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
14-67593946-T-C		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
14-67600018-C-T		PIGH-related disorder	Benign (Nov 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGH	protein_coding	protein_coding	ENST00000216452	4	18333

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.231	0.739	125719	0	12	125731	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.948	69	95.0	0.726	0.00000441	1200
Missense in Polyphen		20	25.009	0.79972		317
Synonymous	1.73	25	38.7	0.646	0.00000179	376
Loss of Function	1.81	2	7.26	0.276	3.07e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000118	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000812	0.0000791
Middle Eastern	0.000118	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the complex catalyzing the transfer of N- acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, the first step of GPI biosynthesis.
• 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: 0.125

Intolerance Scores

• loftool: 0.392
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.252
• hipred: N
• hipred_score: 0.336
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.571

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigh
• Phenotype: homeostasis/metabolism 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: cellular protein modification process;GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane
• Cellular component: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex;endoplasmic reticulum;endoplasmic reticulum membrane
• Molecular function: catalytic activity;phosphatidylinositol N-acetylglucosaminyltransferase activity