PIGQ

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

Basic information

Region (hg38): 16:566995-584109

Links

ENSG00000007541 ∙ NCBI:9091 ∙ OMIM:605754 ∙ HGNC:14135 ∙ Uniprot:Q9BRB3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 77 (Moderate), mode of inheritance: AR
• developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 77 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple congenital anomalies-hypotonia-seizures syndrome 4	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	Craniofacial; Musculoskeletal; Neurologic	24463883; 25558065; 31148362

ClinVar

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

• Epilepsy (23 variants)
• Developmental and epileptic encephalopathy, 77 (3 variants)
• Inborn genetic diseases (2 variants)
• Global developmental delay;Optic atrophy;Intractable seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGQ 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			7	169	7	183
missense		1	287	25	9	322
nonsense	12	1	5	1		19
start loss			1			1
frameshift	11	2	5			18
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			14	13		27
non coding	1	1	2	55	40	99
Total	25	8	310	250	56

Highest pathogenic variant AF is 0.0000263

Variants in PIGQ

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

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

Position	Type	Phenotype	Significance	ClinVar
16-568065-C-A			Likely benign (Mar 01, 2022)
16-568126-G-A		not specified	Uncertain significance (Feb 05, 2024)
16-568277-G-A		not specified	Uncertain significance (Feb 14, 2023)
16-568402-C-T		not specified	Uncertain significance (Dec 12, 2023)
16-572565-A-G		Developmental and epileptic encephalopathy, 77 • not specified	Benign (Jul 15, 2024)
16-574075-A-C		Epilepsy	Uncertain significance (Jul 23, 2022)
16-574086-G-A		Epilepsy	Uncertain significance (Mar 09, 2021)
16-574086-G-T		Epilepsy	Uncertain significance (Jan 01, 2021)
16-574093-T-G		Epilepsy • Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
16-574095-C-T		Epilepsy	Likely benign (Mar 23, 2023)
16-574097-C-A		Epilepsy	Uncertain significance (Aug 30, 2023)
16-574101-G-A		Epilepsy	Benign (Feb 01, 2024)
16-574102-T-G		Epilepsy	Uncertain significance (Mar 18, 2022)
16-574107-C-T		Epilepsy	Likely benign (Nov 28, 2022)
16-574108-G-A		Epilepsy	Benign (Feb 01, 2024)
16-574112-C-G		Epilepsy	Uncertain significance (Mar 03, 2022)
16-574112-C-T		Epilepsy	Uncertain significance (Feb 04, 2022)
16-574113-G-A		Epilepsy	Likely benign (Dec 13, 2023)
16-574113-GA-AG		Epilepsy	Uncertain significance (Jul 05, 2022)
16-574114-A-G		Epilepsy • Developmental and epileptic encephalopathy, 77 • not specified	Benign (Jul 15, 2024)
16-574114-AC-GT		Epilepsy	Uncertain significance (Mar 11, 2022)
16-574115-C-T		Epilepsy • Inborn genetic diseases • PIGQ-related disorder	Likely benign (Dec 27, 2023)
16-574116-G-A		Epilepsy	Likely benign (Apr 01, 2023)
16-574122-C-T		Epilepsy	Likely benign (Jan 14, 2024)
16-574123-G-A		PIGQ-related disorder	Uncertain significance (May 25, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGQ	protein_coding	protein_coding	ENST00000026218	9	17142

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000136	0.957	125639	0	37	125676	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0950	488	482	1.01	0.0000324	4773
Missense in Polyphen		130	126.08	1.0311		1285
Synonymous	-1.91	260	224	1.16	0.0000156	1701
Loss of Function	1.91	13	22.9	0.568	0.00000115	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000328	0.000301
Ashkenazi Jewish	0.00	0.00
East Asian	0.000273	0.000272
Finnish	0.0000993	0.0000924
European (Non-Finnish)	0.000195	0.000185
Middle Eastern	0.000273	0.000272
South Asian	0.00	0.00
Other	0.000344	0.000326

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 (Consensus)

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.829
• rvis_EVS: 0.08
• rvis_percentile_EVS: 59.21

Haploinsufficiency Scores

• pHI: 0.122
• hipred: N
• hipred_score: 0.170
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.394

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigq

Gene ontology

• Biological process: carbohydrate metabolic process;preassembly of GPI anchor in ER membrane
• Cellular component: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex;endoplasmic reticulum membrane;integral component of membrane
• Molecular function: phosphatidylinositol N-acetylglucosaminyltransferase activity