PGAP6

post-GPI attachment to proteins 6, the group of TMEM8 family

Basic information

Region (hg38): 16:370787-387113

Previous symbols: [ "TMEM6", "TMEM8", "TMEM8A" ]

Links

ENSG00000129925 ∙ NCBI:58986 ∙ OMIM:619342 ∙ HGNC:17205 ∙ Uniprot:Q9HCN3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PGAP6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PGAP6 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			82	9		91
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	82	10	0

Variants in PGAP6

This is a list of pathogenic ClinVar variants found in the PGAP6 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-372012-C-G		not specified	Uncertain significance (May 18, 2022)
16-372054-G-A		not specified	Uncertain significance (Nov 17, 2022)
16-372062-C-G		not specified	Uncertain significance (Apr 17, 2024)
16-372067-G-A		not specified	Uncertain significance (Jan 23, 2024)
16-372075-G-A		not specified	Uncertain significance (Oct 12, 2021)
16-372085-G-T			Likely benign (May 01, 2023)
16-372150-T-C		not specified	Uncertain significance (Mar 25, 2024)
16-372151-A-G		not specified	Uncertain significance (Dec 15, 2022)
16-372184-C-T		not specified	Likely benign (May 22, 2024)
16-372187-T-A		not specified	Uncertain significance (Jun 11, 2021)
16-372202-T-C		not specified	Uncertain significance (Jul 06, 2021)
16-372208-C-T		not specified	Likely benign (Jan 26, 2022)
16-372211-C-T		not specified	Uncertain significance (Sep 09, 2021)
16-372261-C-T		not specified	Uncertain significance (Feb 03, 2022)
16-372271-C-T		not specified	Uncertain significance (Dec 17, 2023)
16-372614-C-T		not specified	Uncertain significance (Jan 09, 2024)
16-372624-A-T		not specified	Uncertain significance (Jan 29, 2024)
16-372627-A-C		not specified	Uncertain significance (Jan 29, 2024)
16-372649-G-A		not specified	Uncertain significance (Jul 05, 2023)
16-372675-C-T		not specified	Uncertain significance (May 21, 2024)
16-372694-T-C		not specified	Uncertain significance (Feb 27, 2023)
16-374024-A-T		not specified	Uncertain significance (May 24, 2023)
16-374028-G-A		not specified	Uncertain significance (May 17, 2023)
16-374050-C-A		not specified	Uncertain significance (Jan 30, 2024)
16-374079-C-T		not specified	Uncertain significance (Mar 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PGAP6	protein_coding	protein_coding	ENST00000431232	13	16341

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.37e-10	0.940	125402	0	154	125556	0.000613

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.13	565	494	1.14	0.0000340	4898
Missense in Polyphen		201	180.51	1.1135		1812
Synonymous	-2.30	273	229	1.19	0.0000176	1639
Loss of Function	2.00	20	32.3	0.620	0.00000156	330

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000817	0.000805
Ashkenazi Jewish	0.000100	0.0000994
East Asian	0.00104	0.00103
Finnish	0.00108	0.00102
European (Non-Finnish)	0.000453	0.000423
Middle Eastern	0.00104	0.00103
South Asian	0.00151	0.00134
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchor proteins (GPI-AP). Has phospholipase A2 activity that removes an acyl-chain at the sn-2 position of GPI-anchors during the remodeling of GPI. Required for the shedding of the GPI-AP TDGF1, but not CFC1, at the cell surface. Shedding of TDGF1 modulates Nodal signaling by allowing soluble TDGF1 to act as a Nodal coreceptor on other cells (PubMed:27881714). Also indirectly involved in the translocation of RAC1 from the cytosol to the plasma membrane by maintaining the steady state amount of CAV1-enriched plasma membrane subdomains, stabilizing RAC1 at the plasma membrane (PubMed:27835684). In contrast to myomaker (TMEM8C), has no fusogenic activity (PubMed:26858401). {ECO:0000269|PubMed:26858401, ECO:0000269|PubMed:27835684, ECO:0000269|PubMed:27881714}.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.807
• rvis_EVS: 0.12
• rvis_percentile_EVS: 62.4

Haploinsufficiency Scores

• pHI: 0.174
• hipred: N
• hipred_score: 0.383
• ghis: 0.476

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.176

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem8
• 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); embryo phenotype

Gene ontology

• Biological process: biological_process
• Cellular component: lysosomal membrane;plasma membrane;integral component of plasma membrane;extracellular exosome
• Molecular function: molecular_function;phospholipase A2 activity;protein binding;phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine);phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine)