PGAP6

protein-coding

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

Gene summary

Predicted to enable A2-type glycerophospholipase activity. Predicted to be involved in lipid metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

TMEM6
TMEM8
TMEM8A

MANE transcript

NM_021259.3

Inheritance

—

ClinVar variants

U:218B:19

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr16:370,788-387,113

External References & Databases

Ensembl (ENSG00000129925)

Transcript & Mutation Effects

hg38 • Region Span ~16.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PGAP6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 218

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021259.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	1 clinvar		7
missense			207 clinvar	18 clinvar		225
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	218	19	0	237

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021259.3	RefSeq	NP_067082.2	13	MANE Select
ENST00000431232.7	Ensembl	ENSP00000401338.2	13	MANE Select
ENST00000250930.7	Ensembl	ENSP00000250930.3	10	Standard
ENST00000250930.8	Ensembl	ENSP00000250930.3	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process

Molecular Function

molecular_function
phospholipase A2 activity
protein binding
phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine)
phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine)

Cellular Component

lysosomal membrane
plasma membrane
integral component of plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000431232
Coding exons: 13
Length: 16341
Individuals with no LoFs: 125402
Homozygous LoFs: 0
Heterozygous LoFs: 154
Defined: 125556
p: 0.000613

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.13	565	494	1.14	0.0000340	4898
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00044	0.00043	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0010	0.0010	notable
Finnish	0.0011	0.0010	notable
European (Non-Finnish)	0.00045	0.00042	rare
South Asian	0.0015	0.0013	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.176

Gene Damage Prediction

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