PGAP4

Summary

PGAP4 (post-GPI attachment to proteins GalNAc transferase 4, HGNC:28180) is a protein-coding gene on chromosome 9q31.1, encoding GPI-N-acetylgalactosamine transferase PGAP4 (Q9BRR3). Golgi-resident glycosylphosphatidylinositol (GPI)-N-acetylgalactosamine transferase that catalyzes the N-acetyl-beta-D-galactosamine transfer from an UDP-N-acetyl-alpha-D-galactosamine to the 4-OH-position of the first mannose of the glycosylphosphatidylinositol (GPI) of a GPI-a….

Enables glycosyltransferase activity. Involved in GPI anchor biosynthetic process. Located in Golgi membrane.

Source: NCBI Gene 84302 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_032342

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28180
Approved symbol	PGAP4
Name	post-GPI attachment to proteins GalNAc transferase 4
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC12992
Ensembl gene	ENSG00000165152
Ensembl biotype	protein_coding
OMIM	620264
Entrez	84302

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374847, ENST00000374848, ENST00000374851, ENST00000482920, ENST00000851105, ENST00000851106, ENST00000851107, ENST00000851108, ENST00000851109, ENST00000851110, ENST00000851111, ENST00000945510

RefSeq mRNA: 4 — MANE Select: NM_032342 NM_001303107, NM_001303108, NM_001371233, NM_032342

CCDS: CCDS6757

Canonical transcript exons

ENST00000374848 — 2 exons

Exon	Start	End
ENSE00001090796	101486949	101487173
ENSE00003850419	101473170	101477169

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 96.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9823 / max 106.9342, expressed in 1229 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101760	5.0497	1151
101759	3.9083	1065
101761	0.0243	5

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	96.12	gold quality
cerebellar vermis	UBERON:0004720	95.58	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.53	gold quality
frontal pole	UBERON:0002795	94.36	gold quality
superior vestibular nucleus	UBERON:0007227	93.93	gold quality
paraflocculus	UBERON:0005351	93.74	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.51	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.36	gold quality
prefrontal cortex	UBERON:0000451	92.05	gold quality
substantia nigra pars compacta	UBERON:0001965	92.01	gold quality
superior frontal gyrus	UBERON:0002661	91.61	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.58	gold quality
orbitofrontal cortex	UBERON:0004167	91.27	gold quality
parietal lobe	UBERON:0001872	91.25	gold quality
ventral tegmental area	UBERON:0002691	91.19	gold quality
postcentral gyrus	UBERON:0002581	91.04	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.95	gold quality
myocardium	UBERON:0002349	90.88	gold quality
left ventricle myocardium	UBERON:0006566	90.81	gold quality
frontal cortex	UBERON:0001870	90.75	gold quality
colonic mucosa	UBERON:0000317	90.54	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.54	gold quality
penis	UBERON:0000989	90.34	gold quality
trigeminal ganglion	UBERON:0001675	90.24	gold quality
entorhinal cortex	UBERON:0002728	90.08	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.79	gold quality
neocortex	UBERON:0001950	89.67	gold quality
middle frontal gyrus	UBERON:0002702	89.60	gold quality
cerebellum	UBERON:0002037	89.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.24
E-MTAB-7303	no	1406.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting PGAP4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-10394-5P	99.65	66.83	1852

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgap4	ENSDARG00000061553
mus_musculus	Pgap4	ENSMUSG00000039611
rattus_norvegicus	Pgap4	ENSRNOG00000006800
caenorhabditis_elegans		WBGENE00009403

Protein

Protein identifiers

GPI-N-acetylgalactosamine transferase PGAP4 — Q9BRR3 (reviewed: Q9BRR3)

Alternative names: Post-GPI attachment to proteins GalNAc transferase 4, Post-GPI attachment to proteins factor 4, Transmembrane protein 246

All UniProt accessions (1): Q9BRR3

UniProt curated annotations — full annotation on UniProt →

Function. Golgi-resident glycosylphosphatidylinositol (GPI)-N-acetylgalactosamine transferase that catalyzes the N-acetyl-beta-D-galactosamine transfer from an UDP-N-acetyl-alpha-D-galactosamine to the 4-OH-position of the first mannose of the glycosylphosphatidylinositol (GPI) of a GPI-anchored protein (GPI-AP). This modification occurs after the fatty acid remodeling step of the GPI-anchor maturation.

Subcellular location. Golgi apparatus membrane.

Post-translational modifications. Glycosylated.

Domain organisation. Contains three transmembrane domains, including a tandem transmembrane domain insertion into its glycosyltransferase-A fold. Transmembrane domain 1 functions as a signal for Golgi targeting. The conserved DXD motif is involved in enzyme activity.

Similarity. Belongs to the PGAP4 family.

RefSeq proteins (4): NP_001290036, NP_001290037, NP_001358162, NP_115718* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029675	PGAP4	Family

Catalyzed reactions (Rhea), 1 shown:

• [protein]-C-terminal carboxyl phosphoethanolamide-(1-radyl,2-octadecanoyl)-GPI(deacylinositol-H7) + UDP-N-acetyl-alpha-D-galactosamine = [protein]-C-terminal carboxyl phosphoethanolamide-GalNAc-(1-radyl-2-octadecanoyl)-GPI(deacylinositol-H7) + UDP + H(+) (RHEA:83855)

UniProt features (35 total): mutagenesis site 18, topological domain 4, binding site 4, disulfide bond 3, transmembrane region 3, chain 1, glycosylation site 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRR3-F1	88.19	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 334; 335; 362; 109

Disulfide bonds (3): 132–136, 144–194, 332–333

Glycosylation sites (1): 87

Mutagenesis-validated functional residues (18):

Position	Phenotype
87	loss of glycosylation. not glycosylated; when associated with n-283. glycosylated; when associated with n-347.
109	reduces gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
211	loss of gpi-galnac transferase activity.
213	loss of gpi-galnac transferase activity.
247	reduces gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
249	slightly reduces gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
260	no effect on gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
270	no effect on gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
283	not glycosylated; when associated with a-87.
302	no effect on gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
311	no effect on gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
313	reduces gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
317	strongly reduces gpi-galnac transferase activity. accumulates in the endoplasmic reticulum.
334	almost abolishes gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
335	reduces gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
347	glycosylated; when associated with a-87.
362	reduces gpi-galnac transferase activity. no effect on golgi apparatus membrane location.
363	loss of gpi-galnac transferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 118 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (1): GPI anchor biosynthetic process (GO:0006506)

GO Molecular Function (2): glycosyltransferase activity (GO:0016757), transferase activity (GO:0016740)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GPI anchor metabolic process	1
glycolipid biosynthetic process	1
glycerophospholipid biosynthetic process	1
GPI anchored protein biosynthesis	1
transferase activity	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGAP4	PIGZ	Q86VD9	664
PGAP4	PIGO	Q8TEQ8	541
PGAP4	B3GALT4	O96024	507
PGAP4	WDR31	Q8NA23	461
PGAP4	PGAP3	Q96FM1	448
PGAP4	PIGB	Q92521	446
PGAP4	FREM1	Q5H8C1	443
PGAP4	PGAP2	Q9UHJ9	417
PGAP4	PIGS	Q96S52	417
PGAP4	ST3GAL5	Q9UNP4	416
PGAP4	B4GALT5	O43286	410
PGAP4	RGS9BP	Q6ZS82	404
PGAP4	ALG9	Q9H6U8	395
PGAP4	PGAP1	Q75T13	391
PGAP4	RXYLT1	Q9Y2B1	356

IntAct

66 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
PGAP4	B3GNT2	psi-mi:“MI:0915”(physical association)	0.370
Clspn	MCM3	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
VIPR2	C15orf61	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
BSCL2	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMTM5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
OPRL1	METTL15	psi-mi:“MI:0914”(association)	0.350
VIPR2	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350
GP9	ESYT2	psi-mi:“MI:0914”(association)	0.350
RTN3	ESYT2	psi-mi:“MI:0914”(association)	0.350
KCNK1	TMEM223	psi-mi:“MI:0914”(association)	0.350
ACKR2	TMEM223	psi-mi:“MI:0914”(association)	0.350
HLA-C	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TSPAN8	POTEF	psi-mi:“MI:0914”(association)	0.350
SLC1A1	UBXN8	psi-mi:“MI:0914”(association)	0.350
AQP3	UBXN8	psi-mi:“MI:0914”(association)	0.350

BioGRID (80): TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Affinity Capture-MS), TMEM246 (Biochemical Activity)

ESM2 similar proteins: A0A4Z3, A1Y9I9, A4FUH1, B6CZ46, B6CZ56, B6CZ62, D3ZNQ3, G3V9Q9, O43505, O60512, O60909, O94766, P14616, P14617, P58158, Q09326, Q10469, Q2NKH9, Q2YDM8, Q3V1N9, Q3V5L5, Q4R5T7, Q5EA01, Q5EB73, Q5JU69, Q5M936, Q5NVN3, Q5R4S2, Q5R868, Q5YB40, Q5ZLK4, Q64716, Q6AYR4, Q765H6, Q7Z4J2, Q8BGT9, Q8BWP8, Q8IXK2, Q8NCL4, Q8R1J9

Diamond homologs: Q5EB73, Q5R868, Q91YV9, Q9BRR3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-425366	7	20.8×	1e-05
SLC-mediated transmembrane transport	9	8.7×	5e-05
Transport of small molecules	11	4.5×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
intracellular monoatomic cation homeostasis	5	72.0×	1e-06
zinc ion transmembrane transport	5	45.0×	1e-05
intracellular zinc ion homeostasis	5	30.9×	6e-05
amino acid transport	7	28.0×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

53 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

316 predictions. Top by Δscore:

Variant	Effect	Δscore
9:101477165:CAAAC:C	acceptor_gain	0.9900
9:101477168:ACC:A	acceptor_loss	0.9900
9:101477170:C:CA	acceptor_loss	0.9900
9:101486942:AACCT:A	donor_loss	0.9900
9:101486943:ACCT:A	donor_loss	0.9900
9:101486944:CCTA:C	donor_loss	0.9900
9:101486945:CTACC:C	donor_loss	0.9900
9:101486946:TAC:T	donor_loss	0.9900
9:101486947:A:AC	donor_gain	0.9900
9:101486947:AC:A	donor_gain	0.9900
9:101486947:ACCCG:A	donor_loss	0.9900
9:101486948:C:CC	donor_gain	0.9900
9:101486948:C:CT	donor_loss	0.9900
9:101486948:CC:C	donor_gain	0.9900
9:101486948:CCCGG:C	donor_gain	0.9800
9:101477170:C:CC	acceptor_gain	0.9700
9:101477166:AAAC:A	acceptor_gain	0.9500
9:101477168:AC:A	acceptor_gain	0.9500
9:101477169:CC:C	acceptor_gain	0.9500
9:101477167:AAC:A	acceptor_gain	0.9400
9:101486948:CCCG:C	donor_gain	0.9400
9:101486947:ACC:A	donor_gain	0.9000
9:101486948:CCC:C	donor_gain	0.9000
9:101475874:TGGC:T	donor_gain	0.8800
9:101477170:C:T	acceptor_gain	0.8600
9:101475910:G:T	donor_gain	0.8100
9:101485975:A:T	donor_gain	0.8100
9:101476286:G:A	donor_gain	0.7500
9:101486310:G:T	donor_gain	0.7500
9:101477185:G:C	acceptor_gain	0.7300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010521 (9:101505503 T>G), RS1000129225 (9:101529862 C>G), RS1000131591 (9:101511182 A>T), RS1000131941 (9:101472886 C>T), RS1000186981 (9:101483116 A>G), RS1000194219 (9:101474362 C>G,T), RS1000197012 (9:101483394 G>A), RS1000214363 (9:101490979 T>C), RS1000250150 (9:101510673 C>T), RS1000266650 (9:101490743 G>A), RS1000316540 (9:101523831 G>C,T), RS1000326675 (9:101495980 G>A), RS1000395402 (9:101485322 A>G), RS1000404115 (9:101523693 C>T), RS1000430178 (9:101505829 G>C,T)

Disease associations

OMIM: gene MIM:620264 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001276_8	Liver enzyme levels (alkaline phosphatase)	1.000000e-09
GCST009652_14	Serum alkaline phosphatase levels	1.000000e-14
GCST90011900_209	Serum alkaline phosphatase levels	1.000000e-67
GCST90013406_152	Liver enzyme levels (alkaline phosphatase)	5.000000e-73

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
bisphenol A	affects cotreatment, affects methylation, increases expression	2
Lead	increases expression, affects expression	2
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
abrine	decreases expression	1
MRK 003	decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects binding, increases expression	1
Parathion	increases methylation	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.