PGGHG

Summary

PGGHG (protein-glucosylgalactosylhydroxylysine glucosidase, HGNC:26210) is a protein-coding gene on chromosome 11p15.5, encoding Protein-glucosylgalactosylhydroxylysine glucosidase (Q32M88). Catalyzes the hydrolysis of glucose from the disaccharide unit linked to hydroxylysine residues of collagen and collagen-like proteins.

Enables protein-glucosylgalactosylhydroxylysine glucosidase activity. Involved in carbohydrate metabolic process. Located in cytosol.

Source: NCBI Gene 80162 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_025092

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26210
Approved symbol	PGGHG
Name	protein-glucosylgalactosylhydroxylysine glucosidase
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22635
Ensembl gene	ENSG00000142102
Ensembl biotype	protein_coding
OMIM	617032
Entrez	80162

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000397660, ENST00000409479, ENST00000409548, ENST00000409655, ENST00000474221, ENST00000476372, ENST00000482937, ENST00000529087, ENST00000865174, ENST00000865175, ENST00000865176, ENST00000865177, ENST00000865178, ENST00000935432, ENST00000935433, ENST00000943937, ENST00000943938

RefSeq mRNA: 1 — MANE Select: NM_025092 NM_025092

CCDS: CCDS31322

Canonical transcript exons

ENST00000409548 — 14 exons

Exon	Start	End
ENSE00001492785	293366	293502
ENSE00001492806	293163	293235
ENSE00001584341	289126	289239
ENSE00001607402	290678	291113
ENSE00002159295	294556	296107
ENSE00003470125	294267	294478
ENSE00003477800	293594	293727
ENSE00003549512	291976	292095
ENSE00003559650	292886	292997
ENSE00003596264	292546	292677
ENSE00003621402	290390	290600
ENSE00003648187	289804	290075
ENSE00003649557	293830	293925
ENSE00003683502	294099	294196

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4109 / max 318.5008, expressed in 1732 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112167	9.1963	1641
112168	4.9520	1455
206070	0.2625	120

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.43	gold quality
granulocyte	CL:0000094	98.61	gold quality
right lung	UBERON:0002167	98.27	gold quality
tendon of biceps brachii	UBERON:0008188	98.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.53	gold quality
right uterine tube	UBERON:0001302	96.98	gold quality
upper lobe of left lung	UBERON:0008952	96.88	gold quality
spleen	UBERON:0002106	96.87	gold quality
left lobe of thyroid gland	UBERON:0001120	96.74	gold quality
left uterine tube	UBERON:0001303	96.70	gold quality
right lobe of thyroid gland	UBERON:0001119	96.47	gold quality
metanephros cortex	UBERON:0010533	96.40	gold quality
mucosa of transverse colon	UBERON:0004991	96.35	gold quality
right lobe of liver	UBERON:0001114	95.88	gold quality
thyroid gland	UBERON:0002046	95.45	gold quality
endocervix	UBERON:0000458	95.40	gold quality
upper lobe of lung	UBERON:0008948	95.40	gold quality
small intestine	UBERON:0002108	95.33	gold quality
tibial nerve	UBERON:0001323	94.79	gold quality
lymph node	UBERON:0000029	94.72	gold quality
minor salivary gland	UBERON:0001830	94.60	gold quality
descending thoracic aorta	UBERON:0002345	94.40	gold quality
blood	UBERON:0000178	94.28	gold quality
ascending aorta	UBERON:0001496	94.03	gold quality
thoracic aorta	UBERON:0001515	93.96	gold quality
gall bladder	UBERON:0002110	93.70	gold quality
omental fat pad	UBERON:0010414	93.69	gold quality
left coronary artery	UBERON:0001626	93.68	gold quality
peritoneum	UBERON:0002358	93.64	gold quality
coronary artery	UBERON:0001621	93.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting PGGHG, 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-4447	99.85	67.81	2900
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-6076	98.61	65.69	637
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-6891-3P	95.80	65.76	683
HSA-MIR-2277-3P	91.94	62.27	299
HSA-MIR-1204	89.50	65.56	109

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgghg	ENSDARG00000014311
mus_musculus	Pgghg	ENSMUSG00000062031
rattus_norvegicus	Pgghg	ENSRNOG00000014783
drosophila_melanogaster	CG16965	FBGN0032387

Protein

Protein identifiers

Protein-glucosylgalactosylhydroxylysine glucosidase — Q32M88 (reviewed: Q32M88)

Alternative names: Acid trehalase-like protein 1

All UniProt accessions (6): Q32M88, A0A024R1Z9, B8ZZ60, E7EMA9, H0YCL6, H3BM00

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of glucose from the disaccharide unit linked to hydroxylysine residues of collagen and collagen-like proteins.

Similarity. Belongs to the glycosyl hydrolase 65 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q32M88-1	1	yes
Q32M88-2	2

RefSeq proteins (1): NP_079368* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005195	Glyco_hydro_65_M	Domain
IPR008928	6-hairpin_glycosidase_sf	Homologous_superfamily
IPR012341	6hp_glycosidase-like_sf	Homologous_superfamily

Pfam: PF03632

Catalyzed reactions (Rhea), 1 shown:

• (5R)-5-O-[alpha-D-glucosyl-(1->2)-beta-D-galactosyl]-5-hydroxy-L-lysyl-[collagen] + H2O = (5R)-5-O-(beta-D-galactosyl)-5-hydroxy-L-lysyl-[collagen] + D-glucose (RHEA:11068)

UniProt features (14 total): mutagenesis site 5, binding site 2, splice variant 2, chain 1, region of interest 1, sequence conflict 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9SD5	X-RAY DIFFRACTION	1.36
9SD7	X-RAY DIFFRACTION	1.39
9SD8	X-RAY DIFFRACTION	1.61
9SD6	X-RAY DIFFRACTION	1.7
9SD4	X-RAY DIFFRACTION	2.39

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q32M88-F1	91.66	0.89

Functional residue map

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

Catalytic / active sites (1): 430 (proton donor)

Ligand- & substrate-binding residues (2): 300–301; 498–499

Mutagenesis-validated functional residues (5):

Position	Phenotype
429	significantly impairs catalytic activity.
430	abolishes catalytic activity.
574	abolishes catalytic activity.
301	abolishes catalytic activity.
429	abolishes catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, HOEBEKE_LYMPHOID_STEM_CELL_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, KIM_WT1_TARGETS_DN, GOMF_GLUCOSIDASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_GLYCOSYL_BONDS, GOMF_HYDROLASE_ACTIVITY_HYDROLYZING_O_GLYCOSYL_COMPOUNDS, GUTIERREZ_CHRONIC_LYMPHOCYTIC_LEUKEMIA_DN, VDR_Q6, LEE_DIFFERENTIATING_T_LYMPHOCYTE, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN, LEE_BMP2_TARGETS_UP, KRAS.600.LUNG.BREAST_UP.V1_DN, KRAS.BREAST_UP.V1_DN

GO Biological Process (1): carbohydrate metabolic process (GO:0005975)

GO Molecular Function (4): protein-glucosylgalactosylhydroxylysine glucosidase activity (GO:0047402), catalytic activity (GO:0003824), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (1): cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
glucosidase activity	1
catalytic activity, acting on a protein	1
molecular_function	1
catalytic activity	1
hydrolase activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGGHG	B4GALNT4	Q76KP1	705
PGGHG	IFITM5	A6NNB3	590
PGGHG	TREH	O43280	575
PGGHG	NLRP6	P59044	532
PGGHG	IFITM10	A6NMD0	529
PGGHG	PKP3	Q9Y446	521
PGGHG	SYNDIG1L	A6NDD5	497
PGGHG	IFITM2	Q01629	452
PGGHG	IFITM1	P13164	420
PGGHG	IFITM3	Q01628	415
PGGHG	TMEM91	Q6ZNR0	409
PGGHG	ZNF329	Q86UD4	380
PGGHG	PRRT1	Q99946	377
PGGHG	GAPDH	P00354	375
PGGHG	PSMD13	Q9UNM6	360

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ECE1	PGGHG	psi-mi:“MI:0915”(physical association)	0.370
PGGHG	ECE1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (7): ATHL1 (Affinity Capture-RNA), ATHL1 (Affinity Capture-MS), ATHL1 (Affinity Capture-RNA), ATHL1 (Affinity Capture-MS), ATHL1 (Affinity Capture-RNA), ATHL1 (Two-hybrid), ATHL1 (Affinity Capture-Western)

ESM2 similar proteins: A0JND9, E1BPW0, O14773, O18956, O35795, O55026, O75173, O75355, O75356, O75578, O89023, O93295, P08514, P08648, P11688, P17405, P49961, P55772, P56201, P79784, P97687, Q04519, Q0VD19, Q12794, Q32M88, Q49HH9, Q49KI5, Q5DRK1, Q5IS74, Q5MY95, Q5RFL1, Q5RFQ8, Q60HH1, Q6P3E7, Q6P6S9, Q717C1, Q717C2, Q7RTX0, Q8BFW6, Q8BNJ2

Diamond homologs: A0A1H1XG33, A0JMP0, A5FBJ5, B8D049, F1NZI4, M1RNJ8, N1P212, O06993, P48016, P78617, Q32M88, Q54KX5, Q5AAU5, Q8BP56, Q8RBL8, E6ENP7, Q8GRC3, Q8L163, A9KT32, D6XZ22, P9WN14, P9WN15, A0PMI0, A0QKN5, A1KP65, A5U846, B2HDP8, E1WGG9, F4I1A6, F4KFG5, G4RK44, O64896, P0CL50, P55611, P65070, P9WFZ4, P9WFZ5, P9WKZ6, P9WKZ7, Q0D6F4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2541 predictions. Top by Δscore:

Variant	Effect	Δscore
11:290593:G:GT	donor_gain	1.0000
11:290596:GCCCG:G	donor_gain	1.0000
11:292096:G:GA	donor_loss	1.0000
11:292097:T:G	donor_loss	1.0000
11:292543:CAGGG:C	acceptor_gain	1.0000
11:292544:A:AG	acceptor_gain	1.0000
11:292544:AG:A	acceptor_gain	1.0000
11:292544:AGGGA:A	acceptor_gain	1.0000
11:292545:G:GA	acceptor_loss	1.0000
11:292545:G:GG	acceptor_gain	1.0000
11:292545:GG:G	acceptor_gain	1.0000
11:292545:GGGA:G	acceptor_gain	1.0000
11:292545:GGGAG:G	acceptor_gain	1.0000
11:292674:CCAGG:C	donor_loss	1.0000
11:292675:CAG:C	donor_loss	1.0000
11:292676:AGG:A	donor_loss	1.0000
11:292677:GGTGA:G	donor_loss	1.0000
11:292679:T:A	donor_loss	1.0000
11:293415:A:AG	acceptor_gain	1.0000
11:293416:G:GG	acceptor_gain	1.0000
11:293416:GCCA:G	acceptor_gain	1.0000
11:293726:GG:G	donor_gain	1.0000
11:293727:GG:G	donor_gain	1.0000
11:293821:T:TA	acceptor_gain	1.0000
11:293828:A:AG	acceptor_gain	1.0000
11:293829:G:GG	acceptor_gain	1.0000
11:293829:GA:G	acceptor_gain	1.0000
11:293829:GAGC:G	acceptor_gain	1.0000
11:293829:GAGCA:G	acceptor_gain	1.0000
11:294265:AG:A	acceptor_gain	1.0000

AlphaMissense

4762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:293830:A:C	S539R	0.985
11:293832:C:A	S539R	0.985
11:293832:C:G	S539R	0.985
11:293484:T:C	F488L	0.983
11:293486:C:A	F488L	0.983
11:293486:C:G	F488L	0.983
11:294138:T:C	F584L	0.982
11:294140:C:A	F584L	0.982
11:294140:C:G	F584L	0.982
11:292943:T:C	F406L	0.979
11:292945:T:A	F406L	0.979
11:292945:T:G	F406L	0.979
11:294102:T:A	W572R	0.979
11:294102:T:C	W572R	0.979
11:291048:A:C	S281R	0.975
11:291050:T:A	S281R	0.975
11:291050:T:G	S281R	0.975
11:293920:T:C	F569L	0.973
11:293922:C:A	F569L	0.973
11:293922:C:G	F569L	0.973
11:294137:C:A	N583K	0.973
11:294137:C:G	N583K	0.973
11:290395:T:C	F89L	0.971
11:290397:T:A	F89L	0.971
11:290397:T:G	F89L	0.971
11:292042:C:A	R325S	0.971
11:292567:A:C	S350R	0.969
11:292569:T:A	S350R	0.969
11:292569:T:G	S350R	0.969
11:291105:T:A	W300R	0.967

dbSNP variants (sampled 300 via entrez): RS1000116014 (11:295525 C>G,T), RS1000120544 (11:289157 G>A,C), RS1000274492 (11:289550 G>C), RS1000383447 (11:293665 C>T), RS1000514908 (11:288941 T>C), RS1000848576 (11:292392 C>T), RS1000922085 (11:292260 G>A), RS1001108474 (11:287919 G>A,C), RS1001540140 (11:288174 G>A), RS1001747142 (11:295709 T>C), RS1001777134 (11:288681 C>A,T), RS1001853854 (11:291693 C>T), RS1002099434 (11:295489 G>A,C), RS1002284161 (11:294027 G>A), RS1002380069 (11:290221 C>A,G,T)

Disease associations

OMIM: gene MIM:617032 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006016_19	Serum alkaline phosphatase levels	3.000000e-38
GCST90011900_65	Serum alkaline phosphatase levels	1.000000e-71

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

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases expression, affects cotreatment	1
bufotalin	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Nickel	increases expression	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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