ALG5

Summary

ALG5 (ALG5 dolichyl-phosphate beta-glucosyltransferase, HGNC:20266) is a protein-coding gene on chromosome 13q13.3, encoding Dolichyl-phosphate beta-glucosyltransferase (Q9Y673). Dolichyl-phosphate beta-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. It is a selective cancer dependency (DepMap: 11.9% of cell lines).

This gene encodes a member of the glycosyltransferase 2 family. The encoded protein participates in glucosylation of the oligomannose core in N-linked glycosylation of proteins. The addition of glucose residues to the oligomannose core is necessary to ensure substrate recognition, and therefore, effectual transfer of the oligomannose core to the nascent glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 29880 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polycystic kidney disease 7 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 88 total — 12 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 31
• Cancer dependency (DepMap): dependent in 11.9% of screened cell lines
• MANE Select transcript: NM_013338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20266
Approved symbol	ALG5
Name	ALG5 dolichyl-phosphate beta-glucosyltransferase
Location	13q13.3
Locus type	gene with protein product
Status	Approved
Aliases	bA421P11.2
Ensembl gene	ENSG00000120697
Ensembl biotype	protein_coding
OMIM	604565
Entrez	29880

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 15 protein_coding, 9 retained_intron, 8 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000239891, ENST00000443765, ENST00000460230, ENST00000486410, ENST00000496689, ENST00000679397, ENST00000679572, ENST00000679673, ENST00000679760, ENST00000679837, ENST00000680012, ENST00000680127, ENST00000680488, ENST00000680671, ENST00000680795, ENST00000680949, ENST00000681016, ENST00000681043, ENST00000681110, ENST00000681151, ENST00000681208, ENST00000681214, ENST00000681553, ENST00000681581, ENST00000681727, ENST00000681763, ENST00000681892, ENST00000681893, ENST00000857204, ENST00000857206, ENST00000857207, ENST00000857208, ENST00000939859

RefSeq mRNA: 2 — MANE Select: NM_013338 NM_001142364, NM_013338

CCDS: CCDS45033, CCDS9361

Canonical transcript exons

ENST00000239891 — 10 exons

Exon	Start	End
ENSE00000680657	36971977	36972036
ENSE00000817128	36985627	36985740
ENSE00000817131	36994989	36995035
ENSE00001900700	36949738	36950057
ENSE00003475927	36952514	36952599
ENSE00003478825	36989484	36989576
ENSE00003545294	36995425	36995596
ENSE00003561940	36993604	36993672
ENSE00003589257	36965575	36965726
ENSE00003842203	36999235	36999340

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.4008 / max 137.0229, expressed in 1817 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136809	23.8351	1817
136810	0.3582	163
136808	0.1296	9
136811	0.0778	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.52	gold quality
body of pancreas	UBERON:0001150	97.47	gold quality
corpus epididymis	UBERON:0004359	97.16	gold quality
tibia	UBERON:0000979	96.44	gold quality
palpebral conjunctiva	UBERON:0001812	95.96	gold quality
pancreas	UBERON:0001264	95.87	gold quality
renal glomerulus	UBERON:0000074	95.60	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.50	gold quality
caput epididymis	UBERON:0004358	95.41	gold quality
metanephric glomerulus	UBERON:0004736	95.41	gold quality
islet of Langerhans	UBERON:0000006	95.36	gold quality
parietal pleura	UBERON:0002400	95.15	gold quality
periodontal ligament	UBERON:0008266	95.08	gold quality
rectum	UBERON:0001052	95.03	gold quality
seminal vesicle	UBERON:0000998	95.02	gold quality
pleura	UBERON:0000977	95.00	gold quality
nephron tubule	UBERON:0001231	94.77	gold quality
colonic mucosa	UBERON:0000317	94.69	gold quality
visceral pleura	UBERON:0002401	94.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.51	gold quality
kidney epithelium	UBERON:0004819	94.32	gold quality
nasal cavity mucosa	UBERON:0001826	94.18	gold quality
skin of hip	UBERON:0001554	94.00	gold quality
upper leg skin	UBERON:0004262	93.70	gold quality
metanephros	UBERON:0000081	93.66	gold quality
germinal epithelium of ovary	UBERON:0001304	93.60	gold quality
epithelial cell of pancreas	CL:0000083	93.55	gold quality
saliva-secreting gland	UBERON:0001044	93.38	gold quality
ileal mucosa	UBERON:0000331	93.16	gold quality
bronchial epithelial cell	CL:0002328	93.00	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	89.89
E-ANND-3	yes	21.58
E-CURD-46	yes	19.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4, MYC

miRNA regulators (miRDB)

19 targeting ALG5, 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-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-6511A-5P	98.13	67.47	1770

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. (PMID:35896117)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	alg5	ENSDARG00000061235
mus_musculus	Alg5	ENSMUSG00000036632
rattus_norvegicus	Alg5	ENSRNOG00000058694
drosophila_melanogaster	wol	FBGN0261020
caenorhabditis_elegans		WBGENE00019276

Paralogs (1): DPM1 (ENSG00000000419)

Protein

Protein identifiers

Dolichyl-phosphate beta-glucosyltransferase — Q9Y673 (reviewed: Q9Y673)

Alternative names: Asparagine-linked glycosylation protein 5 homolog

All UniProt accessions (15): A0A7P0T850, A0A7P0T882, A0A7P0T8X9, A0A7P0T901, A0A7P0T9B8, A0A7P0T9C7, A0A7P0T9X2, A0A7P0TA95, A0A7P0TA98, A0A7P0TAI2, A0A7P0TAL2, A0A7P0TB27, A0A7P0Z4I2, B4DR67, Q9Y673

UniProt curated annotations — full annotation on UniProt →

Function. Dolichyl-phosphate beta-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-linked oligosaccharides begins on the cytosolic side of the endoplasmic reticulum membrane and finishes in its lumen. The sequential addition of sugars to dolichol pyrophosphate produces dolichol-linked oligosaccharides containing fourteen sugars, including two GlcNAcs, nine mannoses and three glucoses. Once assembled, the oligosaccharide is transferred from the lipid to nascent proteins by oligosaccharyltransferases. Dolichyl-phosphate beta-glucosyltransferase produces dolichyl beta-D-glucosyl phosphate/Dol-P-Glc, the glucose donor substrate used sequentially by ALG6, ALG8 and ALG10 to add glucose residues on top of the Man(9)GlcNAc(2)-PP-Dol structure. These are the three last steps in the biosynthetic pathway of dolichol-linked oligosaccharides to produce Glc(3)Man(9)GlcNAc(2)-PP-Dol. The enzyme is most probably active on the cytoplasmic side of the endoplasmic reticulum while its product Dol-P-Glc is the substrate for ALG6, ALG8 and ALG11 in the lumen of the endoplasmic reticulum.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in pancreas, placenta, liver, heart, brain, kidney, skeletal muscle, and lung.

Disease relevance. Polycystic kidney disease 7 (PKD7) [MIM:620056] A form of polycystic kidney disease, a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occur in other organs, particularly the liver. PKD7 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y673-1	1	yes
Q9Y673-2	2

RefSeq proteins (2): NP_001135836, NP_037470* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001173	Glyco_trans_2-like	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR035518	DPG_synthase	Domain

Pfam: PF00535

Catalyzed reactions (Rhea), 1 shown:

• a di-trans,poly-cis-dolichyl phosphate + UDP-alpha-D-glucose = a di-trans,poly-cis-dolichyl beta-D-glucosyl phosphate + UDP (RHEA:15401)

UniProt features (8 total): sequence variant 3, topological domain 2, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y673-F1	92.29	0.80

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-480985	Synthesis of dolichyl-phosphate-glucose
R-HSA-392499	Metabolism of proteins
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 248 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KEGG_N_GLYCAN_BIOSYNTHESIS, chr13q13, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_SPECIFICATION_OF_SYMMETRY, ONKEN_UVEAL_MELANOMA_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, DANG_BOUND_BY_MYC, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_CYTOPLASMIC_SIDE_OF_MEMBRANE, GOCC_ROUGH_ENDOPLASMIC_RETICULUM, GOCC_ROUGH_ENDOPLASMIC_RETICULUM_MEMBRANE, GAVIN_FOXP3_TARGETS_CLUSTER_T7

GO Biological Process (5): protein N-linked glycosylation (GO:0006487), dolichol-linked oligosaccharide biosynthetic process (GO:0006488), determination of left/right symmetry (GO:0007368), obsolete protein N-linked glycosylation via asparagine (GO:0018279), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (4): dolichyl-phosphate beta-glucosyltransferase activity (GO:0004581), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554), cytoplasmic side of rough endoplasmic reticulum membrane (GO:0098556), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1
Asparagine N-linked glycosylation	1
Post-translational protein modification	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoprotein biosynthetic process	1
protein N-linked glycosylation	1
carbohydrate derivative biosynthetic process	1
determination of bilateral symmetry	1
left/right pattern formation	1
UDP-glucosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
endoplasmic reticulum membrane	1
cytoplasmic side of membrane	1
rough endoplasmic reticulum membrane	1
cytoplasmic side of endoplasmic reticulum membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALG5	ALG6	Q9Y672	854
ALG5	ALG8	Q9BVK2	811
ALG5	ALG1	Q9BT22	762
ALG5	ALG3	Q92685	744
ALG5	ALG12	Q9BV10	731
ALG5	DPAGT1	Q9H3H5	719
ALG5	ALG11	Q2TAA5	711
ALG5	ALG14	Q96F25	670
ALG5	ALG13	Q9NP73	623
ALG5	DOLPP1	Q86YN1	616
ALG5	RPN1	P04843	610
ALG5	MOGS	Q13724	597
ALG5	DPM3	Q9P2X0	552
ALG5	DPM2	O94777	541
ALG5	NECTIN3	Q9NQS3	530
ALG5	DOLK	Q9UPQ8	530

IntAct

54 interactions, top by confidence:

A	B	Type	Score
	HMOX1	psi-mi:“MI:0914”(association)	0.740
ALG5		psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ADCY9	NEMP1	psi-mi:“MI:0914”(association)	0.640
	XPO1	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3B1	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
PSEN2	ALG5	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	PLOD2	psi-mi:“MI:0914”(association)	0.350
	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CACNG1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
DLK2	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350
PVR	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (103): ALG5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), SLC1A5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS), ALG5 (Affinity Capture-MS)

ESM2 similar proteins: A2DSR8, A2DZE8, A2E3C6, A2EK20, A2ELE6, G5EDL5, O60061, O64749, O94314, P00175, P16661, P27680, P28321, P31327, P32191, P32784, P36148, P40350, P41888, P43636, P53878, P53954, Q06490, Q54DM9, Q54J42, Q54P13, Q54QC1, Q559Z0, Q59S72, Q67VS7, Q6BVA4, Q6C3K2, Q6C3V7, Q6CLD6, Q6CVU2, Q6CWQ0, Q6FJJ9, Q6FLZ2, Q6FWD1, Q6UDF0

Diamond homologs: A0A0H2URH7, A0A0H3JPC6, A0A0H3JVA1, A1KMV1, A5U6W5, B5L3F2, D4GYG7, D4GYH2, E0U4V7, H2K893, O06483, O32268, P0A5A0, P26401, P47271, P74165, P75086, P9WMX6, P9WMX7, Q07755, Q077R2, Q0P9C6, Q15JF5, Q46632, Q48214, Q48215, Q4V9J0, Q54J42, Q57022, Q67FW5, Q6GV29, Q7BLV3, Q8L0V4, Q8U4M3, Q9CMP0, Q9DB25, Q9LM93, Q9Y673, A0A0H3M5A8, A0KGY7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	3
Uncertain significance	48
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
150360	GRCh38/hg38 13q12.3-13.3(chr13:30313809-39267681)x1	Pathogenic
154802	GRCh38/hg38 13q12.3-13.3(chr13:29321454-36995348)x3	Pathogenic
1708161	NM_013338.5(ALG5):c.703_704del (p.Gln235fs)	Pathogenic
1708162	NM_013338.5(ALG5):c.773G>A (p.Trp258Ter)	Pathogenic
1708163	NM_013338.5(ALG5):c.635G>A (p.Arg212His)	Pathogenic
1708164	NM_013338.5(ALG5):c.623G>A (p.Arg208His)	Pathogenic
1809134	GRCh37/hg19 13q13.3-14.11(chr13:35501428-40901176)x1	Pathogenic
3244195	NC_000013.10:g.(?37393495)(37583436_?)del	Pathogenic
3764100	NM_013338.5(ALG5):c.235C>T (p.Arg79Trp)	Pathogenic
3906913	GRCh37/hg19 13q13.3(chr13:35531799-39607778)x1	Pathogenic
57640	GRCh38/hg38 13q13.3-14.11(chr13:35232476-41375955)x1	Pathogenic
59853	GRCh38/hg38 13q11-13.3(chr13:18676442-37656039)x3	Pathogenic
3066151	NM_013338.5(ALG5):c.672G>A (p.Trp224Ter)	Likely pathogenic
3236195	NM_013338.5(ALG5):c.115C>T (p.Arg39Ter)	Likely pathogenic
3256865	NM_013338.5(ALG5):c.239-2A>G	Likely pathogenic

SpliceAI

1964 predictions. Top by Δscore:

Variant	Effect	Δscore
13:36952509:CTCA:C	donor_loss	1.0000
13:36952510:TCA:T	donor_loss	1.0000
13:36952511:CAC:C	donor_loss	1.0000
13:36952512:A:AC	donor_gain	1.0000
13:36952512:AC:A	donor_gain	1.0000
13:36952513:C:CC	donor_gain	1.0000
13:36952513:CC:C	donor_gain	1.0000
13:36952513:CCTT:C	donor_gain	1.0000
13:36952596:TGCC:T	acceptor_gain	1.0000
13:36952598:CC:C	acceptor_gain	1.0000
13:36952599:CC:C	acceptor_gain	1.0000
13:36952600:C:CC	acceptor_gain	1.0000
13:36952600:CTA:C	acceptor_loss	1.0000
13:36952601:T:A	acceptor_loss	1.0000
13:36985625:A:AC	donor_gain	1.0000
13:36985626:C:CC	donor_gain	1.0000
13:36992266:CAT:C	donor_gain	1.0000
13:36993599:TTTAC:T	donor_loss	1.0000
13:36993600:TTA:T	donor_loss	1.0000
13:36993601:TACC:T	donor_loss	1.0000
13:36993602:A:C	donor_loss	1.0000
13:36993603:C:CT	donor_loss	1.0000
13:36993668:CGTTT:C	acceptor_gain	1.0000
13:36993669:GTTT:G	acceptor_gain	1.0000
13:36993670:TTT:T	acceptor_gain	1.0000
13:36993671:TT:T	acceptor_gain	1.0000
13:36993672:TCTGC:T	acceptor_loss	1.0000
13:36993673:C:CA	acceptor_loss	1.0000
13:36993673:C:CC	acceptor_gain	1.0000
13:36993674:T:A	acceptor_loss	1.0000

AlphaMissense

2099 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:36965576:A:G	W258R	0.998
13:36965576:A:T	W258R	0.998
13:36965643:C:A	Q235H	0.998
13:36965643:C:G	Q235H	0.998
13:36965650:T:G	D233A	0.998
13:36952529:A:G	W282R	0.997
13:36952529:A:T	W282R	0.997
13:36965631:T:A	K239N	0.997
13:36965631:T:G	K239N	0.997
13:36965650:T:A	D233V	0.997
13:36965651:C:G	D233H	0.997
13:36985700:T:A	D163V	0.997
13:36989502:T:A	K143N	0.997
13:36989502:T:G	K143N	0.997
13:36989503:T:A	K143I	0.997
13:36952534:A:T	V280D	0.996
13:36965638:C:T	G237E	0.996
13:36965650:T:C	D233G	0.996
13:36972014:C:T	G195E	0.996
13:36985693:A:C	D165E	0.996
13:36985693:A:T	D165E	0.996
13:36985699:A:C	D163E	0.996
13:36985699:A:T	D163E	0.996
13:36989503:T:G	K143T	0.996
13:36989504:T:G	K143Q	0.996
13:36952527:C:A	W282C	0.995
13:36952527:C:G	W282C	0.995
13:36952593:A:C	F260L	0.995
13:36952593:A:T	F260L	0.995
13:36952595:A:G	F260L	0.995

dbSNP variants (sampled 300 via entrez): RS1000050038 (13:36981738 G>A,C), RS1000065292 (13:36959590 G>A,C,T), RS1000234291 (13:36976675 G>A,C), RS1000261591 (13:36997015 T>C), RS1000416435 (13:36970944 T>C,G), RS1000453906 (13:36963944 A>C,G), RS1000576901 (13:37001050 C>T), RS1000638797 (13:37001286 G>A), RS1000699694 (13:36970975 AG>A), RS1000768109 (13:36950643 G>A), RS1000820446 (13:36951013 A>T), RS1000868608 (13:36995233 C>G), RS1000968725 (13:36988556 A>C), RS1000982117 (13:36995104 C>T), RS1000993630 (13:36994777 C>T)

Disease associations

OMIM: gene MIM:604565 | disease phenotypes: MIM:620056, MIM:209920

GenCC curated gene-disease

Disease	Classification	Inheritance
polycystic kidney disease 7	Strong	Autosomal dominant
autosomal dominant polycystic kidney disease	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal dominant polycystic kidney disease	Moderate	AD

Mondo (3): polycystic kidney disease 7 (MONDO:0031062), MHC class II deficiency (MONDO:0008855), autosomal dominant polycystic kidney disease (MONDO:0004691)

Orphanet (1): Immunodeficiency by defective expression of MHC class II (Orphanet:572)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000083	Renal insufficiency
HP:0000105	Enlarged kidney
HP:0000107	Renal cyst
HP:0000790	Hematuria
HP:0000791	Uric acid nephrolithiasis
HP:0000822	Hypertension
HP:0001407	Hepatic cysts
HP:0001634	Mitral valve prolapse
HP:0001737	Pancreatic cysts
HP:0002616	Aortic root aneurysm
HP:0003259	Elevated circulating creatinine concentration
HP:0003581	Adult onset
HP:0003774	Stage 5 chronic kidney disease
HP:0004944	Dilatation of the cerebral artery
HP:0005562	Multiple renal cysts
HP:0006557	Polycystic liver disease
HP:0008672	Calcium oxalate nephrolithiasis
HP:0011004	Abnormal systemic arterial morphology
HP:0011760	Pituitary growth hormone cell adenoma
HP:0012207	Reduced sperm motility
HP:0012213	Decreased glomerular filtration rate
HP:0012330	Pyelonephritis
HP:0012585	Renal atrophy
HP:0012591	Abnormal urinary electrolyte concentration
HP:0012592	Albuminuria
HP:0012622	Chronic kidney disease
HP:0030157	Flank pain
HP:0032948	Renal interstitial fibrosis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006102_9	Interleukin-10 levels	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004750	interleukin 10 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016891	Polycystic Kidney, Autosomal Dominant	C12.050.351.968.419.403.875.500; C12.200.777.419.403.875.500; C12.950.419.403.875.500; C16.131.077.717.500; C16.320.184.625.500
C537079	Bare lymphocyte syndrome 2 (supp.)

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
sodium arsenite	affects expression, decreases expression	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Thapsigargin	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
bisphenol B	increases expression	1
bisphenol S	affects expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Testosterone	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414440	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT03273413	PHASE4	ACTIVE_NOT_RECRUITING	Statin Therapy in Patients With Early Stage ADPKD
NCT03949894	PHASE4	COMPLETED	Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease
NCT00309283	PHASE3	COMPLETED	Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study
NCT00346918	PHASE3	COMPLETED	Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT00428948	PHASE3	COMPLETED	Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01022424	PHASE3	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (2) [Extension of Study 156-05-002]
NCT01214421	PHASE3	COMPLETED	Tolvaptan Extension Study in Participants With ADPKD
NCT01377246	PHASE3	COMPLETED	Somatostatin In Patients With Autosomal Dominant Polycystic Kidney Disease And Moderate To Severe Renal Insufficiency
NCT01616927	PHASE3	UNKNOWN	Study of Lanreotide to Treat Polycystic Kidney Disease
NCT01853553	PHASE3	COMPLETED	Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02115659	PHASE3	UNKNOWN	Triptolide-Containing Formulation as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02134899	PHASE3	COMPLETED	The Efficacy of Everolimus in Reducing Total Native Kidney Volume in Polycystic Kidney Disease Transplanted Recipients
NCT02160145	PHASE3	COMPLETED	Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease
NCT02964273	PHASE3	COMPLETED	Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)
NCT03764605	PHASE3	UNKNOWN	Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT03918447	PHASE3	TERMINATED	A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
NCT04064346	PHASE3	TERMINATED	Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT04152837	PHASE3	TERMINATED	Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease
NCT04939935	PHASE3	RECRUITING	Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)
NCT05373264	PHASE3	RECRUITING	HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
NCT00841568	PHASE2	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Study 156-04-001]
NCT01210560	PHASE2	COMPLETED	Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
NCT01336972	PHASE2	COMPLETED	Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01451827	PHASE2	COMPLETED	8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT01932450	PHASE2	UNKNOWN	Radiofrequency Ablation for ADPKD Blood Pressure and Disease Progression Control
NCT02527863	PHASE2	COMPLETED	Effect of the Aquaretic Tolvaptan on Nitric Oxide System
NCT02616055	PHASE2	TERMINATED	Long-Term Treatment and Follow up of Subjects Completing 24 Months of Treatment With Tesevatinib on Study KD019-101
NCT03203642	PHASE2	COMPLETED	Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
NCT03487913	PHASE2	COMPLETED	The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
NCT03541447	PHASE2	COMPLETED	Tolvaptan-Octreotide LAR Combination in ADPKD
NCT04284657	PHASE2	COMPLETED	Pravastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT04578548	PHASE2	TERMINATED	A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT05190744	PHASE2	COMPLETED	Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration
NCT05870007	PHASE2	ENROLLING_BY_INVITATION	Atorvastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT06100133	PHASE2	UNKNOWN	Treat Autosomal Dominant Polycystic Kidney Disease With Oral Ketone Ester?
NCT06289998	PHASE2	ACTIVE_NOT_RECRUITING	Study of Tamibarotene in Patients With ADPKD
NCT06435858	PHASE2	RECRUITING	Short-term Effects of an SGLT2 Inhibitor on Divalent Ions in Autosomal Dominant Polycystic Kidney Disease
NCT06800651	PHASE2	RECRUITING	Trial of JMKX003142 in Participants With Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)