ALG9

Summary

ALG9 (ALG9 alpha-1,2-mannosyltransferase, HGNC:15672) is a protein-coding gene on chromosome 11q23.1, encoding Alpha-1,2-mannosyltransferase ALG9 (Q9H6U8). Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.

This gene encodes an alpha-1,2-mannosyltransferase enzyme that functions in lipid-linked oligosaccharide assembly. Mutations in this gene result in congenital disorder of glycosylation type Il. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79796 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ALG9-associated autosomal dominant polycystic kidney disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 400 total — 15 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 141
• MANE Select transcript: NM_024740

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15672
Approved symbol	ALG9
Name	ALG9 alpha-1,2-mannosyltransferase
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000086848
Ensembl biotype	protein_coding
OMIM	606941
Entrez	79796

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 10 protein_coding, 6 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000398006, ENST00000524671, ENST00000525910, ENST00000526272, ENST00000527212, ENST00000527294, ENST00000527714, ENST00000530723, ENST00000530851, ENST00000531154, ENST00000532425, ENST00000612489, ENST00000613181, ENST00000614444, ENST00000616540, ENST00000618252, ENST00000619129, ENST00000857227, ENST00000857228, ENST00000857229, ENST00000928987, ENST00000943100

RefSeq mRNA: 19 — MANE Select: NM_024740 NM_001077690, NM_001077691, NM_001077692, NM_001352409, NM_001352410, NM_001352411, NM_001352412, NM_001352413, NM_001352414, NM_001352415, NM_001352416, NM_001352417, NM_001352418, NM_001352419, NM_001352420, NM_001352421, NM_001352422, NM_001352423, NM_024740

CCDS: CCDS41714, CCDS53709, CCDS73379, CCDS73380

Canonical transcript exons

ENST00000616540 — 15 exons

Exon	Start	End
ENSE00003472311	111840655	111840809
ENSE00003485249	111857602	111857737
ENSE00003491934	111809643	111809773
ENSE00003603533	111838249	111838399
ENSE00003611961	111853649	111853736
ENSE00003636914	111836165	111836294
ENSE00003663468	111844601	111844723
ENSE00003667869	111837468	111837615
ENSE00003668757	111853380	111853485
ENSE00003716609	111871352	111871581
ENSE00003717948	111868602	111868736
ENSE00003726740	111865181	111865251
ENSE00003738201	111870232	111870370
ENSE00003738951	111860547	111860635
ENSE00003841852	111782195	111786520

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 93.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.4309 / max 125.1086, expressed in 1815 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122276	15.6517	1805
122275	4.2346	1611
122277	2.0041	1276
122274	1.4700	1009
122256	0.2959	125
122259	0.1851	106
122257	0.1844	91
122258	0.1484	80
122266	0.1407	29
122267	0.0600	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	93.57	gold quality
body of pancreas	UBERON:0001150	92.98	gold quality
ganglionic eminence	UBERON:0004023	91.45	gold quality
cortical plate	UBERON:0005343	91.19	gold quality
pancreas	UBERON:0001264	90.49	gold quality
skin of leg	UBERON:0001511	90.29	gold quality
omental fat pad	UBERON:0010414	90.21	gold quality
ventricular zone	UBERON:0003053	90.19	gold quality
peritoneum	UBERON:0002358	90.15	gold quality
skin of abdomen	UBERON:0001416	89.94	gold quality
bone marrow cell	CL:0002092	89.69	gold quality
lower esophagus mucosa	UBERON:0035834	89.62	gold quality
mucosa of stomach	UBERON:0001199	89.47	gold quality
stromal cell of endometrium	CL:0002255	89.29	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.27	gold quality
left coronary artery	UBERON:0001626	89.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.03	gold quality
tibial artery	UBERON:0007610	88.95	gold quality
popliteal artery	UBERON:0002250	88.93	gold quality
smooth muscle tissue	UBERON:0001135	88.88	gold quality
islet of Langerhans	UBERON:0000006	88.77	gold quality
right lung	UBERON:0002167	88.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.52	gold quality
right lobe of liver	UBERON:0001114	88.51	gold quality
colonic epithelium	UBERON:0000397	88.50	gold quality
aorta	UBERON:0000947	88.21	gold quality
zone of skin	UBERON:0000014	88.20	gold quality
ectocervix	UBERON:0012249	88.12	gold quality
body of stomach	UBERON:0001161	88.06	gold quality
tibial nerve	UBERON:0001323	87.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	563.08
E-ANND-3	yes	7.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

211 targeting ALG9, 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-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505

Literature-anchored findings (GeneRIF, showing 7)

• Due to the ALG9 deficiency, cells accumulated the lipid-linked oligosaccharides Man(6)GlcNAc(2)-PP-dolichol and Man(8)GlcNAc(2)-PP-dolichol. (PMID:19451548)
• Our study shows that some pathogenic variants in ALG9 can present as a lethal skeletal dysplasia with visceral malformations as the most severe phenotype (PMID:25966638)
• ALG9 is upregulated in peripheral blood mononuclear cells of galactosaemia patients. (PMID:26733289)
• ALG9 is a novel disease gene in the genetically heterogeneous autosomal dominant polycystic kidney disease (ADPKD) spectrum. (PMID:31395617)
• LncRNA MEG3 contributes to drug resistance in acute myeloid leukemia by positively regulating ALG9 through sponging miR-155. (PMID:32359033)
• Missense variant c.1460 T > C (p.L487P) enhances protein degradation of ER mannosyltransferase ALG9 in two new ALG9-CDG patients presenting with West syndrome and review of the literature. (PMID:35839600)
• Heterozygosity of ALG9 in Association with Autosomal Dominant Polycystic Liver Disease. (PMID:37761895)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	alg9	ENSDARG00000012840
mus_musculus	Alg9	ENSMUSG00000032059
rattus_norvegicus	Alg9	ENSRNOG00000010877
drosophila_melanogaster	Alg9	FBGN0039293
caenorhabditis_elegans		WBGENE00007556

Paralogs (2): PIGB (ENSG00000069943), ALG12 (ENSG00000182858)

Protein

Protein identifiers

Alpha-1,2-mannosyltransferase ALG9 — Q9H6U8 (reviewed: Q9H6U8)

Alternative names: Asparagine-linked glycosylation protein 9 homolog, Disrupted in bipolar disorder protein 1, Dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase, Dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase

All UniProt accessions (8): Q9H6U8, A0A087WTZ3, A0A087WVC0, A0A087WX16, A0A087WZY8, H0YCW6, H0YEX8, H0YF48

UniProt curated annotations — full annotation on UniProt →

Function. Mannosyltransferase 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. In the lumen of the endoplasmic reticulum, catalyzes the addition of the seventh and ninth alpha-1,2-linked mannose residues to Man(6)GlcNAc(2)-PP-dolichol and Man(8)GlcNAc(2)-PP-dolichol respectively.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitously expressed; with highest levels in heart, liver and pancreas.

Disease relevance. A chromosomal aberration involving ALG9 is found in a family with bipolar affective disorder. Translocation t(9;11)(p24;q23). However, common variations in ALG9 do not play a major role in predisposition to bipolar affective disorder. Congenital disorder of glycosylation 1L (CDG1L) [MIM:608776] A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. The disease is caused by variants affecting the gene represented in this entry. Gillessen-Kaesbach-Nishimura syndrome (GIKANIS) [MIM:263210] A rare autosomal recessive syndrome characterized by severe skeletal dysplasia, facial dysmorphic features, polycystic kidney disease and other visceral malformations. It may be lethal in utero or early in life. The skeletal features uniformly comprise a round pelvis, mesomelic shortening of the upper limbs and defective ossification of the cervical spine. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 22 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H6U8-1	1	yes
Q9H6U8-2	2
Q9H6U8-3	3
Q9H6U8-4	4

RefSeq proteins (19): NP_001071158, NP_001071159, NP_001071160, NP_001339338, NP_001339339, NP_001339340, NP_001339341, NP_001339342, NP_001339343, NP_001339344, NP_001339345, NP_001339346, NP_001339347, NP_001339348, NP_001339349, NP_001339350, NP_001339351, NP_001339352, NP_079016* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005599	GPI_mannosylTrfase	Family

Pfam: PF03901

Enzyme classification (BRENDA):

• EC 2.4.1.259 — dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase (BRENDA: 5 organisms, 3 substrates, 0 inhibitors, 0 Km, 0 kcat entries)
• EC 2.4.1.261 — dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase (BRENDA: 5 organisms, 2 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

• an alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate = an alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:29531)
• an alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate = an alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:29539)

UniProt features (33 total): topological domain 9, transmembrane region 8, sequence variant 7, glycosylation site 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9S6S	ELECTRON MICROSCOPY	2.89
9S6U	ELECTRON MICROSCOPY	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6U8-F1	88.35	0.77

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): 340 (breakpoint for translocation)

Glycosylation sites (2): 77, 593

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-4720454	Defective ALG9 causes CDG-1l
R-HSA-1643685	Disease
R-HSA-3781860	Diseases associated with N-glycosylation of proteins
R-HSA-3781865	Diseases of glycosylation
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 453 (showing top): TGCGCANK_UNKNOWN, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KEGG_N_GLYCAN_BIOSYNTHESIS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_LUMENAL_SIDE_OF_MEMBRANE, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_SIDE_OF_MEMBRANE, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_HEXOSYLTRANSFERASE_ACTIVITY

GO Biological Process (3): protein N-linked glycosylation (GO:0006487), dolichol-linked oligosaccharide biosynthetic process (GO:0006488), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (5): alpha-1,2-mannosyltransferase activity (GO:0000026), dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity (GO:0052918), dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity (GO:0052926), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), lumenal side of endoplasmic reticulum membrane (GO:0098553), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Asparagine N-linked glycosylation	1
Diseases associated with N-glycosylation of proteins	1
Diseases of glycosylation	1
Diseases of metabolism	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
alpha-1,2-mannosyltransferase activity	2
GlcNAc(2)-PP-Dol mannosyltransferase activity	2
glycoprotein biosynthetic process	1
protein N-linked glycosylation	1
carbohydrate derivative biosynthetic process	1
mannosyltransferase activity	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
lumenal side of membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

970 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALG9	PMM2	O15305	700
ALG9	ALG12	Q9BV10	582
ALG9	ALG3	Q92685	494
ALG9	ALG8	Q9BVK2	487
ALG9	GANAB	Q14697	471
ALG9	ALG1	Q9BT22	420
ALG9	DNAJB11	Q9UBS4	419
ALG9	DZIP1L	Q8IYY4	410
ALG9	ALG11	Q2TAA5	400
ALG9	PGAP4	Q9BRR3	395
ALG9	ALG13	Q9NP73	378
ALG9	ZNF189	O75820	368
ALG9	PIGV	Q9NUD9	358
ALG9	MOGS	Q13724	355
ALG9	SNX7	Q9UNH6	350

IntAct

68 interactions, top by confidence:

A	B	Type	Score
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
WNT3	WNT3A	psi-mi:“MI:0914”(association)	0.640
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
TMPRSS12	FZD6	psi-mi:“MI:0914”(association)	0.530
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
SCNN1D	ABHD16A	psi-mi:“MI:0914”(association)	0.530
GABRA3	HLA-C	psi-mi:“MI:0914”(association)	0.530
STS	GJA1	psi-mi:“MI:0914”(association)	0.530
BHMT	ALG9	psi-mi:“MI:0915”(physical association)	0.370
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
CHPT1	BPGM	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSPB1	DYNC1H1	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
ZACN	FAM234B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TMPRSS3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL17RC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
KLRC4	RAP1BL	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
KIR2DS5	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (129): ALG9 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), CORO1C (Co-fractionation), HNRNPF (Co-fractionation), ALG9 (Proximity Label-MS), ALG9 (Proximity Label-MS), ALG9 (Proximity Label-MS), ALG9 (Proximity Label-MS), ALG9 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), ALG9 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVZ9, A4IFN5, A5PK40, A6NH52, A6NI61, B2LYG4, B2RZC9, B6ID01, D2HKB0, D3ZG27, P86229, Q0VDI3, Q15012, Q15546, Q17QJ2, Q1RLT2, Q2TA01, Q4R4I5, Q4R6E8, Q5H8A4, Q5R7Q1, Q5RAH0, Q5RL79, Q5U3C3, Q5VTY9, Q5ZML7, Q64232, Q6PHN7, Q6QRN8, Q719N3, Q71SV0, Q8BWB6, Q8IY49, Q8N6M3, Q8NFT2, Q8R189, Q8VD53, Q8VDI9, Q8VDR5, Q9CQC4

Diamond homologs: P53868, P54002, Q8VDI9, Q9H6U8, Q9P7Q9, Q9VBV8, Q9FZ49

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
Neurotransmitter receptors and postsynaptic signal transmission	6	8.8×	2e-03
Transmission across Chemical Synapses	6	6.7×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
monoatomic ion transmembrane transport	9	19.5×	5e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	19
Uncertain significance	178
Likely benign	109
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1434153	NM_024740.2(ALG9):c.992del (p.Met331fs)	Pathogenic
1698703	NM_024740.2(ALG9):c.1460T>C (p.Leu487Pro)	Pathogenic
1808702	GRCh37/hg19 11q22.3-23.3(chr11:109328787-116414966)x1	Pathogenic
2011582	NM_024740.2(ALG9):c.1296dup (p.Phe433fs)	Pathogenic
2014762	NM_024740.2(ALG9):c.754_757del (p.Phe252fs)	Pathogenic
3345062	NM_024740.2(ALG9):c.1163_1164del (p.Ser388fs)	Pathogenic
3656725	NM_024740.2(ALG9):c.1441C>T (p.Arg481Ter)	Pathogenic
3665027	NM_024740.2(ALG9):c.126del (p.Thr43fs)	Pathogenic
3900614	NM_024740.2(ALG9):c.761G>A (p.Trp254Ter)	Pathogenic
3906840	NM_024740.2(ALG9):c.1695G>A (p.Trp565Ter)	Pathogenic
3906843	NM_024740.2:c.896_1602del	Pathogenic
4531701	NM_024740.2(ALG9):c.1534G>T (p.Gly512Ter)	Pathogenic
488404	ALG9, GLU359LYS	Pathogenic
631493	NM_024740.2(ALG9):c.1109G>A (p.Arg370Lys)	Pathogenic
631494	NM_024740.2(ALG9):c.681G>A (p.Trp227Ter)	Pathogenic
1179143	NM_024740.2(ALG9):c.701+1G>A	Likely pathogenic
2007716	NM_024740.2(ALG9):c.896-2A>G	Likely pathogenic
2120195	NM_024740.2(ALG9):c.131+1G>C	Likely pathogenic
2633266	NM_024740.2(ALG9):c.522del (p.Ala175fs)	Likely pathogenic
3066316	NM_024740.2(ALG9):c.65_66insTC (p.Ala23fs)	Likely pathogenic
3598953	NM_024740.2(ALG9):c.1651G>T (p.Glu551Ter)	Likely pathogenic
3598955	NM_024740.2(ALG9):c.1605_1608del	Likely pathogenic
3598956	NM_024740.2(ALG9):c.1602+1G>A	Likely pathogenic
3598959	NM_024740.2(ALG9):c.1496C>G (p.Ser499Ter)	Likely pathogenic
3598964	NM_024740.2(ALG9):c.1324+2T>C	Likely pathogenic
3598966	NM_024740.2(ALG9):c.1209dup (p.Val404fs)	Likely pathogenic
3598976	NM_024740.2(ALG9):c.789+1G>A	Likely pathogenic
3598981	NM_024740.2(ALG9):c.704del (p.Leu235fs)	Likely pathogenic
3598990	NM_024740.2(ALG9):c.530T>A (p.Leu177Ter)	Likely pathogenic
3598992	NM_024740.2(ALG9):c.563C>G (p.Ser188Ter)	Likely pathogenic

SpliceAI

2531 predictions. Top by Δscore:

Variant	Effect	Δscore
11:111786517:AGAT:A	acceptor_gain	1.0000
11:111786518:GAT:G	acceptor_gain	1.0000
11:111786519:ATCTG:A	acceptor_loss	1.0000
11:111786520:TCTGA:T	acceptor_loss	1.0000
11:111786521:C:CC	acceptor_gain	1.0000
11:111786521:C:T	acceptor_loss	1.0000
11:111786522:T:C	acceptor_loss	1.0000
11:111809638:CATA:C	donor_loss	1.0000
11:111809639:ATACC:A	donor_loss	1.0000
11:111809640:TA:T	donor_loss	1.0000
11:111809640:TACCT:T	donor_loss	1.0000
11:111809641:ACCTA:A	donor_loss	1.0000
11:111809642:C:A	donor_loss	1.0000
11:111809769:TCAAT:T	acceptor_gain	1.0000
11:111809770:CAAT:C	acceptor_gain	1.0000
11:111809770:CAATC:C	acceptor_gain	1.0000
11:111809772:ATC:A	acceptor_loss	1.0000
11:111809772:ATCT:A	acceptor_loss	1.0000
11:111809773:TC:T	acceptor_loss	1.0000
11:111809773:TCT:T	acceptor_loss	1.0000
11:111809774:C:CC	acceptor_gain	1.0000
11:111809775:T:C	acceptor_loss	1.0000
11:111836163:A:AC	donor_gain	1.0000
11:111836164:C:CC	donor_gain	1.0000
11:111836164:CATAT:C	donor_gain	1.0000
11:111836168:T:C	donor_gain	1.0000
11:111836295:C:CC	acceptor_gain	1.0000
11:111837461:AACTT:A	donor_loss	1.0000
11:111837462:ACTTA:A	donor_loss	1.0000
11:111837463:CTT:C	donor_loss	1.0000

AlphaMissense

4010 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:111837488:G:C	S477R	0.999
11:111837488:G:T	S477R	0.999
11:111837490:T:G	S477R	0.999
11:111837520:A:G	C467R	0.999
11:111837522:A:T	V466D	0.999
11:111840715:A:C	F371L	0.999
11:111840715:A:T	F371L	0.999
11:111840717:A:G	F371L	0.999
11:111840727:T:A	K367N	0.999
11:111840727:T:G	K367N	0.999
11:111857721:G:C	S194R	0.999
11:111857721:G:T	S194R	0.999
11:111857723:T:G	S194R	0.999
11:111857724:A:C	S193R	0.999
11:111857724:A:T	S193R	0.999
11:111857726:T:G	S193R	0.999
11:111860572:G:C	S180R	0.999
11:111860572:G:T	S180R	0.999
11:111860574:T:G	S180R	0.999
11:111860602:A:C	S170R	0.999
11:111860602:A:T	S170R	0.999
11:111860604:T:G	S170R	0.999
11:111868698:C:A	W103C	0.999
11:111868698:C:G	W103C	0.999
11:111868700:A:G	W103R	0.999
11:111868700:A:T	W103R	0.999
11:111870244:G:C	N86K	0.999
11:111870244:G:T	N86K	0.999
11:111870257:T:A	D82V	0.999
11:111870296:C:A	R69M	0.999

dbSNP variants (sampled 300 via entrez): RS1000024562 (11:111830365 T>C), RS1000055671 (11:111823065 C>T), RS1000167332 (11:111806130 G>A,C), RS1000177556 (11:111850376 G>A,C), RS1000262179 (11:111843951 T>C), RS1000308010 (11:111792007 C>G,T), RS1000313838 (11:111830075 C>T), RS1000381108 (11:111786107 T>C,G), RS1000443667 (11:111792343 G>A,T), RS1000482888 (11:111867396 T>A), RS1000488457 (11:111837219 G>A), RS1000508018 (11:111804651 G>C), RS1000605807 (11:111849339 C>A,T), RS1000743586 (11:111844161 T>C), RS1000753192 (11:111799413 T>C)

Disease associations

OMIM: gene MIM:606941 | disease phenotypes: MIM:168000, MIM:171300, MIM:606864, MIM:615106, MIM:608776, MIM:263210, MIM:245348, MIM:261640, MIM:174050, MIM:173900

GenCC curated gene-disease

Disease	Classification	Inheritance
ALG9-congenital disorder of glycosylation	Strong	Autosomal recessive
ALG9-associated autosomal dominant polycystic kidney disease	Strong	Autosomal dominant
Gillessen-Kaesbach-Nishimura syndrome	Moderate	Autosomal recessive
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
ALG9-associated autosomal dominant polycystic kidney disease	Definitive	AD

Mondo (14): pheochromocytoma/paraganglioma syndrome 1 (MONDO:0008192), pheochromocytoma (MONDO:0008233), Carney-Stratakis syndrome (MONDO:0011740), Cowden syndrome 3 (MONDO:0014045), ALG9-congenital disorder of glycosylation (MONDO:0012117), Gillessen-Kaesbach-Nishimura syndrome (MONDO:0009890), ALG9-associated autosomal dominant polycystic kidney disease (MONDO:0700000), breast ductal adenocarcinoma (MONDO:0005590), pyruvate dehydrogenase E2 deficiency (MONDO:0009502), BH4-deficient hyperphenylalaninemia A (MONDO:0009863), familial cystic renal disease (MONDO:0019741), autosomal dominant polycystic kidney disease (MONDO:0004691), autosomal dominant polycystic liver disease (MONDO:0000447), polycystic kidney disease 1 (MONDO:0008263)

Orphanet (11): Cowden syndrome (Orphanet:201), Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Carney-Stratakis syndrome (Orphanet:97286), ALG9-CDG (Orphanet:79328), 6-pyruvoyl-tetrahydropterin synthase deficiency (Orphanet:13), Hyperphenylalaninemia due to tetrahydrobiopterin deficiency (Orphanet:238583), Pyruvate dehydrogenase deficiency (Orphanet:765), Pyruvate dehydrogenase E2 deficiency (Orphanet:79244), Genetic cystic renal disease (Orphanet:93587), Autosomal dominant polycystic kidney disease (Orphanet:730), Isolated polycystic liver disease (Orphanet:2924)

HPO phenotypes

141 total (30 of 141 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000083	Renal insufficiency
HP:0000105	Enlarged kidney
HP:0000107	Renal cyst
HP:0000113	Polycystic kidney dysplasia
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000193	Bifid uvula
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000260	Wide anterior fontanel
HP:0000270	Delayed cranial suture closure
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000430	Underdeveloped nasal alae
HP:0000444	Convex nasal ridge
HP:0000470	Short neck
HP:0000473	Torticollis
HP:0000474	Thickened nuchal skin fold
HP:0000506	Telecanthus

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST007564_5	Asthma or allergic disease (pleiotropy)	6.000000e-11
GCST010135_36	Oily fish consumption	9.000000e-09
GCST010140_26	Pork consumption	9.000000e-09
GCST010142_27	Fish- and plant-related diet	3.000000e-09
GCST010703_266	Brain morphology (MOSTest)	4.000000e-13
GCST90020024_420	A body shape index	3.000000e-11
GCST90020024_422	A body shape index	6.000000e-12
GCST90020025_651	Waist-to-hip ratio adjusted for BMI	2.000000e-11
GCST90020025_652	Waist-to-hip ratio adjusted for BMI	9.000000e-11
GCST90020027_1629	Waist-hip index	7.000000e-12
GCST90020027_1630	Waist-hip index	1.000000e-11
GCST90020029_248	Waist circumference adjusted for body mass index	8.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D010673	Pheochromocytoma	C04.557.465.625.650.700.725; C04.557.580.625.650.700.725
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
C535325	6-pyruvoyl-tetrahydropterin synthase deficiency (supp.)
C564650	Carney-Stratakis Syndrome (supp.)
C535750	Congenital disorder of glycosylation type 1L (supp.)
C564881	Polycystic Kidney Disease, Potter Type I, with Microbrachycephaly, Hypertelorism, and Brachymelia (supp.)
C536326	Polycystic kidney disease, type 1 (supp.)
C565448	Pyruvate Dehydrogenase E2 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	2
methylmercuric chloride	decreases expression	1
glycidyl methacrylate	decreases expression	1
beta-lapachone	decreases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
licochalcone B	decreases expression	1
Resveratrol	decreases expression	1
Glyphosate	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Selenium	affects cotreatment, increases expression	1
Theophylline	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Vitamin E	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SC32	HAP1 ALG9 (-) 1	Cancer cell line	Male
CVCL_SC33	HAP1 ALG9 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

257 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
NCT01379898	PHASE4	COMPLETED	Phenoxybenzamine Versus Doxazosin in PCC Patients
NCT01959711	PHASE4	COMPLETED	Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy
NCT05702944	PHASE4	RECRUITING	The Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma
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
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00126412	PHASE3	COMPLETED	Meta-Iodobenzylguanidine (123I mIBG) Scintigraphy in Patients Being Evaluated for Phaeochromocytoma or Neuroblastoma
NCT01373736	PHASE3	UNKNOWN	123I-MIBG Scintigraphy in Patients Being Evaluated for Neuroendocrine Tumors
NCT03176693	PHASE3	COMPLETED	Preoperative Alpha Blockade for Pheochromocytoma
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
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