ALG11

Summary

ALG11 (ALG11 alpha-1,2-mannosyltransferase, HGNC:32456) is a protein-coding gene on chromosome 13q14.3, encoding GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (Q2TAA5). GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19.

Source: NCBI Gene 440138 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ALG11-congenital disorder of glycosylation (Strong, GenCC)
• Clinical variants (ClinVar): 321 total — 15 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 52
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_001004127

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32456
Approved symbol	ALG11
Name	ALG11 alpha-1,2-mannosyltransferase
Location	13q14.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0266, CDG1P
Ensembl gene	ENSG00000253710
Ensembl biotype	protein_coding
OMIM	613666
Entrez	440138

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 8 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000519151, ENST00000521508, ENST00000523764, ENST00000616513, ENST00000649340, ENST00000649651, ENST00000649708, ENST00000650049, ENST00000679359, ENST00000679495, ENST00000679544, ENST00000680058, ENST00000680793, ENST00000680950, ENST00000681047, ENST00000681053, ENST00000681145, ENST00000681226

RefSeq mRNA: 1 — MANE Select: NM_001004127 NM_001004127

CCDS: CCDS31977

Canonical transcript exons

ENST00000521508 — 4 exons

Exon	Start	End
ENSE00002243097	52028319	52033600
ENSE00002251727	52012398	52012462
ENSE00002321395	52018913	52019143
ENSE00003662053	52024006	52024937

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 90.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4860 / max 301.4259, expressed in 1766 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135220	15.4860	1766

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	90.81	gold quality
calcaneal tendon	UBERON:0003701	90.69	gold quality
adrenal tissue	UBERON:0018303	89.61	gold quality
endometrium	UBERON:0001295	89.32	gold quality
colonic epithelium	UBERON:0000397	88.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.51	gold quality
bone marrow cell	CL:0002092	87.93	gold quality
bone marrow	UBERON:0002371	87.22	gold quality
placenta	UBERON:0001987	87.14	gold quality
tonsil	UBERON:0002372	87.03	gold quality
corpus callosum	UBERON:0002336	86.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.38	gold quality
smooth muscle tissue	UBERON:0001135	85.87	gold quality
stromal cell of endometrium	CL:0002255	85.86	gold quality
rectum	UBERON:0001052	85.65	gold quality
monocyte	CL:0000576	85.59	gold quality
leukocyte	CL:0000738	85.11	gold quality
sural nerve	UBERON:0015488	83.78	gold quality
duodenum	UBERON:0002114	83.55	gold quality
gall bladder	UBERON:0002110	82.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.85	gold quality
muscle tissue	UBERON:0002385	82.49	gold quality
pancreas	UBERON:0001264	82.15	gold quality
vermiform appendix	UBERON:0001154	82.08	gold quality
ganglionic eminence	UBERON:0004023	81.67	gold quality
skeletal muscle tissue	UBERON:0001134	81.63	gold quality
cortical plate	UBERON:0005343	81.47	gold quality
urinary bladder	UBERON:0001255	80.96	gold quality
lymph node	UBERON:0000029	80.60	gold quality
adrenal gland	UBERON:0002369	80.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting ALG11, 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-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• Deficiency of the endoplasmatic mannosyltransferase hALG11 leads to congenital disorder of glycosylation. (PMID:20080937)
• After identifying the congenital disorders of glycosylation-Ip index patient, study describe three more cases suffering from an ALG11 deficiency. (PMID:22213132)
• Hence, we concluded that there is different transcriptional control mechanism between mALG11 and hALG11 (PMID:25036826)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	alg11	ENSDARG00000031202
mus_musculus	Alg11	ENSMUSG00000063362
rattus_norvegicus	Alg11	ENSRNOG00000012841
drosophila_melanogaster	Alg11	FBGN0037108
caenorhabditis_elegans		WBGENE00015162

Paralogs (3): ALG2 (ENSG00000119523), GLT1D1 (ENSG00000151948), PIGA (ENSG00000165195)

Protein

Protein identifiers

GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase — Q2TAA5 (reviewed: Q2TAA5)

Alternative names: Asparagine-linked glycosylation protein 11 homolog, Glycolipid 2-alpha-mannosyltransferase

All UniProt accessions (10): A0A087WYL8, A0A3B3IS90, A0A3B3ISP7, A0A3B3ISU2, A0A7P0T8B1, A0A7P0T8Y4, A0A7P0T9G5, A0A7P0Z4B5, Q2TAA5, Q5TAP0

UniProt curated annotations — full annotation on UniProt →

Function. GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-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. Catalyzes, on the cytoplasmic face of the endoplasmic reticulum, the addition of the fourth and fifth mannose residues to the dolichol-linked oligosaccharide chain, to produce Man(5)GlcNAc(2)-PP-dolichol core oligosaccharide. Man(5)GlcNAc(2)-PP-dolichol is a substrate for ALG3, the following enzyme in the biosynthetic pathway.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Congenital disorder of glycosylation 1P (CDG1P) [MIM:613661] 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.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.

RefSeq proteins (1): NP_001004127* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001296	Glyco_trans_1	Domain
IPR031814	ALG11_N	Domain
IPR038013	ALG11	Family

Pfam: PF00534, PF15924

Enzyme classification (BRENDA):

• EC 2.4.1.131 — GDP-Man:Man3GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase (BRENDA: 7 organisms, 20 substrates, 20 inhibitors, 4 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-MAN-ALPHA-(1->3)-(D-MAN-ALPHA-(1->6))-D-MAN-BE	0.0006	1
GDP-D-MANNOSE	0.0047	1
GDPMANNOSE	0.0047	1
OLIGOSACCHARIDE-LIPID ACCEPTOR	0.0006	1

Catalyzed reactions (Rhea), 1 shown:

• an 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 + 2 GDP-alpha-D-mannose = an alpha-D-Man-(1->2)-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 + 2 GDP + 2 H(+) (RHEA:29523)

UniProt features (17 total): sequence variant 6, topological domain 4, mutagenesis site 2, intramembrane region 2, chain 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2TAA5-F1	91.40	0.74

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
86	no effect on gdp-man:man3glcnac2-pp-dol alpha-1,2-mannosyltransferase activity.
86	decreased gdp-man:man3glcnac2-pp-dol alpha-1,2-mannosyltransferase activity.

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-4551295	Defective ALG11 causes CDG-1p
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: 166 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, chr13q14, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_HEXOSYLTRANSFERASE_ACTIVITY, GOMF_MANNOSYLTRANSFERASE_ACTIVITY, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_GLYCOPROTEIN_BIOSYNTHETIC_PROCESS, RAO_BOUND_BY_SALL4

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), GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity (GO:0004377), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), 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
glycoprotein biosynthetic process	1
protein N-linked glycosylation	1
carbohydrate derivative biosynthetic process	1
mannosyltransferase activity	1
alpha-1,2-mannosyltransferase activity	1
GlcNAc(2)-PP-Dol mannosyltransferase 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
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2042 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALG11	RFT1	Q96AA3	951
ALG11	ALG1	Q9BT22	933
ALG11	PMM2	O15305	871
ALG11	ALG12	Q9BV10	796
ALG11	ALG6	Q9Y672	795
ALG11	ALG13	Q9NP73	773
ALG11	ALG3	Q92685	765
ALG11	DPAGT1	Q9H3H5	760
ALG11	ALG8	Q9BVK2	758
ALG11	ALG14	Q96F25	746
ALG11	ALG5	Q9Y673	711
ALG11	DPM1	O60762	672
ALG11	CANX	P27824	667
ALG11	CD4	P01730	654
ALG11	DPM2	O94777	633

IntAct

81 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
TMEM213	METAP2	psi-mi:“MI:0914”(association)	0.530
rep	IDE	psi-mi:“MI:0914”(association)	0.530
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
DCT	CANX	psi-mi:“MI:0914”(association)	0.530
CD63	LGALS8	psi-mi:“MI:0914”(association)	0.530
SMPD1	CLGN	psi-mi:“MI:0914”(association)	0.530
PVR	ORC4	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
GLA	ALG11	psi-mi:“MI:0915”(physical association)	0.500
ECE1	ALG11	psi-mi:“MI:0915”(physical association)	0.370
TSPAN5	KLHL2	psi-mi:“MI:0914”(association)	0.350
PVR	QSOX1	psi-mi:“MI:0914”(association)	0.350
RAET1E	GOLIM4	psi-mi:“MI:0914”(association)	0.350
HAUS7	GOLIM4	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
rep	CEBPZOS	psi-mi:“MI:0914”(association)	0.350
IGHM	ESYT2	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
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TSPAN31	TMEM120B	psi-mi:“MI:0914”(association)	0.350
RUSF1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TSPAN10	KLRG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-RNA), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ALG11 (Proximity Label-MS)

ESM2 similar proteins: A2VDC2, A5A6K3, D4AAT7, O35952, P00937, P34949, P40939, Q01415, Q08B22, Q09669, Q1PEY5, Q1ZXF1, Q28C91, Q28FR6, Q29554, Q2HJ73, Q2TAA5, Q3KRD0, Q3TZM9, Q42942, Q55GS6, Q561R9, Q58EB4, Q5EAD2, Q5F4K8, Q5HZQ8, Q5R6J8, Q5R7Z6, Q5XF59, Q5XIE6, Q5ZJ60, Q61753, Q64428, Q68FH4, Q68FX1, Q6NMB0, Q6NVY1, Q6PI48, Q84MD8, Q8BIP0

Diamond homologs: A0JZ09, A0LQY9, A0PVZ1, A0QLK5, A0QQZ8, A0R043, A0R2E2, A1KFW0, A1R8N8, A1SP12, A1T3B5, A1UAM8, A2Y8X2, A3PU84, A4FQ08, A4QB40, A4T324, A4X1R6, A5TZL4, A5U3B9, A5WJJ8, A6W6D9, A7TZT2, A8LDJ8, A8LZG1, B1MHQ0, B1VEI4, B1VS68, B2HQV2, B8HCF8, B8ZT88, C0ZUT0, C1AKG4, C1AZ64, C3PK12, C4LLD6, C6DT68, C6WPK3, C7MSY6, C7Q4Y6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ALG11	“up-regulates quantity”	alpha-D-Man-(1->2)-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(PP-Dol)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	10
Uncertain significance	215
Likely benign	47
Benign	10

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
1073825	NC_000013.10:g.(?52585403)(52602726_?)del	Pathogenic
1527772	GRCh37/hg19 13q14.11-14.3(chr13:44573371-53324137)	Pathogenic
154070	GRCh38/hg38 13q14.2-21.31(chr13:47765202-62058520)x1	Pathogenic
18393	NM_001004127.3(ALG11):c.257T>C (p.Leu86Ser)	Pathogenic
280305	NM_001004127.3(ALG11):c.1123_1126del (p.Asn375fs)	Pathogenic
2898658	NM_001004127.3(ALG11):c.27C>A (p.Cys9Ter)	Pathogenic
3063283	GRCh37/hg19 13q14.11-21.2(chr13:44076923-60520078)x1	Pathogenic
31645	NM_001004127.3(ALG11):c.1142T>C (p.Leu381Ser)	Pathogenic
31647	NM_001004127.3(ALG11):c.953A>C (p.Gln318Pro)	Pathogenic
3250479	NM_001004127.3(ALG11):c.416T>G (p.Val139Gly)	Pathogenic
3339549	NC_000013.10:g.(?52586533)(52607737_?)del	Pathogenic
3632809	NM_001004127.3(ALG11):c.887del (p.Lys296fs)	Pathogenic
831527	NC_000013.11:g.(?51934736)(52028610_?)del	Pathogenic
832302	NC_000013.11:g.(?52011277)(52029658_?)del	Pathogenic
833271	NC_000013.11:g.(?51934746)(52029658_?)del	Pathogenic
1028907	NM_001004127.3(ALG11):c.1A>G (p.Met1Val)	Likely pathogenic
1210215	NM_001004127.3(ALG11):c.1184T>C (p.Met395Thr)	Likely pathogenic
1700351	NM_001004127.3(ALG11):c.45-2A>T	Likely pathogenic
265035	NM_001004127.3(ALG11):c.1402C>T (p.Arg468Cys)	Likely pathogenic
3255371	NM_001004127.3(ALG11):c.1403G>A (p.Arg468His)	Likely pathogenic
3255372	NM_001004127.3(ALG11):c.1307G>T (p.Gly436Val)	Likely pathogenic
422475	NM_001004127.3(ALG11):c.935A>G (p.Glu312Gly)	Likely pathogenic
422476	NM_001004127.3(ALG11):c.1223T>G (p.Met408Arg)	Likely pathogenic
564080	GRCh37/hg19 13q14.3-21.32(chr13:51939350-66854666)x3	Likely pathogenic
565290	Single allele	Likely pathogenic

SpliceAI

1707 predictions. Top by Δscore:

Variant	Effect	Δscore
13:52072113:T:TC	acceptor_gain	1.0000
13:52076057:TCTTA:T	donor_loss	1.0000
13:52076058:CTTAC:C	donor_loss	1.0000
13:52076059:TTA:T	donor_loss	1.0000
13:52076060:TA:T	donor_loss	1.0000
13:52076061:ACC:A	donor_loss	1.0000
13:52076062:C:CA	donor_loss	1.0000
13:52076140:TGTC:T	acceptor_gain	1.0000
13:52012459:TGAGG:T	donor_loss	0.9900
13:52012460:GAGG:G	donor_loss	0.9900
13:52012461:AGGTG:A	donor_loss	0.9900
13:52012462:GGTGA:G	donor_loss	0.9900
13:52012463:GTGAG:G	donor_loss	0.9900
13:52012464:T:G	donor_loss	0.9900
13:52024933:GATTG:G	donor_gain	0.9900
13:52024935:TTGG:T	donor_loss	0.9900
13:52024936:TGGT:T	donor_loss	0.9900
13:52024937:GGTG:G	donor_loss	0.9900
13:52024938:G:GG	donor_gain	0.9900
13:52024938:GTG:G	donor_loss	0.9900
13:52024939:T:G	donor_loss	0.9900
13:52024940:GAGT:G	donor_loss	0.9900
13:52028318:GGA:G	acceptor_gain	0.9900
13:52065608:CC:C	acceptor_gain	0.9900
13:52065609:CC:C	acceptor_gain	0.9900
13:52072113:T:C	acceptor_gain	0.9900
13:52075822:CCCTT:C	acceptor_gain	0.9900
13:52075823:CCTTC:C	acceptor_gain	0.9900
13:52076067:G:C	donor_gain	0.9900
13:52076097:T:A	donor_gain	0.9900

AlphaMissense

3226 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:52024322:C:G	H198D	0.999
13:52024502:T:C	S258P	0.999
13:52024923:A:T	E398V	0.999
13:52024501:T:A	N257K	0.998
13:52024501:T:G	N257K	0.998
13:52024503:C:T	S258F	0.998
13:52024923:A:C	E398A	0.998
13:52024924:G:C	E398D	0.998
13:52024924:G:T	E398D	0.998
13:52019084:C:G	C72W	0.997
13:52019104:A:T	E79V	0.997
13:52019115:T:A	W83R	0.997
13:52019115:T:C	W83R	0.997
13:52024928:T:C	F400L	0.997
13:52024930:T:A	F400L	0.997
13:52024930:T:G	F400L	0.997
13:52019073:C:G	H69D	0.996
13:52019108:A:C	R80S	0.996
13:52019108:A:T	R80S	0.996
13:52024337:A:C	S203R	0.996
13:52024339:C:A	S203R	0.996
13:52024339:C:G	S203R	0.996
13:52024508:T:A	W260R	0.996
13:52024508:T:C	W260R	0.996
13:52024659:G:C	R310T	0.996
13:52024659:G:T	R310M	0.996
13:52028531:T:C	F474L	0.996
13:52028533:C:A	F474L	0.996
13:52028533:C:G	F474L	0.996
13:52024029:T:A	V100D	0.995

dbSNP variants (sampled 300 via entrez): RS1000600431 (13:52027753 C>T), RS1000682028 (13:52016624 A>G), RS1000778840 (13:52020982 T>C), RS1001366045 (13:52019954 A>T), RS1001573540 (13:52015706 T>A), RS1001837925 (13:52026540 G>A), RS1001901117 (13:52021583 C>A), RS1002006731 (13:52032227 GAAAAA>G,GAAAA), RS1002015849 (13:52021868 A>G), RS1002042673 (13:52032479 C>G), RS1002249932 (13:52028573 G>A,T), RS1002293435 (13:52013882 T>C), RS1002490507 (13:52015402 T>C), RS1002590603 (13:52011404 G>A), RS1002690095 (13:52013621 A>G)

Disease associations

OMIM: gene MIM:613666 | disease phenotypes: MIM:613661, MIM:277900

GenCC curated gene-disease

Disease	Classification	Inheritance
ALG11-congenital disorder of glycosylation	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ALG11-congenital disorder of glycosylation	Moderate	AR

Mondo (3): ALG11-congenital disorder of glycosylation (MONDO:0013349), Wilson disease (MONDO:0010200), intellectual disability (MONDO:0001071)

Orphanet (3): ALG11-CDG (Orphanet:280071), Wilson disease (Orphanet:905), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000294	Low anterior hairline
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000504	Abnormality of vision
HP:0000958	Dry skin
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001319	Neonatal hypotonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0001987	Hyperammonemia
HP:0001999	Abnormal facial shape
HP:0002013	Vomiting
HP:0002059	Cerebral atrophy
HP:0002179	Opisthotonus
HP:0002282	Gray matter heterotopia
HP:0002375	Hypokinesia
HP:0002500	Abnormal cerebral white matter morphology
HP:0002509	Limb hypertonia

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006527	Hepatolenticular Degeneration	C06.552.413; C10.228.140.079.493; C10.228.140.163.100.360; C10.228.662.400; C10.574.500.487; C16.320.400.361; C16.320.565.189.360; C16.320.565.618.403; C18.452.132.100.360; C18.452.648.189.360; C18.452.648.618.403
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Coal	decreases expression, increases abundance	1
Gallic Acid	decreases expression	1
Ivermectin	decreases expression	1
Smoke	increases abundance, decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004338	PHASE4	COMPLETED	Study of Zinc for Wilson Disease
NCT02426905	PHASE4	UNKNOWN	Study to Assess Long-Term Outcomes of Trientine in Wilson Disease Patients Withdrawn From Therapy With d-Penicillamine
NCT05305872	PHASE4	UNKNOWN	Gandouling in the Treatment of Wilson’s Disease
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00004339	PHASE3	COMPLETED	Study of Tetrathiomolybdate in Patients With Wilson Disease
NCT00212355	PHASE3	COMPLETED	Efficacy and Safety, Long-term Study of Zinc Acetate to Treat Wilson’s Disease in Japan.
NCT03403205	PHASE3	TERMINATED	Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
NCT03539952	PHASE3	COMPLETED	Trientine Tetrahydrochloride (TETA 4HCL) for the Treatment of Wilson’s Disease
NCT05047523	PHASE3	TERMINATED	Study of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease
NCT07465718	PHASE3	NOT_YET_RECRUITING	Trientine Tetrahydrochloride Administered Once a Day for the First Line Treatment of Wilson’s Disease Patients.
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02273596	PHASE2	COMPLETED	Efficacy and Safety Study of WTX101 (ALXN1840) in Adult Wilson Disease Patients
NCT04422431	PHASE2	COMPLETED	Copper Concentration & Histopathologic Changes in Liver Biopsy in Participants With Wilson Disease Treated With ALXN1840
NCT04573309	PHASE2	COMPLETED	Copper and Molybdenum Balance in Participants With Wilson Disease Treated With ALXN1840
NCT07010575	PHASE2	COMPLETED	Patient Preference Study: Standard of Care Versus Once-daily Trientine Tetrahydrochloride
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT01874028	PHASE1	COMPLETED	A Phase 1 Study to Assess the Effects in the Body of a Single Dose of Trientine Dihydrochloride in Wilson’s Disease Patients
NCT04526197	PHASE1	COMPLETED	Phase 1 Study of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.
NCT04526210	PHASE1	COMPLETED	Study of ALXN1840 on the Metabolism of a CYP2B6 Substrate in Healthy Participants
NCT05641311	PHASE1	COMPLETED	Pharmacokinetic Study of Oral ALXN1840 in Japanese and Non-Japanese Adult Healthy Participants
NCT06128954	PHASE1	COMPLETED	Study Comparing Once Daily Dose of 900mg of TETA 4HCL Against Cuprior® (450mg Trientine Base, Twice Daily).
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT04537377	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Phase I/II Study of VTX-801 in Adult Patients With Wilson’s Disease
NCT04884815	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Phase 1/2/3 Study of UX701 Gene Therapy in Adults With Wilson Disease
NCT07173933	PHASE1/PHASE2	NOT_YET_RECRUITING	Phase I/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of GC310 Injection in Patients With Wilson’s Disease (WD)
NCT03957720	EARLY_PHASE1	UNKNOWN	The Individual Therapy for Patients With Wilson’s Disease
NCT06650319	EARLY_PHASE1	RECRUITING	A Clinical Study to Evaluate the Safety and Efficacy of LY-M003 Injection in Patients With Wilson Disease
NCT01378182	Not specified	COMPLETED	Efficacy of Invitro Expanded Bone Marrow Derived Allogeneic Mesenchymal Stem Cell Transplantation Via Portal Vein or Hepatic Artery or Peripheral Vein in Patients With Wilson Cirrhosis
NCT01472874	Not specified	COMPLETED	Single Daily Dosage of Trientine for Maintenance Treatment for Wilson Disease
NCT01980433	Not specified	COMPLETED	Inhibitory rTMS in Dystonic Wilson Patients