ALG13

Summary

ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit, HGNC:30881) is a protein-coding gene on chromosome Xq23, encoding UDP-N-acetylglucosamine transferase subunit ALG13 (Q9NP73). Catalytic subunit of the UDP-N-acetylglucosamine transferase complex 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: 85.3% of cell lines).

The protein encoded by this gene is a subunit of a bipartite UDP-N-acetylglucosamine transferase. It heterodimerizes with asparagine-linked glycosylation 14 homolog to form a functional UDP-GlcNAc glycosyltransferase that catalyzes the second sugar addition of the highly conserved oligosaccharide precursor in endoplasmic reticulum N-linked glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79868 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,458 total — 2 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 51
• Cancer dependency (DepMap): dependent in 85.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001099922

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30881
Approved symbol	ALG13
Name	ALG13 UDP-N-acetylglucosaminyltransferase subunit
Location	Xq23
Locus type	gene with protein product
Status	Approved
Aliases	MDS031, YGL047W, FLJ23018, TDRD13, CDG1S
Ensembl gene	ENSG00000101901
Ensembl biotype	protein_coding
OMIM	300776
Entrez	79868

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 17 nonsense_mediated_decay, 13 protein_coding, 9 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000371979, ENST00000394780, ENST00000436609, ENST00000460092, ENST00000461669, ENST00000468657, ENST00000470704, ENST00000470971, ENST00000471924, ENST00000473389, ENST00000474121, ENST00000482374, ENST00000482742, ENST00000485371, ENST00000486353, ENST00000486578, ENST00000487141, ENST00000487243, ENST00000489033, ENST00000490774, ENST00000492038, ENST00000495283, ENST00000622986, ENST00000622997, ENST00000623144, ENST00000623148, ENST00000623189, ENST00000623255, ENST00000623310, ENST00000623622, ENST00000624161, ENST00000624881, ENST00000635768, ENST00000635824, ENST00000635931, ENST00000636363, ENST00000637022, ENST00000637213, ENST00000699748, ENST00000699778, ENST00000927365, ENST00000927366

RefSeq mRNA: 17 — MANE Select: NM_001099922 NM_001039210, NM_001099922, NM_001168385, NM_001257230, NM_001257231, NM_001257234, NM_001257235, NM_001257237, NM_001257239, NM_001257240, NM_001257241, NM_001324290, NM_001324291, NM_001324292, NM_001324293, NM_001324294, NM_018466

CCDS: CCDS14559, CCDS55477, CCDS59173, CCDS76011, CCDS76013

Canonical transcript exons

ENST00000394780 — 27 exons

Exon	Start	End
ENSE00000846436	111759734	111760649
ENSE00001631314	111726809	111727055
ENSE00001674918	111724934	111725061
ENSE00001710443	111723798	111723898
ENSE00003531475	111721603	111721711
ENSE00003650344	111720095	111720170
ENSE00003688824	111682132	111682294
ENSE00003720687	111722793	111722857
ENSE00003722395	111684965	111685103
ENSE00003744462	111727614	111727770
ENSE00003747677	111718112	111718274
ENSE00003756501	111717846	111717927
ENSE00003756505	111681170	111681299
ENSE00003757013	111727332	111727445
ENSE00003759267	111744668	111744904
ENSE00003759340	111728185	111728305
ENSE00003977477	111711675	111711725
ENSE00003977480	111735051	111735122
ENSE00003977481	111730525	111730580
ENSE00003977482	111757588	111757762
ENSE00003977484	111730395	111730427
ENSE00003977485	111708027	111708393
ENSE00003977486	111712484	111712530
ENSE00003977488	111713225	111713297
ENSE00003977489	111736714	111736879
ENSE00003977492	111752790	111752830
ENSE00003977494	111708965	111709048

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 95.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.7790 / max 465.3557, expressed in 1820 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197291	33.7304	1818
197293	1.7446	675
197298	1.4441	709
197294	1.2998	331
197292	0.8336	408
197295	0.3212	108
197296	0.2124	72
197297	0.1928	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.88	gold quality
adrenal tissue	UBERON:0018303	95.71	gold quality
right uterine tube	UBERON:0001302	95.49	gold quality
endothelial cell	CL:0000115	95.47	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.64	gold quality
endocervix	UBERON:0000458	94.63	gold quality
left ovary	UBERON:0002119	94.47	gold quality
body of uterus	UBERON:0009853	94.28	gold quality
adenohypophysis	UBERON:0002196	94.23	gold quality
colonic mucosa	UBERON:0000317	94.06	gold quality
left uterine tube	UBERON:0001303	94.03	gold quality
right ovary	UBERON:0002118	94.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.99	gold quality
pituitary gland	UBERON:0000007	93.75	gold quality
right coronary artery	UBERON:0001625	93.75	gold quality
ovary	UBERON:0000992	93.68	gold quality
spleen	UBERON:0002106	93.67	gold quality
palpebral conjunctiva	UBERON:0001812	93.64	gold quality
left lobe of thyroid gland	UBERON:0001120	93.58	gold quality
tibial nerve	UBERON:0001323	93.49	gold quality
omental fat pad	UBERON:0010414	93.49	gold quality
ectocervix	UBERON:0012249	93.49	gold quality
vagina	UBERON:0000996	93.47	gold quality
germinal epithelium of ovary	UBERON:0001304	93.47	gold quality
peritoneum	UBERON:0002358	93.47	gold quality
monocyte	CL:0000576	93.46	gold quality
right lung	UBERON:0002167	93.45	gold quality
minor salivary gland	UBERON:0001830	93.37	gold quality
gall bladder	UBERON:0002110	93.36	gold quality
lymph node	UBERON:0000029	93.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting ALG13, 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-656-3P	100.00	72.15	2788
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-567	99.63	68.57	1219

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 85.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• ALG13 and ALG14 form a functional endoplasmic reticulum UDP-N-acetylglucosamine transferase (PMID:16100110)
• We report on a novel missense variant in the ALG13 gene in a nonconsanguineous Arab family that co-segregates with nonsyndromic intellectual disability. (PMID:24501762)
• ALG13-is2 could be an important modifier of renal filtration defects (PMID:28178702)
• A female patient heterozygous for ALG13 Asn107Ser variant presented with infantile spasms, developmental delay, and dysmorphic features. The patient showed normal pattern of glycosylated transferrin and random pattern of X-inactivation. (PMID:28778787)
• X-Linked ALG13 Gene Variant as a Cause of Epileptic Encephalopathy in Girls. (PMID:31444733)
• The phenotypic spectrum of X-linked, infantile onset ALG13-related developmental and epileptic encephalopathy. (PMID:33410528)
• Expanding the phenotype, genotype and biochemical knowledge of ALG3-CDG. (PMID:33583022)
• ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. (PMID:33734437)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	alg13	ENSDARG00000054374
mus_musculus	Alg13	ENSMUSG00000041718
rattus_norvegicus	Alg13l1	ENSRNOG00000005753

Protein

Protein identifiers

UDP-N-acetylglucosamine transferase subunit ALG13 — Q9NP73 (reviewed: Q9NP73)

Alternative names: Asparagine-linked glycosylation 13 homolog, Glycosyltransferase 28 domain-containing protein 1

All UniProt accessions (16): Q9NP73, A0A087WT15, A0A087WTT9, A0A087WVG5, A0A087WX01, A0A087WX43, A0A096LNJ4, A0A096LNJ5, A0A096LNL2, A0A096LP10, A0A096LP54, A0A096LPI3, A0A096LPK3, A0A1B0GVW6, A0A8V8TQ59, D6RE84

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the UDP-N-acetylglucosamine transferase complex 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. On the cytoplasmic face of the endoplasmic reticulum, the dimeric ALG13/ALG14 complex catalyzes the second step of dolichol pyrophosphate biosynthesis, transferring a beta1,4-linked N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to GlcNAc-pyrophosphatedolichol (Gn-PDol) to produce N,N’-diacetylchitobiosyl diphosphodolichol. N,N’-diacetylchitobiosyl diphosphodolichol is a substrate for ALG1, the following enzyme in the biosynthetic pathway. Catalytic subunit of the UDP-N-acetylglucosamine transferase complex 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. On the cytoplasmic face of the endoplasmic reticulum, the dimeric ALG13/ALG14 complex catalyzes the second step of dolichol pyrophosphate biosynthesis, transferring a beta1,4-linked N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to GlcNAc-pyrophosphatedolichol (Gn-PDol) to produce N,N’-diacetylchitobiosyl diphosphodolichol. N,N’-diacetylchitobiosyl diphosphodolichol is a substrate for ALG1, the following enzyme in the biosynthetic pathway. No glycosyltransferase or deubiquitinase activity is detected for this potential multifunctional enzyme.

Subunit / interactions. Forms with ALG14 the active heterodimeric UDP-N-acetylglucosamine transferase complex. Not able to interact with ALG14 to form an active UDP-N-acetylglucosamine transferase complex.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Developmental and epileptic encephalopathy 36 (DEE36) [MIM:300884] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. Some DEE36 patients may present with an abnormal isoelectric focusing of serum transferrin, consistent with a diagnostic classification of congenital disorder of glycosylation type I. 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 28 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NP73-1	1	yes
Q9NP73-2	2
Q9NP73-3	3
Q9NP73-4	4

RefSeq proteins (17): NP_001034299, NP_001093392, NP_001161857, NP_001244159, NP_001244160, NP_001244163, NP_001244164, NP_001244166, NP_001244168, NP_001244169, NP_001244170, NP_001311219, NP_001311220, NP_001311221, NP_001311222, NP_001311223, NP_060936 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002999	Tudor	Domain
IPR003323	OTU_dom	Domain
IPR007235	Glyco_trans_28_C	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR039042	Alg13-like	Family
IPR047387	OTU_ALG13	Domain

Pfam: PF02338, PF04101

Catalyzed reactions (Rhea), 1 shown:

• an N-acetyl-alpha-D-glucosaminyl-diphospho-di-trans,poly-cis-dolichol + UDP-N-acetyl-alpha-D-glucosamine = an N,N’-diacetylchitobiosyl-diphospho-di-trans,poly-cis-dolichol + UDP + H(+) (RHEA:23380)

UniProt features (34 total): sequence conflict 11, splice variant 6, region of interest 4, active site 3, sequence variant 3, domain 2, mutagenesis site 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP73-F1	54.42	0.18

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 (3): 242 (nucleophile; for deubiquitinase activity); 345 (for deubiquitinase activity); 239 (for deubiquitinase activity)

Mutagenesis-validated functional residues (2):

Position	Phenotype
17	decreased n-acetylglucosaminyldiphosphodolichol n-acetylglucosaminyltransferase activity.
81	decreased n-acetylglucosaminyldiphosphodolichol n-acetylglucosaminyltransferase 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-5633231	Defective ALG14 causes ALG14-CMS
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: 251 (showing top): GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, ONKEN_UVEAL_MELANOMA_UP, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GARY_CD5_TARGETS_DN, BASAKI_YBX1_TARGETS_DN, ZHANG_BREAST_CANCER_PROGENITORS_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, PITX2_Q2, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS

GO Biological Process (3): protein N-linked glycosylation (GO:0006487), dolichol-linked oligosaccharide biosynthetic process (GO:0006488), proteolysis (GO:0006508)

GO Molecular Function (10): N-acetylglucosaminyldiphosphodolichol N-acetylglucosaminyltransferase activity (GO:0004577), cysteine-type peptidase activity (GO:0008234), catalytic activity (GO:0003824), cysteine-type deubiquitinase activity (GO:0004843), protein binding (GO:0005515), peptidase activity (GO:0008233), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758), hydrolase activity (GO:0016787)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), UDP-N-acetylglucosamine transferase complex (GO:0043541), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

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
catalytic activity	2
endoplasmic reticulum membrane	2
cellular anatomical structure	2
glycoprotein biosynthetic process	1
protein N-linked glycosylation	1
carbohydrate derivative biosynthetic process	1
protein metabolic process	1
acetylglucosaminyltransferase activity	1
peptidase activity	1
molecular_function	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
transferase activity	1
glycosyltransferase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
transferase complex, transferring phosphorus-containing groups	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
cytoplasmic side of membrane	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALG13	ALG14	Q96F25	999
ALG13	DPAGT1	Q9H3H5	995
ALG13	ALG11	Q2TAA5	773
ALG13	ALG1	Q9BT22	772
ALG13	ALG12	Q9BV10	760
ALG13	ALG6	Q9Y672	744
ALG13	ALG3	Q92685	730
ALG13	ALG8	Q9BVK2	718
ALG13	DPM1	O60762	688
ALG13	DPM2	O94777	642
ALG13	ALG5	Q9Y673	623
ALG13	ALG2	Q9H553	593
ALG13	CDKL5	O76039	575
ALG13	DPM3	Q9P2X0	573
ALG13	GABRB3	P28472	530

IntAct

28 interactions, top by confidence:

A	B	Type	Score
PRG2	YPEL5	psi-mi:“MI:0914”(association)	0.640
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
MYCBP	AKAP8	psi-mi:“MI:0914”(association)	0.550
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
CD63	LGALS8	psi-mi:“MI:0914”(association)	0.530
ALG13	SLC2A4	psi-mi:“MI:0915”(physical association)	0.400
ALG13		psi-mi:“MI:0915”(physical association)	0.370
	SCAMP3	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
TRIM52	MEIOC	psi-mi:“MI:0914”(association)	0.350
LOX	VWA8	psi-mi:“MI:0914”(association)	0.350
EGFL6	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PRG2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PLOD1	PLK4	psi-mi:“MI:0914”(association)	0.350
PRPS2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
FADS3	PGRMC2	psi-mi:“MI:0914”(association)	0.350
FBL	ZNF850	psi-mi:“MI:2364”(proximity)	0.270
KHDRBS1	ALG13	psi-mi:“MI:0915”(physical association)	0.000
	ALG13	psi-mi:“MI:0915”(physical association)	0.000
ATN1	ALG13	psi-mi:“MI:0915”(physical association)	0.000
RERE	ALG13	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (217): ALG13 (Two-hybrid), ALG13 (Two-hybrid), ALG13 (Affinity Capture-MS), ALG13 (Reconstituted Complex), ALG13 (Affinity Capture-MS), ALG13 (Affinity Capture-MS), ALG13 (Affinity Capture-MS), ALG13 (Affinity Capture-MS), ALG13 (Affinity Capture-MS), ALG13 (Affinity Capture-MS), ALG13 (Affinity Capture-MS), ALG13 (Affinity Capture-MS), ALG13 (Two-hybrid), ALG13 (Affinity Capture-MS), ALG13 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8GWK2, A0A571BF63, A0JMA8, A0JNE3, A2BGA0, A4IIG7, O00443, P13056, P24781, P28701, P28705, P43354, P45448, P48443, P51128, P51129, Q04913, Q06219, Q07917, Q08E53, Q09555, Q0GFF6, Q0IHW3, Q0VC20, Q1LVF3, Q26622, Q33E94, Q505F1, Q5BJR8, Q5FWP2, Q5R5Y4, Q5RAY1, Q5RCZ5, Q5REL6, Q5RJH6, Q61194, Q64287, Q68F67, Q6DHP9, Q7TNK1

Diamond homologs: B2RRE7, F4K3M6, P10383, Q01804, Q08BW0, Q2YDU3, Q3U2S4, Q5T2D3, Q640H3, Q6GL44, Q7ZX21, Q96G74, Q9D8C3, Q9NP73, Q9XIP2, B1AZ99, Q0V869, Q5ZIP6, Q6IE21, Q7L8S5, Q8LBW2, O14190, P0CN88, P0CN89, P53178, Q4WQN1, Q5ABE5, Q5I0K7, Q6BST1, Q6C3P1, Q6CXY0, Q6FVR6, Q750J3, Q9VR20, Q5VV17, Q9CUB6, Q9SGA5, A0AKD5, A3DE27, A4XI04

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1458 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	8
Uncertain significance	500
Likely benign	570
Benign	54

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1685519	NM_001099922.3(ALG13):c.120A>C (p.Gln40His)	Pathogenic
39775	NM_001099922.3(ALG13):c.280A>G (p.Lys94Glu)	Pathogenic
1184824	NM_001099922.3(ALG13):c.204AGA[1] (p.Glu69del)	Likely pathogenic
1344836	NM_001099922.3(ALG13):c.2272G>T (p.Val758Phe)	Likely pathogenic
1676180	NM_001099922.3(ALG13):c.1438C>G (p.Leu480Val)	Likely pathogenic
2663907	NM_001099922.3(ALG13):c.131G>A (p.Gly44Glu)	Likely pathogenic
3242594	NM_001099922.3(ALG13):c.412dup (p.Ser138fs)	Likely pathogenic
545380	Single allele	Likely pathogenic
598969	NM_001099922.3(ALG13):c.50T>A (p.Ile17Asn)	Likely pathogenic
870209	NM_001099922.3(ALG13):c.320A>T (p.Asn107Ile)	Likely pathogenic

SpliceAI

642 predictions. Top by Δscore:

Variant	Effect	Δscore
X:111681300:G:GG	donor_gain	1.0000
X:111682131:GAAA:G	acceptor_gain	1.0000
X:111684957:A:AG	acceptor_gain	1.0000
X:111684958:T:G	acceptor_gain	1.0000
X:111684960:TGTA:T	acceptor_loss	1.0000
X:111684961:GTAG:G	acceptor_loss	1.0000
X:111684963:A:AG	acceptor_gain	1.0000
X:111684963:AG:A	acceptor_gain	1.0000
X:111684963:AGGT:A	acceptor_gain	1.0000
X:111684964:G:GC	acceptor_gain	1.0000
X:111684964:GG:G	acceptor_gain	1.0000
X:111684964:GGT:G	acceptor_gain	1.0000
X:111684964:GGTG:G	acceptor_gain	1.0000
X:111684964:GGTGC:G	acceptor_gain	1.0000
X:111685100:GCAG:G	donor_gain	1.0000
X:111685101:CAGGT:C	donor_loss	1.0000
X:111685102:AGGTA:A	donor_loss	1.0000
X:111685105:T:A	donor_loss	1.0000
X:111687885:A:AG	acceptor_gain	1.0000
X:111687886:G:GG	acceptor_gain	1.0000
X:111687886:GCAC:G	acceptor_gain	1.0000
X:111681398:A:T	donor_gain	0.9900
X:111682126:TTTCA:T	acceptor_loss	0.9900
X:111682127:TTCAG:T	acceptor_loss	0.9900
X:111682128:TCA:T	acceptor_loss	0.9900
X:111682129:CA:C	acceptor_loss	0.9900
X:111682130:A:AG	acceptor_gain	0.9900
X:111682130:A:AT	acceptor_loss	0.9900
X:111682131:G:GG	acceptor_gain	0.9900
X:111682131:GA:G	acceptor_gain	0.9900

AlphaMissense

7430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:111682285:A:C	S79R	0.999
X:111682287:T:A	S79R	0.999
X:111682287:T:G	S79R	0.999
X:111708341:G:C	R233P	0.999
X:111708373:T:C	F244L	0.999
X:111708374:T:C	F244S	0.999
X:111708375:T:A	F244L	0.999
X:111708375:T:G	F244L	0.999
X:111708377:G:C	R245P	0.999
X:111708386:C:G	S248W	0.999
X:111708999:G:C	R262T	0.999
X:111708999:G:T	R262M	0.999
X:111709000:G:C	R262S	0.999
X:111709000:G:T	R262S	0.999
X:111712515:T:C	L306P	0.999
X:111717927:G:C	A363P	0.999
X:111721655:T:C	L460P	0.999
X:111723874:T:A	V526D	0.999
X:111708340:C:G	R233G	0.998
X:111708358:G:C	D239H	0.998
X:111708379:G:C	A246P	0.998
X:111708385:T:C	S248P	0.998
X:111709007:T:C	C265R	0.998
X:111711703:T:C	L288P	0.998
X:111713241:T:G	Y317D	0.998
X:111717853:T:C	L338P	0.998
X:111717921:T:C	C361R	0.998
X:111718130:T:C	L369P	0.998
X:111718132:T:G	Y370D	0.998
X:111721673:G:C	R466P	0.998

dbSNP variants (sampled 300 via entrez): RS1000038115 (X:111743091 G>C), RS1000138434 (X:111679514 G>C), RS1000153165 (X:111718016 T>C), RS1000314512 (X:111688198 C>G), RS1000390181 (X:111697658 A>G), RS1000505098 (X:111727934 A>G), RS1000582426 (X:111750140 C>T), RS1000609370 (X:111693023 T>A,C), RS1000642100 (X:111697970 C>A), RS1000659657 (X:111685812 T>C), RS1000684442 (X:111757939 G>A), RS1000689491 (X:111685332 T>G), RS1000725875 (X:111751859 C>G,T), RS1000749186 (X:111694900 C>A), RS1000757948 (X:111739902 C>T)

Disease associations

OMIM: gene MIM:300776 | disease phenotypes: MIM:300884, MIM:117000, MIM:308350, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 36	Strong	X-linked
non-syndromic X-linked intellectual disability	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	XL

Mondo (11): developmental and epileptic encephalopathy, 36 (MONDO:0010472), congenital disorder of glycosylation (MONDO:0015286), microcephaly (MONDO:0001149), developmental and epileptic encephalopathy (MONDO:0100620), hereditary ataxia (MONDO:0100309), intellectual disability (MONDO:0001071), congenital myopathy (MONDO:0019952), developmental and epileptic encephalopathy, 1 (MONDO:0010632), schizophrenia (MONDO:0005090), focal segmental glomerulosclerosis (MONDO:0100313), non-syndromic X-linked intellectual disability (MONDO:0019181)

Orphanet (7): ALG13-CDG (Orphanet:324422), Congenital disorder of glycosylation (Orphanet:137), Hereditary ataxia (Orphanet:183518), Congenital myopathy (Orphanet:97245), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000331	Short chin
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000666	Horizontal nystagmus
HP:0000717	Autism
HP:0000742	Self-mutilation
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0001181	Adducted thumb
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001371	Flexion contracture
HP:0001417	X-linked inheritance
HP:0001892	Abnormal bleeding
HP:0002059	Cerebral atrophy
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002188	Delayed CNS myelination
HP:0002240	Hepatomegaly
HP:0002283	Global brain atrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005790_48	Rosacea symptom severity	2.000000e-06
GCST011377_9	Shoulder impingement or rotator cuff tear	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009180	rosacea severity measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C531684	Hereditary spinal ataxia (supp.)
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression, affects expression	8
sodium arsenite	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
methacrylaldehyde	affects expression, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, affects expression, increases abundance	2
Air Pollutants	affects cotreatment, affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Ozone	affects expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
alpha-pinene	affects expression, increases abundance, affects cotreatment	1
arsenite	affects expression	1
cobaltous chloride	decreases expression	1
zinc chromate	increases abundance, increases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	decreases methylation	1
chromium hexavalent ion	increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
ICG 001	increases expression	1
dorsomorphin	decreases expression, increases expression, affects cotreatment	1
NSC 689534	increases expression, affects binding	1
Arsenic Trioxide	increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Calcitriol	decreases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	decreases methylation	1
Quercetin	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_8633	VACO 425	Cancer cell line	Male
CVCL_RG00	PFIZi022-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
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
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
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
NCT07572825	PHASE1	NOT_YET_RECRUITING	Assessing the Safety and Tolerability of NMN in DHDDS-CDG
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
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)
NCT02089789	Not specified	RECRUITING	Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
NCT02503267	Not specified	UNKNOWN	Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects
NCT02955264	Not specified	COMPLETED	Using D-Galactose as a Food Supplement in Congenital Disorders of Glycosylation
NCT03250728	Not specified	COMPLETED	Role of the Endothelium in Stroke-like Episode Among CDG Patients
NCT03560570	Not specified	COMPLETED	Study of Hemostasis in Patients With Congenital Disorder of Glycosylation
NCT04198987	Not specified	COMPLETED	Dietary Monosaccharide Supplementation in Patients With Congenital Disorders of Glycosylation
NCT04199000	Not specified	RECRUITING	Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
NCT04201067	Not specified	COMPLETED	Large-Scale Metabolomic Profiling for the Diagnosis of Inborn Errors of Metabolism
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.