ALG11-congenital disorder of glycosylation

Summary

ALG11-congenital disorder of glycosylation (MONDO:0013349) is a disease caused by ALG11 (GenCC Strong), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ALG11 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 127
• Phenotypes (HPO): 40

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

40 HPO clinical features (Orphanet curated; top 40 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0003160	Abnormal isoelectric focusing of serum transferrin	Very frequent (80-99%)
HP:0003642	Type I transferrin isoform profile	Very frequent (80-99%)
HP:0008947	Floppy infant	Very frequent (80-99%)
HP:0012760	Reduced social responsiveness	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000504	Abnormality of vision	Frequent (30-79%)
HP:0001276	Hypertonia	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0000278	Retrognathia	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000348	High forehead	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000958	Dry skin	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0002059	Cerebral atrophy	Occasional (5-29%)
HP:0002179	Opisthotonus	Occasional (5-29%)
HP:0002282	Gray matter heterotopia	Occasional (5-29%)
HP:0002375	Hypokinesia	Occasional (5-29%)
HP:0002500	Abnormal cerebral white matter morphology	Occasional (5-29%)
HP:0002509	Limb hypertonia	Occasional (5-29%)
HP:0002572	Episodic vomiting	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Occasional (5-29%)
HP:0003186	Inverted nipples	Occasional (5-29%)
HP:0005968	Temperature instability	Occasional (5-29%)
HP:0008000	Decreased corneal reflex	Occasional (5-29%)
HP:0008936	Axial hypotonia	Occasional (5-29%)
HP:0009124	Abnormal adipose tissue morphology	Occasional (5-29%)
HP:0010851	EEG with burst suppression	Occasional (5-29%)
HP:0011842	Abnormality of skeletal morphology	Occasional (5-29%)
HP:0012448	Delayed myelination	Occasional (5-29%)
HP:0012704	Widened subarachnoid space	Occasional (5-29%)
HP:0012762	Cerebral white matter atrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	ALG11-congenital disorder of glycosylation
Mondo ID	MONDO:0013349
OMIM	613661
Orphanet	280071
DOID	DOID:0080567
SNOMED CT	733085004
UMLS	C3150913
MedGen	462263
GARD	0012396
Is cancer (heuristic)	no

Also known as: ALG11-CDG · ALG11-CDG (CDG-Ip) · ALG11-congenital disorder of glycosylation · carbohydrate deficient glycoprotein syndrome type Ip · CDG syndrome type Ip · CDG-Ip · CDG1P · congenital disorder of glycosylation type 1p · congenital disorder of glycosylation type Ip · congenital disorder of glycosylation, type Ip

Data availability: 127 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › congenital disorder of glycosylation type I › ALG11-congenital disorder of glycosylation

Related subtypes (27): PMM2-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 36, SSR4-congenital disorder of glycosylation, ALG3-congenital disorder of glycosylation, MPI-congenital disorder of glycosylation, ALG6-congenital disorder of glycosylation 1C, ALG12-congenital disorder of glycosylation, ALG2-congenital disorder of glycosylation, DPAGT1-congenital disorder of glycosylation, ALG8-congenital disorder of glycosylation, ALG1-congenital disorder of glycosylation, ALG9-congenital disorder of glycosylation, congenital disorder of glycosylation type 1E, MPDU1-congenital disorder of glycosylation, DK1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, SRD5A3-congenital disorder of glycosylation, DPM3-congenital disorder of glycosylation, DDOST-congenital disorder of glycosylation, PGM1-congenital disorder of glycosylation, congenital muscular dystrophy with intellectual disability and severe epilepsy, STT3A-congenital disorder of glycosylation, STT3B-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 50, congenital disorder of glycosylation, type IAA, congenital disorder of glycosylation, type ICC, SSR3-CDG

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

127 retrieved; paginated sample, class counts are floors:

64 uncertain significance, 26 likely benign, 8 likely pathogenic, 8 conflicting classifications of pathogenicity, 7 pathogenic, 7 benign, 5 benign/likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073825	NC_000013.10:g.(?52585403)(52602726_?)del	ALG11	Pathogenic	criteria provided, single submitter
18393	NM_001004127.3(ALG11):c.257T>C (p.Leu86Ser)	ALG11	Pathogenic	no assertion criteria provided
2898658	NM_001004127.3(ALG11):c.27C>A (p.Cys9Ter)	ALG11	Pathogenic	criteria provided, single submitter
31643	NM_001004127.3(ALG11):c.623_642del (p.Ser208fs)	ALG11	Pathogenic/Likely pathogenic	no assertion criteria provided
31644	NM_001004127.3(ALG11):c.836A>C (p.Tyr279Ser)	ALG11	Pathogenic/Likely pathogenic	no assertion criteria provided
31645	NM_001004127.3(ALG11):c.1142T>C (p.Leu381Ser)	ALG11	Pathogenic	no assertion criteria provided
31647	NM_001004127.3(ALG11):c.953A>C (p.Gln318Pro)	ALG11	Pathogenic	no assertion criteria provided
3339549	NC_000013.10:g.(?52586533)(52607737_?)del	ALG11	Pathogenic	criteria provided, single submitter
3632809	NM_001004127.3(ALG11):c.887del (p.Lys296fs)	ALG11	Pathogenic	criteria provided, single submitter
1028907	NM_001004127.3(ALG11):c.1A>G (p.Met1Val)	ALG11	Likely pathogenic	criteria provided, single submitter
1210215	NM_001004127.3(ALG11):c.1184T>C (p.Met395Thr)	ALG11	Likely pathogenic	criteria provided, single submitter
1700351	NM_001004127.3(ALG11):c.45-2A>T	ALG11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3255371	NM_001004127.3(ALG11):c.1403G>A (p.Arg468His)	ALG11	Likely pathogenic	criteria provided, single submitter
3255372	NM_001004127.3(ALG11):c.1307G>T (p.Gly436Val)	ALG11	Likely pathogenic	no assertion criteria provided
422475	NM_001004127.3(ALG11):c.935A>G (p.Glu312Gly)	ALG11	Likely pathogenic	criteria provided, single submitter
422476	NM_001004127.3(ALG11):c.1223T>G (p.Met408Arg)	ALG11	Likely pathogenic	criteria provided, single submitter
1184605	NM_001004127.3(ALG11):c.2T>C (p.Met1Thr)	LOC130009841	Likely pathogenic	no assertion criteria provided
235513	NM_021645.6(UTP14C):c.508A>G (p.Ile170Val)	ALG11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312412	NM_001004127.3(ALG11):c.535G>A (p.Ala179Thr)	ALG11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312416	NM_001004127.3(ALG11):c.1208-6T>C	ALG11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420418	NM_001004127.3(ALG11):c.983AGA[1] (p.Lys329del)	ALG11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
882013	NM_001004127.3(ALG11):c.1269G>A (p.Lys423=)	ALG11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312414	NM_001004127.3(ALG11):c.1029A>G (p.Gly343=)	UTP14C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312421	NM_021645.6(UTP14C):c.192T>C (p.Ser64=)	UTP14C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
93443	NM_001004127.3(ALG11):c.1241T>A (p.Ile414Asn)	UTP14C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015385	NM_001004127.3(ALG11):c.636T>G (p.Asn212Lys)	ALG11	Uncertain significance	criteria provided, single submitter
1028908	NM_001004127.3(ALG11):c.991G>T (p.Val331Phe)	ALG11	Uncertain significance	criteria provided, single submitter
1061831	NM_001004127.3(ALG11):c.522T>G (p.Asp174Glu)	ALG11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1063818	NM_001004127.3(ALG11):c.187A>T (p.Met63Leu)	ALG11	Uncertain significance	criteria provided, single submitter
1303283	NM_001004127.3(ALG11):c.1160A>C (p.Glu387Ala)	ALG11	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ALG11	Strong	Autosomal recessive	ALG11-congenital disorder of glycosylation	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALG11	Orphanet:280071	ALG11-CDG
ATP7B	Orphanet:905	Wilson disease

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALG11	HGNC:32456	ENSG00000253710	Q2TAA5	GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase	gencc,clinvar
UTP14C	HGNC:20321	ENSG00000253797	Q5TAP6	U3 small nucleolar RNA-associated protein 14 homolog C	clinvar
ATP7B	HGNC:870	ENSG00000123191	P35670	Copper-transporting ATPase 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALG11	GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase	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.
UTP14C	U3 small nucleolar RNA-associated protein 14 homolog C	Essential for spermatogenesis.
ATP7B	Copper-transporting ATPase 2	Copper ion transmembrane transporter involved in the export of copper out of the cells.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	4.0×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALG11	Enzyme (other)	yes	2.4.1.131	Glyco_trans_1, ALG11_N, ALG11
UTP14C	Other/Unknown	no		SSU_processome_Utp14
ATP7B	Transcription factor	no	7.2.2.8	P_typ_ATPase, HMA_dom, HMA_Cu_ion-bd

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
calcaneal tendon	1
islet of Langerhans	1
ganglionic eminence	1
primordial germ cell in gonad	1
ventricular zone	1
nasal cavity epithelium	1
nasal cavity mucosa	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALG11	134	ubiquitous	marker	islet of Langerhans, calcaneal tendon, adrenal tissue
UTP14C	127		yes	primordial germ cell in gonad, ventricular zone, ganglionic eminence
ATP7B	205	ubiquitous	marker	nasal cavity epithelium, right testis, nasal cavity mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP7B	2,536
ALG11	2,224
UTP14C	1,984

Intra-cohort edges

A	B	Sources
ALG11	UTP14C	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP7B	P35670	13

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALG11	Q2TAA5	91.40
UTP14C	Q5TAP6	66.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ALG11 causes CDG-1p	1	3806.7×	0.004	ALG11
Diseases associated with N-glycosylation of proteins	1	211.5×	0.033	ALG11
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	69.2×	0.045	ALG11
Ion transport by P-type ATPases	1	69.2×	0.045	ATP7B
rRNA modification in the nucleus and cytosol	1	62.4×	0.045	UTP14C
Diseases of glycosylation	1	43.8×	0.053	ALG11
Ion channel transport	1	32.0×	0.062	ATP7B
Diseases of metabolism	1	26.8×	0.064	ALG11
Major pathway of rRNA processing in the nucleolus and cytosol	1	20.6×	0.069	UTP14C
Asparagine N-linked glycosylation	1	20.0×	0.069	ALG11
Transport of small molecules	1	8.4×	0.146	ATP7B
Post-translational protein modification	1	6.4×	0.173	ALG11
Disease	1	4.4×	0.223	ALG11
Metabolism of proteins	1	4.1×	0.223	ALG11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
copper ion export	1	1872.4×	0.006	ATP7B
obsolete sequestering of calcium ion	1	1123.5×	0.006	ATP7B
viral translational frameshifting	1	936.2×	0.006	ATP7B
copper ion import	1	802.5×	0.006	ATP7B
copper ion transport	1	561.7×	0.006	ATP7B
response to copper ion	1	510.7×	0.006	ATP7B
xenobiotic detoxification by transmembrane export across the plasma membrane	1	374.5×	0.007	ATP7B
intracellular copper ion homeostasis	1	312.1×	0.008	ATP7B
dolichol-linked oligosaccharide biosynthetic process	1	280.9×	0.008	ALG11
intracellular zinc ion homeostasis	1	160.5×	0.012	ATP7B
lactation	1	140.4×	0.012	ATP7B
protein N-linked glycosylation	1	87.8×	0.018	ALG11
meiotic cell cycle	1	81.4×	0.018	UTP14C
monoatomic ion transmembrane transport	1	69.3×	0.019	ATP7B
protein maturation	1	54.5×	0.022	ATP7B
establishment of localization in cell	1	53.5×	0.022	ATP7B
rRNA processing	1	47.2×	0.024	UTP14C
spermatogenesis	1	11.7×	0.087	UTP14C
cell differentiation	1	9.7×	0.100	UTP14C

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALG11	0	0
UTP14C	0	0
ATP7B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALG11	2.4.1.131	GDP-Man:Man3GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase
ATP7B	7.2.2.8, 7.2.2.9	P-type Cu+ transporter, P-type Cu2+ transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ALG11
E	Difficult family or no structure, no drug	2	UTP14C, ATP7B

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ALG11	0	—
UTP14C	0	—
ATP7B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.