Polycystic liver disease 3 with or without kidney cysts
diseaseOn this page
Also known as PCLD3
Summary
Polycystic liver disease 3 with or without kidney cysts (MONDO:0054743) is a disease caused by ALG8 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: ALG8 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 123
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | polycystic liver disease 3 with or without kidney cysts |
| Mondo ID | MONDO:0054743 |
| OMIM | 617874 |
| DOID | DOID:0060976 |
| UMLS | C4693472 |
| MedGen | 1646969 |
| GARD | 0025967 |
| Is cancer (heuristic) | no |
Also known as: PCLD3 · polycystic liver disease 3 with or without kidney cysts
Data availability: 123 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant polycystic liver disease › polycystic liver disease 3 with or without kidney cysts
Related subtypes (4): polycystic liver disease 1, polycystic liver disease 2, polycystic liver disease 4 with or without kidney cysts, SEC61B-related polycystic liver disease
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
123 retrieved; paginated sample, class counts are floors:
72 uncertain significance, 24 likely pathogenic, 10 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 6 likely benign, 2 benign/likely benign, 2 pathogenic, 1 no classifications from unflagged records
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1437904 | NM_024079.5(ALG8):c.802del (p.Arg268fs) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2230523 | NM_024079.5(ALG8):c.309dup (p.Leu104fs) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2506353 | NM_024079.5(ALG8):c.272del (p.Asn91fs) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2561 | NM_024079.5(ALG8):c.139A>C (p.Thr47Pro) | ALG8 | Pathogenic | criteria provided, single submitter |
| 280116 | NM_024079.5(ALG8):c.1090C>T (p.Arg364Ter) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2982294 | NM_024079.5(ALG8):c.824del (p.Gly275fs) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3574056 | NM_024079.5(ALG8):c.740T>G (p.Leu247Ter) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4531361 | NM_024079.5(ALG8):c.967C>T (p.Gln323Ter) | ALG8 | Pathogenic | criteria provided, single submitter |
| 492977 | NM_024079.5(ALG8):c.535C>T (p.Arg179Ter) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 854540 | NM_024079.5(ALG8):c.761dup (p.Pro255fs) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 956334 | NM_024079.5(ALG8):c.981dup (p.Val328fs) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 96090 | NM_024079.5(ALG8):c.121C>T (p.Arg41Ter) | ALG8 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1328207 | NM_024079.5(ALG8):c.685C>T (p.Arg229Ter) | ALG8 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1333512 | NM_024079.5(ALG8):c.710_719dup (p.Leu241fs) | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 1344961 | NM_024079.5(ALG8):c.95+1G>A | ALG8 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2562 | NM_024079.5(ALG8):c.673+4A>G | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 2563 | NM_024079.5(ALG8):c.824G>A (p.Gly275Asp) | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 2683953 | NM_024079.5(ALG8):c.544C>T (p.Gln182Ter) | ALG8 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3574028 | NM_024079.5(ALG8):c.1354G>T (p.Glu452Ter) | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 3574032 | NM_024079.5(ALG8):c.1276+1G>A | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 3574034 | NM_024079.5(ALG8):c.1218del (p.Phe406_Leu407insTer) | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 3574035 | NM_024079.5(ALG8):c.1184_1187delinsGTT (p.Leu395fs) | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 3574036 | NM_024079.5(ALG8):c.1179-7_1179-2del | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 3574038 | NM_024079.5(ALG8):c.1131del (p.Trp378fs) | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 3574039 | NM_024079.5(ALG8):c.1114dup (p.Ser372fs) | ALG8 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3574041 | NM_024079.5(ALG8):c.1057del (p.Trp353fs) | ALG8 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3574046 | NM_024079.5(ALG8):c.867C>G (p.Tyr289Ter) | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 3574061 | NM_024079.5(ALG8):c.674-2A>G | ALG8 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3574064 | NM_024079.5(ALG8):c.643C>T (p.Arg215Ter) | ALG8 | Likely pathogenic | criteria provided, single submitter |
| 3574073 | NM_024079.5(ALG8):c.219G>A (p.Trp73Ter) | ALG8 | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 9 · 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 |
|---|---|---|---|---|
| ALG8 | Strong | Autosomal dominant | polycystic liver disease 3 with or without kidney cysts | 9 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| ALG8 | Orphanet:2924 | Isolated polycystic liver disease |
| ALG8 | Orphanet:79325 | ALG8-CDG |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| ALG8 | HGNC:23161 | ENSG00000159063 | Q9BVK2 | Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| ALG8 | Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase | Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
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 | 12.0× | 0.083 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| ALG8 | Enzyme (other) | yes | 2.4.1.265 | Glyco_trans_ALG6/ALG8 |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene 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) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| left testis | 1 |
| right testis | 1 |
| testis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| ALG8 | 282 | ubiquitous | marker | right testis, left testis, testis |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ALG8 | 1,010 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ALG8 | Q9BVK2 | 92.07 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Defective ALG8 causes CDG-1h | 1 | 11420.0× | 8e-04 | ALG8 |
| Diseases associated with N-glycosylation of proteins | 1 | 634.4× | 0.007 | ALG8 |
| Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein | 1 | 207.6× | 0.014 | ALG8 |
| Diseases of glycosylation | 1 | 131.3× | 0.017 | ALG8 |
| Diseases of metabolism | 1 | 80.4× | 0.022 | ALG8 |
| Asparagine N-linked glycosylation | 1 | 60.1× | 0.025 | ALG8 |
| Post-translational protein modification | 1 | 19.2× | 0.067 | ALG8 |
| Disease | 1 | 13.1× | 0.081 | ALG8 |
| Metabolism of proteins | 1 | 12.4× | 0.081 | ALG8 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| dolichol-linked oligosaccharide biosynthetic process | 1 | 842.6× | 0.002 | ALG8 |
| obsolete protein N-linked glycosylation via asparagine | 1 | 674.1× | 0.002 | ALG8 |
| protein N-linked glycosylation | 1 | 263.3× | 0.004 | ALG8 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| ALG8 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| ALG8 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ALG8 | 2.4.1.265 | dolichyl-P-Glc:Glc1Man9GlcNAc2-PP-dolichol alpha-1,3-glucosyltransferase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; 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 | ALG8 |
| E | Difficult family or no structure, no drug | 0 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| ALG8 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: ALG8