Polycystic liver disease 2

Summary

Polycystic liver disease 2 (MONDO:0014860) is a disease caused by SEC63 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: SEC63 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 252

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polycystic liver disease 2
Mondo ID	MONDO:0014860
OMIM	617004
DOID	DOID:0060975
UMLS	C4310769
MedGen	934736
GARD	0016174
Is cancer (heuristic)	no

Also known as: PCLD2 · polycystic liver disease 2 · polycystic liver disease 2; PCLD2 · polycystic liver disease type 2

Data availability: 252 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 2

Related subtypes (4): polycystic liver disease 1, polycystic liver disease 4 with or without kidney cysts, polycystic liver disease 3 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

252 retrieved; paginated sample, class counts are floors:

135 uncertain significance, 41 benign, 20 benign/likely benign, 19 likely pathogenic, 14 likely benign, 9 conflicting classifications of pathogenicity, 8 pathogenic, 6 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
960517	NM_001122769.3(LCA5):c.763C>T (p.Arg255Ter)	LCA5	Pathogenic	criteria provided, multiple submitters, no conflicts
1048655	NM_007214.5(SEC63):c.1023C>A (p.Cys341Ter)	SEC63	Pathogenic	criteria provided, single submitter
1255587	NM_007214.5(SEC63):c.1895C>A (p.Ser632Ter)	SEC63	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1255624	NM_007214.5(SEC63):c.2006_2007del (p.His669fs)	SEC63	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1255633	NM_007214.5(SEC63):c.292C>T (p.Arg98Ter)	SEC63	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1255636	NM_007214.5(SEC63):c.715C>T (p.Arg239Ter)	SEC63	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1448518	NM_007214.5(SEC63):c.1188_1191dup (p.Val398fs)	SEC63	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805345	NM_007214.5(SEC63):c.1094dup (p.Asn365fs)	SEC63	Pathogenic	criteria provided, single submitter
194646	NM_007214.5(SEC63):c.1605dup (p.Pro536fs)	SEC63	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2167	NM_007214.5(SEC63):c.173G>A (p.Trp58Ter)	SEC63	Pathogenic	no assertion criteria provided
2168	NM_007214.5(SEC63):c.442_443insA (p.Ala148fs)	SEC63	Pathogenic	no assertion criteria provided
2169	NM_007214.5(SEC63):c.733+1G>A	SEC63	Pathogenic	criteria provided, multiple submitters, no conflicts
3075701	NM_007214.5(SEC63):c.1331_1332del (p.Tyr444fs)	SEC63	Pathogenic	criteria provided, single submitter
522474	NM_007214.5(SEC63):c.514+1G>A	SEC63	Pathogenic	no assertion criteria provided
1255634	NM_007214.5(SEC63):c.1864C>T (p.Arg622Ter)	SEC63	Likely pathogenic	criteria provided, single submitter
1325047	NM_007214.5(SEC63):c.1942C>T (p.Gln648Ter)	SEC63	Likely pathogenic	criteria provided, single submitter
2010941	NM_007214.5(SEC63):c.625-2A>G	SEC63	Likely pathogenic	criteria provided, multiple submitters, no conflicts
225118	NM_007214.5(SEC63):c.452+1G>A	SEC63	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2575058	NM_007214.5(SEC63):c.1440+1G>A	SEC63	Likely pathogenic	criteria provided, single submitter
2575059	NM_007214.5(SEC63):c.1936-2A>T	SEC63	Likely pathogenic	no assertion criteria provided
3382138	NM_007214.5(SEC63):c.599_600del (p.Phe200fs)	SEC63	Likely pathogenic	criteria provided, single submitter
3592889	NM_007214.5(SEC63):c.1786_1787del (p.Asp596fs)	SEC63	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3592898	NM_007214.5(SEC63):c.1500+1G>A	SEC63	Likely pathogenic	criteria provided, single submitter
3592900	NM_007214.5(SEC63):c.1326dup (p.Pro443fs)	SEC63	Likely pathogenic	criteria provided, single submitter
3592911	NM_007214.5(SEC63):c.962-2A>G	SEC63	Likely pathogenic	criteria provided, single submitter
3592921	NM_007214.5(SEC63):c.506_514+3del	SEC63	Likely pathogenic	criteria provided, single submitter
3592925	NM_007214.5(SEC63):c.304G>T (p.Glu102Ter)	SEC63	Likely pathogenic	criteria provided, single submitter
3592926	NM_007214.5(SEC63):c.292dup (p.Arg98fs)	SEC63	Likely pathogenic	criteria provided, single submitter
3592932	NM_007214.5(SEC63):c.125_126del	SEC63	Likely pathogenic	criteria provided, single submitter
4292005	NM_007214.5(SEC63):c.1649del (p.Lys550fs)	SEC63	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · 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
SEC63	Definitive	Autosomal dominant	polycystic liver disease 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEC63	Orphanet:2924	Isolated polycystic liver disease
LCA5	Orphanet:364055	Severe early-childhood-onset retinal dystrophy
LCA5	Orphanet:65	Leber congenital amaurosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SEC63	HGNC:21082	ENSG00000025796	Q9UGP8	Translocation protein SEC63 homolog	gencc,clinvar
LCA5	HGNC:31923	ENSG00000135338	Q86VQ0	Lebercilin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SEC63	Translocation protein SEC63 homolog	Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER).
LCA5	Lebercilin	Involved in intraflagellar protein (IFT) transport in photoreceptor cilia.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEC63	Other/Unknown	no		DnaJ_domain, Sec63-dom, Ig_E-set
LCA5	Other/Unknown	no		Lebercilin-like, Lebercilin_dom

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
colonic epithelium	1
parotid gland	1
bronchial epithelial cell	1
bronchus	1
mucosa of paranasal sinus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEC63	295	ubiquitous	marker	colonic epithelium, body of pancreas, parotid gland
LCA5	214	ubiquitous	marker	mucosa of paranasal sinus, bronchial epithelial cell, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SEC63	3,355
LCA5	1,027

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SEC63	Q9UGP8	77.71
LCA5	Q86VQ0	64.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nitrogen cycle metabolic process	1	4213.0×	0.002	SEC63
SRP-dependent cotranslational protein targeting to membrane	1	1053.2×	0.003	SEC63
post-translational protein targeting to membrane, translocation	1	1053.2×	0.003	SEC63
post-translational protein targeting to endoplasmic reticulum membrane	1	702.2×	0.003	SEC63
intraciliary transport	1	280.9×	0.006	LCA5
photoreceptor cell maintenance	1	179.3×	0.008	LCA5
protein targeting to membrane	1	147.8×	0.009	SEC63
liver development	1	110.9×	0.010	SEC63
protein transport	1	21.9×	0.045	LCA5

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SEC63	0	0
LCA5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SEC63	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
E	Difficult family or no structure, no drug	2	SEC63, LCA5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SEC63	1	—
LCA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.