Congenital pulmonary veins anomaly

Summary

Congenital pulmonary veins anomaly (MONDO:0020295) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital pulmonary veins anomaly
Mondo ID	MONDO:0020295
Orphanet	98729
NCIT	C110942
SNOMED CT	111322000
UMLS	C0265914
MedGen	539575
GARD	0019559
Is cancer (heuristic)	no

Also known as: congenital anomaly of pulmonary veins

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › congenital pulmonary veins anomaly

Related subtypes (22): congenital heart defects, multiple types, heart septal defect, tetralogy of fallot, heart defects-limb shortening syndrome, tricuspid atresia, patent ductus arteriosus, coronary artery congenital malformation, mitral atresia disorder, persistent truncus arteriosus, dextro-looped transposition of the great arteries, aortic valve atresia, mehta lewis patton syndrome, structural congenital heart disease, multiple types - GATA4, GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes, GATA5-related congenital heart defects, RBFOX2-related congenital heart disorder, syndromic congenital heart disease, ACTC1-related distal arthrogryposis with congenital heart disease, HAND1 related congenital heart defect, HAND2 related congenital heart defect, TFAP2B-related congenital heart disease spectrum disorder, PLD1-related congenital heart disease

Subtypes (4): alveolar capillary dysplasia with misalignment of pulmonary veins, congenital pulmonary venous return anomaly, congenital alveolar dysplasia, alveolar capillary dysplasia without misalignment of pulmonary veins

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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1804031	NM_002804.5(PSMC3):c.910C>T (p.Arg304Trp)	PSMC3	Pathogenic	criteria provided, single submitter
523286	GRCh37/hg19 7q36.3(chr7:156333296-156556779)	LMBR1	Uncertain significance	criteria provided, single submitter
523287	GRCh37/hg19 7q36.3(chr7:156656444-156866708)	NOM1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LMBR1	Orphanet:2378	Laurin-Sandrow syndrome
LMBR1	Orphanet:931	Isolated acheiropodia
LMBR1	Orphanet:93321	Isolated radial hemimelia
LMBR1	Orphanet:93336	Polydactyly of a triphalangeal thumb
LMBR1	Orphanet:93405	Syndactyly type 4
LMBR1	Orphanet:988	Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome

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
LMBR1	HGNC:13243	ENSG00000105983	Q8WVP7	Limb region 1 protein homolog	clinvar
NOM1	HGNC:13244	ENSG00000146909	Q5C9Z4	Nucleolar MIF4G domain-containing protein 1	clinvar
PSMC3	HGNC:9549	ENSG00000165916	P17980	26S proteasome regulatory subunit 6A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LMBR1	Limb region 1 protein homolog	Putative membrane receptor.
NOM1	Nucleolar MIF4G domain-containing protein 1	Plays a role in targeting PPP1CA to the nucleolus.
PSMC3	26S proteasome regulatory subunit 6A	Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LMBR1	Other/Unknown	no		LMBR1-like_membr_prot, LIMR
NOM1	Other/Unknown	no		MIF4G-like_typ-3, Initiation_fac_eIF4g_MI, ARM-type_fold
PSMC3	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS

Expression context

Cohort genes with no expression data: 0.

3 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
sural nerve	1
epithelial cell of pancreas	1
germinal epithelium of ovary	1
visceral pleura	1
apex of heart	1
gastrocnemius	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LMBR1	249	ubiquitous	marker	adrenal tissue, sural nerve, calcaneal tendon
NOM1	251	ubiquitous	marker	epithelial cell of pancreas, visceral pleura, germinal epithelium of ovary
PSMC3	289	ubiquitous	marker	apex of heart, gastrocnemius, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSMC3	4,843
NOM1	1,796
LMBR1	977

Intra-cohort edges

A	B	Sources
LMBR1	NOM1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSMC3	P17980	130

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LMBR1	Q8WVP7	79.49
NOM1	Q5C9Z4	70.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 68. Enrichment computed across 3 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
Regulation of activated PAK-2p34 by proteasome mediated degradation	1	278.5×	0.009	PSMC3
Regulation of ornithine decarboxylase (ODC)	1	271.9×	0.009	PSMC3
Vpu mediated degradation of CD4	1	265.6×	0.009	PSMC3
Autodegradation of the E3 ubiquitin ligase COP1	1	265.6×	0.009	PSMC3
Ubiquitin-dependent degradation of Cyclin D	1	265.6×	0.009	PSMC3
Cross-presentation of soluble exogenous antigens (endosomes)	1	253.8×	0.009	PSMC3
Vif-mediated degradation of APOBEC3G	1	253.8×	0.009	PSMC3
AUF1 (hnRNP D0) binds and destabilizes mRNA	1	248.3×	0.009	PSMC3
Degradation of AXIN	1	248.3×	0.009	PSMC3
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	1	248.3×	0.009	PSMC3
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	1	248.3×	0.009	PSMC3
Hh mutants are degraded by ERAD	1	243.0×	0.009	PSMC3
SCF-beta-TrCP mediated degradation of Emi1	1	237.9×	0.009	PSMC3
Degradation of DVL	1	237.9×	0.009	PSMC3
Negative regulation of NOTCH4 signaling	1	237.9×	0.009	PSMC3
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	1	237.9×	0.009	PSMC3
Regulation of RUNX3 expression and activity	1	233.1×	0.009	PSMC3
Somitogenesis	1	233.1×	0.009	PSMC3
NIK–>noncanonical NF-kB signaling	1	228.4×	0.009	PSMC3
SPOP-mediated proteasomal degradation of PD-L1(CD274)	1	228.4×	0.009	PSMC3
Degradation of GLI1 by the proteasome	1	223.9×	0.009	PSMC3
Degradation of GLI2 by the proteasome	1	223.9×	0.009	PSMC3
GLI3 is processed to GLI3R by the proteasome	1	223.9×	0.009	PSMC3
Defective CFTR causes cystic fibrosis	1	219.6×	0.009	PSMC3
Degradation of CRY and PER proteins	1	219.6×	0.009	PSMC3
Dectin-1 mediated noncanonical NF-kB signaling	1	215.5×	0.009	PSMC3
Hedgehog ligand biogenesis	1	211.5×	0.009	PSMC3
SCF(Skp2)-mediated degradation of p27/p21	1	207.6×	0.009	PSMC3
Asymmetric localization of PCP proteins	1	203.9×	0.009	PSMC3
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	1	203.9×	0.009	PSMC3

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
host-mediated perturbation of viral transcription	1	5617.3×	0.002	PSMC3
hair follicle maturation	1	702.2×	0.006	NOM1
positive regulation of proteasomal protein catabolic process	1	330.4×	0.009	PSMC3
blastocyst development	1	224.7×	0.010	PSMC3
embryonic digit morphogenesis	1	100.3×	0.018	LMBR1
ribosomal small subunit biogenesis	1	75.9×	0.020	NOM1
proteasome-mediated ubiquitin-dependent protein catabolic process	1	17.4×	0.073	PSMC3
signal transduction	1	5.3×	0.188	LMBR1
positive regulation of transcription by RNA polymerase II	1	5.0×	0.188	PSMC3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PSMC3	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PSMC3	2	4
LMBR1	0	0
NOM1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BORTEZOMIB	4	PSMC3
CARFILZOMIB	4	PSMC3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PSMC3	27	Binding:27
NOM1	1	Binding:1

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
BORTEZOMIB	4	PSMC3
CARFILZOMIB	4	PSMC3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PSMC3
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	LMBR1, NOM1

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)
LMBR1	0	—
NOM1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.