Lymphatic malformation 9

Summary

Lymphatic malformation 9 (MONDO:0030270) is a disease caused by CELSR1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CELSR1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lymphatic malformation 9
Mondo ID	MONDO:0030270
OMIM	619319
UMLS	C5543365
MedGen	1779656
GARD	0025527
Is cancer (heuristic)	no

Also known as: LMPHM9 · lymphatic malformation 9

Data availability: 46 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › lymphatic malformation › lymphatic malformation 9

Related subtypes (27): microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, lymphatic malformation 1, lymphatic malformation 5, yellow nail syndrome, lymphedema-distichiasis syndrome, campomelia, Cumming type, Dahlberg-Borer-Newcomer syndrome, Norman-Roberts syndrome, anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome, MPI-congenital disorder of glycosylation, hypotrichosis-lymphedema-telangiectasia syndrome, lymphatic malformation 2, lymphatic malformation 3, deafness-lymphedema-leukemia syndrome, lymphatic malformation 4, lymphatic malformation 6, lymphatic malformation 7, Hennekam syndrome, Noonan syndrome, hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, lymphatic malformation 10, lymphatic malformation 11, lymphatic malformation 12, lymphatic malformation 8, congenital primary lymphedema of Gordon, lymphatic malformation 13, lymphatic malformation 14

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

46 retrieved; paginated sample, class counts are floors:

37 uncertain significance, 4 pathogenic, 4 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1096924	NM_001378328.1(CELSR1):c.5871G>A (p.Trp1957Ter)	CELSR1	Pathogenic	no assertion criteria provided
1096930	NM_001378328.1(CELSR1):c.5121dup (p.Ile1708fs)	CELSR1	Pathogenic	no assertion criteria provided
598932	NM_001378328.1(CELSR1):c.5226+2T>A	CELSR1	Pathogenic	criteria provided, single submitter
598933	NM_001378328.1(CELSR1):c.6739+1G>A	CELSR1	Pathogenic	criteria provided, single submitter
3075687	NM_001378328.1(CELSR1):c.5512C>T (p.Arg1838Ter)	CELSR1	Likely pathogenic	criteria provided, single submitter
4077063	NM_001378328.1(CELSR1):c.847_856del (p.Tyr283fs)	CELSR1	Likely pathogenic	criteria provided, single submitter
4293727	NM_001378328.1(CELSR1):c.5412+1G>C	CELSR1	Likely pathogenic	criteria provided, single submitter
590904	NM_001378328.1(CELSR1):c.868G>T (p.Glu290Ter)	CELSR1	Likely pathogenic	criteria provided, single submitter
1341349	NM_001378328.1(CELSR1):c.7640C>T (p.Ala2547Val)	CELSR1	Uncertain significance	criteria provided, single submitter
2208761	NM_001378328.1(CELSR1):c.1849G>T (p.Ala617Ser)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2280833	NM_001378328.1(CELSR1):c.7792G>A (p.Gly2598Arg)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2357936	NM_001378328.1(CELSR1):c.4552G>C (p.Val1518Leu)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442586	NM_001378328.1(CELSR1):c.4928G>A (p.Arg1643Gln)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2482941	NM_001378328.1(CELSR1):c.2918G>C (p.Arg973Pro)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2569761	NM_001378328.1(CELSR1):c.6514G>A (p.Gly2172Ser)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2580939	NM_001378328.1(CELSR1):c.7797C>A (p.Asn2599Lys)	CELSR1	Uncertain significance	criteria provided, single submitter
2672129	NM_001378328.1(CELSR1):c.4903G>A (p.Gly1635Arg)	CELSR1	Uncertain significance	criteria provided, single submitter
2672159	NM_001378328.1(CELSR1):c.6160G>T (p.Gly2054Cys)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2672160	NM_001378328.1(CELSR1):c.7492T>C (p.Ser2498Pro)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2672173	NM_001378328.1(CELSR1):c.4270G>A (p.Gly1424Ser)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2672179	NM_001378328.1(CELSR1):c.6463A>G (p.Thr2155Ala)	CELSR1	Uncertain significance	criteria provided, single submitter
3142021	NM_001378328.1(CELSR1):c.8863G>A (p.Ala2955Thr)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3237429	NM_001378328.1(CELSR1):c.3169C>T (p.Arg1057Cys)	CELSR1	Uncertain significance	criteria provided, single submitter
3237431	NM_001378328.1(CELSR1):c.7256C>T (p.Ala2419Val)	CELSR1	Uncertain significance	criteria provided, single submitter
3237440	NM_001378328.1(CELSR1):c.7715G>A (p.Arg2572Gln)	CELSR1	Uncertain significance	criteria provided, single submitter
3237445	NM_001378328.1(CELSR1):c.692G>T (p.Arg231Leu)	CELSR1	Uncertain significance	criteria provided, single submitter
3237447	NM_001378328.1(CELSR1):c.6544G>A (p.Asp2182Asn)	CELSR1	Uncertain significance	criteria provided, single submitter
3265757	NM_001378328.1(CELSR1):c.3968G>A (p.Arg1323Gln)	CELSR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3393111	NM_001378328.1(CELSR1):c.1592C>G (p.Ser531Trp)	CELSR1	Uncertain significance	criteria provided, single submitter
3588108	NM_001378328.1(CELSR1):c.7387G>A (p.Gly2463Arg)	CELSR1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
CELSR1	Strong	Autosomal dominant	lymphatic malformation 9	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CELSR1	Orphanet:569816	CELSR1-related late-onset primary lymphedema

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
CELSR1	HGNC:1850	ENSG00000075275	Q9NYQ6	Cadherin EGF LAG seven-pass G-type receptor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CELSR1	Cadherin EGF LAG seven-pass G-type receptor 1	Receptor that may have an important role in cell/cell signaling during nervous system formation.

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CELSR1	GPCR	yes		EGF-type_Asp/Asn_hydroxyl_site, GPS, EGF

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
bronchial epithelial cell	1
lower esophagus mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CELSR1	224	ubiquitous	marker	ventricular zone, lower esophagus mucosa, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CELSR1	1,166

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CELSR1	Q9NYQ6	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis	1	5617.3×	8e-04	CELSR1
planar dichotomous subdivision of terminal units involved in lung branching morphogenesis	1	5617.3×	8e-04	CELSR1
lateral sprouting involved in lung morphogenesis	1	5617.3×	8e-04	CELSR1
protein localization involved in establishment of planar polarity	1	5617.3×	8e-04	CELSR1
establishment of planar polarity of embryonic epithelium	1	4213.0×	8e-04	CELSR1
establishment of body hair planar orientation	1	3370.4×	8e-04	CELSR1
establishment of planar polarity	1	1053.2×	0.002	CELSR1
apical protein localization	1	991.3×	0.002	CELSR1
Wnt signaling pathway, planar cell polarity pathway	1	455.5×	0.004	CELSR1
cell-cell adhesion mediated by cadherin	1	411.0×	0.004	CELSR1
Rho protein signal transduction	1	247.8×	0.006	CELSR1
neural tube closure	1	187.2×	0.008	CELSR1
axonogenesis	1	160.5×	0.008	CELSR1
regulation of actin cytoskeleton organization	1	157.5×	0.008	CELSR1
homophilic cell-cell adhesion	1	140.4×	0.008	CELSR1
neuron migration	1	133.8×	0.008	CELSR1
central nervous system development	1	115.4×	0.009	CELSR1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
CELSR1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	CELSR1
D	Druggable family + AlphaFold only, no drug	0
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)
CELSR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.