Lymphedema-posterior choanal atresia syndrome

Summary

Lymphedema-posterior choanal atresia syndrome (MONDO:0013324) is a disease caused by PTPN14 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PTPN14 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 26

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	lymphedema-posterior choanal atresia syndrome
Mondo ID	MONDO:0013324
OMIM	613611
Orphanet	99141
UMLS	C3150875
MedGen	462225
GARD	0016898
Is cancer (heuristic)	no

Also known as: CATLPH

Data availability: 26 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › benign neoplasm › cardiovascular organ benign neoplasm › lymphangioma › lymphedema-posterior choanal atresia syndrome

Related subtypes (11): colonic lymphangioma, capillary lymphangioma, lymphangioendothelioma, Gorham-Stout disease, cystic hygroma, diffuse lymphatic malformation, mixed cystic lymphatic malformation, multifocal lymphangioendotheliomatosis-thrombocytopenia syndrome, macrocystic lymphatic malformation, microcystic lymphatic malformation, skin lymphangioma

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

26 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 7 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
599260	NM_005401.5(PTPN14):c.401_402insTT (p.Leu135fs)	PTPN14	Pathogenic	no assertion criteria provided
6620	NM_005401.5(PTPN14):c.581+60_669+877del	PTPN14	Pathogenic	no assertion criteria provided
2238889	NM_005401.5(PTPN14):c.2859A>G (p.Ile953Met)	PTPN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
2359361	NM_005401.5(PTPN14):c.2596A>G (p.Met866Val)	PTPN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
2359362	NM_005401.5(PTPN14):c.3500T>C (p.Ile1167Thr)	PTPN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435285	NM_005401.5(PTPN14):c.-154-42562G>A	PTPN14	Uncertain significance	criteria provided, single submitter
2435286	NM_005401.5(PTPN14):c.-154-22749A>G	PTPN14	Uncertain significance	criteria provided, single submitter
2435287	NM_005401.5(PTPN14):c.679G>T (p.Gly227Ter)	PTPN14	Uncertain significance	criteria provided, single submitter
2435288	NM_005401.5(PTPN14):c.*6320C>T	PTPN14	Uncertain significance	criteria provided, single submitter
2454414	NM_005401.5(PTPN14):c.1712C>A (p.Pro571Gln)	PTPN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
2672139	NM_005401.5(PTPN14):c.715A>T (p.Ile239Phe)	PTPN14	Uncertain significance	criteria provided, single submitter
2672216	NM_005401.5(PTPN14):c.1574C>T (p.Pro525Leu)	PTPN14	Uncertain significance	criteria provided, single submitter
2672235	NM_005401.5(PTPN14):c.2164C>T (p.Pro722Ser)	PTPN14	Uncertain significance	criteria provided, single submitter
3237384	NM_005401.5(PTPN14):c.2216C>T (p.Ala739Val)	PTPN14	Uncertain significance	criteria provided, single submitter
3237421	NM_005401.5(PTPN14):c.1583C>T (p.Pro528Leu)	PTPN14	Uncertain significance	criteria provided, single submitter
3237448	NM_005401.5(PTPN14):c.456C>G (p.Asp152Glu)	PTPN14	Uncertain significance	criteria provided, single submitter
3600433	NM_005401.5(PTPN14):c.1882C>G (p.Leu628Val)	PTPN14	Uncertain significance	criteria provided, single submitter
3600437	NM_005401.5(PTPN14):c.1754A>C (p.His585Pro)	PTPN14	Uncertain significance	criteria provided, single submitter
4279924	NM_005401.5(PTPN14):c.511-3T>C	PTPN14	Uncertain significance	criteria provided, single submitter
1180900	NM_005401.5(PTPN14):c.*26G>A	PTPN14	Benign	criteria provided, multiple submitters, no conflicts
1241432	NM_005401.5(PTPN14):c.978A>G (p.Arg326=)	PTPN14	Benign	criteria provided, multiple submitters, no conflicts
1242532	NM_005401.5(PTPN14):c.929+24del	PTPN14	Benign	criteria provided, multiple submitters, no conflicts
1245797	NM_005401.5(PTPN14):c.-26G>A	PTPN14	Benign	criteria provided, multiple submitters, no conflicts
1259740	NM_005401.5(PTPN14):c.2688+26C>T	PTPN14	Benign	criteria provided, multiple submitters, no conflicts
1263765	NM_005401.5(PTPN14):c.3252A>G (p.Glu1084=)	PTPN14	Benign	criteria provided, multiple submitters, no conflicts
1274316	NM_005401.5(PTPN14):c.758+5T>G	PTPN14	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
PTPN14	Strong	Autosomal recessive	lymphedema-posterior choanal atresia syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTPN14	Orphanet:99141	Lymphedema-posterior choanal atresia syndrome

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
PTPN14	HGNC:9647	ENSG00000152104	Q15678	Tyrosine-protein phosphatase non-receptor type 14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPN14	Tyrosine-protein phosphatase non-receptor type 14	Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell-matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial-mes…

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPN14	Phosphatase	yes	3.1.3.48	PTP_cat, FERM_domain, Tyr_Pase_dom

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
buccal mucosa cell	1
parietal pleura	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPN14	257	ubiquitous	marker	buccal mucosa cell, parietal pleura, tibia

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPN14	1,623

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN14	Q15678	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Interleukin-37 signaling	1	519.1×	0.002	PTPN14

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
regulation of protein export from nucleus	1	1532.0×	0.002	PTPN14
lymphangiogenesis	1	1203.7×	0.002	PTPN14
protein dephosphorylation	1	221.7×	0.006	PTPN14
negative regulation of cell population proliferation	1	42.1×	0.024	PTPN14

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
PTPN14	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
PTPN14	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPN14	3.1.3.48	protein-tyrosine-phosphatase

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	PTPN14
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)
PTPN14	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.