Lymphatic malformation 12

Summary

Lymphatic malformation 12 (MONDO:0031043) is a disease caused by MDFIC (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: MDFIC (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lymphatic malformation 12
Mondo ID	MONDO:0031043
OMIM	620014
DOID	DOID:0081030
UMLS	C5774203
MedGen	1823976
GARD	0025681
Is cancer (heuristic)	no

Also known as: central conducting lymphatic anomaly · LMPHM12 · lymphatic malformation 12

Data availability: 5 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › lymphatic malformation › lymphatic malformation 12

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 9, lymphatic malformation 11, 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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1702938	NM_001166345.3(MDFIC):c.391dup (p.Met131fs)	MDFIC	Pathogenic	criteria provided, multiple submitters, no conflicts
1702940	NM_001166345.3(MDFIC):c.371del (p.Leu123_Ser124insTer)	MDFIC	Pathogenic	no assertion criteria provided
1702941	NM_001166345.3(MDFIC):c.187G>T (p.Gly63Ter)	MDFIC	Pathogenic	no assertion criteria provided
3342253	NM_001166345.3(MDFIC):c.255_256delinsAT (p.Gln86Ter)	MDFIC	Likely pathogenic	criteria provided, single submitter
1702939	NM_001166345.3(MDFIC):c.732T>G (p.Phe244Leu)	MDFIC	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
MDFIC	Strong	Autosomal recessive	lymphatic malformation 12	3

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
MDFIC	HGNC:28870	ENSG00000135272	Q9P1T7	MyoD family inhibitor domain-containing protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MDFIC	MyoD family inhibitor domain-containing protein	Required to control the activity of various transcription factors through their sequestration in the cytoplasm.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MDFIC	Other/Unknown	no		MDFI/MDFIC

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
amniotic fluid	1
choroid plexus epithelium	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MDFIC	273	ubiquitous	marker	amniotic fluid, tibia, choroid plexus epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MDFIC	711

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MDFIC	Q9P1T7	5

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
positive regulation of viral transcription	1	5617.3×	0.001	MDFIC
negative regulation of protein import into nucleus	1	936.2×	0.002	MDFIC
regulation of Wnt signaling pathway	1	887.0×	0.002	MDFIC
regulation of JNK cascade	1	887.0×	0.002	MDFIC
negative regulation of DNA-templated transcription	1	31.6×	0.036	MDFIC
positive regulation of DNA-templated transcription	1	27.9×	0.036	MDFIC

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
MDFIC	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MDFIC

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)
MDFIC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02399527	Not specified	RECRUITING	Lymphatic Anomalies Registry for the Assessment of Outcome Data