MDFIC

Chr 7AR

MyoD family inhibitor domain containing

Also known as: HIC, LMPHM12, MDFIC1

NCBI Gene: 29969ENSG00000135272UniProt: Q9P1T7

This gene product is a member of a family of proteins characterized by a specific cysteine-rich C-terminal domain, which is involved in transcriptional regulation of viral genome expression. Alternative translation initiation from an upstream non-AUG (GUG), and an in-frame, downstream AUG codon, results in the production of two isoforms, p40 and p32, respectively, which have different subcellular localization; p32 is mainly found in the cytoplasm, whereas p40 is targeted to the nucleolus. Both isoforms have transcriptional regulatory activity that is attributable to the cysteine-rich C-terminal domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Lymphatic malformation 12MIM #620014
AR
108
ClinVar variants
30
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— MDFIC
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 69 VUS of 108 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.86LOEUF
pLI 0.038
Z-score 1.88
OE 0.38 (0.18–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.29Z-score
OE missense 1.07 (0.94–1.21)
167 obs / 156.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.18–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.94–1.21)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 4 / 10.6Missense obs/exp: 167 / 156.8Syn Z: -0.10

ClinVar Variant Classifications

108 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS69
Likely Benign9
27
Pathogenic
3
Likely Pathogenic
69
VUS
9
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
26
0
27
Likely Pathogenic
0
0
3
0
3
VUS
0
65
4
0
69
Likely Benign
0
6
1
2
9
Benign
0
0
0
0
0
Total171342108

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MDFIC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Lymphatic malformation 12

MIM #620014

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathogenic variants in MDFIC cause recessive central conducting lymphatic anomaly with lymphedema.
Byrne AB et al.·Sci Transl Med
2022
Genetic causes of lymphatic disorders: recent updates on the clinical and molecular aspects of lymphatic disease.
Bowman C et al.·Curr Opin Cardiol
2024Review
Phenotype of FOXP2 haploinsufficiency in a mother and son.
Rice GM et al.·Am J Med Genet A
2012Case report
Acquired genetic alterations in tumor cells dictate the development of high-risk neuroblastoma and clinical outcomes.
Khan FH et al.·BMC Cancer
2015
Genome-wide association study of lymphoblast cell viability after clozapine exposure.
de With SA et al.·Am J Med Genet B Neuropsychiatr Genet
2015
RNA sequencing reveals the transcriptomic landscape and alternative splicing events induced by LGALS1 silencing in non-small cell lung cancer.
Shi H et al.·Adv Clin Exp Med
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools