MDFIC

Chr 7AR

MyoD family inhibitor domain containing

Also known as: HIC, LMPHM12, MDFIC1

NCBI Gene: 29969 ENSG00000135272 UniProt: Q9P1T7 OMIM: 614511

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lymphatic malformation 12MIM #620014

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Lymphatic malformation 12; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.038

Z-score 1.88

OE 0.38 (0.18–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.29Z-score

OE missense 1.07 (0.94–1.21)

167 obs / 156.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.38 (0.18–0.86)

0≤0.351.4

Missense OE?1.07 (0.94–1.21)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 4 / 10.6Missense obs/exp: 167 / 156.8Syn Z: -0.10

Background carrier burden — how many people carry a rare variant somewhere in MDFIC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

408 rare PASS variants

Rare truncating (LoF)

1 in 1,200

49 rare PASS variants

Rare synonymous (reference)

1 in 370

137 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MDFIC. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 1,800
South Asian	~43k	1 in 150	1 in 910
Remaining (unassigned)	~30k	1 in 98	1 in 1,100
European (Finnish)	~27k	1 in 450	≈ 1 in 13,000
Admixed American	~22k	1 in 100	1 in 1,200
African / African American	~21k	1 in 160	1 in 1,200
East Asian	~20k	1 in 150	1 in 880
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 150	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 4 coding exons well covered in gnomAD exomes; exons 2, 3 marginal. Genomes: all 4.? see exons ↓