MDFIC

Summary

MDFIC (MyoD family inhibitor domain containing, HGNC:28870) is a protein-coding gene on chromosome 7q31.1-q31.2, encoding MyoD family inhibitor domain-containing protein (Q9P1T7). Required to control the activity of various transcription factors through their sequestration in the cytoplasm.

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.

Source: NCBI Gene 29969 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lymphatic malformation 12 (Strong, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 66 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_001166345

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28870
Approved symbol	MDFIC
Name	MyoD family inhibitor domain containing
Location	7q31.1-q31.2
Locus type	gene with protein product
Status	Approved
Aliases	HIC, MDFIC1
Ensembl gene	ENSG00000135272
Ensembl biotype	protein_coding
OMIM	614511
Entrez	29969

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 nonsense_mediated_decay

ENST00000393486, ENST00000423503, ENST00000427207, ENST00000431629, ENST00000448022, ENST00000498196, ENST00000904588, ENST00000904589, ENST00000904590, ENST00000904591, ENST00000904592, ENST00000926204, ENST00000963678, ENST00000963679, ENST00000963680, ENST00000963681, ENST00000963682, ENST00000963683

RefSeq mRNA: 3 — MANE Select: NM_001166345 NM_001166345, NM_001166346, NM_199072

CCDS: CCDS55155

Canonical transcript exons

ENST00000393486 — 5 exons

Exon	Start	End
ENSE00000919355	114979506	114979781
ENSE00001015831	115015688	115019917
ENSE00003473327	114922927	114923127
ENSE00003490177	114922094	114922636
ENSE00003569378	114942275	114942397

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.9416 / max 485.8039, expressed in 1612 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80579	12.7241	1552
80583	11.4180	994
80574	5.1367	1301
80572	3.0751	1042
80581	2.4356	1210
204656	0.8614	559
80575	0.5522	323
80580	0.5194	308
80573	0.3819	192
80582	0.3470	198

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	97.38	gold quality
tibia	UBERON:0000979	96.98	gold quality
choroid plexus epithelium	UBERON:0003911	95.56	gold quality
mammary duct	UBERON:0001765	95.54	gold quality
skin of hip	UBERON:0001554	95.46	gold quality
visceral pleura	UBERON:0002401	95.05	gold quality
germinal epithelium of ovary	UBERON:0001304	94.95	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.89	gold quality
periodontal ligament	UBERON:0008266	94.76	gold quality
oral cavity	UBERON:0000167	94.71	gold quality
pleura	UBERON:0000977	94.60	gold quality
superficial temporal artery	UBERON:0001614	94.44	gold quality
decidua	UBERON:0002450	94.41	gold quality
parietal pleura	UBERON:0002400	94.26	gold quality
epithelium of mammary gland	UBERON:0003244	94.19	gold quality
stromal cell of endometrium	CL:0002255	94.09	gold quality
palpebral conjunctiva	UBERON:0001812	94.09	gold quality
renal glomerulus	UBERON:0000074	93.55	gold quality
calcaneal tendon	UBERON:0003701	93.41	gold quality
thoracic mammary gland	UBERON:0005200	93.39	gold quality
mammary gland	UBERON:0001911	93.30	gold quality
cartilage tissue	UBERON:0002418	93.29	gold quality
metanephric glomerulus	UBERON:0004736	93.18	gold quality
adipose tissue	UBERON:0001013	92.90	gold quality
trabecular bone tissue	UBERON:0002483	92.86	gold quality
connective tissue	UBERON:0002384	92.81	gold quality
synovial joint	UBERON:0002217	92.46	gold quality
upper leg skin	UBERON:0004262	92.33	gold quality
biceps brachii	UBERON:0001507	92.31	gold quality
bronchial epithelial cell	CL:0002328	92.13	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	4.44
E-ANND-3	yes	4.27
E-MTAB-5061	no	3.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RBPJ, TP53

miRNA regulators (miRDB)

212 targeting MDFIC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 10)

• Two isoforms, resulting from the use of a non-AUG (GUG) and a downstream in-frame AUG translation initiation codon, have different subcellular localization. (PMID:10671520)
• This study describes that the immune expression of HIC is cell-specific, dynamic, and identifies the HIC gene as an IL-2 responsive gene. (PMID:19428567)
• strict regulation of HIC expression at the levels of mRNA stability, translation efficiency and protein stability suggests that expression of the HIC protein and its involvement in the various pathways is required only under specific cellular conditions (PMID:19582149)
• These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3beta complex. (PMID:20417616)
• We demonstrate that HIC selectively interferes with Rev NLS interaction with importin beta and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. (PMID:21401918)
• HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. (PMID:26469549)
• GR directly represses the MDFIC gene, revealing a negative feedback loop by which glucocorticoids limit MDFIC activity. These findings identify a new binding partner for cytoplasmic GR that modulates the receptor transcriptome and contributes to the tissue-specific actions of glucocorticoids. (PMID:28223352)
• Opposite Roles of the JMJD1A Interaction Partners MDFI and MDFIC in Colorectal Cancer. (PMID:32457453)
• Pathogenic variants in MDFIC cause recessive central conducting lymphatic anomaly with lymphedema. (PMID:35235341)
• MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels. (PMID:37590348)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mdfic	ENSDARG00000074223
mus_musculus	Mdfic	ENSMUSG00000041390
rattus_norvegicus	Mdfic	ENSRNOG00000053787

Paralogs (2): MDFI (ENSG00000112559), MDFIC2 (ENSG00000242120)

Protein

Protein identifiers

MyoD family inhibitor domain-containing protein — Q9P1T7 (reviewed: Q9P1T7)

Alternative names: I-mfa domain-containing protein

All UniProt accessions (5): Q9P1T7, C9J104, C9J784, H7BZY3, H7C4B9

UniProt curated annotations — full annotation on UniProt →

Function. Required to control the activity of various transcription factors through their sequestration in the cytoplasm. Retains nuclear Zic proteins ZIC1, ZIC2 and ZIC3 in the cytoplasm and inhibits their transcriptional activation. Modulates the expression from cellular promoters. Binds to the axin complex, resulting in an increase in the level of free beta-catenin. Affects axin regulation of the WNT and JNK signaling pathways. Involved in the development of lymphatic vessel valves. Required to promote lymphatic endothelial cell migration, in a process that involves down-regulation of integrin beta 1 activation and control of cell adhesion to the extracellular matrix. Regulates the activity of mechanosensitive Piezo channel. (Microbial infection) Modulates the expression from viral promoters. Down-regulates Tat-dependent transcription of the human immunodeficiency virus type 1 (HIV-1) LTR by interacting with HIV-1 Tat and Rev and impairing their nuclear import, probably by rendering the NLS domains inaccessible to importin-beta (PubMed:12944466, PubMed:16260749, Ref.6). Also stimulates activation of human T-cell leukemia virus type I (HTLV-I) LTR.

Subunit / interactions. Interacts with HAND1; the interaction sequesters HAND1 into the nucleolus and inhibits its activity. Interacts (via C-terminus) with ZIC2. Interacts (via C-terminus) with AXIN1, the histidine-rich region of CCNT1/cyclin-T and weakly with LEF1. Interacts with CCNT2. Interacts with GATA2. Interacts (via C-terminus) with Piezo channel composed of PIEZO1 or PIEZO2; the interaction prolongs Piezo channel inactivation. (Microbial infection) Interacts (via C-terminus) with HIV-1 Tat and Rev.

Subcellular location. Nucleus. Nucleolus Cytoplasm. Secreted.

Tissue specificity. Expressed in lymphatic tissues. Detected in the spleen, thymus, peripheral blood leukocytes as well as prostate, uterus and small intestine. Expressed in lymphatic endothelial cells.

Post-translational modifications. Palmitoylated.

Disease relevance. Lymphatic malformation 12 (LMPHM12) [MIM:620014] A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM12 is an autosomal recessive, severe form often resulting in fetal or perinatal demise. It is characterized by dysfunction of core collecting lymphatic vessels, including the thoracic duct and cisterna chyli, non-immune hydrops fetalis, chylothorax, pleural effusions, and chylous ascites. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The cysteine-rich C-terminus is involved in its granular distribution in the cytoplasm. The cysteine-rich C-terminus mediates protein-protein interactions, including interaction with HIV-1 Tat, transcription factors, AXIN1, CCNT1.

Miscellaneous. Major isoform. Minor isoform. Initiates from a GTG codon. Contains a Nucleolar localization signal at positions 45-63.

Similarity. Belongs to the MDFI family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P1T7-2	2, p32	yes
Q9P1T7-1	1, p40

RefSeq proteins (3): NP_001159817, NP_001159818, NP_951038 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026134	MDFI/MDFIC	Family

Pfam: PF15316

UniProt features (12 total): modified residue 3, sequence variant 2, compositionally biased region 2, chain 1, domain 1, helix 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8ZU3	ELECTRON MICROSCOPY	3.1
8YFC	ELECTRON MICROSCOPY	3.2
9VMX	ELECTRON MICROSCOPY	3.2
9VEF	ELECTRON MICROSCOPY	3.75
8YFG	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P1T7-F1	53.05	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 128, 140, 143

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 430 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BASSO_B_LYMPHOCYTE_NETWORK, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOLDRATH_ANTIGEN_RESPONSE, GOBP_NUCLEAR_TRANSPORT, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, CDP_01, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (7): regulation of Wnt signaling pathway (GO:0030111), negative regulation of protein import into nucleus (GO:0042308), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), regulation of JNK cascade (GO:0046328), positive regulation of viral transcription (GO:0050434), regulation of gene expression (GO:0010468)

GO Molecular Function (4): cyclin binding (GO:0030332), Tat protein binding (GO:0030957), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of DNA-templated transcription	2
cellular anatomical structure	2
regulation of signal transduction	1
Wnt signaling pathway	1
protein import into nucleus	1
regulation of protein import into nucleus	1
negative regulation of nucleocytoplasmic transport	1
negative regulation of intracellular protein transport	1
negative regulation of protein localization to nucleus	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
JNK cascade	1
regulation of MAPK cascade	1
viral transcription	1
regulation of viral transcription	1
positive regulation of viral process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
protein binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MDFIC	CTCF	P49711	720
MDFIC	CHIA	Q9BZP6	713
MDFIC	CCNT1	O60563	531
MDFIC	RAD21	O60216	506
MDFIC	FBL	P22087	442
MDFIC	THBS1	P07996	437
MDFIC	ZIC2	O95409	411
MDFIC	PIAS1	O75925	408
MDFIC	CTCFL	Q8NI51	399
MDFIC	LGR5	O75473	396
MDFIC	SMC3	Q9UQE7	392
MDFIC	TMEM168	Q9H0V1	386
MDFIC	CNTN2	P78432	376
MDFIC	MAP3K1	Q13233	374
MDFIC	PSAP	P07292	373

IntAct

18 interactions, top by confidence:

A	B	Type	Score
MDFIC	RPS6KA5	psi-mi:“MI:0915”(physical association)	0.370
SOCS4	MDFIC	psi-mi:“MI:0915”(physical association)	0.370
tat	MDFIC	psi-mi:“MI:0914”(association)	0.350
MFSD10	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NIPAL3	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC18A3	ORC4	psi-mi:“MI:0914”(association)	0.350
SLC19A1	TAPBP	psi-mi:“MI:0914”(association)	0.350
SLC22A6	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC22A9	ESYT2	psi-mi:“MI:0914”(association)	0.350
MDFIC	glpK	psi-mi:“MI:0915”(physical association)	0.000
	MDFIC	psi-mi:“MI:0915”(physical association)	0.000
metI	MDFIC	psi-mi:“MI:0915”(physical association)	0.000
MDFIC		psi-mi:“MI:0915”(physical association)	0.000
proW	MDFIC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): MDFIC (Two-hybrid), CCNT1 (Two-hybrid), MDFIC (Two-hybrid), CCNT1 (Affinity Capture-Western), CDK9 (Affinity Capture-Western), CCNT1 (Reconstituted Complex), CDK9 (Reconstituted Complex), MDFIC (Affinity Capture-MS), MDFIC (Proximity Label-MS), MDFIC (Proximity Label-MS), MDFIC (Proximity Label-MS), MDFIC (Proximity Label-MS), MDFIC (Proximity Label-MS), MDFIC (Proximity Label-MS), MDFIC (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A0A1L8GR68, B3KU38, B5DF41, F7AQ22, O15079, P0C6S7, P0DPB3, P0DPB4, P18444, P49797, P50478, P51608, P51826, Q00566, Q497H0, Q4R3X1, Q5FWF5, Q5R4B7, Q5RD40, Q5U2M7, Q68FE8, Q69Z61, Q69Z69, Q6DC60, Q6N043, Q6P2K3, Q6ZNC4, Q7SXV2, Q7Z6G8, Q80U23, Q86VQ1, Q86YI8, Q8BH50, Q8BIZ1, Q8IW50, Q8K2W6, Q8K3I9, Q8R3B7, Q95LG8

Diamond homologs: A0A1B0GVS7, Q8BX65, Q98SK0, Q9P1T7, Q99750, P70331

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

66 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	47
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1702938	NM_001166345.3(MDFIC):c.391dup (p.Met131fs)	Pathogenic
1702940	NM_001166345.3(MDFIC):c.371del (p.Leu123_Ser124insTer)	Pathogenic
1702941	NM_001166345.3(MDFIC):c.187G>T (p.Gly63Ter)	Pathogenic
1676080	NM_001166345.3(MDFIC):c.585del (p.Ile194_Cys195insTer)	Likely pathogenic
3342253	NM_001166345.3(MDFIC):c.255_256delinsAT (p.Gln86Ter)	Likely pathogenic

SpliceAI

1418 predictions. Top by Δscore:

Variant	Effect	Δscore
7:114922635:AGGTA:A	donor_loss	1.0000
7:114922636:GGTA:G	donor_loss	1.0000
7:114922637:GTAG:G	donor_loss	1.0000
7:114938861:GGC:G	donor_gain	1.0000
7:114942270:TTCAG:T	acceptor_loss	1.0000
7:114942271:TCAGG:T	acceptor_loss	1.0000
7:114942272:CAGG:C	acceptor_loss	1.0000
7:114942273:A:AG	acceptor_gain	1.0000
7:114942273:AGGA:A	acceptor_loss	1.0000
7:114942274:G:A	acceptor_loss	1.0000
7:114942274:G:GG	acceptor_gain	1.0000
7:114942274:GGA:G	acceptor_gain	1.0000
7:114942274:GGAA:G	acceptor_gain	1.0000
7:114942274:GGAAA:G	acceptor_gain	1.0000
7:114942393:TAGAA:T	donor_gain	1.0000
7:114942394:AGAA:A	donor_gain	1.0000
7:114942395:GAA:G	donor_gain	1.0000
7:114942395:GAAG:G	donor_gain	1.0000
7:114942396:AA:A	donor_gain	1.0000
7:114942397:AG:A	donor_loss	1.0000
7:114942398:G:GG	donor_gain	1.0000
7:114942399:T:A	donor_loss	1.0000
7:114942400:AAGTA:A	donor_loss	1.0000
7:114981435:A:G	donor_gain	1.0000
7:115014031:A:T	donor_gain	1.0000
7:115014077:T:G	donor_gain	1.0000
7:115014077:T:TG	donor_gain	1.0000
7:114922602:G:GT	donor_gain	0.9900
7:114922633:GGAG:G	donor_gain	0.9900
7:114922634:GAG:G	donor_gain	0.9900

AlphaMissense

1632 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:115015892:T:C	L233S	0.998
7:115015898:T:C	I235T	0.998
7:115015714:T:C	C174R	0.997
7:115015888:T:C	C232R	0.997
7:115015895:A:T	E234V	0.997
7:115015898:T:G	I235S	0.997
7:115015900:T:C	C236R	0.997
7:115015902:T:G	C236W	0.997
7:115015909:T:C	C239R	0.997
7:115015924:T:C	F244L	0.997
7:115015926:T:A	F244L	0.997
7:115015926:T:G	F244L	0.997
7:115015901:G:A	C236Y	0.996
7:115015921:T:C	C243R	0.996
7:115015724:G:A	C177Y	0.995
7:115015870:T:C	C226R	0.995
7:115015898:T:A	I235N	0.995
7:115015906:G:A	E238K	0.995
7:115015907:A:T	E238V	0.995
7:115015919:T:C	I242T	0.995
7:115015925:T:G	F244C	0.995
7:115015720:T:C	F176L	0.994
7:115015722:C:A	F176L	0.994
7:115015722:C:G	F176L	0.994
7:115015723:T:C	C177R	0.994
7:115015894:G:A	E234K	0.994
7:115015912:T:C	C240R	0.994
7:115015871:G:A	C226Y	0.993
7:115015913:G:A	C240Y	0.993
7:115015919:T:G	I242S	0.993

dbSNP variants (sampled 300 via entrez): RS1000027299 (7:114970678 A>G), RS1000065749 (7:114926378 T>A), RS1000076731 (7:114999949 C>T), RS1000085112 (7:114945655 C>G,T), RS1000097352 (7:114964544 C>G,T), RS1000121791 (7:114970908 C>T), RS1000142349 (7:114933281 C>T), RS1000176544 (7:114951660 G>C,T), RS1000237626 (7:114933570 A>G), RS1000271087 (7:114938826 A>G), RS1000284858 (7:114982054 T>C), RS1000294843 (7:114983344 A>C), RS1000320600 (7:115018436 C>A), RS1000336964 (7:114968905 G>A), RS1000368015 (7:114951799 G>A)

Disease associations

OMIM: gene MIM:614511 | disease phenotypes: MIM:620014

GenCC curated gene-disease

Disease	Classification	Inheritance
lymphatic malformation 12	Strong	Autosomal recessive

Mondo (1): lymphatic malformation 12 (MONDO:0031043)

Orphanet (0):

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000034	Hydrocele testis
HP:0000962	Hyperkeratosis
HP:0001004	Lymphedema
HP:0001561	Polyhydramnios
HP:0001790	Nonimmune hydrops fetalis
HP:0001791	Fetal ascites
HP:0002643	Neonatal respiratory distress
HP:0003577	Congenital onset
HP:0003811	Neonatal death
HP:0011421	Death in adolescence
HP:0025671	Fetal pericardial effusion
HP:0025676	Fetal pleural effusion
HP:0025677	Fetal chylothorax
HP:0031944	Pleural thickening
HP:0034197	Third trimester onset
HP:0034198	Second trimester onset
HP:0200117	Recurrent upper and lower respiratory tract infections

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001732_2	Obesity	4.000000e-06
GCST002777_17	Clozapine-induced cytotoxicity	1.000000e-08
GCST003995_22	Tonsillectomy	8.000000e-10
GCST004286_4	Midgestational circulating levels of PBDEs (fetal genetic effect)	6.000000e-07
GCST004904_39	Body mass index	4.000000e-08
GCST005014_127	Tonsillectomy	8.000000e-10
GCST005951_59	Body mass index	1.000000e-08
GCST007323_30	Risk-taking tendency (4-domain principal component model)	2.000000e-08
GCST007324_67	Adventurousness	8.000000e-15
GCST007325_139	General risk tolerance (MTAG)	1.000000e-10
GCST007325_200	General risk tolerance (MTAG)	2.000000e-08
GCST007325_54	General risk tolerance (MTAG)	8.000000e-31
GCST007326_104	Number of sexual partners	2.000000e-11
GCST007327_113	Smoking status (ever vs never smokers)	2.000000e-09
GCST007630_3	Drug experimentation measurement	6.000000e-07
GCST008162_106	Hip circumference	7.000000e-06
GCST012291_3	Schizophrenia, bipolar disorder or recurrent major depressive disorder	5.000000e-06

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0007959	fetal genotype effect measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0007964	gestational serum measurement
EFO:0004340	body mass index
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0007010	drug use measurement
EFO:0004952	disease recurrence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
trichostatin A	increases expression, affects cotreatment	3
Estradiol	affects expression, increases reaction	3
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, affects expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
butyraldehyde	decreases expression	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Cyclophosphamide	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E9DH	CHO(I-mfa)	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

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