MIF4GD

Summary

MIF4GD (MIF4G domain containing, HGNC:24030) is a protein-coding gene on chromosome 17q25.1, encoding MIF4G domain-containing protein (A9UHW6). Functions in replication-dependent translation of histone mRNAs which differ from other eukaryotic mRNAs in that they do not end with a poly-A tail but a stem-loop.

This gene encodes a protein which interacts with the N-terminus of the stem-loop binding protein (SLBP) and the 3’ end of histone mRNA. This interaction facilitates the activation of histone mRNA translation. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 57409 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 50 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 16 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.12 (unconstrained)
• MANE Select transcript: NM_001370592
• Notable: 50 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24030
Approved symbol	MIF4GD
Name	MIF4G domain containing
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	AD023, MGC45027, SLIP1
Ensembl gene	ENSG00000125457
Ensembl biotype	protein_coding
OMIM	612072
Entrez	57409

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 33 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000325102

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 6, TSL 5: 2

ENST00000325102, ENST00000245551, ENST00000577240, ENST00000577542, ENST00000578305, ENST00000579119, ENST00000579194, ENST00000579297, ENST00000579612, ENST00000580099, ENST00000580571, ENST00000580717, ENST00000581777, ENST00000618645, ENST00000649805, ENST00000678201, ENST00000886601, ENST00000886602, ENST00000886603, ENST00000886604, ENST00000886605, ENST00000886606, ENST00000886607, ENST00000886608, ENST00000886609, ENST00000886610, ENST00000886611, ENST00000886612, ENST00000886613, ENST00000886614, ENST00000886615, ENST00000941498, ENST00000941499, ENST00000941500, ENST00000941501, ENST00001023588, ENST00001023589

RefSeq mRNA: 12 — MANE Select: NM_001370592 NM_001242498, NM_001242500, NM_001242501, NM_001363806, NM_001365751, NM_001365752, NM_001365753, NM_001365754, NM_001365755, NM_001370592, NM_001411093, NM_020679

CCDS: CCDS11719, CCDS56044, CCDS58598, CCDS92390, CCDS92391

Canonical transcript exons

ENST00000325102 — 6 exons

Exon	Start	End
ENSE00000855713	75267746	75267901
ENSE00000855714	75268083	75268192
ENSE00002705855	75271144	75271231
ENSE00002723024	75266228	75266967
ENSE00003482026	75270114	75270245
ENSE00003519892	75267538	75267630

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 95.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3414 / max 104.6527, expressed in 1769 samples.

Highest expression (Bgee): upper arm skin, saphenous vein, granulocyte, nipple, gastrocnemius.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MIF4GD is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 16 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	4.9e-24	+0.24	17:75271750:G:T
Nerve Tibial	eqtl	8.2e-11	+0.19	17:75271750:G:T
Thyroid	eqtl	2.0e-10	-0.24	17:75273958:C:T
Skin Sun Exposed Lower leg	eqtl	2.0e-08	-0.20	17:75252915:A:G
Lung	eqtl	7.7e-08	+0.18	17:75271088:A:C
Nerve Tibial	sqtl	4.7e-07	+0.31	17:75259727:C:T
Esophagus Mucosa	eqtl	1.6e-06	+0.25	17:75252943:A:C
Artery Tibial	eqtl	3.2e-06	-0.18	17:75273958:C:T
Artery Aorta	sqtl	3.7e-06	-0.41	17:75268430:G:A
Cells EBV-transformed lymphocytes	sqtl	5.0e-06	+0.42	17:75268430:G:A
Spleen	eqtl	5.8e-06	+0.27	17:75275957:C:G
Adipose Subcutaneous	eqtl	1.4e-05	+0.15	17:75300502:G:A
Testis	eqtl	1.6e-05	-0.32	17:75271437:C:T
Lung	sqtl	3.8e-05	+0.26	17:75268430:G:A
Thyroid	sqtl	4.5e-05	+0.31	17:75256665:A:G
Skin Not Sun Exposed Suprapubic	eqtl	6.4e-05	+0.43	17:75366246:G:A
Skin Sun Exposed Lower leg	sqtl	2.3e-04	+0.26	17:75256665:A:G
Artery Tibial	sqtl	2.7e-04	-0.28	17:75307136:G:A
Artery Aorta	eqtl	2.9e-04	-0.23	17:75252915:A:G
Esophagus Gastroesophageal Junction	sqtl	7.9e-04	-0.46	17:75259727:C:T

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
168055	6.6239	1634
168057	2.3574	1361
168056	0.7849	499
168054	0.2628	130
168053	0.1903	85
168052	0.1222	22

Top tissues by expression

showing 100 of 260 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	95.76	gold quality
saphenous vein	UBERON:0007318	95.21	gold quality
granulocyte	CL:0000094	93.70	gold quality
nipple	UBERON:0002030	93.29	gold quality
gastrocnemius	UBERON:0001388	93.15	gold quality
penis	UBERON:0000989	92.95	gold quality
tibialis anterior	UBERON:0001385	92.64	gold quality
superior surface of tongue	UBERON:0007371	92.57	gold quality
muscle of leg	UBERON:0001383	92.50	gold quality
tibial artery	UBERON:0007610	92.47	gold quality
popliteal artery	UBERON:0002250	92.46	gold quality
medial globus pallidus	UBERON:0002477	92.21	gold quality
quadriceps femoris	UBERON:0001377	92.11	gold quality
tendon of biceps brachii	UBERON:0008188	91.92	gold quality
endothelial cell	CL:0000115	91.90	gold quality
tongue	UBERON:0001723	91.86	gold quality
aorta	UBERON:0000947	91.79	gold quality
vastus lateralis	UBERON:0001379	91.75	gold quality
mucosa of stomach	UBERON:0001199	91.66	gold quality
pharyngeal mucosa	UBERON:0000355	91.46	gold quality
lymph node	UBERON:0000029	91.39	gold quality
right coronary artery	UBERON:0001625	91.38	gold quality
parotid gland	UBERON:0001831	91.26	gold quality
kidney epithelium	UBERON:0004819	91.22	gold quality
body of tongue	UBERON:0011876	91.17	gold quality
leukocyte	CL:0000738	91.05	gold quality
oocyte	CL:0000023	90.96	gold quality
ascending aorta	UBERON:0001496	90.94	gold quality
thoracic aorta	UBERON:0001515	90.94	gold quality
coronary artery	UBERON:0001621	90.88	gold quality
monocyte	CL:0000576	90.85	gold quality
deltoid	UBERON:0001476	90.75	gold quality
left coronary artery	UBERON:0001626	90.74	gold quality
globus pallidus	UBERON:0001875	90.73	gold quality
left ventricle myocardium	UBERON:0006566	90.71	gold quality
thymus	UBERON:0002370	90.70	gold quality
urethra	UBERON:0000057	90.45	gold quality
oral cavity	UBERON:0000167	90.38	gold quality
synovial joint	UBERON:0002217	90.36	gold quality
nasal cavity epithelium	UBERON:0005384	90.23	gold quality
blood	UBERON:0000178	90.18	gold quality
bone marrow	UBERON:0002371	90.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.10	gold quality
lower esophagus	UBERON:0013473	90.09	gold quality
descending thoracic aorta	UBERON:0002345	89.99	gold quality
skeletal muscle tissue	UBERON:0001134	89.98	gold quality
renal medulla	UBERON:0000362	89.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.58	gold quality
spleen	UBERON:0002106	89.50	gold quality
skin of leg	UBERON:0001511	89.47	gold quality
vena cava	UBERON:0004087	89.46	gold quality
muscle tissue	UBERON:0002385	89.40	gold quality
trabecular bone tissue	UBERON:0002483	89.40	gold quality
epithelium of mammary gland	UBERON:0003244	89.20	gold quality
apex of heart	UBERON:0002098	89.18	gold quality
amniotic fluid	UBERON:0000173	89.14	gold quality
mammary duct	UBERON:0001765	89.14	gold quality
layer of synovial tissue	UBERON:0007616	89.11	gold quality
lower esophagus mucosa	UBERON:0035834	89.04	gold quality
mammalian vulva	UBERON:0000997	88.95	gold quality
tibial nerve	UBERON:0001323	88.78	gold quality
esophagus	UBERON:0001043	88.75	gold quality
trachea	UBERON:0003126	88.68	gold quality
right lung	UBERON:0002167	88.67	gold quality
vermiform appendix	UBERON:0001154	88.60	gold quality
biceps brachii	UBERON:0001507	88.52	gold quality
zone of skin	UBERON:0000014	88.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.44	gold quality
bronchus	UBERON:0002185	88.39	gold quality
bronchial epithelial cell	CL:0002328	88.31	gold quality
gingival epithelium	UBERON:0001949	88.23	gold quality
caecum	UBERON:0001153	88.18	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.18	gold quality
epithelium of nasopharynx	UBERON:0001951	88.08	gold quality
skin of abdomen	UBERON:0001416	87.93	gold quality
gingiva	UBERON:0001828	87.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.77	gold quality
esophagus mucosa	UBERON:0002469	87.71	gold quality
mucosa of transverse colon	UBERON:0004991	87.69	gold quality
pylorus	UBERON:0001166	87.65	gold quality
superficial temporal artery	UBERON:0001614	87.65	gold quality
skin of hip	UBERON:0001554	87.64	gold quality
spinal cord	UBERON:0002240	87.63	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.60	gold quality
left adrenal gland cortex	UBERON:0035825	87.47	gold quality
adrenal cortex	UBERON:0001235	87.41	gold quality
adult organism	UBERON:0007023	87.37	gold quality
gall bladder	UBERON:0002110	87.31	gold quality
left adrenal gland	UBERON:0001234	87.30	gold quality
right adrenal gland	UBERON:0001233	87.25	gold quality
adipose tissue	UBERON:0001013	87.21	gold quality
myocardium	UBERON:0002349	87.17	gold quality
inferior vagus X ganglion	UBERON:0005363	87.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.13	gold quality
right adrenal gland cortex	UBERON:0035827	87.11	gold quality
smooth muscle tissue	UBERON:0001135	87.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.95	gold quality
bone marrow cell	CL:0002092	86.85	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-110499	no	819.75
E-MTAB-6524	no	83.63
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	58.4
Spinal cord	tissue	57.5
Substantia nigra	tissue	50.2
Medulla oblongata	tissue	49.8
Midbrain	tissue	48.1
Thalamus	tissue	46.5
Superior colliculi	tissue	45.7
Pons	tissue	45.4
Bone marrow	tissue	41.2	medium
Periaqueductal gray	tissue	41.1
Hypothalamus	tissue	39.2
Putamen	tissue	38.9
Hippocampal formation	tissue	34.6
Cerebral cortex	tissue	33.7	low
Motor cortex	tissue	33.7
Ventral forebrain	tissue	32.3
Lymph node	tissue	31.1	medium
Septum	tissue	30.8
Skeletal muscle	tissue	29.8	medium
Prefrontal cortex	tissue	28.0
Occipital cortex	tissue	27.9
Somatosensory cortex	tissue	27.8
Cerebellum	tissue	27.1	not detected
Retrosplenial cortex	tissue	27.1
Amygdala	tissue	26.8
Insular cortex	tissue	26.7
Entorhinal cortex	tissue	26.6
Temporal cortex	tissue	26.4
Tonsil	tissue	25.3	high
Basal ganglia	tissue	25.0	low
Tongue	tissue	24.9
Retrosplenial and cingulate cortex	tissue	24.8
Thymus	tissue	22.9
Esophagus	tissue	22.2	high
Olfactory bulb	tissue	20.5
Parathyroid gland	tissue	20.2	medium
Spleen	tissue	19.9	low
Lung	tissue	18.6	medium
Vagina	tissue	17.8	medium
Appendix	tissue	17.7	high
Fallopian tube	tissue	17.1	high
Heart muscle	tissue	16.8	medium
Pancreas	tissue	16.8	high
Skin 1	tissue	16.6	high
Gallbladder	tissue	16.2	high
Smooth muscle	tissue	15.8	medium
Urinary bladder	tissue	14.9	high
Colon	tissue	14.7	high
Rectum	tissue	14.2	high
Seminal vesicle	tissue	13.5	high
Small intestine	tissue	13.4	high
Caudate putamen	tissue	13.3
Adipose tissue	tissue	13.2	not detected
Breast	tissue	12.9	high
Cervix	tissue	12.7	high
Liver	tissue	12.5	high
Endometrium 1	tissue	11.8	high
Duodenum	tissue	11.8	high
Kidney	tissue	11.7	high
Placenta	tissue	11.6	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (58.4), Ventral spinal cord (57.5), Dorsal spinal cord (53.4), Blood vessel (40.6), Dorsal hippocampus (34.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MIF4GD by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 49 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
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-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-593-5P	99.34	69.50	965

Functional genomics

gnomAD constraint: pLI 9.32e-07, LOEUF 1.12, missense Z 0.693 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000325102 — one region, missense o/e 0.94.

Literature-anchored findings (GeneRIF, showing 5)

• downregulation of endogenous SLIP1 reduces the rate of translation of endogenous histone mRNA and also reduces cell viability. (PMID:18025107)
• INT6 and MIF4GD were observed to colocalize in cytoplasmic foci. It was concluded that INT6, by establishing interactions with MIF4GD and SLBP, plays an important role in translation of poly(A) minus histone mRNAs. (PMID:22532700)
• Data suggest that oligomerization and SLBP phosphorylation regulate SLBP-SLIP1-histone-mRNA complex formation/disassociation; sequential and ordered assembly is required. (PMID:23286197)
• This paper describes the oligomeric state of SLIP1 and the SLIP1-SLBP complex and how it is regulated by SLBP phosphorylation. Using alanine scanning mutagenesis, the authors demonstrate that the binding site on SLIP1 for SLBP lies close to the dimer interface. A single-point mutant near the SLIP1 homodimer interface abolished interaction with SLBP in vitro and reduced the abundance of histone mRNA in vivo. (PMID:23286197)
• Results suggest that MIF4GD is a potential regulator of p27-dependent cell proliferation in HCC. (PMID:24336329)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mif4gda	ENSDARG00000102080
danio_rerio	mif4gdb	ENSDARG00000102578
mus_musculus	Mif4gd	ENSMUSG00000020743
rattus_norvegicus	Mif4gd	ENSRNOG00000081690
drosophila_melanogaster	CG13124	FBGN0032156
caenorhabditis_elegans		WBGENE00018405

Paralogs (2): CTIF (ENSG00000134030), PAIP1 (ENSG00000172239)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1916924) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal retina outer nuclear layer morphology	1
increased bone mineral content	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3ZC21	97.7%	Diamond
Xenopus laevis	A3KND5	92.8%	Diamond
Xenopus tropicalis	Q28H63	92.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GGA3	protein-coding	23163
GRB2	protein-coding	2885
MRPS7	protein-coding	51081
SLC25A19	protein-coding	60386
MIF4GD-DT	ncRNA	100287042
SUMO2	protein-coding	6613
NUP85	protein-coding	79902
JPT1	protein-coding	51155

Protein

Protein identifiers

MIF4G domain-containing protein — A9UHW6 (reviewed: A9UHW6)

Alternative names: SLBP-interacting protein 1

All UniProt accessions (12): A0A0S2Z5K9, A0A0S2Z5S7, A0A0S2Z5T5, A0A3B3IU65, A9UHW6, J3KSB8, J3KSU6, J3QKW3, J3QLD1, J3QLJ5, J3QLN4, J3QRZ6

UniProt curated annotations — full annotation on UniProt →

Function. Functions in replication-dependent translation of histone mRNAs which differ from other eukaryotic mRNAs in that they do not end with a poly-A tail but a stem-loop. May participate in circularizing those mRNAs specifically enhancing their translation.

Subunit / interactions. Interacts with EIF4G1, EIF4G2 and SLBP; probably tethered by SLBP to the 3’-end of mRNAs ending with the histone stem-loop, it also interacts with EIF4G1 which is bound to their 5’-end.

Subcellular location. Cytoplasm. Nucleus.

Miscellaneous. Depletion of MIF4GD results in cell death and reduced histone mRNA translation.

Similarity. Belongs to the MIF4GD family.

Isoforms (3)

UniProt ID	Names	Canonical?
A9UHW6-1	1	yes
A9UHW6-2	2
A9UHW6-3	3

RefSeq proteins (12): NP_001229427, NP_001229429, NP_001229430, NP_001350735, NP_001352680, NP_001352681, NP_001352682, NP_001352683, NP_001352684, NP_001357521, NP_001398022, NP_065730 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003890	MIF4G-like_typ-3	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR051367	mRNA_TranslReg/HistoneTransl	Family

Pfam: PF02854

UniProt features (4 total): splice variant 2, chain 1, domain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A9UHW6-F1	92.03	0.83

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli; cytosol; golgi apparatus

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 157 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_TRANSLATIONAL_INITIATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, MARTINEZ_RB1_TARGETS_UP, MODULE_256, GOBP_CYTOPLASMIC_TRANSLATIONAL_INITIATION, MODULE_480, DOUGLAS_BMI1_TARGETS_DN, HU_GENOTOXIN_ACTION_DIRECT_VS_INDIRECT_24HR, ACEVEDO_LIVER_CANCER_UP, MODULE_333, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, MODULE_427

GO Biological Process (4): cap-dependent translational initiation (GO:0002191), regulation of translational initiation (GO:0006446), regulation of translation (GO:0006417), positive regulation of translation (GO:0045727)

GO Molecular Function (4): RNA binding (GO:0003723), translation activator activity (GO:0008494), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), histone mRNA stem-loop binding complex (GO:0062073), nucleus (GO:0005634)

GO top-level categories

21 GO namespaces:

Category	Terms
regulation of translation	2
translation	2
cellular anatomical structure	2
cytoplasm	2
cytoplasmic translational initiation	1
cap-dependent translation initiation factor activity	1
translational initiation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
nucleic acid binding	1
translation regulator activity	1
positive regulation of translation	1
protein binding	1
binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
cap-dependent translational initiation	BP	direct assay
cytosol	CC	direct assay
nucleolus	CC	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 402 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIF4GD	SLBP	Q14493	953
MIF4GD	NCBP1	Q09161	540
MIF4GD	PCNX3	Q9H6A9	488
MIF4GD	PAIP1	Q9H074	450
MIF4GD	ZCCHC17	Q9NP64	449
MIF4GD	STARD9	Q9P2P6	446
MIF4GD	EIF4G1	Q04637	443
MIF4GD	GLE1	Q53GS7	423
MIF4GD	GALNT10	Q86SR1	378
MIF4GD	MPHOSPH9	Q99550	366
MIF4GD	UBB	P02248	365
MIF4GD	NOM1	Q5C9Z4	354
MIF4GD	RNMT	O43148	349
MIF4GD	EIF3G	O75821	343
MIF4GD	EIF2B3	Q9NR50	338

IntAct

Human interaction partners of MIF4GD in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

16 partners by confidence:

Partner	Interaction type	MIscore	Records
DDX19B	physical association	0.870	12
DDX19A	physical association	0.860	9
SLBP	direct interaction	0.760	10
HGS	physical association	0.740	5
HDAC4	physical association	0.600	4
PDE4DIP	physical association	0.560	3
EIF3G	physical association	0.510	2
ERI1	physical association	0.510	2
MYC	physical association	0.510	2
CDK16	physical association	0.370	1
PPARG	physical association	0.370	1
SMARCB1	physical association	0.370	1
CTIF	association	0.350	3
SAMTOR	association	0.350	1
SVIL	colocalization	0.270	1
UBQLN4	physical association	0.000	1

BioGRID (71 interactions; top human partners by supporting records): CTIF (Affinity Capture-MS; 6 records), DDX19A (Two-hybrid; 5 records), DDX19B (Two-hybrid; 5 records), HGS (Two-hybrid; 4 records), KLK3 (Affinity Capture-MS; 3 records), HDAC4 (Affinity Capture-Western; 2 records), SLBP (Affinity Capture-MS; 2 records), APEX1 (Affinity Capture-RNA), AQP1 (Two-hybrid), ARHGEF5 (Affinity Capture-MS), ATPAF2 (Two-hybrid), C6orf165 (Two-hybrid), C7orf60 (Affinity Capture-MS), CHCHD2 (Two-hybrid), CRYBA4 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for MIF4GD: 50 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	1
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 599):

Position(s)	Effect	Δscore	Sites
17:75266968–75266969	acceptor_loss	1.0000	4
17:75267536–75267537	donor_loss	1.0000	4
17:75267631–75267632	acceptor_loss	1.0000	6
17:75267785	donor_gain	1.0000
17:75267910–75267911	acceptor_gain	1.0000	2
17:75268098	donor_gain	1.0000
17:75268115	donor_gain	1.0000
17:75270113	donor_loss	1.0000	2
17:75266969	acceptor_loss	0.9900
17:75266972	acceptor_gain	0.9900

AlphaMissense

549 missense substitutions predicted likely pathogenic (of 1,454 scored), across 146 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F75	8	0.974	0.997
F112	8	0.931	0.989
M170	8	0.861	0.976
F181	8	0.860	0.979
F107	8	0.780	0.964
W206	7	0.990	0.998
W101	7	0.979	0.997
E200	7	0.962	0.983
E197	7	0.959	0.990
Q84	7	0.901	0.982
F51	7	0.890	0.963
F174	7	0.876	0.957
E66	7	0.853	0.930
F201	7	0.823	0.963
D179	7	0.820	0.920
E147	7	0.793	0.923
D149	7	0.783	0.874
D113	7	0.698	0.859
D48	7	0.679	0.763
E219	7	0.676	0.800

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:612072 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression, increases abundance	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Acetaminophen	affects response to substance	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4D4	SEES3-1V human MIF4GD, clone1	Embryonic stem cell	Male
CVCL_A4D5	SEES3-1V human MIF4GD, clone2	Embryonic stem cell	Male
CVCL_A4D6	SEES3-1V human MIF4GD, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.