MID1IP1

Summary

MID1IP1 (MID1 interacting protein 1, HGNC:20715) is a protein-coding gene on chromosome Xp11.4, encoding Mid1-interacting protein 1 (Q9NPA3). Plays a role in the regulation of lipogenesis in liver.

Predicted to enable enzyme activator activity and ligase regulator activity. Predicted to be involved in several processes, including negative regulation of microtubule depolymerization; positive regulation of fatty acid biosynthetic process; and positive regulation of ligase activity. Predicted to be located in microtubule cytoskeleton. Predicted to be active in cytosol.

Source: NCBI Gene 58526 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 29 total — 2 pathogenic
• MANE Select transcript: NM_021242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20715
Approved symbol	MID1IP1
Name	MID1 interacting protein 1
Location	Xp11.4
Locus type	gene with protein product
Status	Approved
Aliases	STRAIT11499, FLJ10386, MIG12, THRSPL, G12-like
Ensembl gene	ENSG00000165175
Ensembl biotype	protein_coding
OMIM	300961
Entrez	58526

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000336949, ENST00000378474, ENST00000457894, ENST00000614558, ENST00000854109, ENST00000854110, ENST00000854111, ENST00000854112, ENST00000854113, ENST00000854114, ENST00000914555, ENST00000914556, ENST00000914557

RefSeq mRNA: 3 — MANE Select: NM_021242 NM_001098790, NM_001098791, NM_021242

CCDS: CCDS14249

Canonical transcript exons

ENST00000614558 — 3 exons

Exon	Start	End
ENSE00001421692	38801459	38801487
ENSE00003747180	38802535	38804413
ENSE00003822039	38804683	38806532

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.4625 / max 795.9144, expressed in 1808 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195959	23.9649	1755
195954	6.6878	1528
195958	2.4767	1057
195960	1.6288	802
195953	0.6410	436
195963	0.6121	296
195962	0.2111	84
195964	0.1385	45
195955	0.1016	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.91	gold quality
spinal cord	UBERON:0002240	97.44	gold quality
hypothalamus	UBERON:0001898	96.19	gold quality
amygdala	UBERON:0001876	96.16	gold quality
gastrocnemius	UBERON:0001388	96.04	gold quality
putamen	UBERON:0001874	95.83	gold quality
muscle of leg	UBERON:0001383	95.63	gold quality
inferior vagus X ganglion	UBERON:0005363	95.32	gold quality
caudate nucleus	UBERON:0001873	94.87	gold quality
mucosa of stomach	UBERON:0001199	94.80	gold quality
muscle organ	UBERON:0001630	94.79	gold quality
diaphragm	UBERON:0001103	94.62	gold quality
substantia nigra	UBERON:0002038	94.60	gold quality
midbrain	UBERON:0001891	94.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.41	gold quality
nucleus accumbens	UBERON:0001882	94.29	gold quality
monocyte	CL:0000576	94.22	gold quality
mononuclear cell	CL:0000842	94.19	gold quality
cranial nerve II	UBERON:0000941	94.18	gold quality
body of pancreas	UBERON:0001150	94.18	gold quality
leukocyte	CL:0000738	94.11	gold quality
globus pallidus	UBERON:0001875	93.80	gold quality
subthalamic nucleus	UBERON:0001906	93.80	gold quality
ventral tegmental area	UBERON:0002691	93.62	gold quality
medial globus pallidus	UBERON:0002477	93.55	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.29	gold quality
anterior cingulate cortex	UBERON:0009835	93.18	gold quality
cingulate cortex	UBERON:0003027	93.16	gold quality
lateral globus pallidus	UBERON:0002476	92.99	gold quality
body of stomach	UBERON:0001161	92.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	80.03
E-ANND-3	yes	15.40
E-GEOD-130148	yes	9.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting MID1IP1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-548A-3P	99.76	70.58	3524

Literature-anchored findings (GeneRIF, showing 6)

• show that MIG12, a 22 kDa cytosolic protein of previously unknown function, binds to acetyl-CoA carboxylase and lowers the threshold for citrate activation into the physiological range. (PMID:20457939)
• The results of the present study indicated that Spot14/S14R were differently expressed in MSC adipogenesis in AIS patients, and they may be important in the abnormal adipogenic differentiation in AIS. (PMID:27082501)
• Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2. (PMID:32316188)
• MIG12 is involved in the LXR activation-mediated induction of the polymerization of mammalian acetyl-CoA carboxylase. (PMID:34153683)
• Inhibition of CNOT2 Induces Apoptosis via MID1IP1 in Colorectal Cancer Cells by Activating p53. (PMID:34680125)
• Midline 1 interacting protein 1 promotes cancer metastasis through FOS-like 1-mediated matrix metalloproteinase 9 signaling in HCC. (PMID:36632999)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mid1ip1a	ENSDARG00000041051
mus_musculus	Mid1ip1	ENSMUSG00000008035
rattus_norvegicus	Mid1ip1	ENSRNOG00000003228
drosophila_melanogaster	CG2765	FBGN0035087

Paralogs (1): THRSP (ENSG00000151365)

Protein

Protein identifiers

Mid1-interacting protein 1 — Q9NPA3 (reviewed: Q9NPA3)

Alternative names: Gastrulation-specific G12-like protein, Mid1-interacting G12-like protein, Protein STRAIT11499, Spot 14-related protein

All UniProt accessions (1): Q9NPA3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of lipogenesis in liver. Up-regulates ACACA enzyme activity. Required for efficient lipid biosynthesis, including triacylglycerol, diacylglycerol and phospholipid. Involved in stabilization of microtubules.

Subunit / interactions. Homodimer in the absence of THRSP. Heterodimer with THRSP. The homodimer interacts with ACACA and ACACB. Promotes polymerization of Acetyl-CoA carboxylase to form complexes that contain MID1IP1 and ACACA and/or ACACB. Interaction with THRSP interferes with ACACA binding.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the SPOT14 family.

RefSeq proteins (3): NP_001092260, NP_001092261, NP_067065* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009786	Spot_14	Family
IPR053719	Lipogen_MT_Stabilize_sf	Homologous_superfamily

Pfam: PF07084

UniProt features (4 total): modified residue 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPA3-F1	69.09	0.23

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): 1, 75, 79

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-200425	Carnitine shuttle
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 272 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, TSENG_IRS1_TARGETS_UP, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, USF_C, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_FATTY_ACID_METABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_FATTY_ACID_BIOSYNTHETIC_PROCESS, GTGCCTT_MIR506

GO Biological Process (6): lipid metabolic process (GO:0006629), negative regulation of microtubule depolymerization (GO:0007026), positive regulation of fatty acid biosynthetic process (GO:0045723), regulation of lipid biosynthetic process (GO:0046890), protein polymerization (GO:0051258), positive regulation of ligase activity (GO:0051351)

GO Molecular Function (4): enzyme activator activity (GO:0008047), identical protein binding (GO:0042802), ligase regulator activity (GO:0055103), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytosol (GO:0005829), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ligase activity	2
enzyme regulator activity	2
cellular anatomical structure	2
primary metabolic process	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
fatty acid biosynthetic process	1
regulation of fatty acid biosynthetic process	1
positive regulation of fatty acid metabolic process	1
positive regulation of lipid biosynthetic process	1
lipid biosynthetic process	1
regulation of biosynthetic process	1
regulation of lipid metabolic process	1
protein-containing complex assembly	1
positive regulation of catalytic activity	1
catalytic activity	1
molecular function activator activity	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MID1IP1	MID1	O15344	555
MID1IP1	ACACA	Q13085	518
MID1IP1	ZBTB8A	Q96BR9	479
MID1IP1	GINM1	Q9NU53	406
MID1IP1	GPI	P06744	366
MID1IP1	S100A5	P33763	360
MID1IP1	LCTL	Q6UWM7	358
MID1IP1	JRKL	Q9Y4A0	355
MID1IP1	PDZD11	Q5EBL8	353
MID1IP1	MLXIPL	Q9NP71	348
MID1IP1	PJA2	O43164	347
MID1IP1	S100A14	Q9HCY8	341
MID1IP1	ELOVL6	Q9H5J4	337
MID1IP1	TATDN2	Q93075	336
MID1IP1	PIP4K2C	Q8TBX8	332

IntAct

52 interactions, top by confidence:

A	B	Type	Score
CD9	IGSF8	psi-mi:“MI:0914”(association)	0.760
SUFU	MID1IP1	psi-mi:“MI:0915”(physical association)	0.660
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
MID1IP1	AK8	psi-mi:“MI:0915”(physical association)	0.560
MID1IP1	MID2	psi-mi:“MI:0915”(physical association)	0.560
AK8	MID1IP1	psi-mi:“MI:0915”(physical association)	0.560
MID2	MID1IP1	psi-mi:“MI:0915”(physical association)	0.560
SUV39H1	MAGEC1	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
TMA16	TNPO2	psi-mi:“MI:0914”(association)	0.530
RAD51AP1	USP12	psi-mi:“MI:0914”(association)	0.530
MID1IP1	ACACB	psi-mi:“MI:0914”(association)	0.530
TSHR	MID1IP1	psi-mi:“MI:0915”(physical association)	0.510
MID1IP1	TSHR	psi-mi:“MI:0915”(physical association)	0.510
THEMIS	PTPN6	psi-mi:“MI:0914”(association)	0.500
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
MID1IP1	SLC25A23	psi-mi:“MI:0915”(physical association)	0.400
MID1IP1	GSK3B	psi-mi:“MI:0915”(physical association)	0.370
GCH1	SECTM1	psi-mi:“MI:0914”(association)	0.350
ATP6V0D1		psi-mi:“MI:0914”(association)	0.350
SLC45A2	TMEM63A	psi-mi:“MI:0914”(association)	0.350
KLF5		psi-mi:“MI:0914”(association)	0.350
KLF8		psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
ABCF3	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): MID1IP1 (Two-hybrid), AK8 (Two-hybrid), MID1IP1 (Affinity Capture-MS), MID1IP1 (Two-hybrid), MID1IP1 (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), MID1IP1 (Proximity Label-MS), MID1IP1 (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), TSHR (Affinity Capture-Western), MID1IP1 (Two-hybrid)

ESM2 similar proteins: A0A7P0TBJ1, A0A804C8T0, A2BE76, A2RRV3, A4IG66, A4IIE8, D4A4K3, O75182, P57095, P97578, Q02225, Q08AY9, Q09YG9, Q09YK4, Q1JPG0, Q28C41, Q2IBF8, Q2QL82, Q2QLF8, Q2QLG9, Q4QQM5, Q503U3, Q5BLE2, Q5M836, Q5XJS0, Q62141, Q62671, Q68EF0, Q6DFB7, Q6GR21, Q6NRB7, Q6P7D5, Q6PCG6, Q7L4E1, Q86YS3, Q8BG30, Q8BHS8, Q8BK03, Q8BQP8, Q8NAN2

Diamond homologs: P04143, P47805, Q1LUV9, Q62264, Q6P7D5, Q8AWD1, Q92748, Q9CQ20, Q9NPA3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MID1IP1	“up-regulates activity”	ACACA	binding
MID1IP1	“up-regulates activity”	ACACB	binding
THRSP	“down-regulates activity”	MID1IP1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	18
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
153937	GRCh38/hg38 Xp22.33-q24(chrX:251879-118847157)x3	Pathogenic
394146	GRCh37/hg19 Xp11.4(chrX:38135974-38957292)x1	Pathogenic

SpliceAI

515 predictions. Top by Δscore:

Variant	Effect	Δscore
X:38804682:GGCCA:G	acceptor_gain	1.0000
X:38801484:GGGT:G	donor_gain	0.9900
X:38801485:GGTG:G	donor_gain	0.9900
X:38801486:GT:G	donor_gain	0.9900
X:38802612:GT:G	donor_gain	0.9900
X:38804671:T:TA	acceptor_gain	0.9900
X:38804674:A:AG	acceptor_gain	0.9900
X:38804675:T:G	acceptor_gain	0.9900
X:38804680:CA:C	acceptor_loss	0.9900
X:38804681:A:AC	acceptor_loss	0.9900
X:38804681:A:AG	acceptor_gain	0.9900
X:38804682:G:GG	acceptor_gain	0.9900
X:38804682:GGCC:G	acceptor_gain	0.9900
X:38801488:G:GG	donor_gain	0.9800
X:38803563:A:T	donor_gain	0.9800
X:38804669:C:CA	acceptor_gain	0.9800
X:38804677:A:AG	acceptor_gain	0.9800
X:38804678:A:G	acceptor_gain	0.9800
X:38804681:AG:A	acceptor_gain	0.9800
X:38804682:GG:G	acceptor_gain	0.9800
X:38804682:GGC:G	acceptor_gain	0.9800
X:38801470:G:GT	donor_gain	0.9700
X:38804678:AACAG:A	acceptor_gain	0.9700
X:38804679:ACAGG:A	acceptor_gain	0.9700
X:38804680:CAGG:C	acceptor_gain	0.9700
X:38804681:AGGC:A	acceptor_gain	0.9700
X:38801483:C:T	donor_gain	0.9500
X:38801837:T:G	donor_gain	0.9500
X:38804663:C:CA	acceptor_gain	0.9500
X:38801483:CGGGT:C	donor_gain	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000082079 (X:38805360 C>T), RS1000872613 (X:38800870 C>A), RS1001089223 (X:38801218 T>A), RS1001241052 (X:38803875 C>G), RS1003116700 (X:38801302 T>C,G), RS1003335059 (X:38803591 G>A), RS1003502471 (X:38801619 G>A,C), RS1003889657 (X:38799848 A>C,G), RS1004201441 (X:38805617 G>A), RS1004315963 (X:38806359 G>A), RS1004893218 (X:38801520 G>A,C,T), RS1006123120 (X:38805222 G>A), RS1006997226 (X:38802771 A>G), RS1007111702 (X:38803223 C>A), RS1007258302 (X:38802223 C>A)

Disease associations

OMIM: gene MIM:300961 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003791_12	Response to metformin (IC50)	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
trichostatin A	increases expression, affects expression, affects cotreatment	4
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Cyclosporine	affects expression, decreases expression	3
bisphenol A	increases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Cisplatin	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	increases expression	1
dimethylselenide	increases expression, increases oxidation	1
sodium arsenite	decreases expression, increases abundance	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
cupric chloride	increases expression	1
dibenzo(a,l)pyrene	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1

Clinical trials (associated diseases)

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