MIIP

Summary

MIIP (migration and invasion inhibitory protein, HGNC:25715) is a protein-coding gene on chromosome 1p36.22, encoding Migration and invasion-inhibitory protein (Q5JXC2). Inhibits glioma cells invasion and down-regulates adhesion- and motility-associated genes such as NFKB2 and ICAM1.

This gene encodes a protein that interacts with the oncogene protein insulin-like growth factor binding protein 2 and may function as an inhibitor of cell migration and invasion. This protein also interacts with the cell division protein 20 and may be involved in regulating mitotic progression. This protein may function as a tumor suppressor by inhibiting the growth or certain cancers.

Source: NCBI Gene 60672 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 109 total
• MANE Select transcript: NM_021933

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25715
Approved symbol	MIIP
Name	migration and invasion inhibitory protein
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12438, IIp45
Ensembl gene	ENSG00000116691
Ensembl biotype	protein_coding
OMIM	608772
Entrez	60672

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000235332, ENST00000460823, ENST00000466860, ENST00000478299, ENST00000478749, ENST00000492256, ENST00000498685, ENST00000857908, ENST00000857909, ENST00000857910, ENST00000921479, ENST00000921480, ENST00000971610

RefSeq mRNA: 1 — MANE Select: NM_021933 NM_021933

CCDS: CCDS143

Canonical transcript exons

ENST00000235332 — 10 exons

Exon	Start	End
ENSE00000818973	12021645	12021840
ENSE00001841836	12031722	12032045
ENSE00003513763	12029033	12029141
ENSE00003517689	12022095	12022442
ENSE00003546551	12029223	12029281
ENSE00003579615	12030028	12030124
ENSE00003617293	12031266	12031403
ENSE00003636418	12029765	12029894
ENSE00003645178	12022833	12022917
ENSE00003850430	12019498	12019552

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 95.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.1700 / max 847.8642, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
675	27.8661	1817
674	0.3039	137

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.60	gold quality
type B pancreatic cell	CL:0000169	94.06	silver quality
vena cava	UBERON:0004087	93.29	silver quality
monocyte	CL:0000576	93.17	gold quality
mononuclear cell	CL:0000842	93.06	gold quality
tibial nerve	UBERON:0001323	92.79	gold quality
leukocyte	CL:0000738	92.71	gold quality
olfactory bulb	UBERON:0002264	92.51	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.22	gold quality
spleen	UBERON:0002106	92.19	gold quality
right ovary	UBERON:0002118	92.13	gold quality
oocyte	CL:0000023	92.04	gold quality
apex of heart	UBERON:0002098	91.87	gold quality
tendon of biceps brachii	UBERON:0008188	91.79	silver quality
left ovary	UBERON:0002119	91.77	gold quality
blood	UBERON:0000178	91.45	gold quality
cervix squamous epithelium	UBERON:0006922	91.22	silver quality
right testis	UBERON:0004534	91.12	gold quality
left testis	UBERON:0004533	91.11	gold quality
body of uterus	UBERON:0009853	90.76	gold quality
left uterine tube	UBERON:0001303	90.73	gold quality
putamen	UBERON:0001874	90.48	gold quality
nucleus accumbens	UBERON:0001882	90.41	gold quality
nipple	UBERON:0002030	90.41	gold quality
gluteal muscle	UBERON:0002000	90.38	gold quality
mucosa of transverse colon	UBERON:0004991	90.36	gold quality
right lobe of thyroid gland	UBERON:0001119	90.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.27	gold quality
parotid gland	UBERON:0001831	90.18	silver quality
triceps brachii	UBERON:0001509	90.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.26
E-MTAB-6386	no	676.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting MIIP, 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-4487	99.96	64.58	1252
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-558	97.50	67.16	977

Literature-anchored findings (GeneRIF, showing 14)

• identified a gene, invasion inhibitory protein 45 (IIp45), whose protein product bound to IGFBP-2 through the thyroglobulin-RGD region of the C terminus of IGFBP-2 (PMID:14617774)
• IIp45 gene is inactivated by a tumor-specific alternative splicing that generates an aberrant and unstable IIp45 isoform in infiltrative gliomas. (PMID:15867349)
• Data show a novel mechanism by which IIp45 inhibits cell motility through inhibition of HDAC6. (PMID:20008322)
• Results suggest MIIP K167E as a functional genetic marker of breast cancer development and prognosis. (PMID:20103646)
• MIIP attenuates mitotic transition and increases mitotic catastrophe, thereby inhibiting glioma development and progression. (PMID:20418911)
• MIIP expression in esophageal squamous-cell carcinoma tissues was increased significantly in comparison with the paired paracancerous normal epithelia and was associated with cell differentiation. Patients with low MIIP expression had improved overall and disease-free survival. MIIP expression was an independent prognostic factor in ESCC OS and DFS. (PMID:26825982)
• MIIP haploinsufficiency induces chromosomal instability and promotes tumour progression in colorectal cancer. (PMID:27741356)
• MIIP may function as a tumor suppressor gene for endometrial carcinoma. MIIP attenuates Rac1 signaling through a protein interaction network, and loss of this regulator may contribute to EC metastasis. (PMID:27760566)
• Data show that protein kinase C epsilon (PKCepsilon) phosphorylates migration and invasion inhibitory protein (MIIP) at Ser303 and promotes its binding to RelA/p65, facilitating colorectal cancer metastasis. (PMID:29038521)
• Dysregulated miR-646 and MIIP expression was correlated with advanced tumor stage, lymphatic invasion, metastasis and shorter overall survival in Pancreatic cancer patients. (PMID:29343850)
• MIIP was significantly decreased and IGFBP2 was significantly increased in breast cancer tissues versus para cancerous. (PMID:31078343)
• MIIP suppresses oncogenic AKT-mTOR signaling in prostate cancer by facilitating PP1-mediated AKT dephosphorylation. (PMID:31092266)
• MIIP inhibits malignant progression of hepatocellular carcinoma through regulating AKT. (PMID:32196585)
• MIIP inhibits clear cell renal cell carcinoma proliferation and angiogenesis via negative modulation of the HIF-2alpha-CYR61 axis. (PMID:34931765)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	miip	ENSDARG00000088346
mus_musculus	Miip	ENSMUSG00000029022
rattus_norvegicus	Miip	ENSRNOG00000024139

Protein

Protein identifiers

Migration and invasion-inhibitory protein — Q5JXC2 (reviewed: Q5JXC2)

Alternative names: IGFBP2-binding protein, Invasion-inhibitory protein 45

All UniProt accessions (1): Q5JXC2

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits glioma cells invasion and down-regulates adhesion- and motility-associated genes such as NFKB2 and ICAM1. Exhibits opposing effects to IGFBP2 on cell invasion.

Subunit / interactions. Interacts with IGFBP2.

Tissue specificity. Ubiquitous. Isoform 1 is expressed in brain but underexpressed in glioma tissues, at protein level. Isoform 2 is not detected in normal organs, but is expressed in gliomas with increasing levels with glioma progression. On the contrary, at protein level, isoform 2 is not detected in gliomas, suggesting that this isoform is unstable in glioma cells.

Post-translational modifications. Isoform 2 is degraded by the ubiquitin-proteasome pathway.

Induction. Up-regulated by IGFBP2.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JXC2-1	1	yes
Q5JXC2-2	2, IIP45S

RefSeq proteins (1): NP_068752* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031466	MIIP	Family

Pfam: PF15734

UniProt features (18 total): sequence variant 6, region of interest 4, compositionally biased region 3, modified residue 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JXC2-F1	57.42	0.10

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 (2): 141, 303

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 92 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_MITOTIC_CELL_CYCLE, GOBP_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, FISCHER_DREAM_TARGETS, GOBP_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN

GO Biological Process (2): negative regulation of G2/M transition of mitotic cell cycle (GO:0010972), negative regulation of cell migration (GO:0030336)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G2/M phase transition	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
binding	1

Protein interactions and networks

STRING

198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIIP	IGFBP2	P18065	862
MIIP	RELA	Q04206	495
MIIP	ICAM1	P05362	491
MIIP	KIAA2013	Q8IYS2	488
MIIP	PID1	Q7Z2X4	476
MIIP	PPP1CA	P08129	468
MIIP	RHOT2	Q8IXI1	424
MIIP	RPL10A	P52859	421
MIIP	HDAC6	Q9UBN7	349
MIIP	TNFSF8	P32971	348
MIIP	NFKB1	P19838	332
MIIP	C1orf167	Q5SNV9	327
MIIP	TMEM234	Q8WY98	290
MIIP	PLOD1	Q02809	275
MIIP	KLF17	Q5JT82	263

IntAct

118 interactions, top by confidence:

A	B	Type	Score
MIIP	STK16	psi-mi:“MI:0915”(physical association)	0.670
STK16	MIIP	psi-mi:“MI:0915”(physical association)	0.670
MLLT3	MIIP	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
MED28	MIIP	psi-mi:“MI:0915”(physical association)	0.560
TEKT4	MIIP	psi-mi:“MI:0915”(physical association)	0.560
CCDC120	MIIP	psi-mi:“MI:0915”(physical association)	0.560
ZNF417	MIIP	psi-mi:“MI:0915”(physical association)	0.560
BCAS2	MIIP	psi-mi:“MI:0915”(physical association)	0.560
MOB2	MIIP	psi-mi:“MI:0915”(physical association)	0.560
EFHC1	MIIP	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	MIIP	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	MIIP	psi-mi:“MI:0915”(physical association)	0.560
KRT34	MIIP	psi-mi:“MI:0915”(physical association)	0.560
MIIP	KPRP	psi-mi:“MI:0915”(physical association)	0.560
MIIP	USHBP1	psi-mi:“MI:0915”(physical association)	0.560
TLE5	MIIP	psi-mi:“MI:0915”(physical association)	0.560
MIIP	TCHP	psi-mi:“MI:0915”(physical association)	0.560
OIP5	MIIP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (66): MIIP (Two-hybrid), MIIP (Two-hybrid), MIIP (Proximity Label-MS), MIIP (Proximity Label-MS), MIIP (Proximity Label-MS), MIIP (Affinity Capture-MS), MIIP (Proximity Label-MS), MIIP (Affinity Capture-RNA), MIIP (Two-hybrid), MIIP (Two-hybrid), MIIP (Two-hybrid), MIIP (Two-hybrid), MIIP (Two-hybrid), MIIP (Two-hybrid), MIIP (Two-hybrid)

ESM2 similar proteins: A0A1B0GUS0, A0A5F9ZHS7, A7E346, A7MB34, A8MZG2, B2RU40, D4A9R4, O08574, O75593, P0C1Z6, P0CG20, Q0VG99, Q0ZCJ7, Q17QH7, Q29RM2, Q2KIS6, Q2M2S6, Q2M3G4, Q2NL68, Q32LE6, Q3U1J1, Q5JXC2, Q5R815, Q5SW24, Q61660, Q63247, Q6NZ36, Q6PBC9, Q6ZN01, Q6ZRI6, Q7TN08, Q7Z591, Q80VF6, Q86WR7, Q8BG26, Q8BP99, Q8BXQ8, Q8IYS4, Q8N9Y4, Q8NAV2

Diamond homologs: A2A7Y5, Q5JXC2, Q6AYH0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCE	“up-regulates activity”	MIIP	phosphorylation
MIIP	“up-regulates activity”	RELA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	152.3×	1e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	134.3×	2e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	134.3×	2e-12
Activation of BH3-only proteins	7	99.3×	2e-11
RHO GTPases activate PKNs	7	63.4×	4e-10
Intrinsic Pathway for Apoptosis	7	58.6×	6e-10
FOXO-mediated transcription	5	48.0×	8e-07
SARS-CoV-1-host interactions	7	35.1×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	35.9×	5e-05
intracellular protein localization	8	16.4×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	11
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

1492 predictions. Top by Δscore:

Variant	Effect	Δscore
1:12019548:GCCGG:G	donor_gain	1.0000
1:12019550:CGG:C	donor_gain	1.0000
1:12019551:GG:G	donor_gain	1.0000
1:12019551:GGG:G	donor_gain	1.0000
1:12019552:GG:G	donor_gain	1.0000
1:12019552:GGTG:G	donor_loss	1.0000
1:12019553:G:A	donor_loss	1.0000
1:12019553:G:GG	donor_gain	1.0000
1:12019554:T:A	donor_loss	1.0000
1:12022832:GCCC:G	acceptor_gain	1.0000
1:12022832:GCCCA:G	acceptor_gain	1.0000
1:12022916:AGG:A	donor_loss	1.0000
1:12022917:GGT:G	donor_loss	1.0000
1:12022918:G:GA	donor_loss	1.0000
1:12022919:T:A	donor_loss	1.0000
1:12029028:ACCAG:A	acceptor_gain	1.0000
1:12029120:A:T	donor_gain	1.0000
1:12029140:GA:G	donor_gain	1.0000
1:12029142:G:GG	donor_gain	1.0000
1:12029764:GGC:G	acceptor_gain	1.0000
1:12029764:GGCGT:G	acceptor_gain	1.0000
1:12030023:C:CA	acceptor_gain	1.0000
1:12030026:AG:A	acceptor_gain	1.0000
1:12030027:GG:G	acceptor_gain	1.0000
1:12030123:GG:G	donor_gain	1.0000
1:12030124:GG:G	donor_gain	1.0000
1:12031265:GC:G	acceptor_gain	1.0000
1:12031265:GCACT:G	acceptor_gain	1.0000
1:12019549:CCGG:C	donor_gain	0.9900
1:12022830:CA:C	acceptor_loss	0.9900

AlphaMissense

2464 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:12029098:T:C	F205L	0.989
1:12029100:T:A	F205L	0.989
1:12029100:T:G	F205L	0.989
1:12029797:T:C	F250L	0.977
1:12029799:C:A	F250L	0.977
1:12029799:C:G	F250L	0.977
1:12029099:T:C	F205S	0.976
1:12031281:T:A	W320R	0.971
1:12031281:T:C	W320R	0.971
1:12030032:A:C	S284R	0.970
1:12030034:C:A	S284R	0.970
1:12030034:C:G	S284R	0.970
1:12031271:C:G	C316W	0.967
1:12029099:T:G	F205C	0.963
1:12031269:T:C	C316R	0.963
1:12030089:A:C	S303R	0.960
1:12030091:C:A	S303R	0.960
1:12030091:C:G	S303R	0.960
1:12031283:G:C	W320C	0.957
1:12031283:G:T	W320C	0.957
1:12022908:T:A	W180R	0.955
1:12022908:T:C	W180R	0.955
1:12029102:G:C	R206P	0.955
1:12029077:T:C	F198L	0.952
1:12029079:C:A	F198L	0.952
1:12029079:C:G	F198L	0.952
1:12031270:G:A	C316Y	0.946
1:12029827:T:C	C260R	0.944
1:12031268:C:A	H315Q	0.942
1:12031268:C:G	H315Q	0.942

dbSNP variants (sampled 300 via entrez): RS1000083820 (1:12019226 T>A,C), RS1000364491 (1:12023513 C>G,T), RS1001072325 (1:12028990 C>A,T), RS1001111675 (1:12023439 T>A), RS1001283656 (1:12028607 G>A), RS1001479469 (1:12023137 C>T), RS1001816328 (1:12018148 C>T), RS1002557257 (1:12021873 G>A), RS1003075967 (1:12031274 G>A,T), RS1003087349 (1:12031044 G>A), RS1003174355 (1:12027358 C>T), RS1003243777 (1:12030460 A>G), RS1003397060 (1:12032253 C>T), RS1003635629 (1:12027421 C>G), RS1003815437 (1:12022094 G>A,T)

Disease associations

OMIM: gene MIM:608772 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004923_1	Tuberculosis	1.000000e-11
GCST009798_30	Asthma	8.000000e-13
GCST011353_31	Serum alkaline phosphatase levels	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
sodium arsenite	affects methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Vehicle Emissions	decreases methylation	1
Benzene	decreases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Selenium	increases expression	1
Smoke	decreases expression	1
Sulindac	increases expression	1
Valproic Acid	increases methylation	1
Asbestos, Serpentine	increases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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