NMI

Summary

NMI (N-myc and STAT interactor, HGNC:7854) is a protein-coding gene on chromosome 2q23.3, encoding N-myc-interactor (Q13287). Acts as a signaling pathway regulator involved in innate immune system response.

NMYC interactor (NMI) encodes a protein that interacts with NMYC and CMYC (two members of the oncogene Myc family), and other transcription factors containing a Zip, HLH, or HLH-Zip motif. The NMI protein also interacts with all STATs except STAT2 and augments STAT-mediated transcription in response to cytokines IL2 and IFN-gamma. The NMI mRNA has low expression levels in all human fetal and adult tissues tested except brain and has high expression in cancer cell line-myeloid leukemias.

Source: NCBI Gene 9111 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_004688

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7854
Approved symbol	NMI
Name	N-myc and STAT interactor
Location	2q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123609
Ensembl biotype	protein_coding
OMIM	603525
Entrez	9111

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 retained_intron

ENST00000243346, ENST00000414946, ENST00000477072, ENST00000491771, ENST00000883656, ENST00000883657, ENST00000883658, ENST00000883659, ENST00000883660, ENST00000930648

RefSeq mRNA: 1 — MANE Select: NM_004688 NM_004688

CCDS: CCDS2192

Canonical transcript exons

ENST00000243346 — 8 exons

Exon	Start	End
ENSE00000840467	151270470	151270875
ENSE00000840468	151271626	151271732
ENSE00000840469	151275484	151275670
ENSE00000840470	151275758	151275864
ENSE00000840471	151278828	151278990
ENSE00000840472	151281948	151282043
ENSE00001829262	151289593	151289668
ENSE00003544009	151282868	151282954

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 98.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7029 / max 438.5849, expressed in 1700 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31107	9.8520	1595
31112	8.1088	1462
31108	0.5471	278
31110	0.4803	213
31111	0.4097	197
31109	0.2687	141
31106	0.0363	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.27	gold quality
mononuclear cell	CL:0000842	98.16	gold quality
leukocyte	CL:0000738	98.04	gold quality
granulocyte	CL:0000094	96.07	gold quality
trabecular bone tissue	UBERON:0002483	95.48	gold quality
blood	UBERON:0000178	95.27	gold quality
bone marrow	UBERON:0002371	95.24	gold quality
palpebral conjunctiva	UBERON:0001812	94.87	gold quality
epithelium of nasopharynx	UBERON:0001951	94.69	gold quality
parietal pleura	UBERON:0002400	94.44	gold quality
tendon of biceps brachii	UBERON:0008188	94.38	gold quality
germinal epithelium of ovary	UBERON:0001304	94.25	gold quality
pleura	UBERON:0000977	94.11	gold quality
vermiform appendix	UBERON:0001154	94.07	gold quality
visceral pleura	UBERON:0002401	93.93	gold quality
jejunal mucosa	UBERON:0000399	93.28	gold quality
caecum	UBERON:0001153	92.88	gold quality
bone marrow cell	CL:0002092	92.47	gold quality
spleen	UBERON:0002106	92.39	gold quality
cartilage tissue	UBERON:0002418	92.29	gold quality
amniotic fluid	UBERON:0000173	92.24	gold quality
bronchial epithelial cell	CL:0002328	91.93	gold quality
gingiva	UBERON:0001828	91.87	gold quality
esophagus squamous epithelium	UBERON:0006920	91.87	gold quality
lymph node	UBERON:0000029	91.86	gold quality
rectum	UBERON:0001052	91.82	gold quality
skin of hip	UBERON:0001554	91.49	gold quality
oral cavity	UBERON:0000167	91.44	gold quality
duodenum	UBERON:0002114	91.28	gold quality
gingival epithelium	UBERON:0001949	91.25	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	41.56
E-HCAD-13	yes	21.58
E-MTAB-9388	yes	13.57
E-ANND-3	yes	10.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

26 targeting NMI, 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-1193	100.00	65.93	529
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4703-3P	96.68	68.61	545

Literature-anchored findings (GeneRIF, showing 32)

• Dissociation of the IFN-induced protein NMI from IFP35 is a newly defined specific cytoplasmic event occurring during apoptosis. (PMID:11911807)
• complex with BRCA1 and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene promoter activity in breast cancer (PMID:11916966)
• Apoptin mutant T1 still interacted with Nmi, suggesting that its C-terminal 11 AA was not essential for the interaction. (PMID:12019454)
• STAT1 and Nmi are downstream targets of Ets-1 in MCF-7 human breast cancer cells (PMID:15996661)
• identified an association of Sox10 with the N-myc interactor Nmi, which was mediated by the high-mobility group of Sox10 and the central region of Nmi; Nmi modulated the transcriptional activity of Sox10 (PMID:16214168)
• The results provide a novel role of CKIP-1 in cytokine signaling response and the biochemical mechanism, by which two previously identified modulators IFP35 and Nmi are involved via interactions. (PMID:17197158)
• Activation of PKCdelta in response to Camptothecin treatment requires Myc and is important in CPT-mediated apoptosis signaling. (PMID:17565738)
• Data suggest that overexpression of Nmi inhibits the Wnt/beta-catenin signaling via up-regulation of Dkk1 and retards tumor growth. (PMID:19358268)
• Thus our work reveals a novel NMI-mediated, transcription-independent ARF induction pathway in response to cellular stresses. (PMID:23034180)
• identified NMI induction as a novel negative feedback mechanism that decreases IRE1alpha-dependent activation of JNK and apoptosis in cytokine-exposed beta cells (PMID:24936061)
• Results show that aberrant miR-29 expression may account for reduced NMI expression in breast tumors and mesenchymal phenotype of cancer cells that promotes invasive growth. (PMID:25174825)
• Its potential function in transcriptional activation of NMI. (PMID:25387807)
• overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. (PMID:25669971)
• The results showed that SARS coronavirus protein 6 can promote the ubiquitin-dependent proteosomal degradation of Nmi. (PMID:25907116)
• N-myc and STAT interactor sensitizes breast cancer cells to cisplatin treatment through DRAM1 dependent autophagy. (PMID:26146406)
• Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral response (PMID:26342464)
• N-Myc-interacting protein (NMI) negatively regulates epithelial-mesenchymal transition by inhibiting the acetylation of NF-kappaB/p65 in histone deacetylase-dependent manner. (PMID:27012186)
• Data suggest that N-myc (and STAT) interactor (NMI) could improve its downstream target bradykinin B2 receptor (BDKRB2) expression to induce extracellular signal-regulated kinases (ERK) 1/2 activation, and thereby further evoke malignant progression of hepatocellular carcinoma (HCC). (PMID:28077802)
• results provide new insights into understanding the regulatory mechanism of cancer stem cells and suggest that the NMI-YY1-hTERT signaling axis may be a potential therapeutic target for breast cancers. (PMID:28492540)
• These results revealed that IRF-1 is involved in the IFN-inducible expression of Nmi. (PMID:28913576)
• Our study showed that NMI suppressed tumor growth by inhibiting PI3K/AKT, MMP2/MMP9, COX-2/PGE2 signaling pathways and p300-mediated NF-kappaB acetylation, and predicted a favorable prognosis in human lung adenocarcinomas, suggesting that NMI was a potential tumor suppressor in lung cancer. (PMID:29025423)
• These investigations demonstrated etoposide-induced NMI can suppress tumor proliferation and promote cell apoptosis by activating the ARF-p53 signaling pathway in lung carcinoma. Our results provide an alternative mechanism for etoposide in lung carcinoma and suggest NMI has a critical role in suppressing lung carcinoma progression. (PMID:29030066)
• Damage-associated molecular patterns (DAMP) are important mediators of innate immunity. Here the authors show that N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs to promote inflammation by activating macrophages via the Toll-like receptor 4 and NF-kappaB pathways. (PMID:29038465)
• Negatively Regulates TNF-alpha-Induced NF-kappaB Transcriptional Activity by Sequestering NF-kappaB/p65 in the Cytoplasm (PMID:29109532)
• Nmi has a distinct role in the differentiation process of mammary luminal epithelial cell compartment and developmental aberrations resulting from Nmi absence contribute to metastasis. (PMID:29326438)
• NMI and RAC1 might represent two new key genes related to gastric cancer (PMID:29859005)
• Elevated serum NMI (>/= 198.5 pg/mL) was correlated with poor survival rate of acute-on-chronic liver failure of hepatitis B virus patients. (PMID:30771232)
• NMI promotes cell proliferation through TGFbeta/Smad pathway by upregulating STAT1 in colorectal cancer. (PMID:31230364)
• N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction. (PMID:33781665)
• IFP35 family proteins promote neuroinflammation and multiple sclerosis. (PMID:34362845)
• NMI promotes tumor progression and gemcitabine resistance in pancreatic cancer via STAT3-IFIT3 axis. (PMID:37846815)
• N-Myc and STAT Interactor is an Endometriosis Suppressor. (PMID:39125716)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nmi	ENSMUSG00000026946
rattus_norvegicus	Nmi	ENSRNOG00000027502

Paralogs (2): IFI35 (ENSG00000068079), RBM43 (ENSG00000184898)

Protein

Protein identifiers

N-myc-interactor — Q13287 (reviewed: Q13287)

Alternative names: N-myc and STAT interactor

All UniProt accessions (2): C9JW17, Q13287

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a signaling pathway regulator involved in innate immune system response. In response to interleukin 2/IL2 and interferon IFN-gamma/IFNG, interacts with signal transducer and activator of transcription/STAT which activate the transcription of downstream genes involved in a multitude of signals for development and homeostasis. Enhances the recruitment of CBP/p300 coactivators to STAT1 and STAT5, resulting in increased STAT1- and STAT5-dependent transcription. In response to interferon IFN-alpha, associates in a complex with signaling pathway regulator IFI35 to regulate immune response; the complex formation prevents proteasome-mediated degradation of IFI35. In complex with IFI35, inhibits virus-triggered type I IFN-beta production when ubiquitinated by ubiquitin-protein ligase TRIM21. In complex with IFI35, negatively regulates nuclear factor NF-kappa-B signaling by inhibiting the nuclear translocation, activation and transcription of NF-kappa-B subunit p65/RELA, resulting in the inhibition of endothelial cell proliferation, migration and re-endothelialization of injured arteries. Negatively regulates virus-triggered type I interferon/IFN production by inducing proteosome-dependent degradation of IRF7, a transcriptional regulator of type I IFN, thereby interfering with cellular antiviral responses. Beside its role as an intracellular signaling pathway regulator, also functions extracellularly as damage-associated molecular patterns (DAMPs) to promote inflammation, when actively released by macrophage to the extracellular space during cell injury or pathogen invasion. Macrophage-secreted NMI activates NF-kappa-B signaling in adjacent macrophages through Toll-like receptor 4/TLR4 binding and activation, thereby inducing NF-kappa-B translocation from the cytoplasm into the nucleus which promotes the release of pro-inflammatory cytokines.

Subunit / interactions. Interacts with MYCN and MYC, as well as with other transcription factors with a Zip, HLH or a HLH-Zip motif. Interacts with all STAT proteins except STAT2. Interacts with IRF7, the interaction is direct and leads to the inhibition of IRF7-mediated type I IFN production. Interacts (via coiled-coil domain) with TRIM21 (via the SPRY domain); the interaction leads to ‘Lys-63’-linked ubiquitination of NMI. Interacts with IFI35; the interaction is direct and is facilitated by TRIM21. Interacts with TLR4; the interaction is direct and leads to NF-kappa-B activation. (Microbial infection) Interacts with human cytomegalovirus protein UL23; this interaction inhibits NMI-mediated transcription of interferon-gamma stimulated genes.

Subcellular location. Cytoplasm. Nucleus. Secreted.

Tissue specificity. Expressed in adult spleen, liver, and kidney. Expressed in fetal thymus, liver, placenta, spleen, lung, and kidney but not brain. Expressed in macrophages.

Post-translational modifications. Ubiquitinated. ‘Lys-63’-linked ubiquitination by TRIM21 promotes interaction with IFI35 and inhibits virus-triggered type I IFN-beta production.

Domain organisation. The coiled-coil domain is necessary for interaction with TRIM21 and for TRIM21-mediated ubiquitination of NMI. The NID domains are necessary for the interaction with IFI35. The NID domain 1 is necessary and IRF7.

Induction. Up-regulated by interferon IFN-alpha and IFN-gamma. Induced by IL2/interleukin-2. Induced by Sendai virus.

Similarity. Belongs to the NMI family.

RefSeq proteins (1): NP_004679* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009909	Nmi/IFP35_dom	Domain
IPR009938	Nmi/IFP35_N	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily

Pfam: PF07292, PF07334

UniProt features (16 total): mutagenesis site 6, domain 2, sequence conflict 2, chain 1, region of interest 1, coiled-coil region 1, modified residue 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
21NH	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13287-F1	81.84	0.40

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): 16, 22

Mutagenesis-validated functional residues (6):

Position	Phenotype
56	no change in trim21-mediated ubiquitination; when associated with r-61.
61	no change in trim21-mediated ubiquitination; when associated with r-56.
176	no change in trim21-mediated ubiquitination; when associated with r-183.
183	no change in trim21-mediated ubiquitination; when associated with r-176.
22	loss of trim21-mediated ubiquitination and loss of sendai virus-triggered type i ifn-beta production. loss of trim21-med
27	no change in trim21-mediated ubiquitination and no change in sendai virus-triggered type i ifn-beta production. loss of

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses

MSigDB gene sets: 340 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_INFLAMMATORY_RESPONSE, GOBP_MACROPHAGE_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, BECKER_TAMOXIFEN_RESISTANCE_UP, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, MODULE_16, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, AAAYRNCTG_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE

GO Biological Process (18): macrophage activation involved in immune response (GO:0002281), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), negative regulation of cell population proliferation (GO:0008285), response to virus (GO:0009615), negative regulation of interferon-alpha production (GO:0032687), negative regulation of interferon-beta production (GO:0032688), toll-like receptor 4 signaling pathway (GO:0034142), innate immune response (GO:0045087), positive regulation of innate immune response (GO:0045089), negative regulation of innate immune response (GO:0045824), positive regulation of inflammatory response (GO:0050729), protein K48-linked ubiquitination (GO:0070936), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), positive regulation of protein K48-linked ubiquitination (GO:1902524), immune system process (GO:0002376), negative regulation of type I interferon production (GO:0032480), regulation of innate immune response (GO:0045088)

GO Molecular Function (3): identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SARS-CoV-1-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
innate immune response	3
immune response	2
negative regulation of type I interferon production	2
positive regulation of defense response	2
positive regulation of response to external stimulus	2
regulation of innate immune response	2
non-canonical NF-kappaB signal transduction	2
regulation of non-canonical NF-kappaB signal transduction	2
binding	2
myeloid cell activation involved in immune response	1
leukocyte activation involved in immune response	1
macrophage activation	1
cell surface receptor signaling pathway via STAT	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to other organism	1
interferon-alpha production	1
regulation of interferon-alpha production	1
interferon-beta production	1
regulation of interferon-beta production	1
cell surface toll-like receptor signaling pathway	1
defense response to symbiont	1
positive regulation of response to biotic stimulus	1
positive regulation of immune response	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
negative regulation of immune response	1
inflammatory response	1
regulation of inflammatory response	1
protein polyubiquitination	1
negative regulation of intracellular signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of protein K48-linked ubiquitination	1
protein K48-linked ubiquitination	1
positive regulation of protein polyubiquitination	1
biological_process	1
negative regulation of cytokine production	1

Protein interactions and networks

STRING

744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NMI	MYCN	P04198	988
NMI	STAT2	P52630	902
NMI	MYC	P01106	858
NMI	SOX10	P56693	837
NMI	KAT5	Q92993	829
NMI	STAT1	P42224	700
NMI	CREB3	O43889	675
NMI	FOS	P01100	645
NMI	PLEKHO1	Q53GL0	588
NMI	IFI35	P80217	545
NMI	STAT5B	P51692	488
NMI	BRCA1	P38398	483
NMI	PHF11	Q9UIL8	457
NMI	CREBBP	Q92793	450
NMI	EP300	Q09472	401

IntAct

306 interactions, top by confidence:

A	B	Type	Score
TRAF5	NMI	psi-mi:“MI:0915”(physical association)	0.840
NMI	TRAF5	psi-mi:“MI:0915”(physical association)	0.840
BRMS1	NMI	psi-mi:“MI:0915”(physical association)	0.790
NMI	BRMS1	psi-mi:“MI:0915”(physical association)	0.790
HGS	NMI	psi-mi:“MI:0915”(physical association)	0.780
SNAPC5	NMI	psi-mi:“MI:0915”(physical association)	0.740
NMI	SNAPC5	psi-mi:“MI:0915”(physical association)	0.740
NMI	NMI	psi-mi:“MI:0915”(physical association)	0.740
TXLNA	NMI	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (197): NMI (Two-hybrid), NMI (Two-hybrid), NMI (Two-hybrid), NMI (Two-hybrid), NMI (Two-hybrid), NMI (Two-hybrid), MAD2L1BP (Two-hybrid), SNAPC5 (Two-hybrid), EMILIN1 (Two-hybrid), HHLA3 (Two-hybrid), POMZP3 (Two-hybrid), KDM1A (Two-hybrid), BRMS1 (Two-hybrid), COPS7B (Two-hybrid), MTMR9 (Two-hybrid)

ESM2 similar proteins: A0A1B0GUJ8, A0JPF9, A5A6J9, A6H5X4, B1ARD8, E1C3S7, F6QZ15, G1SRW8, O14862, O14879, O35309, O95256, P0C7P3, P80217, Q13287, Q14B46, Q1LZ50, Q2EMV9, Q2T9U5, Q3B7D9, Q3ZCL3, Q460N5, Q4R7Q1, Q5I0E2, Q5I0J8, Q5RCZ8, Q5XGX5, Q5XIZ9, Q6IEE8, Q6NVF4, Q6ZSC3, Q80VH0, Q8BVM9, Q8C8H8, Q8CAS9, Q8IXQ6, Q8IYM2, Q91VJ1, Q99J64, Q99MV5

Diamond homologs: O35309, P80217, Q13287, Q3ZCL3, Q9D8C4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NMI	“up-regulates activity”	SOX10	binding
NMI	“down-regulates activity”	SOX10	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 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
Interleukin-2 family signaling	6	173.0×	8e-11
Interleukin-20 family signaling	6	115.3×	6e-10
Downstream signal transduction	5	86.5×	1e-07
Signaling by PDGF	5	57.7×	7e-07
Interleukin-4 and Interleukin-13 signaling	5	23.4×	3e-05
Signaling by Interleukins	7	20.4×	9e-07
Cytokine Signaling in Immune system	8	14.8×	9e-07
Signaling by Receptor Tyrosine Kinases	6	14.1×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
response to peptide hormone	6	81.1×	1e-08
cell surface receptor signaling pathway via JAK-STAT	7	70.1×	1e-09
defense response	6	44.7×	3e-07
regulation of cell population proliferation	7	27.9×	3e-07
cytokine-mediated signaling pathway	6	27.0×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:151275497:A:C	F207L	0.985
2:151275497:A:T	F207L	0.985
2:151275499:A:G	F207L	0.985
2:151275575:A:C	F181L	0.984
2:151275575:A:T	F181L	0.984
2:151275577:A:G	F181L	0.984
2:151278841:A:C	F109L	0.981
2:151278841:A:T	F109L	0.981
2:151278843:A:G	F109L	0.981
2:151275576:A:G	F181S	0.980
2:151270777:A:C	F280L	0.977
2:151270777:A:T	F280L	0.977
2:151270779:A:G	F280L	0.977
2:151275510:G:T	A203E	0.976
2:151275511:C:G	A203P	0.974
2:151270778:A:G	F280S	0.967
2:151275588:A:T	L177Q	0.966
2:151278855:C:G	A105P	0.966
2:151271663:A:T	V235D	0.961
2:151275588:A:G	L177P	0.959
2:151275578:G:C	S180R	0.958
2:151275578:G:T	S180R	0.958
2:151275580:T:G	S180R	0.958
2:151275636:A:T	V161D	0.955
2:151275498:A:G	F207S	0.954
2:151270841:A:G	L259P	0.950
2:151278851:A:G	L106P	0.948
2:151275504:A:C	I205S	0.946
2:151270702:A:C	F305L	0.945
2:151270702:A:T	F305L	0.945

dbSNP variants (sampled 300 via entrez): RS1000056449 (2:151284286 A>T), RS1000073841 (2:151283179 C>T), RS1000425291 (2:151283423 G>T), RS1000565159 (2:151278198 A>G), RS1000584114 (2:151272031 A>G), RS1000800803 (2:151290903 T>C), RS1000828231 (2:151285388 T>C), RS1000883229 (2:151290601 T>A,C,G), RS1000944218 (2:151284530 T>C), RS1001010935 (2:151285036 G>A,T), RS1001055543 (2:151284724 A>T), RS1001111517 (2:151270289 A>C), RS1001399995 (2:151289869 A>G), RS1001407843 (2:151276952 G>A), RS1001757632 (2:151277340 A>C,T)

Disease associations

OMIM: gene MIM:603525 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects cotreatment	7
trichostatin A	affects cotreatment, increases expression, affects expression	4
Tetrachlorodibenzodioxin	increases expression, affects cotreatment	4
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Tretinoin	increases expression, increases reaction	2
OTX015	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
methylselenic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
pyrrolidine dithiocarbamic acid	decreases reaction, increases expression, affects cotreatment	1
bathocuproine sulfonate	affects cotreatment, decreases reaction, increases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
chromium hexavalent ion	decreases expression	1
perfluoro-n-nonanoic acid	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	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression, affects cotreatment	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2P5	Abcam A-549 NMI KO	Cancer cell line	Male
CVCL_E1D6	Ubigene THP-1 NMI KO	Cancer cell line	Male
CVCL_TA77	HAP1 NMI (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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