NINJ1

Summary

NINJ1 (ninjurin 1, HGNC:7824) is a protein-coding gene on chromosome 9q22.31, encoding Ninjurin-1 (Q92982). Effector of various programmed cell death, such as pyroptosis and necroptosis, which mediates plasma membrane rupture (cytolysis).

The ninjurin protein is upregulated after nerve injury both in dorsal root ganglion neurons and in Schwann cells (Araki and Milbrandt, 1996 [PubMed 8780658]). It demonstrates properties of a homophilic adhesion molecule and promotes neurite outgrowth from primary cultured dorsal root ganglion neurons.

Source: NCBI Gene 4814 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_004148

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7824
Approved symbol	NINJ1
Name	ninjurin 1
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	NIN1
Ensembl gene	ENSG00000131669
Ensembl biotype	protein_coding
OMIM	602062
Entrez	4814

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000375446, ENST00000461162, ENST00000470314, ENST00000489274, ENST00000490564, ENST00000878643, ENST00000878644, ENST00000878645, ENST00000878646, ENST00000878647, ENST00000878648, ENST00000878649, ENST00000878650, ENST00000937102, ENST00000946696, ENST00000946697

RefSeq mRNA: 1 — MANE Select: NM_004148 NM_004148

CCDS: CCDS6703

Canonical transcript exons

ENST00000375446 — 4 exons

Exon	Start	End
ENSE00001467135	93134143	93134251
ENSE00001881234	93121496	93122230
ENSE00003591245	93126410	93126638
ENSE00003634383	93124899	93125062

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.3773 / max 4218.0724, expressed in 1806 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101475	52.7048	1793
101476	6.0659	1695
101477	4.7379	272
101478	3.6985	385
205564	2.6152	524
101470	0.6149	312
101469	0.5851	273
101474	0.1628	51
101472	0.1257	46
101473	0.0665	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	97.78	gold quality
left adrenal gland	UBERON:0001234	97.64	gold quality
right adrenal gland	UBERON:0001233	97.59	gold quality
left adrenal gland cortex	UBERON:0035825	97.59	gold quality
monocyte	CL:0000576	96.55	gold quality
thoracic aorta	UBERON:0001515	96.36	gold quality
ascending aorta	UBERON:0001496	96.35	gold quality
descending thoracic aorta	UBERON:0002345	96.25	gold quality
leukocyte	CL:0000738	96.23	gold quality
mononuclear cell	CL:0000842	96.17	gold quality
blood	UBERON:0000178	96.17	gold quality
right lobe of liver	UBERON:0001114	96.17	gold quality
metanephros cortex	UBERON:0010533	96.11	gold quality
adrenal cortex	UBERON:0001235	95.99	gold quality
mucosa of stomach	UBERON:0001199	95.93	gold quality
granulocyte	CL:0000094	95.87	gold quality
cartilage tissue	UBERON:0002418	95.82	gold quality
left lobe of thyroid gland	UBERON:0001120	95.80	gold quality
right coronary artery	UBERON:0001625	95.76	gold quality
skin of abdomen	UBERON:0001416	95.73	gold quality
right lobe of thyroid gland	UBERON:0001119	95.61	gold quality
adenohypophysis	UBERON:0002196	95.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.55	gold quality
skin of leg	UBERON:0001511	95.24	gold quality
gall bladder	UBERON:0002110	95.15	gold quality
left uterine tube	UBERON:0001303	95.10	gold quality
right atrium auricular region	UBERON:0006631	95.08	gold quality
aorta	UBERON:0000947	95.07	gold quality
left coronary artery	UBERON:0001626	95.03	gold quality
thyroid gland	UBERON:0002046	94.76	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-76312	yes	221.54
E-MTAB-8142	yes	77.36
E-CURD-122	yes	61.81
E-MTAB-6701	yes	55.76
E-GEOD-135922	yes	48.91
E-MTAB-6678	yes	40.71
E-CURD-46	yes	25.37
E-CURD-114	no	17.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2, TP53

miRNA regulators (miRDB)

37 targeting NINJ1, 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-433-3P	99.98	69.37	1203
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-7112-5P	99.59	65.76	104
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6742-3P	97.95	64.50	1490

Literature-anchored findings (GeneRIF, showing 23)

• Ninjurin1 is able to induce the senescence program. Ninjurin1 may be involved in the regulation of cellular senescence in the liver during carcinogenesis. (PMID:15464245)
• Our data suggests that Ninjurin 1 asp110ala SNP could be a valuable genetic marker of nerve damage in leprosy. (PMID:17825431)
• Data show an important cell-specific role for Ninjurin-1 in the transmigration of inflammatory APCs across the BBB. (PMID:22162058)
• The NINJ1 gene polymorphism plays an important role in nerve degeneration in leprosy patients. (PMID:22326538)
• Ninj1 expression was detected in both HSMCs and HUVECs, and was higher in the former. Ninj1 expression was enhanced by hypoxia in HUVECs. (PMID:25766274)
• Ninj1 modulates TLR4 signaling, which itself plays a major role in systemic inflammatory response syndrome and sepsis. (PMID:25860173)
• Ninj1 suppresses migration, invasion and metastasis of lung cancer via inhibition of the IL-6 signaling pathway in vitro and in vivo. (PMID:26815582)
• Data show that Ninj1 assembles into a homomeric protein complex and that N-glycosylation is a prerequisite for Ninj1 homomer assembly. (PMID:28067406)
• High ninjurin 1 expression is associated with Prostate Cancer. (PMID:28373430)
• Our study demonstrates that Ninj1 is expressed in endometriosis and adenomyosis and is induced by the inflammatory stimuli (PMID:30326781)
• We analyzed cardiac biopsies from aortic-stenosis patients and control patients undergoing elective heart surgery..We conclude that Ninjurin1 contributes to myocyte growth and differentiation, and that these effects are mainly mediated by N-glycosylated Ninjurin1-24. (PMID:31091274)
• Radiation Potentiates Monocyte Infiltration into Tumors by Ninjurin1 Expression in Endothelial Cells. (PMID:32353975)
• Ninjurin1 deficiency aggravates colitis development by promoting M1 macrophage polarization and inducing microbial imbalance. (PMID:32385864)
• NINJ1 mediates plasma membrane rupture during lytic cell death. (PMID:33472215)
• Elevated plasma Ninjurin-1 levels in atrial fibrillation is associated with atrial remodeling and thromboembolic risk. (PMID:35392805)
• Ninjurin1 drives lung tumor formation and progression by potentiating Wnt/beta-Catenin signaling through Frizzled2-LRP6 assembly. (PMID:35395804)
• NINJ1 triggers extravillous trophoblast cell dysfunction through blocking the STAT3 signaling pathway. (PMID:36166142)
• Lower expression of NINJ1 (Ninjurin 1), a mediator of plasma membrane rupture, is associated with advanced disease and worse prognosis in serous ovarian cancer. (PMID:36184655)
• Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. (PMID:36468682)
• NINJ1 Regulates Platelet Activation and PANoptosis in Septic Disseminated Intravascular Coagulation. (PMID:36835580)
• Structural basis of NINJ1-mediated plasma membrane rupture in cell death. (PMID:37198476)
• Calcium/P53/Ninjurin 1 Signaling Mediates Plasma Membrane Rupture of Acinar Cells in Severe Acute Pancreatitis. (PMID:37511311)
• Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection. (PMID:37858098)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ninj1	ENSDARG00000103663
mus_musculus	Ninj1	ENSMUSG00000037966
rattus_norvegicus	Ninj1	ENSRNOG00000016587

Paralogs (1): NINJ2 (ENSG00000171840)

Protein

Protein identifiers

Ninjurin-1 — Q92982 (reviewed: Q92982)

Alternative names: Nerve injury-induced protein 1

All UniProt accessions (1): Q92982

UniProt curated annotations — full annotation on UniProt →

Function. Effector of various programmed cell death, such as pyroptosis and necroptosis, which mediates plasma membrane rupture (cytolysis). Oligomerizes in response to death stimuli and forms ring-like structures on the plasma membrane: acts by cutting and shedding membrane disks, like a cookie cutter, leading to membrane damage and loss that cannot be repaired by the cell. Plasma membrane rupture leads to release intracellular molecules named damage-associated molecular patterns (DAMPs) that propagate the inflammatory response. Mechanistically, mediates plasma membrane rupture by introducing hydrophilic faces of 2 alpha helices into the hydrophobic membrane. Induces plasma membrane rupture downstream of Gasdermin (GSDMA, GSDMB, GSDMC, GSDMD, or GSDME) or MLKL during pyroptosis or necroptosis, respectively. Acts as an effector of PANoptosis downstream of CASP1, CASP4, CASP8 and RIPK3. Also induces plasma membrane rupture in response to cell swelling caused by osmotic stress and ferroptosis downstream of lipid peroxidation. Acts as a regulator of Toll-like receptor 4 (TLR4) signaling triggered by lipopolysaccharide (LPS) during systemic inflammation; directly binds LPS. Involved in leukocyte migration during inflammation by promoting transendothelial migration of macrophages via homotypic binding. Promotes the migration of monocytes across the brain endothelium to central nervous system inflammatory lesions. Also acts as a homophilic transmembrane adhesion molecule involved in various processes such as axonal growth, cell chemotaxis and angiogenesis. Promotes cell adhesion by mediating homophilic interactions via its extracellular N-terminal adhesion motif (N-NAM). Involved in the progression of the inflammatory stress by promoting cell-to-cell interactions between immune cells and endothelial cells. Plays a role in nerve regeneration by promoting maturation of Schwann cells. Acts as a regulator of angiogenesis. Promotes the formation of new vessels by mediating the interaction between capillary pericyte cells and endothelial cells. Promotes osteoclasts development by enhancing the survival of prefusion osteoclasts. Also involved in striated muscle growth and differentiation. Secreted form generated by cleavage, which has chemotactic activity. Acts as an anti-inflammatory mediator by promoting monocyte recruitment, thereby ameliorating atherosclerosis.

Subunit / interactions. Homodimer; in absence of death stimuli, forms an inactive homodimer. Homooligomer; in response to death stimuli, homooligomerizes into long, highly branched filaments and large, ring-shaped structures in the membrane.

Subcellular location. Cell membrane. Synaptic cell membrane Secreted.

Tissue specificity. Widely expressed in both adult and embryonic tissues, primarily those of epithelial origin.

Post-translational modifications. Cleaved by MMP9 protease to generate the Secreted ninjurin-1 form. N-linked glycosylation is required for homooligomerization.

Activity regulation. In response to death stimuli, homooligomerizes and disrupts membrane integrity by introducing the hydrophilic faces of alpha1 and alpha2 helices into the hydrophobic membrane. Homooligomerization and ability to mediate plasma membrane rupture is inhibited by glycine; it is unclear whether glycine directly or indirectly inhibits homooligomerization. In normal conditions, NINJ1 is autoinhibited via formation of a homodimer: in the inactive homodimer, the alpha1 and alpha2 helices (residues 44-74) form a single transmembrane region without a kink, in which hydrophilic faces of alpha1 and alpha2 helices are sequestered.

Domain organisation. Composed of 4 alpha helices: 2 hydrophobic transmembrane regions (alpha3 and alpha4) and 2 alpha helices (alpha1 and alpha2). Alpha1 and alpha2 feature one hydrophobic side and a hydrophilic side. Following NINJ1 activation, alpha1 and alpha2 helices insert into the membrane and drive NINJ1 oligomerization via interactions between alpha3 and alpha4 and the hydrophobic face of alpha1 from an adjacent subunit. Such structures disrupt membrane integrity and form a lesion through the introduction of the hydrophilic faces of alpha1 and alpha2 into the hydrophobic membrane. In absence of death stimuli, NINJ1 is an inactive homodimer, where the alpha1 and alpha2 helices form a single transmembrane region without a kink: in the homodimer, hydrophilic faces of alpha1 and alpha2 helices are sequestered and the binding site for kinked alpha1 and alpha2 helices from neighboring activated NINJ1 molecules are occluded, thereby preventing membrane rupture. The topology shown in the entry corresponds to the activated form.

Induction. By nerve injury both in dorsal root ganglion neurons and in Schwann cells.

Similarity. Belongs to the ninjurin family.

RefSeq proteins (1): NP_004139* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007007	Ninjurin	Family

Pfam: PF04923

UniProt features (53 total): mutagenesis site 30, region of interest 5, helix 5, modified residue 3, topological domain 3, chain 2, transmembrane region 2, site 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8SZA	ELECTRON MICROSCOPY	2.75
9K8S	ELECTRON MICROSCOPY	2.9
9K8T	ELECTRON MICROSCOPY	3.2
8CQR	ELECTRON MICROSCOPY	3.8
8UIP	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92982-F1	63.41	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.

Catalytic / active sites (1): 56–57 (cleavage; by mmp9)

Post-translational modifications (3): 1, 21, 25

Glycosylation sites (1): 60

Mutagenesis-validated functional residues (30):

Position	Phenotype
44–45	strongly reduced ability to mediate plasma membrane rupture.
45	strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis).
47	does not affect ability to homooligomerize in vitro. slightly reduced ability to mediate plasma membrane rupture.
49	strongly reduced ability to mediate plasma membrane rupture.
53	strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis).
76–82	in mutant m4(exo); decreased ability to mediate plasma membrane rupture.
82	does not affect ability to homooligomerize, but shows slightly reduced ability to mediate plasma membrane rupture (cytol
82	does not affect ability to homooligomerize and mediate plasma membrane rupture (cytolysis).
84	strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis).
86	reduced ability to mediate plasma membrane rupture.
90	strongly reduced ability to mediate plasma membrane rupture.
91	strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis).
93	reduced ability to mediate plasma membrane rupture.
93	in mutant m5(cyto); decreased ability to mediate plasma membrane rupture; when associated with v-100, q-117, a-121 and i
95	strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis).
100	in mutant m5(cyto); decreased ability to mediate plasma membrane rupture; when associated with v-93, q-117, a-121 and i-
103	strongly reduced ability to mediate plasma membrane rupture.
111	strongly reduced ability to mediate plasma membrane rupture.
114	slightly reduced ability to mediate plasma membrane rupture.
117	decreased ability to mediate plasma membrane rupture. in mutant m5(cyto); decreased ability to mediate plasma membrane r
121	in mutant m5(cyto); decreased ability to mediate plasma membrane rupture; when associated with v-93, v-100, q-117 and i-
121	does not affect ability to homooligomerize and mediate plasma membrane rupture (cytolysis).
121	does not affect ability to homooligomerize, but shows reduced ability to mediate plasma membrane rupture (cytolysis).
123	strongly reduced ability to homooligomerize and mediate plasma membrane rupture (cytolysis).
124	in mutant m5(cyto); decreased ability to mediate plasma membrane rupture; when associated with v-93, v-100, q-117 and a-

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 354 (showing top): TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, MODULE_522, MODULE_45, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_4_SIGNALING_PATHWAY, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGENERATION, GOBP_HYPEROSMOTIC_RESPONSE

GO Biological Process (18): angiogenesis (GO:0001525), leukocyte chemotaxis involved in inflammatory response (GO:0002232), cell adhesion (GO:0007155), nervous system development (GO:0007399), cytolysis (GO:0019835), killing of cells of another organism (GO:0031640), heterotypic cell-cell adhesion (GO:0034113), positive regulation of toll-like receptor 4 signaling pathway (GO:0034145), tissue regeneration (GO:0042246), muscle cell differentiation (GO:0042692), positive regulation of angiogenesis (GO:0045766), positive regulation of inflammatory response (GO:0050729), protein homooligomerization (GO:0051260), cellular hyperosmotic response (GO:0071474), programmed necrotic cell death (GO:0097300), ferroptosis (GO:0097707), pyroptotic cell death (GO:0141201), inflammatory response (GO:0006954)

GO Molecular Function (4): lipopolysaccharide binding (GO:0001530), cell adhesion mediator activity (GO:0098631), membrane destabilizing activity (GO:0140912), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), synaptic membrane (GO:0097060), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	3
inflammatory response	2
cellular process	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
leukocyte migration involved in inflammatory response	1
leukocyte chemotaxis	1
system development	1
cell killing	1
disruption of cell in another organism	1
cell-cell adhesion	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
regeneration	1
developmental growth	1
cell differentiation	1
muscle structure development	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
protein complex oligomerization	1
hyperosmotic response	1
cellular response to osmotic stress	1
pyroptotic inflammatory response	1
defense response	1
lipid binding	1
carbohydrate derivative binding	1
cell adhesion	1
cell adhesion molecule binding	1
molecular_function	1
binding	1
membrane	1
cell periphery	1
synapse	1
plasma membrane region	1

Protein interactions and networks

STRING

318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NINJ1	NOB1	Q9ULX3	968
NINJ1	PSMD8	P48556	939
NINJ1	GSDMD	P57764	465
NINJ1	MMP1	P03956	389
NINJ1	GSDME	O60443	328
NINJ1	MEFV	O15553	289
NINJ1	CDH10	Q9Y6N8	288
NINJ1	MSLNL	Q96KJ4	286
NINJ1	THEMIS2	Q5TEJ8	282
NINJ1	CDH9	Q9ULB4	277
NINJ1	ALCAM	Q13740	274
NINJ1	LRRC25	Q8N386	271
NINJ1	PKP2	Q99959	266
NINJ1	IL1B	P01584	264
NINJ1	MBP	P02686	261

IntAct

74 interactions, top by confidence:

A	B	Type	Score
NINJ1	KRT40	psi-mi:“MI:0915”(physical association)	0.560
KRT40	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
FNDC9	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
GPX8	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
MUC1	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
NINJ1	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
EBP	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
PVR	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
NINJ1	LIME1	psi-mi:“MI:0915”(physical association)	0.560
CEACAM3	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
NINJ1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
CD200R1	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
AQP6	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
FCGR1A	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
CYB5R3	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
SGCB	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
GOLM1	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
NINJ1	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
NINJ1	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
NINJ1	HIVEP1	psi-mi:“MI:0915”(physical association)	0.370
NINJ1	SGCB	psi-mi:“MI:0915”(physical association)	0.000
NINJ1		psi-mi:“MI:0915”(physical association)	0.000
NINJ1	GPX8	psi-mi:“MI:0915”(physical association)	0.000
NINJ1	MUC1	psi-mi:“MI:0915”(physical association)	0.000
NINJ1	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.000
NINJ1	EBP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): KRT40 (Two-hybrid), NINJ1 (Affinity Capture-MS), NINJ1 (Two-hybrid), NINJ1 (Two-hybrid), NINJ1 (Two-hybrid), NINJ1 (Two-hybrid), GOLM1 (Two-hybrid), TMEM14B (Two-hybrid), EBP (Two-hybrid), FCGR1A (Two-hybrid), TMEM56 (Two-hybrid), CREB3L1 (Two-hybrid), SGCB (Two-hybrid), CD200R1 (Two-hybrid), GPX8 (Two-hybrid)

ESM2 similar proteins: A0A0R4IDX9, A0A2C9VBV6, A2ARJ3, A7T1N0, A7Y2X0, A8Y2U2, O12977, O17386, O35119, O70131, O76689, O80739, P31662, P52166, P70617, P79100, Q05005, Q08469, Q0WMJ8, Q3UP23, Q57UM0, Q5JK32, Q5R9C2, Q5W0B7, Q69RI8, Q6H4R6, Q6NPT7, Q6ZUK4, Q75G84, Q84MS3, Q84MS4, Q8BG16, Q8BJI1, Q8MPP0, Q90X07, Q92982, Q94KB1, Q94KB9, Q9FI00, Q9FY75

Diamond homologs: A0A0R4IDX9, O70131, P70617, Q8MPP0, Q92982, Q9JHE8, Q9JL89, Q9NZG7, Q9VVT9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

840 predictions. Top by Δscore:

Variant	Effect	Δscore
9:93124893:GCTCA:G	donor_loss	1.0000
9:93124894:CTCAC:C	donor_loss	1.0000
9:93124895:TCA:T	donor_loss	1.0000
9:93124896:CAC:C	donor_loss	1.0000
9:93124910:A:AC	donor_gain	1.0000
9:93124911:C:CC	donor_gain	1.0000
9:93124911:CTG:C	donor_gain	1.0000
9:93125058:CTTGA:C	acceptor_gain	1.0000
9:93125059:TTGA:T	acceptor_gain	1.0000
9:93125060:TGA:T	acceptor_gain	1.0000
9:93125061:GA:G	acceptor_gain	1.0000
9:93125061:GAC:G	acceptor_loss	1.0000
9:93125062:AC:A	acceptor_loss	1.0000
9:93125063:C:CA	acceptor_loss	1.0000
9:93125063:C:CC	acceptor_gain	1.0000
9:93125064:T:G	acceptor_loss	1.0000
9:93125070:C:CT	acceptor_gain	1.0000
9:93126405:CCTA:C	donor_loss	1.0000
9:93126406:CTA:C	donor_loss	1.0000
9:93126407:TAC:T	donor_loss	1.0000
9:93126408:A:AC	donor_gain	1.0000
9:93126408:ACC:A	donor_loss	1.0000
9:93126409:C:CA	donor_loss	1.0000
9:93126409:C:CC	donor_gain	1.0000
9:93126470:C:CT	donor_gain	1.0000
9:93126471:C:CT	donor_gain	1.0000
9:93126634:GCCGG:G	acceptor_gain	1.0000
9:93126635:CCGG:C	acceptor_gain	1.0000
9:93126635:CCGGC:C	acceptor_gain	1.0000
9:93126636:CGG:C	acceptor_gain	1.0000

AlphaMissense

993 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:93124968:G:C	N133K	0.996
9:93124968:G:T	N133K	0.996
9:93126519:C:A	K65N	0.994
9:93126519:C:G	K65N	0.994
9:93126533:C:G	A61P	0.994
9:93126550:G:T	A55E	0.994
9:93126555:G:C	D53E	0.994
9:93126555:G:T	D53E	0.994
9:93126430:C:T	G95E	0.993
9:93126523:A:G	L64P	0.993
9:93126534:G:C	N60K	0.993
9:93126534:G:T	N60K	0.993
9:93126441:C:A	Q91H	0.992
9:93126441:C:G	Q91H	0.992
9:93126532:G:T	A61E	0.992
9:93126571:G:T	A48D	0.992
9:93126431:C:G	G95R	0.991
9:93126431:C:T	G95R	0.991
9:93126539:C:G	A59P	0.991
9:93126547:A:G	L56P	0.991
9:93126564:G:C	S50R	0.991
9:93126564:G:T	S50R	0.991
9:93126566:T:G	S50R	0.991
9:93124954:G:T	A138D	0.990
9:93124986:G:C	F127L	0.988
9:93124986:G:T	F127L	0.988
9:93124988:A:G	F127L	0.988
9:93126544:A:G	L57P	0.988
9:93126579:C:A	K45N	0.988
9:93126579:C:G	K45N	0.988

dbSNP variants (sampled 300 via entrez): RS1000086894 (9:93121918 G>A), RS1000195074 (9:93122833 G>A,C), RS1000349185 (9:93133059 T>C), RS1000415519 (9:93122548 A>G), RS1000632855 (9:93127240 C>T), RS1000735935 (9:93129436 C>T), RS1001091945 (9:93123152 C>T), RS1001237839 (9:93128638 G>A), RS1001342164 (9:93134367 G>A,T), RS1001605658 (9:93128456 C>T), RS1001952040 (9:93124711 G>A), RS1002258564 (9:93135692 G>A), RS1002352035 (9:93135426 G>A), RS1002637574 (9:93130254 G>A), RS1003012126 (9:93135516 GA>G)

Disease associations

OMIM: gene MIM:602062 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001957_11	Obesity (early onset extreme)	1.000000e-06
GCST006013_8	Lactate dehydrogenase levels	1.000000e-14
GCST90011898_121	Alanine aminotransferase levels	9.000000e-18
GCST90011899_193	Aspartate aminotransferase levels	1.000000e-22
GCST90013405_36	Liver enzyme levels (alanine transaminase)	9.000000e-18
GCST90013663_23	Alanine aminotransferase levels	8.000000e-12
GCST90013664_83	Aspartate aminotransferase levels	5.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004808	L lactate dehydrogenase measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
nickel sulfate	increases expression	4
Cisplatin	affects cotreatment, increases expression	4
Tretinoin	affects cotreatment, decreases expression, increases expression	3
Dinitrochlorobenzene	increases expression	2
Valproic Acid	affects expression, decreases expression, increases methylation	2
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
4-phenylenediamine	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
adefovir dipivoxil	increases expression	1
pinostrobin	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
jinfukang	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	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Cidofovir	increases expression	1
Acetaminophen	affects expression	1
Air Pollutants, Occupational	increases expression	1
Arsenic	decreases expression	1
Ascorbic Acid	affects cotreatment, decreases expression	1
Aspirin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7VV	Ubigene A-549 NINJ1 KO	Cancer cell line	Male
CVCL_E0J4	Ubigene HeLa NINJ1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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