INA

Summary

INA (internexin neuronal intermediate filament protein alpha, HGNC:6057) is a protein-coding gene on chromosome 10q24.33, encoding Alpha-internexin (Q16352). Class-IV neuronal intermediate filament that is able to self-assemble.

Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and they functionally maintain the neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene is a member of the intermediate filament family and is involved in the morphogenesis of neurons.

Source: NCBI Gene 9118 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 66 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_032727

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6057
Approved symbol	INA
Name	internexin neuronal intermediate filament protein alpha
Location	10q24.33
Locus type	gene with protein product
Status	Approved
Aliases	NF-66
Ensembl gene	ENSG00000148798
Ensembl biotype	protein_coding
OMIM	605338
Entrez	9118

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000369849, ENST00000912062

RefSeq mRNA: 1 — MANE Select: NM_032727 NM_032727

CCDS: CCDS7545

Canonical transcript exons

ENST00000369849 — 3 exons

Exon	Start	End
ENSE00001451043	103288360	103290346
ENSE00001451047	103277138	103278276
ENSE00001644022	103287035	103287159

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 99.34.

FANTOM5 (CAGE): breadth broad, TPM avg 17.3058 / max 1002.3780, expressed in 696 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106790	13.3215	647
106793	2.0614	196
106791	1.4742	344
106789	0.1422	68
106796	0.0915	50
106794	0.0719	46
106795	0.0634	37
106798	0.0318	14
106792	0.0283	11
106797	0.0193	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.34	gold quality
middle temporal gyrus	UBERON:0002771	99.25	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.05	gold quality
pons	UBERON:0000988	99.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.71	gold quality
primary visual cortex	UBERON:0002436	98.24	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.99	gold quality
superior frontal gyrus	UBERON:0002661	97.50	gold quality
frontal pole	UBERON:0002795	97.49	gold quality
superior vestibular nucleus	UBERON:0007227	97.27	gold quality
endothelial cell	CL:0000115	97.26	gold quality
orbitofrontal cortex	UBERON:0004167	97.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.99	gold quality
postcentral gyrus	UBERON:0002581	96.96	gold quality
occipital lobe	UBERON:0002021	96.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.82	gold quality
parietal lobe	UBERON:0001872	96.65	gold quality
frontal cortex	UBERON:0001870	96.60	gold quality
substantia nigra pars compacta	UBERON:0001965	96.60	gold quality
prefrontal cortex	UBERON:0000451	96.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.41	gold quality
paraflocculus	UBERON:0005351	96.27	gold quality
neocortex	UBERON:0001950	96.14	gold quality
hypothalamus	UBERON:0001898	95.91	gold quality
right frontal lobe	UBERON:0002810	95.88	gold quality
cerebellum	UBERON:0002037	95.80	gold quality
cerebellar cortex	UBERON:0002129	95.74	gold quality
cerebellar vermis	UBERON:0004720	95.72	gold quality
cerebellar hemisphere	UBERON:0002245	95.67	gold quality
cerebral cortex	UBERON:0000956	95.41	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	1464.66
E-HCAD-56	yes	1354.20
E-GEOD-81547	yes	454.56
E-HCAD-5	yes	394.25
E-MTAB-10485	yes	356.85
E-MTAB-5061	yes	5.62
E-ANND-3	yes	3.74
E-GEOD-83139	yes	3.72
E-MTAB-8894	no	751.01
E-GEOD-75140	no	194.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF6, POU4F1, POU4F2, POU4F3, REST

miRNA regulators (miRDB)

134 targeting INA, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972

Literature-anchored findings (GeneRIF, showing 17)

• alpha-internexin expression in neuroblastoma (PMID:12209604)
• The discovery of alpha-internexin in the cytoplasmic inclusions implicates novel mechanisms of pathogenesis in inclusion diseeae and other neurological diseases with pathological accumulations of IFs. (PMID:15161649)
• Abnormal neuronal intermediate filament inclusions of alpha-internexin have been identified as the pathological hallmark of neuronal intermediate filament inclusion disease (PMID:16722980)
• Expression of the 2 markers, alpha-internexin and peripherin, in a small round cell tumor strongly favors the diagnosis of neuroblastoma. (PMID:18528283)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• Alpha-Internexin (INA) expression appears to be a simple, reliable prognostic marker and a surrogate marker of 1p19q codeletion. (PMID:19139367)
• the importance of alpha-internexin and NF-L in regulating the conformations of NF-M and NF-H (PMID:20213320)
• INA may provide additional biologic information relevant to delineation of both pancreatic neuroendocrine neoplasms (NEN) tumor phenotypes and clinical behavior. (PMID:21990041)
• High INA expression is associated with grade II gliomas. (PMID:22890969)
• It is a supportive diagnostic marker for oligodendroglial tumors with the 1p/19q co-deletion. (PMID:24197863)
• alpha-Internexin was expressed in 53% of 350 pancreatic neuroendocrine tumors. Reduced expression of alpha-internexin was significantly associated with advanced stage metastases, recurrence and shorter overall survival. (PMID:24483152)
• Gonadotropinomas, null cell pituitary adenomas, and thyrotropinomas exhibit high levels of intracellular INA protein indicating neuronal transdifferentiation. (PMID:25236435)
• It is a neuronal marker, and has been indicated as an immunohistochemical surrogate of chromosome 1p/19q co-deletion in oligodendroglial tumors. (PMID:26233522)
• The proteins UCH-L1 and alpha-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors. (PMID:28526880)
• Data suggest GRINL1A (GCOM1)-NMDA receptor-internexin-alpha (INA) interaction pathway may be relevant to neuroprotection. (PMID:29339073)
• reduced/loss of expression of alpha-internexin was closely related to tumors with aggressiveness and patient’s adverse prognosis (PMID:29940892)
• Epigenetic Inactivation of alpha-Internexin Accelerates Microtubule Polymerization in Colorectal Cancer. (PMID:33051252)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	inaa	ENSDARG00000011862
danio_rerio	inab	ENSDARG00000053248
mus_musculus	Ina	ENSMUSG00000034336
rattus_norvegicus	Ina	ENSRNOG00000020248

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Alpha-internexin — Q16352 (reviewed: Q16352)

Alternative names: 66 kDa neurofilament protein, Neurofilament 5

All UniProt accessions (1): Q16352

UniProt curated annotations — full annotation on UniProt →

Function. Class-IV neuronal intermediate filament that is able to self-assemble. It is involved in the morphogenesis of neurons. It may form an independent structural network without the involvement of other neurofilaments or it may cooperate with NEFL to form the filamentous backbone to which NEFM and NEFH attach to form the cross-bridges. May also cooperate with the neuronal intermediate filament protein PRPH to form filamentous networks.

Subunit / interactions. Forms homodimers (in vitro). Forms heterodimers with NEFL, NEFM or NEFH (in vitro).

Tissue specificity. Found predominantly in adult CNS.

Post-translational modifications. O-glycosylated.

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_116116* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006821	Intermed_filament_DNA-bd	Domain
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain
IPR050405	Intermediate_filament	Family

Pfam: PF00038, PF04732

UniProt features (30 total): sequence conflict 11, region of interest 8, modified residue 6, sequence variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16352-F1	75.42	0.48

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 (6): 72, 219, 290, 335, 469, 496

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 194 (showing top): GNF2_RTN1, BENPORATH_ES_WITH_H3K27ME3, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, WWTAAGGC_UNKNOWN, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_RESPONSE_TO_PEPTIDE, NKX25_02, BROWNE_HCMV_INFECTION_16HR_UP, KANNAN_TP53_TARGETS_DN, RIZKI_TUMOR_INVASIVENESS_3D_DN, CAGCTG_AP4_Q5, SP1_Q2_01, GOBP_CELL_CELL_SIGNALING, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (9): substantia nigra development (GO:0021762), cell differentiation (GO:0030154), intermediate filament organization (GO:0045109), neurofilament cytoskeleton organization (GO:0060052), postsynaptic modulation of chemical synaptic transmission (GO:0099170), cellular response to leukemia inhibitory factor (GO:1990830), nervous system development (GO:0007399), intermediate filament cytoskeleton organization (GO:0045104), postsynaptic intermediate filament cytoskeleton organization (GO:0099185)

GO Molecular Function (3): structural constituent of cytoskeleton (GO:0005200), structural constituent of postsynaptic intermediate filament cytoskeleton (GO:0099184), protein binding (GO:0005515)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), intermediate filament (GO:0005882), neurofilament (GO:0005883), cytoplasmic ribonucleoprotein granule (GO:0036464), Schaffer collateral - CA1 synapse (GO:0098685), postsynaptic intermediate filament cytoskeleton (GO:0099160), intermediate filament cytoskeleton (GO:0045111), postsynapse (GO:0098794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intermediate filament cytoskeleton organization	3
postsynapse	2
cytoskeleton organization	2
cytoskeleton	2
intermediate filament cytoskeleton	2
cytoplasm	2
synapse	2
midbrain development	1
neural nucleus development	1
cellular developmental process	1
supramolecular fiber organization	1
modulation of chemical synaptic transmission	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
system development	1
intermediate filament-based process	1
postsynaptic cytoskeleton organization	1
structural molecule activity	1
structural constituent of cytoskeleton	1
postsynaptic intermediate filament cytoskeleton	1
postsynaptic intermediate filament cytoskeleton organization	1
structural constituent of postsynapse	1
binding	1
polymeric cytoskeletal fiber	1
intermediate filament	1
ribonucleoprotein granule	1
postsynaptic cytoskeleton	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INA	NEFH	P12036	984
INA	NEFL	P07196	983
INA	NEFM	P07197	982
INA	TANC1	Q9C0D5	778
INA	DLGAP1	P78335	680
INA	HOMER1	Q86YM7	626
INA	SYP	P08247	612
INA	GRM1	Q13255	597
INA	CAMK2A	Q9UQM7	577
INA	DLG1	Q12959	554
INA	GRIA1	P42261	546
INA	NES	P48681	535
INA	DLG4	P78352	524
INA	HSPB3	Q12988	507
INA	SYNM	O15061	497

IntAct

162 interactions, top by confidence:

A	B	Type	Score
PIK3CB	PIK3R2	psi-mi:“MI:0914”(association)	0.860
GFAP	NEFL	psi-mi:“MI:0914”(association)	0.850
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
VIM	NEFL	psi-mi:“MI:0914”(association)	0.840
NEFM	NEFL	psi-mi:“MI:0914”(association)	0.800
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PAK5	AURKA	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
MIPEP	INA	psi-mi:“MI:0915”(physical association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
APP	INA	psi-mi:“MI:0915”(physical association)	0.560
SNCA	INA	psi-mi:“MI:0915”(physical association)	0.560
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
MAB21L2	MEIS1	psi-mi:“MI:0914”(association)	0.530

BioGRID (175): INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Proximity Label-MS), INA (Proximity Label-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS), INA (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0N8E3, A6BLY7, A6QQJ3, O62654, P02540, P02541, P02542, P02543, P02544, P03995, P08552, P08670, P09654, P14136, P15331, P17661, P20152, P21807, P23239, P23565, P24789, P24790, P31000, P31001, P35617, P41219, P46660, P47819, P48616, P48670, P48675, P48676, P48677, P84198, Q08DH7, Q0P5J6, Q16352, Q28115, Q28706, Q4R4X4

Diamond homologs: A0A8C0N8E3, A5A6M8, A5A6N0, A6QQJ3, B4F721, O62654, O77788, O93532, O95678, P02538, P02540, P02541, P02542, P02543, P02544, P02547, P02548, P03995, P04259, P05786, P05787, P07196, P07197, P08551, P08552, P08553, P08670, P08729, P08776, P09654, P11679, P12035, P12036, P12839, P13647, P14136, P15331, P16053, P16878, P16884

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	37.9×	2e-08
Activation of BAD and translocation to mitochondria	5	30.7×	2e-05
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	27.1×	4e-05
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	5	20.9×	1e-04
Activation of BH3-only proteins	5	20.0×	2e-04
Chaperone Mediated Autophagy	5	20.0×	2e-04
AURKA Activation by TPX2	13	16.0×	8e-10
Loss of Nlp from mitotic centrosomes	12	15.3×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	7	30.5×	1e-06
intermediate filament organization	19	27.2×	2e-19
morphogenesis of an epithelium	7	14.3×	2e-04
keratinization	7	9.8×	2e-03
mitotic spindle organization	6	9.7×	4e-03
microtubule cytoskeleton organization	9	6.5×	2e-03
intracellular protein localization	10	6.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	63
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
402160	NM_032727.4(INA):c.562G>A (p.Gly188Arg)	Likely pathogenic

SpliceAI

304 predictions. Top by Δscore:

Variant	Effect	Δscore
10:103278274:CAG:C	donor_loss	1.0000
10:103278275:AG:A	donor_loss	1.0000
10:103278278:T:A	donor_loss	1.0000
10:103287030:TTCA:T	acceptor_loss	0.9900
10:103287031:TCAG:T	acceptor_loss	0.9900
10:103287032:CA:C	acceptor_loss	0.9900
10:103287033:A:AG	acceptor_gain	0.9900
10:103287033:A:AT	acceptor_loss	0.9900
10:103287033:AG:A	acceptor_gain	0.9900
10:103287034:G:A	acceptor_loss	0.9900
10:103287034:G:GT	acceptor_gain	0.9900
10:103287034:GG:G	acceptor_gain	0.9900
10:103287034:GGAT:G	acceptor_gain	0.9900
10:103287034:GGATA:G	acceptor_gain	0.9900
10:103287110:G:GT	donor_gain	0.9900
10:103287155:TACAG:T	donor_loss	0.9900
10:103287156:ACAGG:A	donor_loss	0.9900
10:103287157:CAGGT:C	donor_loss	0.9900
10:103287158:AG:A	donor_loss	0.9900
10:103287159:GG:G	donor_loss	0.9900
10:103288354:TTACA:T	acceptor_loss	0.9900
10:103288355:TACAG:T	acceptor_loss	0.9900
10:103288357:CA:C	acceptor_loss	0.9900
10:103288358:A:AG	acceptor_gain	0.9900
10:103288359:G:GG	acceptor_gain	0.9900
10:103288358:AG:A	acceptor_gain	0.9800
10:103288359:GG:G	acceptor_gain	0.9800
10:103287034:GGA:G	acceptor_gain	0.9700
10:103288349:T:A	acceptor_loss	0.9700
10:103288359:GGA:G	acceptor_gain	0.9700

AlphaMissense

3193 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:103277504:T:C	L98P	1.000
10:103277513:T:A	L101H	1.000
10:103277513:T:C	L101P	1.000
10:103277522:G:C	R104P	1.000
10:103277525:T:C	F105S	1.000
10:103277525:T:G	F105C	1.000
10:103277555:T:C	L115P	1.000
10:103287096:T:C	L376P	1.000
10:103287108:A:C	Q380P	1.000
10:103287114:T:C	L382S	1.000
10:103287114:T:G	L382W	1.000
10:103287117:T:C	L383P	1.000
10:103287125:A:G	K386E	1.000
10:103287126:A:T	K386I	1.000
10:103287127:A:C	K386N	1.000
10:103287127:A:T	K386N	1.000
10:103287131:G:C	A388P	1.000
10:103287134:C:T	L389F	1.000
10:103287135:T:A	L389H	1.000
10:103287135:T:C	L389P	1.000
10:103287138:A:C	D390A	1.000
10:103287138:A:G	D390G	1.000
10:103287138:A:T	D390V	1.000
10:103287143:G:A	E392K	1.000
10:103287144:A:G	E392G	1.000
10:103287144:A:T	E392V	1.000
10:103287145:G:C	E392D	1.000
10:103287145:G:T	E392D	1.000
10:103287147:T:A	I393K	1.000
10:103287147:T:C	I393T	1.000

dbSNP variants (sampled 300 via entrez): RS1000047228 (10:103275220 A>C,G), RS1000457739 (10:103283899 C>T), RS1000487413 (10:103283464 C>T), RS1000643193 (10:103276526 T>A), RS1000717869 (10:103289909 A>G), RS1000806741 (10:103282615 C>T), RS1001017836 (10:103276582 C>T), RS1001096141 (10:103290117 C>T), RS1001467465 (10:103285173 A>G), RS1001498607 (10:103285052 C>T), RS1001560311 (10:103290106 A>G), RS1001620804 (10:103277923 C>T), RS1002009460 (10:103290295 A>T), RS1002040146 (10:103283498 G>C), RS1002468682 (10:103286564 T>A)

Disease associations

OMIM: gene MIM:605338 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001563_9	Migraine	9.000000e-06
GCST002149_2	Schizophrenia	4.000000e-13
GCST002539_4	Schizophrenia	6.000000e-19
GCST004521_172	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004946_77	Schizophrenia	4.000000e-17
GCST006803_4	Schizophrenia	7.000000e-18
GCST008361_2	Response to cognitive-behavioural therapy in major depressive disorder	2.000000e-06
GCST008745_76	Estimated glomerular filtration rate in non-diabetics	5.000000e-08
GCST010703_271	Brain morphology (MOSTest)	5.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066296 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.07	Kd	84.51	nM	CHEMBL3752910
6.51	ED50	306	nM	CHEMBL3752910
6.33	Kd	470.1	nM	CHEMBL5653589
5.77	ED50	1702	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148589: Binding affinity to human INA incubated for 45 mins by Kinobead based pull down assay	kd	0.0845	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148589: Binding affinity to human INA incubated for 45 mins by Kinobead based pull down assay	kd	0.4701	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
(+)-JQ1 compound	increases expression	3
Silicon Dioxide	increases expression	2
Tretinoin	decreases expression, increases phosphorylation	2
OTX015	increases expression	1
bisphenol F	increases expression, affects cotreatment	1
mivebresib	increases expression	1
propionaldehyde	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	increases methylation	1
sulforaphane	affects binding	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
tobacco tar	decreases expression	1
1-nitropyrene	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
diallyl trisulfide	increases expression	1
pentanal	increases expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	decreases expression	1
pyrachlostrobin	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651631	Binding	Binding affinity to human INA incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1UI	Abcam HeLa INA KO	Cancer cell line	Female

Clinical trials (associated diseases)

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