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): 67 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 13 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.48 (unconstrained)
• MANE Select transcript: NM_032727
• Notable: 67 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 3 — 3 protein_coding

MANE Select: ENST00000369849

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000369849, ENST00000912062, ENST00001139898

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.

Highest expression (Bgee): cortical plate, middle temporal gyrus, lateral nuclear group of thalamus, pons, Brodmann (1909) area 23.

Genetic regulation across tissues (GTEx eQTL / sQTL)

INA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	2.9e-11	-0.26	10:103273871:G:A
Testis	sqtl	4.2e-08	+0.44	10:103279822:A:G
Brain Frontal Cortex BA9	eqtl	7.6e-07	+0.13	10:103348698:T:C
Esophagus Mucosa	eqtl	2.5e-04	-0.19	10:103417157:A:G
Brain Caudate basal ganglia	eqtl	1.4e-03	+0.07	10:103289348:C:G
Brain Cerebellar Hemisphere	eqtl	1.4e-03	+0.13	10:103364984:T:C
Brain Cortex	eqtl	2.5e-03	+0.08	10:103284400:C:T
Artery Aorta	eqtl	3.5e-03	-0.27	10:103256350:T:C
Skin Sun Exposed Lower leg	eqtl	4.5e-03	-0.16	10:102355638:A:T
Artery Tibial	eqtl	1.7e-02	-0.21	10:103441808:G:A
Brain Putamen basal ganglia	eqtl	1.8e-02	+0.08	10:103325083:C:T
Brain Cerebellum	eqtl	2.2e-02	+0.17	10:103089359:G:C
Skin Not Sun Exposed Suprapubic	eqtl	4.1e-02	+0.15	10:102428502:G:T
Brain Nucleus accumbens basal ganglia	eqtl	4.5e-02	+0.35	10:104259464:G:A

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

showing 100 of 279 tissues 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
substantia nigra pars reticulata	UBERON:0001966	95.31	gold quality
lateral globus pallidus	UBERON:0002476	95.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.21	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.11	gold quality
entorhinal cortex	UBERON:0002728	95.05	gold quality
ganglionic eminence	UBERON:0004023	95.04	gold quality
cingulate cortex	UBERON:0003027	94.72	gold quality
anterior cingulate cortex	UBERON:0009835	94.69	gold quality
middle frontal gyrus	UBERON:0002702	94.58	gold quality
telencephalon	UBERON:0001893	94.14	gold quality
brain	UBERON:0000955	94.06	gold quality
forebrain	UBERON:0001890	93.94	gold quality
nucleus accumbens	UBERON:0001882	93.87	gold quality
central nervous system	UBERON:0001017	93.62	gold quality
temporal lobe	UBERON:0001871	93.18	gold quality
islet of Langerhans	UBERON:0000006	92.47	gold quality
midbrain	UBERON:0001891	92.40	gold quality
substantia nigra	UBERON:0002038	92.36	gold quality
caudate nucleus	UBERON:0001873	92.34	gold quality
medulla oblongata	UBERON:0001896	92.19	gold quality
putamen	UBERON:0001874	92.17	gold quality
amygdala	UBERON:0001876	92.03	gold quality
ventral tegmental area	UBERON:0002691	91.81	gold quality
CA1 field of hippocampus	UBERON:0003881	91.64	gold quality
pituitary gland	UBERON:0000007	91.02	gold quality
Ammon’s horn	UBERON:0001954	90.47	gold quality
inferior olivary complex	UBERON:0002127	90.40	gold quality
adenohypophysis	UBERON:0002196	88.97	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.01	gold quality
secondary oocyte	CL:0000655	84.65	gold quality
embryo	UBERON:0000922	84.52	gold quality
adult organism	UBERON:0007023	83.99	gold quality
oocyte	CL:0000023	81.47	gold quality
ventricular zone	UBERON:0003053	80.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.02	gold quality
spinal cord	UBERON:0002240	79.98	gold quality
globus pallidus	UBERON:0001875	79.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.39	gold quality
medial globus pallidus	UBERON:0002477	78.00	gold quality
inferior vagus X ganglion	UBERON:0005363	77.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.11	gold quality
type B pancreatic cell	CL:0000169	76.66	gold quality
dorsal root ganglion	UBERON:0000044	72.94	gold quality
subthalamic nucleus	UBERON:0001906	72.21	gold quality
sperm	CL:0000019	70.66	silver quality
stromal cell of endometrium	CL:0002255	70.45	gold quality
esophagus squamous epithelium	UBERON:0006920	69.58	gold quality
male germ cell	CL:0000015	69.05	silver quality
muscle layer of sigmoid colon	UBERON:0035805	68.35	gold quality
trigeminal ganglion	UBERON:0001675	67.98	gold quality
pancreas	UBERON:0001264	67.95	gold quality
colonic epithelium	UBERON:0000397	67.86	gold quality
epithelium of esophagus	UBERON:0001976	66.76	gold quality
corpus callosum	UBERON:0002336	66.14	gold quality
pancreatic ductal cell	CL:0002079	65.64	silver quality
choroid plexus epithelium	UBERON:0003911	65.21	silver quality
amniotic fluid	UBERON:0000173	63.65	gold quality
sigmoid colon	UBERON:0001159	63.25	gold quality
tibialis anterior	UBERON:0001385	62.24	silver quality
rectum	UBERON:0001052	62.04	gold quality
squamous epithelium	UBERON:0006914	61.76	gold quality
vermiform appendix	UBERON:0001154	61.64	gold quality
cervix squamous epithelium	UBERON:0006922	61.37	gold quality
caecum	UBERON:0001153	61.12	gold quality
colon	UBERON:0001155	59.15	gold quality
large intestine	UBERON:0000059	59.10	gold quality
fundus of stomach	UBERON:0001160	58.78	gold quality
right adrenal gland	UBERON:0001233	58.18	gold quality
intestine	UBERON:0000160	57.47	gold quality
endometrium epithelium	UBERON:0004811	57.33	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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 62 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	384.8
Pons	tissue	221.1
Basal ganglia	tissue	218.5	medium
Thalamus	tissue	204.0
Superior colliculi	tissue	202.8
Cerebral cortex	tissue	201.7	medium
Occipital cortex	tissue	201.7
Somatosensory cortex	tissue	197.5
Putamen	tissue	194.8
Ventral forebrain	tissue	187.6
Locus coeruleus	tissue	187.2
Prefrontal cortex	tissue	169.5
Motor cortex	tissue	163.0
Substantia nigra	tissue	157.5
Temporal cortex	tissue	157.0
Medulla oblongata	tissue	151.2
Septum	tissue	151.1
Hippocampal formation	tissue	150.5
Entorhinal cortex	tissue	150.5
Retrosplenial and cingulate cortex	tissue	148.7
Midbrain	tissue	148.2
Retrosplenial cortex	tissue	138.4
Hypothalamus	tissue	134.2
Insular cortex	tissue	124.2
Amygdala	tissue	110.4
Periaqueductal gray	tissue	110.3
Frontal cortex	tissue	97.1
Cerebellum	tissue	94.0	high
Retina	tissue	90.1
Caudate putamen	tissue	75.3
Olfactory bulb	tissue	75.1
Spinal cord	tissue	66.6
Nucleus accumbens	tissue	65.4
Hippocampus	tissue	41.7	medium
Pituitary gland	tissue	38.6
Corpus callosum	tissue	13.1
Adrenal gland	tissue	11.5	medium
Choroid plexus	tissue	5.5
Testis	tissue	2.5	high
Pancreas	tissue	1.9	not detected
Thymus	tissue	1.6
Rectum	tissue	1.1	not detected
Colon	tissue	1.1	not detected
Appendix	tissue	1.1	not detected
Stomach 1	tissue	1.0	not detected
Small intestine	tissue	1.0	not detected
Urinary bladder	tissue	0.8	not detected
Skin 1	tissue	0.7	not detected
Smooth muscle	tissue	0.7	not detected
Duodenum	tissue	0.6	not detected
Esophagus	tissue	0.5	not detected
Vagina	tissue	0.4	not detected
Parathyroid gland	tissue	0.4	not detected
Adipose tissue	tissue	0.2	not detected
Lung	tissue	0.2	not detected
Lymph node	tissue	0.1	not detected
Ovary	tissue	0.1	not detected
Placenta	tissue	0.1	not detected
Thyroid gland	tissue	0.1	not detected
Gallbladder	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Lateral hypothalamic area (277.9), Precentral gyrus (267.0), Nucleus raphe magnus (263.0), Nuclei of the trapezoid body (240.3), Pontine nuclei (230.1).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting INA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 134 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 7.37e-13, LOEUF 1.48, missense Z 0.364 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000369849 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
10:103,277,212–103,277,610	215 / 190.6	1.13	no
10:103,277,611–103,288,666	379 / 496.1	0.76	no

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), KRT9 (ENSG00000171403), KRT20 (ENSG00000171431), KRT27 (ENSG00000171446), KRT2 (ENSG00000172867), KRT28 (ENSG00000173908), DES (ENSG00000175084), LMNB2 (ENSG00000176619), SYNM (ENSG00000182253), KRT76 (ENSG00000185069), KRT6B (ENSG00000185479), KRT79 (ENSG00000185640), KRT73 (ENSG00000186049), KRT5 (ENSG00000186081), KRT26 (ENSG00000186393), KRT10 (ENSG00000186395), KRT3 (ENSG00000186442), KRT16 (ENSG00000186832), KRT14 (ENSG00000186847), KRT12 (ENSG00000187242), KRT77 (ENSG00000189182)

+8 more (showing top 60).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Chlorocebus aethiops	P84198	100.0%	Diamond
Macaca fascicularis	Q4R4X4	100.0%	Diamond
Pongo abelii	Q5R408	100.0%	Diamond
Bos taurus	P48616	99.4%	Diamond
Ovis aries	Q9MZA9	99.4%	Diamond
Mesocricetus auratus	P02544	99.3%	Diamond
Cricetulus griseus	P48670	99.3%	Diamond
Sus scrofa	P02547	98.2%	Diamond
Pan troglodytes	Q5R1W8	97.9%	Diamond
Canis lupus familiaris	A0A8C0N8E3	97.4%	Diamond
Carassius auratus	P48677	95.6%	Diamond
Onchocerca volvulus	P31732	93.4%	Diamond
Acanthocheilonema viteae	Q17107	93.4%	Diamond
Xenopus laevis	P24789	92.4%	Diamond
Gallus gallus	P09654	86.7%	Diamond
Oryctolagus cuniculus	P54938	86.1%	Diamond
Xenopus tropicalis	B4F721	80.2%	Diamond
Cyprinus carpio	Q92155	79.6%	Diamond
Coturnix japonica	Q02916	77.8%	Diamond
Oncorhynchus mykiss	P48674	76.3%	Diamond
Tetronarce californica	P23729	60.1%	Diamond
Branchiostoma lanceolatum	Q04948	41.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR1307	ncRNA	100302174
TAF5	protein-coding	6877
RPEL1	protein-coding	729020
PCGF6	protein-coding	84108
ATP5MK	protein-coding	84833
PDCD11	protein-coding	22984
NT5C2	protein-coding	22978
CALHM2	protein-coding	51063

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): intermediate filaments; cytosol

Antibody reliability (HPA): IH enhanced · IF approved

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)

Type	Positions
Phosphoserine	72, 219, 335, 469, 496
N6-acetyllysine	290

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (6): substantia nigra development (GO:0021762), cell differentiation (GO:0030154), intermediate filament organization (GO:0045109), postsynaptic modulation of chemical synaptic transmission (GO:0099170), nervous system development (GO:0007399), 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 (7): 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

26 GO namespaces:

Category	Terms
intermediate filament cytoskeleton organization	2
postsynapse	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
system development	1
animal gross anatomical part developmental process	1
postsynaptic cytoskeleton organization	1
structural molecule activity	1
cytoskeleton organization	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
substantia nigra development	BP	high-throughput mutant
cytoplasmic ribonucleoprotein granule	CC	direct assay

Protein interactions and networks

STRING

showing 16 of 934 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INA	TANC1	Q9C0D5	758
INA	NEFH	P12036	729
INA	NEFM	P07197	718
INA	NEFL	P07196	687
INA	DLGAP1	P78335	686
INA	HOMER1	Q86YM7	645
INA	SYP	P08247	614
INA	GRM1	Q13255	611
INA	CAMK2A	Q9UQM7	610
INA	DLG1	Q12959	554
INA	GRIA1	P42261	544
INA	DLG4	P78352	540
INA	GRIN2B	Q13224	515
INA	TARDBP	Q13148	429
INA	LMO4	P61968	370
INA	NSMF	Q6X4W1	370

IntAct

Human interaction partners of INA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
MIPEP	physical association	0.590	2
APP	physical association	0.560	3
SNCA	physical association	0.560	3
HCN1	physical association	0.500	2
SFN	physical association	0.500	1
STAU1	colocalization	0.430	1
YWHAE	physical association	0.400	2
NAP1L1	physical association	0.400	1
PLEC	physical association	0.400	1
FXR1	physical association	0.370	1
BAZ2B	association	0.350	1
VWA3B	association	0.350	1

BioGRID (176 interactions; top human partners by supporting records): GFAP (Affinity Capture-MS; 4 records), NEFM (Affinity Capture-MS; 4 records), VIM (Affinity Capture-MS; 4 records), CCDC183 (Affinity Capture-MS; 3 records), ERGIC1 (Affinity Capture-MS; 3 records), GAN (Affinity Capture-MS; 3 records), KRT8 (Proximity Label-MS; 3 records), MAB21L2 (Affinity Capture-MS; 3 records), PRMT8 (Affinity Capture-MS; 3 records), CAPN1 (Affinity Capture-MS; 2 records), CCDC120 (Affinity Capture-MS; 2 records), HSP90AA1 (Cross-Linking-MS (XL-MS); 2 records), KRT18 (Proximity Label-MS; 2 records), MIPEP (Affinity Capture-MS; 2 records), NEFH (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for INA: 67 ClinVar records (1 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	64
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
402160	NM_032727.4(INA):c.562G>A (p.Gly188Arg)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore INA’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 176):

Position(s)	Effect	Δscore	Sites
10:103278277–103278278	donor_loss	1.0000	5
10:103287033–103287034	acceptor_loss	0.9900	6
10:103287160–103287161	donor_loss	0.9900	6
10:103288358–103288359	acceptor_loss	0.9900	6
10:103287159	donor_loss	0.9700	2
10:103288349	acceptor_loss	0.9700
10:103288357	acceptor_loss	0.9700
10:103284309	donor_gain	0.9600
10:103288346	acceptor_loss	0.9100
10:103287159	donor_loss	0.8900

AlphaMissense

1,227 missense substitutions predicted likely pathogenic (of 3,193 scored), across 328 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M372	9	0.967	0.998
M387	9	0.943	0.998
D390	8	0.999	1.000
N102	8	0.997	0.999
F105	8	0.996	1.000
N119	8	0.987	0.998
N279	8	0.979	0.995
F226	8	0.969	0.998
D103	8	0.955	0.993
N384	8	0.929	0.997
H375	8	0.899	0.997
H231	8	0.896	0.989
D381	8	0.882	0.983
D260	8	0.868	0.947
D204	8	0.837	0.921
E392	7	0.999	1.000
F108	7	0.998	0.999
I393	7	0.997	1.000
E94	7	0.992	0.998
K386	7	0.990	1.000

HPA cancer prognostics

RNA cancer specificity: Group enriched (Bladder Urothelial Carcinoma, Glioblastoma Multiforme, Testicular Germ Cell Tumor)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	0.000237
Glioblastoma Multiforme (validation)	favorable	0.000278

Disease associations

OMIM: gene MIM:605338 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST002539_77	Schizophrenia	6e-19
GCST006803_98	Schizophrenia	7e-18
GCST004946_67	Schizophrenia	4e-17
GCST004521_123	Autism spectrum disorder or schizophrenia	4e-14
GCST002149_2	Schizophrenia	4e-13
GCST010703_273	Brain morphology (MOSTest)	5e-13
GCST008745_89	Estimated glomerular filtration rate in non-diabetics	5e-8
GCST008361_2	Response to cognitive-behavioural therapy in major depressive disorder	2e-6
GCST001563_9	Migraine	9e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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

60 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
Air Pollutants	increases expression, decreases expression, increases abundance	2
Silicon Dioxide	increases expression	2
Tretinoin	decreases expression, increases phosphorylation	2
OTX015	increases expression	1
bisphenol F	affects cotreatment, increases expression	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

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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for INA across ~30M SureChEMBL compounds — explore on Sugi Predict.