INA

protein-coding

internexin neuronal intermediate filament protein alpha, the group of Intermediate filaments Type IV

Gene summary

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. [provided by RefSeq, Jun 2009]

Previous symbols:

NEF5

MANE transcript

NM_032727.4

Inheritance

—

ClinVar variants

P:1U:63B:2

Top phenotype

High myopia

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr10:103,277,138-103,290,346

External References & Databases

Ensembl (ENSG00000148798)

Transcript & Mutation Effects

hg38 • Region Span ~13.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INA variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 2

High myopiaTotal: 1

Abnormal brain morphologyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032727.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense		1 clinvar	63 clinvar			64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	63	2	0	66

Highest pathogenic variant AF is 0.00004102142

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032727.4	RefSeq	NP_116116.1	3	MANE Select
ENST00000369849.9	Ensembl	ENSP00000358865.4	3	MANE Select
ENST00000912062.1	Ensembl	ENSP00000582121.1	3	Standard
ENST00001139898.1	Ensembl	ENSP00000809622.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
inab	Danio rerio	Structure: VaP motor neuron Quality: branchiness abnormal

Gene / Model

Organism

Observed Phenotype

inab

Danio rerio

Structure: VaP motor neuron

Quality: branchiness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

substantia nigra development
cell differentiation
neurofilament cytoskeleton organization
postsynaptic actin cytoskeleton organization
postsynaptic intermediate filament cytoskeleton organization

Molecular Function

structural constituent of cytoskeleton
structural constituent of postsynaptic actin cytoskeleton
structural constituent of postsynaptic intermediate filament cytoskeleton

Cellular Component

extracellular space
nucleoplasm
neurofilament
nuclear membrane
cytoplasmic ribonucleoprotein granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369849
Coding exons: 3
Length: 13189
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.13	166	263	0.631	0.0000125	3132
Missense (PolyPhen)		61	106.03	0.57533		1248
Synonymous	1.41	100	120	0.836	0.00000587	1070
Loss of Function	0.419	13	14.7	0.882	6.29e-7	189

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.00010	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 NF-L to form the filamentous backbone to which NF-M and NF-H attach to form the cross-bridges.;

Recessive Scores

pRec: 0.263

Intolerance Scores

LoFtool: 0.191
RVIS EVS: -0.1
RVIS percentile EVS: 46.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.853

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium