GeneBe

INO80

protein-coding

INO80 complex ATPase subunit, the group of INO80 complex |DNA helicases

Gene summary

This gene encodes a subunit of the chromatin remodeling complex, which is classified into subfamilies depending on sequence features apart from the conserved ATPase domain. This protein is the catalytic ATPase subunit of the INO80 chromatin remodeling complex, which is characterized by a DNA-binding domain. This protein is proposed to bind DNA and be recruited by the YY1 transcription factor to activate certain genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Previous symbols:
  • INOC1

MANE transcript

NM_017553.3

Inheritance

AR

ClinVar variants

P:2U:178B:48

Top phenotype

INO80-related disorder

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr15:40,978,880-41,116,280

External References & Databases

Ensembl (ENSG00000128908)NCBI Gene (54617)OMIM (610169)HGNC:26956GenCCUniProt (Q9ULG1)AlphaFoldClinVar (INO80)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~137.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inborn error of immunityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0003778

Submitter: PanelApp Australia

immunodeficiency, common variable, 1NO_KNOWN

Inheritance Pattern: AR

Disease ID:MONDO:0011864

Submitter: ClinGen

INO80 was reported in relation autosomal recessive common variable Immunodeficiency in 2015 (Kracker et al., PMID: 25312759). In this study, compound heterozygous missense variants in INO80 were identified in 2 unrelated male patients with an immunoglobulin class-switch repair deficiency. The allele frequencies for the variants in these cases are higher than would be expected for disease-causing variants and were flagged as contradictory evidence. This gene-disease association is supported by in vitro functional assay. Experimental evidence like mouse models and biochemical function highlighted INO80's role in DNA repair, consistent with the mechanism of disease, but the data was insufficient for scoring. Given the allele frequencies in only two the patients reported, there is convincing evidence disputing the relationship between INO80 and autosomal recessive common variable Immunodeficiency. More evidence is needed to either support or refute the role INO80 plays in this disease.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INO80 variants in ClinVar

8 Conditions Cataloged
not specifiedTotal: 188
not providedTotal: 29
INO80-related disorderTotal: 28
INO80-related immunodeficiencyTotal: 2
Primary microcephalyTotal: 2
SeizureTotal: 2
Intellectual disabilityTotal: 2
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017553.3. 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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
31
clinvar
5
clinvar
 41
missense
2
clinvar
165
clinvar
11
clinvar
1
clinvar
 179
nonsense
2
clinvar
 2
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
6
clinvar
 6
Total02178426228

Highest pathogenic variant AF is 0.00021159384

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_017553.3RefSeqNP_060023.135MANE Select
ENST00000648947.1EnsemblENSP00000497609.135MANE Select
ENST00000557849.1EnsemblENSP00000452806.12Standard
ENST00000558357.6EnsemblENSP00000453677.126Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • DNA Repair
  • Post-translational protein modification
  • Metabolism of proteins
  • UCH proteinases
  • Deubiquitination

Biological Process

  • mitotic sister chromatid segregation
  • double-strand break repair via homologous recombination
  • DNA repair
  • double-strand break repair
  • chromatin remodeling

Molecular Function

  • DNA binding
  • actin binding
  • protein binding
  • ATP binding
  • DNA-dependent ATPase activity

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm
  • spindle
  • microtubule

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000361937
Coding exons
35
Length
137475
Individuals with no LoFs
125725
Homozygous LoFs
0
Heterozygous LoFs
23
Defined
125748
p
0.0000915
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.535778700.6630.000049410221
Missense (PolyPhen)144355.70.404844089
Synonymous-0.7203313151.050.00001652960
Loss of Function8.78395.70.03130.000005901029

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000190.00018rare
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.000330.00032rare
European (Non-Finnish)0.0000800.000079rare
South Asian0.0000650.000065rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: ATPase component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and DNA repair (PubMed:16230350, PubMed:16298340, PubMed:17721549, PubMed:20855601, PubMed:20237820). Binds DNA (PubMed:16298340, PubMed:21303910). As part of the INO80 complex, remodels chromatin by shifting nucleosomes (PubMed:16230350, PubMed:21303910). Regulates transcription upon recruitment by YY1 to YY1-activated genes, where it acts as an essential coactivator (PubMed:17721549). Involved in UV-damage excision DNA repair (PubMed:20855601). The contribution to DNA double-strand break repair appears to be largely indirect through transcriptional regulation (PubMed:20687897). Involved in DNA replication (PubMed:20237820). Required for microtubule assembly during mitosis thereby regulating chromosome segregation cycle (PubMed:20237820). {ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:16298340, ECO:0000269|PubMed:17721549, ECO:0000269|PubMed:20237820, ECO:0000269|PubMed:20687897, ECO:0000269|PubMed:20855601, ECO:0000269|PubMed:21303910}.;

Recessive Scores

pRec
0.107

Intolerance Scores

LoFtool
0.0167
RVIS EVS
-1.1
RVIS percentile EVS
6.93

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.948

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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