IREB2

iron responsive element binding protein 2

Basic information

Region (hg38): 15:78437431-78501453

Links

ENSG00000136381

∙ NCBI:3658 ∙ OMIM:147582 ∙ HGNC:6115 ∙ Uniprot:P48200 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia (Strong), mode of inheritance: AR
neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	30915432

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IREB2 gene.

not_provided (165 variants)
Inborn_genetic_diseases (79 variants)
Neurodegeneration,_early-onset,_with_choreoathetoid_movements_and_microcytic_anemia (8 variants)
IREB2-related_disorder (7 variants)
NEURODEGENERATION,_EARLY-ONSET,_WITH_CHOREOATHETOSIS_AND_MICROCYTIC_ANEMIA (4 variants)
Lung_adenocarcinoma (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IREB2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004136.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	50 clinvar	3 clinvar	54
missense			117 clinvar	11 clinvar	2 clinvar	130
nonsense		2 clinvar				2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	2	120	61	5

Highest pathogenic variant AF is 6.84516e-7

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IREB2	protein_coding	protein_coding	ENST00000258886	22	64026

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000867	125730	0	10	125740	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.03	378	507	0.746	0.0000256	6231
Missense in Polyphen		108	183.08	0.58991		2238
Synonymous	-0.221	181	177	1.02	0.00000933	1884
Loss of Function	5.98	6	53.0	0.113	0.00000301	657

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.000118	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000532	0.0000527
Middle Eastern	0.000118	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'- UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA. {ECO:0000269|PubMed:7983023}.;
Pathway: Iron metabolism in placenta;Transport of small molecules;Iron uptake and transport;Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

pRec: 0.318

Intolerance Scores

loftool: 0.293
rvis_EVS: -0.84
rvis_percentile_EVS: 11.45

Haploinsufficiency Scores

pHI: 0.208
hipred: Y
hipred_score: 0.816
ghis: 0.656

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.793

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ireb2
Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Gene ontology

Biological process: tricarboxylic acid cycle;citrate metabolic process;regulation of translation;protoporphyrinogen IX biosynthetic process;iron ion transport;cellular iron ion homeostasis;brain development;aging;post-embryonic development;response to iron(II) ion;response to iron(III) ion;response to zinc ion;skeletal muscle atrophy;response to activity;negative regulation of translation;osteoclast differentiation;response to retinoic acid;erythrocyte homeostasis;response to copper ion;cellular response to iron(III) ion;cellular response to manganese ion;cellular response to retinoic acid;cellular response to epidermal growth factor stimulus;cellular response to hypoxia;cellular response to mercaptoethanol;cellular response to oxygen-glucose deprivation;response to kainic acid;response to hypobaric hypoxia
Cellular component: cytoplasm;mitochondrion;cytosol;axon
Molecular function: regulatory region RNA binding;RNA binding;aconitate hydratase activity;protein binding;iron-responsive element binding;translation repressor activity;metal ion binding;4 iron, 4 sulfur cluster binding