RERE

arginine-glutamic acid dipeptide repeats, the group of Myb/SANT domain containing|Atrophins|GATA zinc finger domain containing

Basic information

Region (hg38): 1:8352396-8848921

Previous symbols: [ "ATN1L" ]

Links

ENSG00000142599 ∙ NCBI:473 ∙ OMIM:605226 ∙ HGNC:9965 ∙ Uniprot:Q9P2R6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (Strong), mode of inheritance: AD
• neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (Strong), mode of inheritance: AD
• neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (Supportive), mode of inheritance: AD
• complex neurodevelopmental disorder with or without congenital anomalies (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Neurologic; Ophthalmologic	27087320

ClinVar

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

• not provided (419 variants)
• Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (112 variants)
• Inborn genetic diseases (102 variants)
• not specified (11 variants)
• RERE-related condition (8 variants)
• See cases (6 variants)
• CHARGE association (1 variants)
• Global developmental delay (1 variants)
• Developmental disorder (1 variants)
• Autism;Intellectual disability (1 variants)
• Neurodevelopmental disorder (1 variants)
• Cerebral visual impairment and intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RERE gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	86	30	117
missense	7	9	276	48	11	351
nonsense	3	1	1			5
start loss						0
frameshift	4	6	1			11
inframe indel	2	2	22	8	4	38
splice donor/acceptor (+/-2bp)		1	1			2
splice region			11	8	2	21
non coding			6	23	8	37
Total	16	19	308	165	53

Variants in RERE

This is a list of pathogenic ClinVar variants found in the RERE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-8355117-T-G			Benign (Jun 15, 2022)
1-8355125-A-G			Likely benign (Jul 26, 2022)
1-8355135-C-T			Likely benign (Dec 02, 2021)
1-8355448-G-A			Likely benign (Mar 29, 2021)
1-8355459-T-C			Uncertain significance (Oct 01, 2023)
1-8355460-G-T		not specified	Uncertain significance (Nov 21, 2022)
1-8355462-G-A		Inborn genetic diseases	Uncertain significance (Jan 07, 2022)
1-8355462-G-T			Uncertain significance (Jan 07, 2024)
1-8355463-G-A			Likely benign (Nov 20, 2022)
1-8355466-G-C		See cases	Uncertain significance (Aug 15, 2022)
1-8355492-T-C			Uncertain significance (Mar 19, 2022)
1-8355495-C-A		Inborn genetic diseases • RERE-related disorder	Uncertain significance (Feb 13, 2024)
1-8355511-G-A			Likely benign (Feb 16, 2023)
1-8355515-G-A		Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart • Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
1-8355524-T-C			Uncertain significance (Mar 02, 2023)
1-8355536-A-T			Likely pathogenic (Oct 23, 2017)
1-8355541-G-A			Likely benign (Nov 01, 2023)
1-8355548-G-A			Uncertain significance (Sep 01, 2023)
1-8355554-A-G			Uncertain significance (Jan 22, 2024)
1-8355557-G-A		Inborn genetic diseases	Uncertain significance (May 02, 2017)
1-8355558-G-T		Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart • RERE-related disorder	Benign/Likely benign (Jan 02, 2024)
1-8355567-T-C			Benign (Jan 22, 2024)
1-8355570-C-T			Uncertain significance (Dec 02, 2021)
1-8355571-C-A			Benign (Jan 29, 2024)
1-8355595-G-T			Likely benign (May 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RERE	protein_coding	protein_coding	ENST00000337907	22	465246

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.65e-9	125713	0	34	125747	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.03	737	909	0.810	0.0000589	10049
Missense in Polyphen		187	316.28	0.59124		3317
Synonymous	-2.83	453	383	1.18	0.0000269	3205
Loss of Function	7.11	3	64.7	0.0463	0.00000377	718

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000254	0.000182
Ashkenazi Jewish	0.000211	0.000198
East Asian	0.000111	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000379	0.000211
Middle Eastern	0.000111	0.0000544
South Asian	0.000247	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role as a transcriptional repressor during development. May play a role in the control of cell survival. Overexpression of RERE recruits BAX to the nucleus particularly to POD and triggers caspase-3 activation, leading to cell death. {ECO:0000269|PubMed:11331249}.
• Disease: DISEASE: Note=A chromosomal aberration involving RERE is found in the neuroblastoma cell line NGP. Translocation t(1;15)(p36.2;q24).; DISEASE: Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH) [MIM:616975]: An autosomal dominant syndrome characterized by developmental delay, intellectual disability, brain anomalies, and neurological abnormalities including seizures, hypotonia, and behavioral problems such as autism spectrum disorders. Brain anomalies include abnormalities and/or thinning of the corpus callosum, diminished white matter volume, abnormal cerebellar vermis, and ventriculomegaly. Congenital defects of the eye, heart and genitourinary system are present in half of the patients. {ECO:0000269|PubMed:27087320}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.0674
• rvis_EVS: -2.63
• rvis_percentile_EVS: 0.78

Haploinsufficiency Scores

• pHI: 0.870
• hipred: Y
• hipred_score: 0.749
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.717

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rere
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; renal/urinary system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal 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); 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); hearing/vestibular/ear phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: rerea
• Affected structure: hair cell
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: chromatin remodeling;regulation of transcription by RNA polymerase II;NLS-bearing protein import into nucleus;cerebellar Purkinje cell layer maturation;cerebellar granule cell precursor proliferation;radial glia guided migration of Purkinje cell;branching morphogenesis of a nerve;dendrite morphogenesis;negative regulation of nucleic acid-templated transcription;positive regulation of nucleic acid-templated transcription
• Cellular component: histone deacetylase complex;nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;DNA binding;chromatin binding;transcription coactivator activity;transcription corepressor activity;protein binding;poly-glutamine tract binding;zinc ion binding;sequence-specific DNA binding