RERE

Chr 1AD

arginine-glutamic acid dipeptide repeats

Also known as: ARG, ARP, ATN1L, DNB1, NEDBEH

NCBI Gene: 473ENSG00000142599UniProt: Q9P2R6

This gene encodes a member of the atrophin family of arginine-glutamic acid (RE) dipeptide repeat-containing proteins. The encoded protein co-localizes with a transcription factor in the nucleus, and its overexpression triggers apoptosis. A similar protein in mouse associates with histone deacetylase and is thought to function as a transcriptional co-repressor during embryonic development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with or without anomalies of the brain, eye, or heartMIM #616975
AD
569
ClinVar variants
39
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— RERE
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder with or without congenital anomalies · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 364 VUS of 569 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.12LOEUF
pLI 1.000
Z-score 7.11
OE 0.05 (0.02–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.03Z-score
OE missense 0.81 (0.76–0.86)
737 obs / 909.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.76–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 3 / 64.7Missense obs/exp: 737 / 909.5Syn Z: -2.83

ClinVar Variant Classifications

569 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic21
VUS364
Likely Benign145
Benign11
Conflicting10
18
Pathogenic
21
Likely Pathogenic
364
VUS
145
Likely Benign
11
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
13
1
18
Likely Pathogenic
11
4
6
0
21
VUS
6
315
39
4
364
Likely Benign
0
35
23
87
145
Benign
0
4
1
6
11
Conflicting
—10
Total213588298569

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RERE · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RERE-related phenocopy of proximal 1p36 deletions

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart

MIM #616975

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — RERE
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Penetrance, variable expressivity and monogenic neurodevelopmental disorders.
de Masfrand S et al.·Eur J Med Genet
2024
Phenotypic variability in RERE-related disorders and the first report of an inherited variant.
Niehaus AD et al.·Am J Med Genet A
2022Review
A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.
Li Q et al.·Clin Genet
2024Case report
RERE deficiency contributes to the development of orofacial clefts in humans and mice.
Kim BJ et al.·Hum Mol Genet
2021
A de novo variant of RERE was identified in a patient with neurodevelopmental disorder, enuresis and scoliosis.
Cai T et al.·Sci Rep
2025Case report
RERE-AS1 as a regulator of immune modulation and therapeutic response in breast cancer.
Jiang S et al.·Cancer Immunol Immunother
2025
Genotype-phenotype correlations in individuals with pathogenic RERE variants.
Jordan VK et al.·Hum Mutat
2018Case report
RERE-AS1 enhances the effect of CDK4/6 inhibitor Ribociclib and suppresses malignant phenotype in breast cancer via MEK/ERK pathway.
Huang Z et al.·J Transl Med
2024
The circular RNome of primary breast cancer.
Smid M et al.·Genome Res
2019
CircRNA RERE Promotes the Oxidative Stress-Induced Apoptosis and Autophagy of Nucleus Pulposus Cells through the miR-299-5p/Galectin-3 Axis.
Wang R et al.·J Healthc Eng
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools