BRAT1

Chr 7AR

BRCA1 associated ATM activator 1

Also known as: BAAT1, C7orf27, NEDCAS, RMFSL

NCBI Gene: 221927ENSG00000106009UniProt: Q6PJG6

The protein encoded by this ubiquitously expressed gene interacts with the tumor suppressing BRCA1 (breast cancer 1) protein and and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint signalling pathways that are required for cellular responses to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein complex BASC (BRAC1-associated genome surveillance complex). The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with cerebellar atrophy and with or without seizuresMIM #618056
AR
Rigidity and multifocal seizure syndrome, lethal neonatalMIM #614498
AR
1441
ClinVar variants
66
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BRAT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 234 VUS of 1441 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.99LOEUF
pLI 0.000
Z-score 1.58
OE 0.71 (0.51–0.99)
Tolerant

Typical tolerance to LoF variation

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.
-0.59Z-score
OE missense 1.08 (1.00–1.16)
532 obs / 494.9 exp
Tolerant

Tolerant to missense variation

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.0.71 (0.51–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (1.00–1.16)
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.1.14
0≤1.21.6
LoF obs/exp: 24 / 33.9Missense obs/exp: 532 / 494.9Syn Z: -1.67

ClinVar Variant Classifications

1441 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic27
VUS234
Likely Benign174
Benign2
Conflicting3
39
Pathogenic
27
Likely Pathogenic
234
VUS
174
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
22
1
39
Likely Pathogenic
15
4
8
0
27
VUS
2
205
25
2
234
Likely Benign
0
6
52
116
174
Benign
0
1
1
0
2
Conflicting
—3
Total33216108119479

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

View in ClinVar →

Protein Context — Lollipop Plot

BRAT1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

BRAT1-related lethal neonatal rigidity and seizure syndrome

strong
ARLoss 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 cerebellar atrophy and with or without seizures

MIM #618056

Molecular basis of disorder known

Autosomal recessive

Rigidity and multifocal seizure syndrome, lethal neonatal

MIM #614498

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures.
Burgess R et al.·Ann Neurol
2019
Clinical characteristics of BRAT1-related disease: a systematic literature review.
Kong W et al.·Acta Neurol Belg
2024Review
Novel variant in BRAT1 with the lethal neonatal rigidity and multifocal seizure syndrome.
Li W et al.·Pediatr Res
2022
BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients.
Engel C et al.·Eur J Hum Genet
2023Cohort
Clinical and Neurophysiologic Phenotypes in Neonates With BRAT1 Encephalopathy.
Carapancea E et al.·Neurology
2023
Clinical variability at the mild end of BRAT1-related spectrum: Evidence from two families with genotype-phenotype discordance.
Nuovo S et al.·Hum Mutat
2022
BRAT1 mutations present with a spectrum of clinical severity.
Srivastava S et al.·Am J Med Genet A
2016Review
Genetics of neonatal-onset epilepsies.
Cornet MC et al.·Handb Clin Neurol
2019Review
BRAT1 links Integrator and defective RNA processing with neurodegeneration.
Cihlarova Z et al.·Nat Commun
2022
BRAT1 mutations are associated with infantile epileptic encephalopathy, mitochondrial dysfunction, and survival into childhood.
Horn D et al.·Am J Med Genet A
2016Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
BRAT1 gene compound heterozygous mutations causing lethal neonatal rigidity and multifocal seizure syndrome: a case report.
Qin DY et al.·Front Pediatr
2026🔓 Open AccessCase report
BRAT1 - a new therapeutic target for glioblastoma.
Haydo A et al.·Cell Mol Life Sci
2025🔓 Open Access
Novel BRAT1 Deep Intronic Variant Affects Splicing Regulatory Elements Causing Cerebellar Hypoplasia Syndrome: Genotypic and Phenotypic Expansion.
Poleg T et al.·Clin Genet
2025
Novel BRAT1 variant associated with neurodevelopmental disorder with cerebellar atrophy and seizure: Case report and a literature review.
Ghasemi MR et al.·Epilepsy Behav Rep
2024🔓 Open AccessReview
Neuronal differentiation requires BRAT1 complex to remove REST from chromatin.
Dokaneheifard S et al.·Proc Natl Acad Sci U S A
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools