BRAT1

Chr 7AR

BRCA1 associated ATM activator 1

Also known as: BAAT1, C7orf27, NEDCAS, RMFSL

NCBI Gene: 221927 ENSG00000106009 UniProt: Q6PJG6 OMIM: 614506

This protein interacts with BRCA1 and ATM proteins in DNA damage response pathways and is involved in cell cycle checkpoint signaling. Biallelic mutations cause autosomal recessive neurodevelopmental disorders ranging from lethal neonatal rigidity with multifocal seizures to milder presentations with cerebellar atrophy and variable seizures. The pathogenic mechanism involves loss of function, as the gene shows tolerance to heterozygous loss-of-function variants but requires biallelic mutations for disease manifestation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with cerebellar atrophy and with or without seizuresMIM #618056

Rigidity and multifocal seizure syndrome, lethal neonatalMIM #614498

Clinical highlights

Gene-disease validity (ClinGen)

neonatal-onset encephalopathy with rigidity and seizures · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.99

LOEUF

LOF

Mechanism· G2P

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GeneReview available — BRAT1