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…

LOFmechanismARLOEUF 0.992 OMIM phenotypes

Clinical Summary— BRAT1

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Gene-Disease Validity (ClinGen)

neonatal-onset encephalopathy with rigidity and seizures · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

124 unique Pathogenic / Likely Pathogenic· 533 VUS of 1381 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — BRAT1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.58

OE 0.71 (0.51–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.59Z-score

OE missense 1.08 (1.00–1.16)

532 obs / 494.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.71 (0.51–0.99)

0≤0.351.4

Missense OE?1.08 (1.00–1.16)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 24 / 33.9Missense obs/exp: 532 / 494.9Syn Z: -1.67

ClinVar Variant Classifications

1381 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic75

Likely Pathogenic49

VUS533

Likely Benign581

Benign52

Conflicting70

Pathogenic

Likely Pathogenic

533

VUS

581

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	62	2	9	2	75
Likely Pathogenic	38	9	2	0	49
VUS	5	498	27	3	533
Likely Benign	0	26	168	387	581
Benign	0	10	35	7	52
Conflicting	—				70
Total	105	545	241	399	1,360

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 62) ClinVar copy-number / structural variants overlap BRAT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →