BRAT1

BRCA1 associated ATM activator 1

Basic information

Region (hg38): 7:2537809-2555694

Previous symbols: [ "C7orf27", "BAAT1" ]

Links

ENSG00000106009 ∙ NCBI:221927 ∙ OMIM:614506 ∙ HGNC:21701 ∙ Uniprot:Q6PJG6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neonatal-onset encephalopathy with rigidity and seizures (Strong), mode of inheritance: AR
• neonatal-onset encephalopathy with rigidity and seizures (Supportive), mode of inheritance: AR
• neonatal-onset encephalopathy with rigidity and seizures (Strong), mode of inheritance: AR
• neonatal-onset encephalopathy with rigidity and seizures (Definitive), mode of inheritance: AR
• neurodevelopmental disorder with cerebellar atrophy and with or without seizures (Definitive), mode of inheritance: AR
• neonatal-onset encephalopathy with rigidity and seizures (Definitive), mode of inheritance: AR
• neurodevelopmental disorder with cerebellar atrophy and with or without seizures (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rigidity and multifocal seizure syndrome, lethal neonatal; Neurodevelopmental disorder with cerebellar atrophy and with or without seizures	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	22279524; 23035047; 25319849; 25500575; 26483087; 26494257; 27282546; 37344571

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRAT1 gene.

• Neonatal-onset encephalopathy with rigidity and seizures (986 variants)
• not provided (280 variants)
• Inborn genetic diseases (71 variants)
• Neurodevelopmental disorder with cerebellar atrophy and with or without seizures (27 variants)
• not specified (12 variants)
• Neurodevelopmental disorder with cerebellar atrophy and with or without seizures;Neonatal-onset encephalopathy with rigidity and seizures (10 variants)
• Neonatal-onset encephalopathy with rigidity and seizures;Neurodevelopmental disorder with cerebellar atrophy and with or without seizures (9 variants)
• Intellectual disability (6 variants)
• BRAT1-related condition (4 variants)
• BRAT1-Related Disorders (2 variants)
• BRAT1-related disorder (2 variants)
• Seizure (2 variants)
• BRAT1-related neurodevelopmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• BRAT1-associated neurodegenerative disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRAT1 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			5	295	7	307
missense		5	456	18	7	486
nonsense	16	8				24
start loss						0
frameshift	17	5	1			23
inframe indel		1	14			15
splice donor/acceptor (+/-2bp)	2	9				11
splice region	1	1	19	33	1	55
non coding			6	104	36	146
Total	35	28	482	417	50

Highest pathogenic variant AF is 0.0000328

Variants in BRAT1

This is a list of pathogenic ClinVar variants found in the BRAT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-2537850-G-T		Neonatal-onset encephalopathy with rigidity and seizures;Neurodevelopmental disorder with cerebellar atrophy and with or without seizures	Likely benign (Aug 16, 2021)
7-2538055-G-A			Likely benign (Jul 15, 2018)
7-2538057-C-G			Benign (Jul 15, 2018)
7-2538059-C-G			Likely benign (Oct 04, 2023)
7-2538076-C-T		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Mar 16, 2022)
7-2538078-G-A		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (Feb 21, 2021)
7-2538080-C-T		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Aug 16, 2022)
7-2538081-G-A		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (Jan 30, 2024)
7-2538082-G-A		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Aug 09, 2022)
7-2538086-C-T		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Oct 25, 2022)
7-2538087-G-A		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (Jan 26, 2024)
7-2538088-TC-T		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Jun 18, 2019)
7-2538093-C-T		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (Sep 29, 2022)
7-2538094-T-C		Inborn genetic diseases	Uncertain significance (Dec 06, 2022)
7-2538101-A-C		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Sep 06, 2022)
7-2538101-A-G		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Jul 15, 2018)
7-2538107-C-T		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Feb 26, 2021)
7-2538108-C-G		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (Sep 25, 2023)
7-2538108-C-T		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (Aug 22, 2022)
7-2538109-G-A		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Nov 15, 2022)
7-2538119-T-C			Uncertain significance (Feb 21, 2023)
7-2538120-G-A		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (May 28, 2021)
7-2538126-C-T		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (Dec 02, 2023)
7-2538129-G-A		Neonatal-onset encephalopathy with rigidity and seizures	Likely benign (Oct 22, 2023)
7-2538140-G-A		Neonatal-onset encephalopathy with rigidity and seizures	Uncertain significance (Aug 28, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRAT1	protein_coding	protein_coding	ENST00000340611	13	17851

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.43e-13	0.635	125555	0	167	125722	0.000664

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.593	532	495	1.07	0.0000329	5116
Missense in Polyphen		141	138.71	1.0165		1578
Synonymous	-1.67	280	247	1.14	0.0000185	1819
Loss of Function	1.58	24	33.9	0.708	0.00000186	341

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00146	0.00145
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000395	0.000381
Finnish	0.000202	0.000185
European (Non-Finnish)	0.000819	0.000792
Middle Eastern	0.000395	0.000381
South Asian	0.000677	0.000653
Other	0.000339	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in DNA damage response; activates kinases ATM, SMC1A and PRKDC by modulating their phosphorylation status following ionizing radiation (IR) stress (PubMed:16452482, PubMed:22977523). Plays a role in regulating mitochondrial function and cell proliferation (PubMed:25070371). Required for protein stability of MTOR and MTOR-related proteins, and cell cycle progress by growth factors (PubMed:25657994). {ECO:0000269|PubMed:16452482, ECO:0000269|PubMed:22977523, ECO:0000269|PubMed:25070371, ECO:0000269|PubMed:25657994}.
• Disease: DISEASE: Rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL) [MIM:614498]: A lethal, neonatal, neurologic disorder characterized by episodic jerking that is apparent in utero, lack of psychomotor development, axial and limb rigidity, frequent multifocal seizures, and dysautonomia. At birth, affected individuals have small heads, overlapping cranial sutures, small or absent fontanels, and depressed frontal bones. Infants show poorly responsive focal jerks of the tongue, face and arms in a nearly continuous sequence throughout life. {ECO:0000269|PubMed:22279524}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 0.77
• rvis_percentile_EVS: 86.91

Haploinsufficiency Scores

• pHI: 0.124
• hipred: N
• hipred_score: 0.146
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Brat1

Gene ontology

• Biological process: positive regulation of protein phosphorylation;glucose metabolic process;apoptotic process;cellular response to DNA damage stimulus;cell population proliferation;response to ionizing radiation;cell migration;positive regulation of cell growth;mitochondrion localization
• Cellular component: nucleus;nucleoplasm;cytoplasm;membrane
• Molecular function: protein binding