ABRAXAS1

protein-coding

abraxas 1, BRCA1 A complex subunit, the group of BRCA1 A complex

Gene summary

This gene encodes a protein that binds to the C-terminal repeats of breast cancer 1 (BRCA1) through a phospho-SXXF motif. The encoded protein recruits ubiquitin interaction motif containing 1 protein to BRCA1 protein and is required for DNA damage resistance, DNA repair, and cell cycle checkpoint control. Pseudogenes of this gene are found on chromosomes 3 and 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

Previous symbols:

CCDC98
FAM175A

MANE transcript

NM_139076.3

Inheritance

—

ClinVar variants

P:3U:592B:276

Top phenotype

Hereditary cancer-predisposing syndrome

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr4:83,459,517-83,523,348

External References & Databases

Ensembl (ENSG00000163322)

Transcript & Mutation Effects

hg38 • Region Span ~63.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABRAXAS1 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 776

not providedTotal: 443

Hereditary cancer-predisposing syndromeTotal: 15

ABRAXAS1-related disorderTotal: 7

Hereditary breast ovarian cancer syndromeTotal: 6

Hereditary breast cancer, ABRAXAS1-relatedTotal: 1

Malignant tumor of breastTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139076.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				227 clinvar	2 clinvar	229
missense		1 clinvar	555 clinvar	46 clinvar		602
nonsense		1 clinvar	11 clinvar			12
start loss			5 clinvar			5
frameshift		1 clinvar	14 clinvar	1 clinvar		16
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	3	592	274	2	871

Highest pathogenic variant AF is 0.000072487295

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_139076.3	RefSeq	NP_620775.2	9	MANE Select
ENST00000321945.12	Ensembl	ENSP00000369857.3	9	MANE Select
NM_001345962.2	RefSeq	NP_001332891.1	5	Standard
ENST00000475656.6	Ensembl	ENSP00000426080.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Homologous recombination - Homo sapiens (human)
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
DNA Repair
Nonhomologous End-Joining (NHEJ)
DNA Double-Strand Break Repair

Biological Process

double-strand break repair
double-strand break repair via nonhomologous end joining
chromatin organization
response to ionizing radiation
protein deubiquitination

Molecular Function

protein binding
polyubiquitin modification-dependent protein binding

Cellular Component

nucleus
nucleoplasm
nuclear body
BRCA1-A complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321945
Coding exons: 9
Length: 62410
Individuals with no LoFs: 125696
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 125748
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0384	211	213	0.993	0.0000104	2715
Missense (PolyPhen)		54	69.833	0.77327		936
Synonymous	-0.428	78	73.3	1.06	0.00000336	730
Loss of Function	1.54	13	20.5	0.634	0.00000112	257

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of BRCA1. The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at DSBs. This complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:22357538, ECO:0000269|PubMed:26778126}.;
Disease: DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:22357538, ECO:0000269|PubMed:25105795}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: 0.95
RVIS percentile EVS: 90.01

Essentials

Essential (gene trap): N