ABR

protein-coding

ABR activator of RhoGEF and GTPase, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing|MicroRNA protein coding host genes|C2 domain containing

Gene summary

This gene encodes a protein that is similar to the protein encoded by the breakpoint cluster region gene located on chromosome 22. The protein encoded by this gene contains a GTPase-activating protein domain, a domain found in members of the Rho family of GTP-binding proteins. Functional studies in mice determined that this protein plays a role in vestibular morphogenesis. Alternatively spliced transcript variants have been reported for this gene. [provided by RefSeq, Feb 2012]

MANE transcript

NM_021962.5

Inheritance

—

ClinVar variants

U:97B:5

Top phenotype

ABR-related disorder

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr17:1,003,519-1,229,738

External References & Databases

Ensembl (ENSG00000159842)

Transcript & Mutation Effects

hg38 • Region Span ~226.2 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 ABR variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 91

not providedTotal: 4

ABR-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021962.5. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			93 clinvar	2 clinvar		95
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	97	4	1	102

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021962.5	RefSeq	NP_068781.2	23	MANE Select
ENST00000302538.10	Ensembl	ENSP00000303909.5	23	MANE Select
NM_001092.5	RefSeq	NP_001083.2	22	Standard
NM_001159746.3	RefSeq	NP_001153218.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases
Regulation of RAC1 activity

Biological Process

negative regulation of cellular extravasation
G protein-coupled receptor signaling pathway
small GTPase mediated signal transduction
brain development
actin cytoskeleton organization

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
GTPase activator activity

Cellular Component

cytosol
plasma membrane
membrane
Schaffer collateral - CA1 synapse
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302538
Coding exons: 23
Length: 225558
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.89	269	518	0.519	0.0000315	5631
Missense (PolyPhen)		84	187.35	0.44836		1947
Synonymous	-0.521	239	229	1.04	0.0000158	1631
Loss of Function	5.00	10	47.0	0.213	0.00000226	559

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000091	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase-activating protein for RAC and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them.;

Intolerance Scores

LoFtool: 0.319
RVIS EVS: -1.04
RVIS percentile EVS: 7.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.528

Gene Damage Prediction

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