RAC3

protein-coding

Rac family small GTPase 3, the group of Receptor ligands|Rho family GTPases

Gene summary

The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

MANE transcript

NM_005052.3

Inheritance

ClinVar variants

P:12U:37B:18

Top phenotype

Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr17:82,031,678-82,034,204

External References & Databases

Ensembl (ENSG00000169750)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with structural brain anomalies and dysmorphic faciesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032820

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with structural brain anomalies and dysmorphic faciesLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032820

Submitter: Ambry Genetics

neurodevelopmental disorder with structural brain anomalies and dysmorphic faciesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032820

Submitter: G2P

neurodevelopmental disorder with structural brain anomalies and dysmorphic faciesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032820

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with structural brain anomalies and dysmorphic faciesAD

Manifestation: Craniofacial; Dental; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 29276006; 30293988; 35851598

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAC3 variants in ClinVar

9 Conditions Cataloged

not providedTotal: 31

Neurodevelopmental disorder with structural brain anomalies and dysmorphic faciesTotal: 19

Inborn genetic diseasesTotal: 19

RAC3-related disorderTotal: 13

not specifiedTotal: 7

Abnormal brain morphologyTotal: 2

Intellectual disabilityTotal: 2

See casesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005052.3. 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			1 clinvar	16 clinvar		17
missense	4 clinvar	8 clinvar	35 clinvar	2 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	4	8	37	18	0	67

Highest pathogenic variant AF is 6.8460423e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005052.3	RefSeq	NP_005043.1	6	MANE Select
ENST00000306897.9	Ensembl	ENSP00000304283.4	6	MANE Select
NM_001316307.2	RefSeq	NP_001303236.1	6	Standard
ENST00000580965.5	Ensembl	ENSP00000463590.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Focal adhesion - Homo sapiens (human)
B cell receptor signaling pathway - Homo sapiens (human)
Fc epsilon RI signaling pathway - Homo sapiens (human)
VEGF signaling pathway - Homo sapiens (human)
Choline metabolism in cancer - Homo sapiens (human)

Biological Process

cell morphogenesis
actin filament organization
Rho protein signal transduction
regulation of neuron maturation
cell migration

Molecular Function

GTPase activity
protein binding
GTP binding
protein kinase binding
calcium-dependent protein binding

Cellular Component

cytoplasm
cytosol
cytoskeleton
plasma membrane
endomembrane system

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306897
Coding exons: 6
Length: 2581
Individuals with no LoFs: 125576
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125583
p: 0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.46	78	124	0.630	0.00000841	1227
Missense (PolyPhen)		13	43.173	0.30111		469
Synonymous	-4.09	96	56.8	1.69	0.00000411	404
Loss of Function	1.06	5	8.28	0.604	3.51e-7	107

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as cell spreading and the formation of actin-based protusions including lamellipodia and membrane ruffles. Promotes cell adhesion and spreading on fibrinogen in a CIB1 and alpha-IIb/beta3 integrin-mediated manner. {ECO:0000269|PubMed:11756406, ECO:0000269|PubMed:11956649}.;

Recessive Scores

pRec: 0.194

Intolerance Scores

LoFtool: 0.263
RVIS EVS: -0.05
RVIS percentile EVS: 49.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

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