RRAD

protein-coding

RRAD, Ras related glycolysis inhibitor and calcium channel regulator, the group of RGK type GTPase family

Gene summary

Predicted to enable GTP binding activity and calcium channel regulator activity. Predicted to be involved in small GTPase-mediated signal transduction. Predicted to be located in T-tubule. Predicted to be active in plasma membrane. Implicated in type 2 diabetes mellitus. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_004165.3

Inheritance

ClinVar variants

U:37B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr16:66,921,685-66,925,535

External References & Databases

Ensembl (ENSG00000166592)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Brugada syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015263

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RRAD variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 38

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004165.3. 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		1
missense			37 clinvar	1 clinvar		38
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	37	2	0	39

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004165.3	RefSeq	NP_004156.1	4	MANE Select
ENST00000299759.11	Ensembl	ENSP00000299759.6	4	MANE Select
NM_001128850.2	RefSeq	NP_001122322.1	4	Standard
ENST00000566577.1	Ensembl	ENSP00000462559.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin Signaling
Validated transcriptional targets of deltaNp63 isoforms

Biological Process

small GTPase mediated signal transduction
negative regulation of high voltage-gated calcium channel activity

Molecular Function

GTPase activity
calcium channel regulator activity
protein binding
calmodulin binding
GTP binding

Cellular Component

plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299759
Coding exons: 4
Length: 3966
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	142	184	0.770	0.0000130	1942
Missense (PolyPhen)		76	91.951	0.82653		868
Synonymous	1.22	62	75.4	0.822	0.00000489	671
Loss of Function	2.30	2	9.74	0.205	5.01e-7	117

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	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play an important role in cardiac antiarrhythmia via the strong suppression of voltage-gated L-type Ca(2+) currents. Regulates voltage-dependent L-type calcium channel subunit alpha- 1C trafficking to the cell membrane (By similarity). Inhibits cardiac hypertrophy through the calmodulin-dependent kinase II (CaMKII) pathway. Inhibits phosphorylation and activation of CAMK2D. {ECO:0000250, ECO:0000269|PubMed:18056528}.;

Recessive Scores

pRec: 0.343

Intolerance Scores

LoFtool: 0.278
RVIS EVS: -0.36
RVIS percentile EVS: 28.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.687

Gene Damage Prediction

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