RACK1

protein-coding

receptor for activated C kinase 1, the group of WD repeat domain containing|SSU processome|Small nucleolar RNA protein coding host genes

Gene summary

Enables several functions, including enzyme binding activity; protein domain specific binding activity; and protein kinase inhibitor activity. Involved in several processes, including positive regulation of protein metabolic process; regulation of signal transduction; and regulation of vesicle-mediated transport. Located in several cellular components, including midbody; perinuclear region of cytoplasm; and phagocytic cup. Part of IRE1-RACK1-PP2A complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

GNB2L1

MANE transcript

NM_006098.5

Inheritance

ClinVar variants

U:14B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr5:181,236,897-181,248,096

External References & Databases

Ensembl (ENSG00000204628)

Transcript & Mutation Effects

hg38 • Region Span ~11.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RACK1 variants in ClinVar

1 Conditions Cataloged

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006098.5. 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			5 clinvar		1 clinvar	6
missense			4 clinvar			4
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	14	0	1	15

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 104 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006098.5	RefSeq	NP_006089.1	8	MANE Select
ENST00000512805.6	Ensembl	ENSP00000426909.1	8	MANE Select
ENST00000376817.8	Ensembl	ENSP00000366013.4	8	Standard
ENST00000376817.9	Ensembl	ENSP00000366013.4	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rack1	Danio rerio	Structure: intersegmental vessel Quality: decreased functionality abnormal

Gene / Model

Organism

Observed Phenotype

rack1

Danio rerio

Structure: intersegmental vessel

Quality: decreased functionality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Measles - Homo sapiens (human)
IGF-Ncore
JAK-STAT-Ncore
Androgen receptor signaling pathway
Brain-Derived Neurotrophic Factor (BDNF) signaling pathway

Biological Process

positive regulation of protein phosphorylation
apoptotic process
activation of cysteine-type endopeptidase activity involved in apoptotic process
cell cycle
gastrulation

Molecular Function

RNA binding
protein kinase C binding
signaling receptor binding
protein binding
ion channel inhibitor activity

Cellular Component

phagocytic cup
nucleus
nucleoplasm
cytoplasm
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000512805
Coding exons: 8
Length: 11188
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.58	49	186	0.263	0.00000988	2064
Missense (PolyPhen)		12	76.944	0.15596		883
Synonymous	-0.0138	72	71.9	1.00	0.00000377	639
Loss of Function	4.01	0	18.7	0.00	9.56e-7	182

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	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). Involved in the initiation of the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, by promoting ubiquitination of a subset of 40S ribosomal subunits (PubMed:28132843). Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. Inhibits the activity of SRC kinases including SRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. Modulates IGF1R- dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. Involved in PKC-dependent translocation of ADAM12 to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulates internalization of the muscarinic receptor CHRM2. Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays a role in regulation of FLT1-mediated cell migration. Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane (PubMed:19674157). Promotes migration of breast carcinoma cells by binding to and activating RHOA (PubMed:20499158). {ECO:0000269|PubMed:11884618, ECO:0000269|PubMed:12589061, ECO:0000269|PubMed:12958311, ECO:0000269|PubMed:17108144, ECO:0000269|PubMed:17244529, ECO:0000269|PubMed:17956333, ECO:0000269|PubMed:18088317, ECO:0000269|PubMed:18258429, ECO:0000269|PubMed:18621736, ECO:0000269|PubMed:19423701, ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:19785988, ECO:0000269|PubMed:20499158, ECO:0000269|PubMed:20541605, ECO:0000269|PubMed:20573744, ECO:0000269|PubMed:20976005, ECO:0000269|PubMed:21212275, ECO:0000269|PubMed:21347310, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:28132843, ECO:0000269|PubMed:9584165}.; FUNCTION: (Microbial infection) Enhances phosphorylation of HIV-1 Nef by PKCs. {ECO:0000269|PubMed:11312657}.; FUNCTION: (Microbial infection) Contributes to the cap-independent internal ribosome entry site (IRES)-mediated translation by some RNA viruses. {ECO:0000269|PubMed:25416947}.;

Recessive Scores

pRec: 0.166

Intolerance Scores

RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (gene trap): E