RIC8B

protein-coding

RIC8 guanine nucleotide exchange factor B, the group of Armadillo like helical domain containing

Gene summary

Enables G-protein alpha-subunit binding activity. Acts upstream of or within regulation of G protein-coupled receptor signaling pathway. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001330145.2

Inheritance

—

ClinVar variants

U:37B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr12:106,774,621-106,889,316

External References & Databases

Ensembl (ENSG00000111785)

Transcript & Mutation Effects

hg38 • Region Span ~114.7 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 RIC8B variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330145.2. 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 clinvar		2
missense			34 clinvar	2 clinvar		36
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	37	3	0	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001330145.2	RefSeq	NP_001317074.1	10	MANE Select
ENST00000392837.9	Ensembl	ENSP00000376582.4	10	MANE Select
NM_001330146.2	RefSeq	NP_001317075.1	9	Standard
NM_001330147.2	RefSeq	NP_001317076.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ric8b	Danio rerio	Structure: melanocyte Quality: irregular spatial pattern abnormal

Gene / Model

Organism

Observed Phenotype

ric8b

Danio rerio

Structure: melanocyte

Quality: irregular spatial pattern

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

G protein-coupled receptor signaling pathway
regulation of G protein-coupled receptor signaling pathway
positive regulation of GTPase activity

Molecular Function

G-protein alpha-subunit binding
guanyl-nucleotide exchange factor activity
GTPase activator activity

Cellular Component

cytoplasm
centrosome
cytosol
plasma membrane
cell cortex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392839
Coding exons: 9
Length: 114718
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125735
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.00	187	282	0.664	0.0000147	3397
Missense (PolyPhen)		60	122.43	0.49008		1495
Synonymous	1.32	93	111	0.840	0.00000596	1012
Loss of Function	4.37	1	24.2	0.0413	0.00000140	304

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
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)	0.000026	0.000018	rare
South Asian	0.000071	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins by exchanging bound GDP for free GTP. Able to potentiate G(olf)-alpha-dependent cAMP accumulation suggesting that it may be an important component for odorant signal transduction. {ECO:0000250}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.140
RVIS EVS: -0.27
RVIS percentile EVS: 34.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.655

Gene Damage Prediction

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