RHOBTB2

Rho related BTB domain containing 2, the group of Rho family GTPases|BTB domain containing

Basic information

Region (hg38): 8:22987417-23020509

Links

ENSG00000008853 ∙ NCBI:23221 ∙ OMIM:607352 ∙ HGNC:18756 ∙ Uniprot:Q9BYZ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 64 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy, 64 (Moderate), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AR
• developmental and epileptic encephalopathy, 64 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 64	AR	General	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	Craniofacial; Neurologic	29276004

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RHOBTB2 gene.

• not provided (4 variants)
• Chorea;Dystonic disorder (1 variants)
• Developmental and epileptic encephalopathy, 64 (1 variants)
• RHOBTB2-related disorder (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHOBTB2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	171	14	187
missense	3	9	215	58	38	323
nonsense		1	11	4		16
start loss			2			2
frameshift	1		14	4		19
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)			4	1		5
splice region			3	20	6	29
non coding			3	46	21	70
Total	4	10	256	285	73

Variants in RHOBTB2

This is a list of pathogenic ClinVar variants found in the RHOBTB2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-22994530-C-T			Benign (May 14, 2021)
8-22994558-C-T			Benign (Mar 01, 2022)
8-22994583-G-A		RHOBTB2-related disorder	Benign (Aug 18, 2020)
8-22994585-T-C			Uncertain significance (Jun 26, 2023)
8-22994588-A-C			Likely benign (Dec 17, 2024)
8-22994590-G-A			Uncertain significance (Oct 21, 2024)
8-22994597-G-A			Uncertain significance (Nov 22, 2022)
8-22994603-G-A		not specified	Conflicting classifications of pathogenicity (Jun 04, 2024)
8-22994603-G-T			Likely benign (Feb 02, 2025)
8-22994604-C-A			Likely benign (May 29, 2024)
8-22994607-C-T			Likely benign (Oct 18, 2023)
8-22994608-G-A			Likely benign (Apr 17, 2024)
8-22994613-C-T			Likely benign (Aug 29, 2024)
8-22994616-C-T			Likely benign (Oct 23, 2024)
8-22994619-G-C			Uncertain significance (Jun 04, 2024)
8-22994621-A-G			Likely benign (Sep 14, 2022)
8-22994623-A-G			Likely benign (Aug 11, 2024)
8-22994625-C-T			Likely benign (Mar 31, 2021)
8-22994631-A-G			Likely benign (Jun 13, 2023)
8-22994637-C-T			Likely benign (Aug 11, 2024)
8-22994643-A-G			Uncertain significance (Aug 29, 2024)
8-22994645-T-A			Uncertain significance (Sep 29, 2024)
8-22994646-A-G			Likely benign (Feb 15, 2024)
8-22994650-A-G			Likely benign (Sep 10, 2022)
8-22994652-T-C			Likely benign (Jan 30, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RHOBTB2	protein_coding	protein_coding	ENST00000519685	10	32783

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0133	0.987	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.66	322	487	0.661	0.0000325	4910
Missense in Polyphen		80	191.11	0.4186		1982
Synonymous	0.379	189	196	0.966	0.0000130	1516
Loss of Function	3.83	10	34.1	0.293	0.00000216	325

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000634	0.000633
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases (Consensus)

Recessive Scores

• pRec: 0.150

Intolerance Scores

• loftool: 0.614
• rvis_EVS: -0.97
• rvis_percentile_EVS: 8.9

Haploinsufficiency Scores

• pHI: 0.175
• hipred: Y
• hipred_score: 0.756
• ghis: 0.481

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.946

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rhobtb2

Gene ontology

• Biological process: cell morphogenesis;actin filament organization;Rho protein signal transduction;cell migration;actin cytoskeleton organization;positive regulation of actin filament polymerization;actin cytoskeleton reorganization;engulfment of apoptotic cell;regulation of small GTPase mediated signal transduction
• Cellular component: cytoplasm;cytosol;cytoskeleton;plasma membrane;cell projection
• Molecular function: GTPase activity;protein binding;GTP binding;protein kinase binding