RHOH

ras homolog family member H, the group of Rho family GTPases

Basic information

Region (hg38): 4:40191011-40246967

Previous symbols: [ "ARHH" ]

Links

ENSG00000168421 ∙ NCBI:399 ∙ OMIM:602037 ∙ HGNC:686 ∙ Uniprot:Q15669 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epidermodysplasia verruciformis (Moderate), mode of inheritance: AR
• epidermodysplasia verruciformis, susceptibility to, 4 (Strong), mode of inheritance: AR
• T-cell immunodeficiency with epidermodysplasia verruciformis (Supportive), mode of inheritance: AR
• epidermodysplasia verruciformis, susceptibility to, 4 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermodysplasia verruciformis, susceptibility to, 4	AR	Allergy/Immunology/Infectious; Oncologic	Individuals have been described with susceptibility to certain infections as well as potential increased risk of malignancy, and awareness may allow prompt diagnosis and management of sequeleae	Allergy/Immunology/Infectious; Dermatologic; Oncologic	22850876

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHOH 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				39		39
missense			27	1		28
nonsense						0
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	29	41	0

Variants in RHOH

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

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

Position	Type	Phenotype	Significance	ClinVar
4-40197302-T-C		Neoplasm	- (-)
4-40243386-G-A		RHOH-related disorder	Likely benign (Apr 12, 2019)
4-40243404-G-A		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Jan 17, 2022)
4-40243413-G-A		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Nov 27, 2023)
4-40243415-T-C		T-cell immunodeficiency with epidermodysplasia verruciformis	Uncertain significance (Jul 19, 2022)
4-40243419-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Jan 22, 2024)
4-40243428-T-C		T-cell immunodeficiency with epidermodysplasia verruciformis • RHOH-related disorder	Likely benign (Oct 24, 2023)
4-40243434-G-C		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Feb 27, 2023)
4-40243461-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Feb 16, 2023)
4-40243464-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (May 05, 2022)
4-40243474-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Uncertain significance (Jun 12, 2019)
4-40243475-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Uncertain significance (Oct 03, 2022)
4-40243485-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Apr 28, 2023)
4-40243487-A-G		T-cell immunodeficiency with epidermodysplasia verruciformis	Uncertain significance (Aug 17, 2023)
4-40243491-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Oct 30, 2020)
4-40243500-C-G		Epidermodysplasia verruciformis, susceptibility to, 4	risk factor (Aug 30, 2024)
4-40243500-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Dec 22, 2023)
4-40243512-G-A		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Aug 23, 2022)
4-40243512-G-C		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Jun 01, 2022)
4-40243518-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Feb 22, 2023)
4-40243525-A-C		not specified	Uncertain significance (Dec 28, 2022)
4-40243530-T-C		T-cell immunodeficiency with epidermodysplasia verruciformis • Epidermodysplasia verruciformis, susceptibility to, 4	Likely benign (Jan 30, 2024)
4-40243551-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Feb 13, 2020)
4-40243560-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Sep 08, 2023)
4-40243566-C-T		T-cell immunodeficiency with epidermodysplasia verruciformis	Likely benign (Jul 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RHOH	protein_coding	protein_coding	ENST00000381799	1	55915

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.149	0.785	125737	0	6	125743	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.67	65	115	0.563	0.00000670	1246
Missense in Polyphen		27	59.295	0.45535		595
Synonymous	-0.758	58	51.1	1.14	0.00000331	393
Loss of Function	1.49	2	5.92	0.338	3.39e-7	57

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000356	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000779	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative regulator of hematopoietic progenitor cell proliferation, survival and migration. Critical regulator of thymocyte development and T-cell antigen receptor (TCR) signaling by mediating recruitment and activation of ZAP70. Required for phosphorylation of CD3Z, membrane translocation of ZAP70 and subsequent activation of the ZAP70-mediated pathways. Essential for efficient beta-selection and positive selection by promoting the ZAP70-dependent phosphorylation of the LAT signalosome during pre-TCR and TCR signaling. Crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Plays critical roles in mast cell function by facilitating phosphorylation of SYK in Fc epsilon RI-mediated signal transduction. Essential for the phosphorylation of LAT, LCP2, PLCG1 and PLCG2 and for Ca(2+) mobilization in mast cells (By similarity). Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Inhibits the activation of NF-kappa-B by TNF and IKKB and the activation of CRK/p38 by TNF. Inhibits activities of RAC1, RHOA and CDC42. Negatively regulates leukotriene production in neutrophils. {ECO:0000250, ECO:0000269|PubMed:11809807, ECO:0000269|PubMed:19414807}.
• Disease: DISEASE: Note=A chromosomal aberration involving RHOH is found in a non-Hodgkin lymphoma cell line. Translocation t(3;4)(q27;p11) with BCL6.
• Pathway: Leukocyte transendothelial migration - Homo sapiens (human);Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases (Consensus)

Recessive Scores

• pRec: 0.310

Intolerance Scores

• loftool: 0.357
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.294
• hipred: Y
• hipred_score: 0.685
• ghis: 0.641

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.891

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rhoh
• Phenotype: immune system phenotype; hematopoietic system phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: regulation of transcription, DNA-templated;actin filament organization;establishment or maintenance of cell polarity;Rho protein signal transduction;regulation of cell shape;actin cytoskeleton organization;T cell differentiation;regulation of actin cytoskeleton organization;negative regulation of kinase activity;negative regulation of GTPase activity;negative regulation of I-kappaB kinase/NF-kappaB signaling;mast cell activation;regulation of small GTPase mediated signal transduction
• Cellular component: immunological synapse;cytoplasm;cytosol;plasma membrane;cell cortex;cell projection
• Molecular function: GTPase activity;GTPase inhibitor activity;protein binding;GTP binding;Rho GTPase binding;kinase inhibitor activity;protein kinase binding