RIPOR2

RHO family interacting cell polarization regulator 2, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 6:24804281-25042170

Previous symbols: [ "C6orf32", "FAM65B" ]

Links

ENSG00000111913 ∙ NCBI:9750 ∙ OMIM:611410 ∙ HGNC:13872 ∙ Uniprot:Q9Y4F9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 104 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 104 (Limited), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 21; Deafness, autosomal recessive 104	AD/AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	24958875; 32631815
The age of onset of hearing loss in Deafness, autosomal dominant 21 has been described as highly variable

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIPOR2 gene.

• not provided (271 variants)
• not specified (41 variants)
• Inborn genetic diseases (17 variants)
• Autosomal recessive nonsyndromic hearing loss 104 (4 variants)
• Autosomal dominant nonsyndromic hearing loss 21;Autosomal recessive nonsyndromic hearing loss 104 (3 variants)
• RIPOR2-related condition (3 variants)
• Autosomal dominant nonsyndromic hearing loss 21 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIPOR2 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			1	39	8	48
missense			69	8	13	90
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			3	7	3	13
non coding			2	42	88	132
Total	0	0	76	89	109

Variants in RIPOR2

This is a list of pathogenic ClinVar variants found in the RIPOR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-24806047-T-C			Likely benign (Jan 16, 2019)
6-24806110-T-C			Benign (Nov 11, 2018)
6-24806366-C-T		not specified • Autosomal recessive nonsyndromic hearing loss 104	Benign (Aug 10, 2021)
6-24806384-T-C		not specified • RIPOR2-related disorder	Conflicting classifications of pathogenicity (May 23, 2023)
6-24806387-C-T		not specified	Uncertain significance (Jun 13, 2022)
6-24806423-A-G		not specified	Uncertain significance (Oct 20, 2023)
6-24806446-T-C			Uncertain significance (Aug 17, 2017)
6-24806454-T-G		RIPOR2-related disorder	Likely benign (Sep 21, 2023)
6-24806461-C-T			Uncertain significance (Jul 29, 2023)
6-24806467-T-C		not specified	Uncertain significance (Apr 13, 2023)
6-24806479-T-C			Likely benign (Feb 01, 2022)
6-24806485-A-G		not specified	Benign (Jan 29, 2024)
6-24806493-C-T			Likely benign (Dec 19, 2023)
6-24806511-C-CTT			Benign (Jun 24, 2018)
6-24806524-A-C			Benign (Jun 24, 2018)
6-24806549-T-A			Benign (Jun 24, 2018)
6-24806695-A-C			Benign (Nov 11, 2018)
6-24809543-A-G			Benign (Mar 29, 2019)
6-24809625-C-T			Benign (Jun 22, 2018)
6-24809646-A-C			Benign (Jun 24, 2018)
6-24809653-T-A			Benign (Jun 22, 2018)
6-24809695-AAAC-A			Likely benign (Jul 06, 2022)
6-24809708-A-T		not specified • Autosomal recessive nonsyndromic hearing loss 104	Benign (Jan 31, 2024)
6-24809769-T-C			Likely benign (Jun 24, 2023)
6-24809779-G-A		not specified	Uncertain significance (Aug 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIPOR2	protein_coding	protein_coding	ENST00000259698	22	244638

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.923	0.0772	124611	0	8	124619	0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.37	400	557	0.718	0.0000292	6954
Missense in Polyphen		150	205.95	0.72834		2690
Synonymous	1.86	192	228	0.843	0.0000130	2099
Loss of Function	5.21	9	47.9	0.188	0.00000242	624

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000284	0.000283
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000465	0.0000464
European (Non-Finnish)	0.00000887	0.00000885
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as an inhibitor of the small GTPase RHOA and plays several roles in the regulation of myoblast and hair cell differentiation, lymphocyte T proliferation and neutrophil polarization (PubMed:17150207, PubMed:24687993, PubMed:23241886, PubMed:24958875, PubMed:25588844, PubMed:27556504). Inhibits chemokine-induced T lymphocyte responses, such as cell adhesion, polarization and migration (PubMed:23241886). Involved also in the regulation of neutrophil polarization, chemotaxis and adhesion (By similarity). Required for normal development of inner and outer hair cell stereocilia within the cochlea of the inner ear (By similarity). Plays a role for maintaining the structural organization of the basal domain of stereocilia (By similarity). Involved in mechanosensory hair cell function (By similarity). Required for normal hearing (PubMed:24958875). {ECO:0000250|UniProtKB:Q80U16, ECO:0000269|PubMed:17150207, ECO:0000269|PubMed:23241886, ECO:0000269|PubMed:24687993, ECO:0000269|PubMed:24958875, ECO:0000269|PubMed:27556504}.
• Disease: DISEASE: Deafness, autosomal recessive, 104 (DFNB104) [MIM:616515]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:24958875}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0981

Intolerance Scores

• rvis_EVS: 2.4
• rvis_percentile_EVS: 98.52

Haploinsufficiency Scores

• pHI: 0.229
• hipred: Y
• hipred_score: 0.696
• ghis: 0.406

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Ripor2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: ripor2
• Affected structure: muscle
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: chemotaxis;cell adhesion;negative regulation of cell adhesion;sensory perception of sound;negative regulation of Rho protein signal transduction;establishment of protein localization;positive regulation of myoblast differentiation;skeletal muscle fiber development;protein homooligomerization;positive regulation of filopodium assembly;auditory receptor cell stereocilium organization;cellular response to mechanical stimulus;positive regulation of neutrophil chemotaxis;positive regulation of myoblast fusion;negative regulation of establishment of T cell polarity;negative regulation of protein localization to cell leading edge;cellular response to chemokine;regulation of establishment of cell polarity;positive regulation of neutrophil extravasation;negative regulation of T cell migration;negative regulation of Rho guanyl-nucleotide exchange factor activity
• Cellular component: cytoplasm;cytoskeleton;apical plasma membrane;filopodium;stereocilium;stereocilium membrane
• Molecular function: protein binding;identical protein binding;14-3-3 protein binding