RORB

RAR related orphan receptor B, the group of RAR related orphan receptors

Basic information

Region (hg38): 9:74497335-74693177

Links

ENSG00000198963 ∙ NCBI:6096 ∙ OMIM:601972 ∙ HGNC:10259 ∙ Uniprot:Q92753 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
• epilepsy, idiopathic generalized, susceptibility to, 15 (Strong), mode of inheritance: AD
• epilepsy, idiopathic generalized, susceptibility to, 15 (Strong), mode of inheritance: AD
• epilepsy (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, idiopathic generalized, susceptibilty to, 15	AD	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	Neurologic	27352968

ClinVar

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

• not provided (16 variants)
• Epilepsy, idiopathic generalized, susceptibility to, 15 (4 variants)
• Inborn genetic diseases (2 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RORB 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				61	7	68
missense	1	5	146	1		153
nonsense	10	3				13
start loss			3			3
frameshift	11	1	3			15
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)		7	2			9
splice region		1	13	15		29
non coding			1	44	8	53
Total	22	17	157	106	15

Variants in RORB

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

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

Position	Type	Phenotype	Significance	ClinVar
9-74497978-T-C			Uncertain significance (Jun 30, 2019)
9-74497978-T-G			Uncertain significance (Oct 22, 2023)
9-74497979-G-C			Uncertain significance (Dec 31, 2022)
9-74497981-G-C			Uncertain significance (Aug 16, 2021)
9-74497989-C-T			Conflicting classifications of pathogenicity (Jun 01, 2022)
9-74497998-G-C			Likely benign (Jan 22, 2023)
9-74498003-C-A			Benign (Jan 27, 2024)
9-74498003-C-T			Benign (Feb 01, 2024)
9-74615594-G-A		RORB-related disorder	Likely benign (May 10, 2019)
9-74630275-C-T			Likely benign (Apr 18, 2022)
9-74630281-G-A		Epilepsy, idiopathic generalized, susceptibility to, 15	Likely pathogenic (Dec 14, 2018)
9-74630290-G-C			Uncertain significance (Jul 19, 2023)
9-74630294-T-G			Uncertain significance (Sep 25, 2023)
9-74630300-C-T			Uncertain significance (Jul 15, 2022)
9-74630301-A-C			Likely benign (Mar 25, 2021)
9-74630313-T-TG			Pathogenic (May 06, 2022)
9-74630316-C-T			Likely benign (Sep 10, 2023)
9-74630317-G-A			Uncertain significance (Oct 22, 2022)
9-74630329-G-A			Uncertain significance (Jan 14, 2022)
9-74630330-G-T			Uncertain significance (Jun 24, 2022)
9-74630333-TC-T			Pathogenic (Apr 14, 2022)
9-74630340-C-T			Likely benign (May 16, 2023)
9-74630341-G-A			Uncertain significance (Dec 15, 2023)
9-74630343-A-C			Likely benign (Jun 15, 2022)
9-74630349-C-T		RORB-related disorder	Benign/Likely benign (Aug 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RORB	protein_coding	protein_coding	ENST00000376896	10	195813

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000859	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.08	116	254	0.456	0.0000135	3033
Missense in Polyphen		8	86.311	0.092688		1042
Synonymous	0.00880	101	101	0.999	0.00000635	827
Loss of Function	4.78	0	26.6	0.00	0.00000134	304

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity (By similarity). {ECO:0000250}.
• Pathway: Circadian rhythm - Homo sapiens (human);NHR;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.807
• hipred: Y
• hipred_score: 0.817
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.922

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rorb
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; reproductive system phenotype; vision/eye 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)

Gene ontology

• Biological process: regulation of transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;G protein-coupled receptor signaling pathway;visual perception;intracellular receptor signaling pathway;amacrine cell differentiation;eye photoreceptor cell development;regulation of circadian rhythm;steroid hormone mediated signaling pathway;negative regulation of osteoblast differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;retinal rod cell development;retinal cone cell development;rhythmic process;retina development in camera-type eye;cellular response to retinoic acid
• Cellular component: nucleus;nucleoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;steroid hormone receptor activity;nuclear receptor activity;protein binding;transcription factor binding;zinc ion binding;melatonin receptor activity