RARB

retinoic acid receptor beta, the group of Retinoic acid receptors

Basic information

Region (hg38): 3:24687886-25597932

Links

ENSG00000077092 ∙ NCBI:5915 ∙ OMIM:180220 ∙ HGNC:9865 ∙ Uniprot:P10826 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microphthalmia, syndromic 12 (Definitive), mode of inheritance: AD
• microphthalmia, syndromic 12 (Strong), mode of inheritance: AD
• microphthalmia, syndromic 12 (Strong), mode of inheritance: AR
• microphthalmia, syndromic 12 (Moderate), mode of inheritance: AD
• Matthew-Wood syndrome (Supportive), mode of inheritance: AD
• microphthalmia, syndromic 12 (Definitive), mode of inheritance: AR
• microphthalmia, syndromic 12 (Strong), mode of inheritance: AD
• microphthalmia, syndromic 12 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, syndromic 12	AD/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	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary	17506106; 22686418; 24075189

ClinVar

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

• not provided (44 variants)
• Microphthalmia, syndromic 12 (38 variants)
• Inborn genetic diseases (6 variants)
• Microphthalmia (4 variants)
• Intellectual disability, autosomal dominant 48 (3 variants)
• Congenital ocular coloboma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RARB 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				10	3	13
missense	1	13	24		2	40
nonsense		1	2			3
start loss						0
frameshift			2			2
inframe indel		1				1
splice donor/acceptor (+/-2bp)	1		1			2
splice region				2		2
non coding			1	3	17	21
Total	2	15	30	13	22

Variants in RARB

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

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

Position	Type	Phenotype	Significance	ClinVar
3-25174525-GC-G		RARB-related disorder	Uncertain significance (Jan 03, 2023)
3-25174527-C-G		RARB-related disorder	Uncertain significance (Jun 16, 2023)
3-25428879-A-G		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)
3-25429095-C-T			Benign (May 22, 2021)
3-25430783-G-A		Microphthalmia, syndromic 12	Uncertain significance (Jan 15, 2024)
3-25461005-C-T			Benign (May 14, 2021)
3-25461178-C-A		Microphthalmia, syndromic 12	Likely benign (Aug 17, 2023)
3-25461184-C-G		Microphthalmia, syndromic 12	Benign (Nov 15, 2023)
3-25461186-A-G		Microphthalmia, syndromic 12	Likely benign (Aug 16, 2023)
3-25461192-G-A		Microphthalmia, syndromic 12	Uncertain significance (Oct 19, 2023)
3-25461254-T-TC		Microphthalmia, syndromic 12	Uncertain significance (Jun 16, 2020)
3-25461266-G-C			Likely benign (Jun 13, 2018)
3-25461299-A-T		Microphthalmia, syndromic 12	Likely benign (Jun 17, 2019)
3-25461304-G-A			Uncertain significance (Feb 20, 2023)
3-25461305-G-A		Microphthalmia, syndromic 12 • RARB-related disorder	Benign (Nov 27, 2023)
3-25461323-C-T		Microphthalmia, syndromic 12	Likely benign (Dec 31, 2019)
3-25461348-A-G		Microphthalmia, syndromic 12	Likely benign (Apr 11, 2023)
3-25461360-G-A		Microphthalmia, syndromic 12	Benign (Jan 29, 2024)
3-25461378-T-G			Benign (May 15, 2021)
3-25501080-G-A			Benign (May 14, 2021)
3-25501097-A-G			Benign (May 14, 2021)
3-25501182-G-T		Microphthalmia	Likely pathogenic (Oct 15, 2022)
3-25501230-C-T		Microphthalmia, syndromic 12	Pathogenic (Oct 03, 2013)
3-25501231-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2023)
3-25501284-C-T		Microphthalmia, syndromic 12	Uncertain significance (May 23, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RARB	protein_coding	protein_coding	ENST00000330688	8	423601

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000169	125645	0	8	125653	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.87	123	251	0.491	0.0000131	2943
Missense in Polyphen		41	109.35	0.37493		1248
Synonymous	-1.82	114	91.8	1.24	0.00000498	851
Loss of Function	4.61	0	24.8	0.00	0.00000164	258

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)	0.0000530	0.0000528
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function. {ECO:0000269|PubMed:12554770}.
• Disease: DISEASE: Microphthalmia, syndromic, 12 (MCOPS12) [MIM:615524]: A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS12 patients manifest variable features, including diaphragmatic hernia, pulmonary hypoplasia, and cardiac abnormalities. {ECO:0000269|PubMed:24075189, ECO:0000269|PubMed:27120018}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Non-small cell lung cancer - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);NHR;Nuclear Receptors;Mesodermal Commitment Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Vitamin A and Carotenoid Metabolism;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;RXR and RAR heterodimerization with other nuclear receptor;Retinoic acid receptors-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.284

Intolerance Scores

• loftool: 0.0156
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.09

Haploinsufficiency Scores

• pHI: 0.563
• hipred: Y
• hipred_score: 0.774
• ghis: 0.626

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rarb
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hearing/vestibular/ear 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); digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;ureteric bud development;liver development;glandular epithelial cell development;outflow tract septum morphogenesis;growth plate cartilage development;transcription initiation from RNA polymerase II promoter;signal transduction;multicellular organism development;negative regulation of cell population proliferation;hormone-mediated signaling pathway;striatum development;cell differentiation;regulation of myelination;negative regulation of chondrocyte differentiation;response to retinoic acid;response to lipid;embryonic hindlimb morphogenesis;multicellular organism growth;positive regulation of apoptotic process;negative regulation of apoptotic process;steroid hormone mediated signaling pathway;positive regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;embryonic eye morphogenesis;retinoic acid receptor signaling pathway;embryonic digestive tract development;gland development;ventricular cardiac muscle cell differentiation;bone morphogenesis;epithelium development;cellular response to retinoic acid
• Cellular component: nucleus;nucleoplasm;cytoplasm;RNA polymerase II transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;steroid hormone receptor activity;transcription factor binding;drug binding;zinc ion binding;nuclear receptor transcription coactivator activity;signaling receptor activity;protein-containing complex binding;retinoid X receptor binding