THRB

thyroid hormone receptor beta, the group of Thyroid hormone receptors

Basic information

Region (hg38): 3:24117152-24495756

Previous symbols: [ "ERBA2", "PRTH" ]

Links

ENSG00000151090 ∙ NCBI:7068 ∙ OMIM:190160 ∙ HGNC:11799 ∙ Uniprot:P10828 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thyroid hormone resistance, generalized, autosomal dominant (Strong), mode of inheritance: AD
• resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta (Supportive), mode of inheritance: AR
• thyroid hormone resistance, generalized, autosomal recessive (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid hormone resistance, generalized, autosomal dominant; Thyroid hormone resistance, selective pituitary; Thyroid hormone resistance, generalized, autosomal recessive	AD/AR	Endocrine	In Thyroid hormone resistance, generalized, unhelpful, potentially invasive treatment regimens that may involve adverse effects may be avoided with efficient (genetic) diagnosis, and medical treatment (eg, with types of triiodothyroacetic acid) may be beneficial related to biological parameters as well as sequelae affecting multiple systems, such as the cardiovascular and neurologic systems; In Thyroid hormone resistance, selective pituitary, affected individuals may more frequently benefit from efforts to lower serum thyroid hormone concentration	Endocrine	4163616; 1159077; 6792914; 6287848; 3571851; 2510172; 2153155; 1991834; 1653889; 8381821; 8450877; 1400869; 8384535; 8496318; 8040303; 15913586; 17596672; 19268523; 19378427; 20020587; 22319036; 22696245; 22947347; 23134553; 23633200

ClinVar

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

• Thyroid hormone resistance, generalized, autosomal dominant (190 variants)
• not provided (86 variants)
• Thyroid hormone resistance syndrome (28 variants)
• not specified (19 variants)
• THRB-related condition (12 variants)
• Inborn genetic diseases (10 variants)
• Selective pituitary resistance to thyroid hormone (3 variants)
• Thyroid hormone resistance, generalized, autosomal recessive (2 variants)
• Thyroid hormone resistance, generalized, autosomal recessive;Thyroid hormone resistance, generalized, autosomal dominant;Selective pituitary resistance to thyroid hormone (2 variants)
• Neurodevelopmental disorder (1 variants)
• Selective pituitary resistance to thyroid hormone;Thyroid hormone resistance, generalized, autosomal dominant;Thyroid hormone resistance, generalized, autosomal recessive (1 variants)
• Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta (1 variants)
• See cases (1 variants)
• Generalized resistance to thyroid hormone (1 variants)
• Macular dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THRB 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			5	5	4	14
missense	19	20	47	5		91
nonsense	3	1				4
start loss			1			1
frameshift	1					1
inframe indel	1	1				2
splice donor/acceptor (+/-2bp)	1	1				2
splice region			3			3
non coding			88	12	73	173
Total	25	23	141	22	77

Highest pathogenic variant AF is 0.00000657

Variants in THRB

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

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

Position	Type	Phenotype	Significance	ClinVar
3-24117156-C-T		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 12, 2018)
3-24117183-T-A		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 13, 2018)
3-24117200-C-T		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 13, 2018)
3-24117313-C-G		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117351-C-T		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 13, 2018)
3-24117453-A-T		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 12, 2018)
3-24117455-G-C		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 12, 2018)
3-24117498-C-G		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117517-G-A		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 12, 2018)
3-24117532-G-A		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 12, 2018)
3-24117589-G-A		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 12, 2018)
3-24117622-G-A		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 12, 2018)
3-24117627-G-T		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117637-A-T		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117690-T-C		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117718-C-G		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117762-T-G		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117888-A-G		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117896-A-G		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 12, 2018)
3-24117909-C-G		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 13, 2018)
3-24117957-C-T		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117964-T-C		Thyroid hormone resistance, generalized, autosomal dominant	Uncertain significance (Jan 13, 2018)
3-24117967-C-T		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 13, 2018)
3-24118060-G-A		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 13, 2018)
3-24118088-A-G		Thyroid hormone resistance, generalized, autosomal dominant	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THRB	protein_coding	protein_coding	ENST00000396671	8	378123

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00324	125725	0	4	125729	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.57	145	262	0.554	0.0000161	3069
Missense in Polyphen		18	87.639	0.20539		971
Synonymous	-1.42	118	99.9	1.18	0.00000653	851
Loss of Function	4.07	1	21.3	0.0470	0.00000119	261

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)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. {ECO:0000269|PubMed:12699376, ECO:0000269|PubMed:14673100, ECO:0000269|PubMed:16781732, ECO:0000269|PubMed:17418816, ECO:0000269|PubMed:18237438, ECO:0000269|PubMed:18798561, ECO:0000269|PubMed:19926848}.
• Disease: DISEASE: Generalized thyroid hormone resistance (GTHR) [MIM:188570]: A disease characterized by goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. GTHR patients also have high levels of circulating thyroid hormones (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). {ECO:0000269|PubMed:10660344, ECO:0000269|PubMed:12511610, ECO:0000269|PubMed:12554782, ECO:0000269|PubMed:1314846, ECO:0000269|PubMed:1324420, ECO:0000269|PubMed:1563081, ECO:0000269|PubMed:1587388, ECO:0000269|PubMed:1619012, ECO:0000269|PubMed:1661299, ECO:0000269|PubMed:16804041, ECO:0000269|PubMed:1846005, ECO:0000269|PubMed:19268523, ECO:0000269|PubMed:2153155, ECO:0000269|PubMed:2510172, ECO:0000269|PubMed:7833659, ECO:0000269|PubMed:8175986, ECO:0000269|PubMed:8514853, ECO:0000269|PubMed:8664910, ECO:0000269|PubMed:8889584}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Generalized thyroid hormone resistance autosomal recessive (GTHRAR) [MIM:274300]: An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. {ECO:0000269|PubMed:1653889}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Selective pituitary thyroid hormone resistance (PRTH) [MIM:145650]: Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established. {ECO:0000269|PubMed:7528740, ECO:0000269|PubMed:8381821}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thyroid hormone signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);NHR;Nuclear Receptors;Angiopoietin Like Protein 8 Regulatory Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Gene expression (Transcription);Generic Transcription Pathway;Prolactin;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;RXR and RAR heterodimerization with other nuclear receptor (Consensus)

Recessive Scores

• pRec: 0.511

Intolerance Scores

• loftool: 0.00875
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.04

Haploinsufficiency Scores

• pHI: 0.879
• hipred: Y
• hipred_score: 0.729
• ghis: 0.584

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Thrb
• Phenotype: respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; reproductive system 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); 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); hematopoietic system phenotype; vision/eye phenotype; limbs/digits/tail phenotype; 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; skeleton phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: thrb
• Affected structure: horizontal cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;thyroid hormone mediated signaling pathway;transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;multicellular organism development;sensory perception of sound;negative regulation of female receptivity;regulation of heart contraction;female courtship behavior;hormone-mediated signaling pathway;animal organ morphogenesis;cell differentiation;intracellular receptor signaling pathway;thyroid gland development;response to lipid;negative regulation of eye photoreceptor cell development;steroid hormone mediated signaling pathway;positive regulation of transcription by RNA polymerase II;retinal cone cell development;type I pneumocyte differentiation;retinal cone cell apoptotic process
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;nuclear body;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;DNA-binding transcription factor activity;steroid hormone receptor activity;transcription corepressor activity;nuclear receptor activity;protein binding;transcription factor binding;zinc ion binding;enzyme binding;nuclear receptor transcription coactivator activity;chromatin DNA binding;signaling receptor activity;thyroid hormone binding