TSHB

thyroid stimulating hormone subunit beta, the group of Receptor ligands|Glycoprotein hormone subunits

Basic information

Region (hg38): 1:115029826-115034302

Links

ENSG00000134200 ∙ NCBI:7252 ∙ OMIM:188540 ∙ HGNC:12372 ∙ Uniprot:P01222 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated thyroid-stimulating hormone deficiency (Definitive), mode of inheritance: AR
• isolated thyroid-stimulating hormone deficiency (Strong), mode of inheritance: AR
• isolated thyroid-stimulating hormone deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypothyroidism, congenital, nongoitrous, 4	AR	Endocrine	The untreated condition can result in severe neurological damage, and recognition can allow early medical treatment with thyroid hormone replacement can prevent such sequelae	Endocrine	2792087; 1971148; 8636437; 9589689; 11297590; 11549695; 12364478; 11788671; 15292359; 16804796

ClinVar

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

• not provided (5 variants)
• Isolated thyroid-stimulating hormone deficiency (2 variants)
• Pituitary hypothyroidism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSHB 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				24		24
missense			11	1	2	14
nonsense		1				1
start loss						0
frameshift	4					4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region	1			3		4
non coding			1	6	3	10
Total	4	1	12	31	5

Highest pathogenic variant AF is 0.000158

Variants in TSHB

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

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

Position	Type	Phenotype	Significance	ClinVar
1-115029849-A-G		Isolated thyroid-stimulating hormone deficiency	Likely benign (Jan 13, 2018)
1-115033094-A-G			Benign (Nov 12, 2018)
1-115033374-C-T			Likely benign (Sep 26, 2023)
1-115033389-GC-G			Pathogenic (Sep 26, 2023)
1-115033402-A-G		not specified • Congenital hypothyroidism • Isolated thyroid-stimulating hormone deficiency	Benign (Feb 01, 2024)
1-115033403-C-T		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
1-115033416-G-A			Likely benign (Jan 27, 2024)
1-115033443-T-C			Likely benign (Sep 08, 2023)
1-115033455-C-T			Likely benign (Jan 17, 2024)
1-115033456-G-T		Isolated thyroid-stimulating hormone deficiency	Pathogenic (May 01, 1990)
1-115033466-AGT-A		Isolated thyroid-stimulating hormone deficiency	Pathogenic (-)
1-115033474-T-C		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
1-115033494-C-T			Likely benign (Jun 28, 2023)
1-115033498-A-T		Inborn genetic diseases	Uncertain significance (May 31, 2022)
1-115033503-T-G		not specified	Uncertain significance (May 22, 2024)
1-115033507-G-A		Isolated thyroid-stimulating hormone deficiency	Pathogenic (May 23, 2024)
1-115033521-A-G			Likely benign (Jan 17, 2024)
1-115033522-C-A			Likely benign (Mar 27, 2023)
1-115033529-G-A		Isolated thyroid-stimulating hormone deficiency	Pathogenic (Feb 20, 2024)
1-115033540-C-T			Benign (Jan 28, 2024)
1-115033541-A-G			Likely benign (Apr 16, 2023)
1-115033542-C-T			Likely benign (Jan 25, 2024)
1-115033861-C-G			Benign (Jun 19, 2021)
1-115033947-T-C		TSHB-related disorder	Uncertain significance (Oct 18, 2023)
1-115033953-C-T			Likely benign (Jul 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSHB	protein_coding	protein_coding	ENST00000256592	2	4527

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00836	0.583	125709	0	8	125717	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.304	66	73.3	0.900	0.00000357	906
Missense in Polyphen		22	25.194	0.87321		319
Synonymous	-0.519	29	25.7	1.13	0.00000127	263
Loss of Function	0.215	3	3.43	0.875	1.45e-7	58

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)	0.0000616	0.0000616
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Indispensable for the control of thyroid structure and metabolism.
• Pathway: Regulation of lipolysis in adipocytes - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Autoimmune thyroid disease - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Human Thyroid Stimulating Hormone (TSH) signaling pathway;Signaling by GPCR;Signal Transduction;Peptide hormone metabolism;Metabolism of proteins;GPCR signaling-G alpha q;Metabolism of amino acids and derivatives;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Metabolism;G alpha (s) signalling events;Hormone ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;TSH;Thyroxine biosynthesis;Amine-derived hormones;Glycoprotein hormones;GPCR downstream signalling;Peptide hormone biosynthesis (Consensus)

Recessive Scores

• pRec: 0.649

Intolerance Scores

• loftool: 0.460
• rvis_EVS: 0.3
• rvis_percentile_EVS: 72.01

Haploinsufficiency Scores

• pHI: 0.629
• hipred: N
• hipred_score: 0.398

Essentials

• essential_gene_CRISPR: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tshb
• Phenotype: growth/size/body region phenotype; reproductive system phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;cell-cell signaling;anatomical structure morphogenesis;hormone-mediated signaling pathway;regulation of signaling receptor activity;peptide hormone processing;response to vitamin A;response to estrogen;response to calcium ion
• Cellular component: extracellular region;extracellular space;cytoplasm
• Molecular function: hormone activity