TSHB

protein-coding

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

Gene summary

The four human glycoprotein hormones chorionic gonadotropin (CG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) are dimers consisting of alpha and beta subunits that are associated noncovalently. The alpha subunits of these hormones are identical, however, their beta chains are unique and confer biological specificity. Thyroid stimulating hormone functions in the control of thyroid structure and metabolism. The protein encoded by this gene is the beta subunit of thyroid stimulating hormone. Mutations in this gene are associated with congenital central and secondary hypothyroidism and Hashimoto's thyroiditis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

MANE transcript

NM_000549.5

Inheritance

ClinVar variants

P:11U:29B:28

Top phenotype

Hypothyroidism, congenital, nongoitrous, 4

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr1:115,029,826-115,034,302

External References & Databases

Ensembl (ENSG00000134200)

Transcript & Mutation Effects

hg38 • Region Span ~4.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated thyroid-stimulating hormone deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010139

Submitter: Labcorp Genetics (formerly Invitae)

isolated thyroid-stimulating hormone deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010139

Submitter: G2P

isolated thyroid-stimulating hormone deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010139

Submitter: Orphanet

isolated thyroid-stimulating hormone deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010139

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hypothyroidism, congenital, nongoitrous, 4AR

Manifestation: Endocrine

Intervention: Endocrine

Rationale: The untreated condition can result in severe neurological damage, and recognition can allow early medical treatment with thyroid hormone replacement can prevent such sequelae

Refs: 2792087; 1971148; 8636437; 9589689; 11297590; 11549695; 12364478; 11788671; 15292359; 16804796

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TSHB variants in ClinVar

6 Conditions Cataloged

not providedTotal: 45

Inborn genetic diseasesTotal: 24

Isolated thyroid-stimulating hormone deficiencyTotal: 15

TSHB-related disorderTotal: 5

not specifiedTotal: 5

Pituitary hypothyroidismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000549.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				26 clinvar		26
missense		1 clinvar	29 clinvar	2 clinvar		32
nonsense	1 clinvar	2 clinvar				3
start loss		1 clinvar				1
frameshift	4 clinvar	2 clinvar				6
splice donor/acceptor (+/-2bp)						0
Total	5	6	29	28	0	68

Highest pathogenic variant AF is 0.0003321555

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000549.5	RefSeq	NP_000540.2	2	MANE Select
ENST00000256592.3	Ensembl	ENSP00000256592.1	2	MANE Select
NM_001277991.1	RefSeq	NP_001264920.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

G protein-coupled receptor signaling pathway
cell-cell signaling
anatomical structure morphogenesis
hormone-mediated signaling pathway
regulation of signaling receptor activity

Molecular Function

hormone activity

Cellular Component

extracellular region
extracellular space
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256592
Coding exons: 2
Length: 4527
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125717
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.304	66	73.3	0.900	0.00000357	906
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Indispensable for the control of thyroid structure and metabolism.;

Recessive Scores

pRec: 0.649

Intolerance Scores

LoFtool: 0.460
RVIS EVS: 0.3
RVIS percentile EVS: 72.01

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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