TPO

thyroid peroxidase, the group of Sushi domain containing

Basic information

Region (hg38): 2:1374066-1543711

Links

ENSG00000115705

∙ NCBI:7173 ∙ OMIM:606765 ∙ HGNC:12015 ∙ Uniprot:P07202 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

thyroid dyshormonogenesis 2A (Strong), mode of inheritance: AR
familial thyroid dyshormonogenesis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid dyshormonogenesis 2A	AR	Endocrine; Oncologic	Medical treatment of hypothyroidism (eg, with T4) can be effective; Thyroid neoplasms have also been reported, and surveillance may be beneficial	Endocrine; Oncologic	1401057; 8027236; 9814507; 10084596

ClinVar

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

not_provided (623 variants)
Deficiency_of_iodide_peroxidase (159 variants)
Inborn_genetic_diseases (72 variants)
not_specified (38 variants)
TPO-related_disorder (22 variants)
Congenital_hypothyroidism (5 variants)
Neurodevelopmental_disorder (1 variants)
Delayed_gross_motor_development (1 variants)
Protruding_tongue (1 variants)
Global_developmental_delay (1 variants)
Delayed_speech_and_language_development (1 variants)
Intellectual_disability,_severe (1 variants)
Short_stature (1 variants)
Hypothyroidism_due_to_TSH_receptor_mutations (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPO gene is commonly pathogenic or not. These statistics are base on transcript: NM_001206744.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		2 clinvar	4 clinvar	313 clinvar	10 clinvar	329
missense	10 clinvar	22 clinvar	136 clinvar	20 clinvar	4 clinvar	192
nonsense	17 clinvar	10 clinvar	1 clinvar			28
start loss						0
frameshift	30 clinvar	14 clinvar	1 clinvar	1 clinvar		46
splice donor/acceptor (+/-2bp)		20 clinvar				20
Total	57	68	142	334	14

Highest pathogenic variant AF is 0.000670944

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPO	protein_coding	protein_coding	ENST00000345913	16	169489

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.82e-21	0.0210	125581	0	167	125748	0.000664

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00335	567	567	1.00	0.0000398	5971
Missense in Polyphen		183	196.02	0.93359		2236
Synonymous	-0.865	276	258	1.07	0.0000213	1938
Loss of Function	0.980	36	42.9	0.839	0.00000226	459

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00125	0.00124
Ashkenazi Jewish	0.00139	0.00139
East Asian	0.00191	0.00190
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000617	0.000615
Middle Eastern	0.00191	0.00190
South Asian	0.000657	0.000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4). {ECO:0000250|UniProtKB:P09933}.;
Disease: DISEASE: Note=An alternative splicing in the thyroperoxidase mRNA can cause Graves' disease.; DISEASE: Thyroid dyshormonogenesis 2A (TDH2A) [MIM:274500]: A disorder due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete. {ECO:0000269|PubMed:10084596, ECO:0000269|PubMed:10468986, ECO:0000269|PubMed:11061528, ECO:0000269|PubMed:11415848, ECO:0000269|PubMed:11874711, ECO:0000269|PubMed:11916616, ECO:0000269|PubMed:12213873, ECO:0000269|PubMed:12490071, ECO:0000269|PubMed:12843174, ECO:0000269|PubMed:12864797, ECO:0000269|PubMed:12938097, ECO:0000269|PubMed:16284446, ECO:0000269|PubMed:16684826, ECO:0000269|PubMed:27305979, ECO:0000269|PubMed:7550241, ECO:0000269|PubMed:9024270, ECO:0000269|PubMed:9924196}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Thyroid hormone synthesis - Homo sapiens (human);Autoimmune thyroid disease - Homo sapiens (human);Tyrosine metabolism - Homo sapiens (human);Thyroid hormone synthesis;Thyroxine (Thyroid Hormone) Production;Differentiation Pathway;Hematopoietic Stem Cell Differentiation;Development of pulmonary dendritic cells and macrophage subsets;Amino Acid metabolism;Metabolism of amino acids and derivatives;thyroid hormone biosynthesis;Tyrosine metabolism;Androgen and estrogen biosynthesis and metabolism;Purine metabolism;Metabolism;Thyroxine biosynthesis;Amine-derived hormones (Consensus)

Recessive Scores

pRec: 0.482

Intolerance Scores

loftool: 0.854
rvis_EVS: -0.14
rvis_percentile_EVS: 42.36

Haploinsufficiency Scores

pHI: 0.186
hipred: N
hipred_score: 0.489
ghis: 0.441

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.764

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tpo
Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear 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; skeleton phenotype; immune system phenotype; vision/eye phenotype;

Gene ontology

Biological process: thyroid hormone generation;response to oxidative stress;embryonic hemopoiesis;hormone biosynthetic process;hydrogen peroxide catabolic process;oxidation-reduction process;cellular oxidant detoxification
Cellular component: extracellular space;plasma membrane;integral component of plasma membrane;cell surface
Molecular function: iodide peroxidase activity;peroxidase activity;calcium ion binding;heme binding