DIO2

iodothyronine deiodinase 2, the group of Selenoproteins

Basic information

Region (hg38): 14:80197525-80387757

Links

ENSG00000211448 ∙ NCBI:1734 ∙ OMIM:601413 ∙ HGNC:2884 ∙ Uniprot:Q92813 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DIO2 gene.

• Inborn genetic diseases (5 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DIO2 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					1	1
missense			4	1		5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	4	1	1

Variants in DIO2

This is a list of pathogenic ClinVar variants found in the DIO2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-80201236-G-A		Levothyroxine response	other (-)
14-80202694-C-A		not specified	Uncertain significance (Nov 04, 2022)
14-80202706-T-C		not specified	Uncertain significance (Feb 27, 2023)
14-80202748-G-A		not specified	Uncertain significance (Oct 06, 2023)
14-80202892-G-C		not specified	Uncertain significance (Feb 02, 2022)
14-80202894-G-A		not specified	Uncertain significance (Apr 17, 2023)
14-80203065-T-G		not specified	Uncertain significance (Dec 19, 2023)
14-80203237-T-C		Levothyroxine response	other (-)
14-80203244-G-C			Benign (Aug 16, 2018)
14-80211286-C-T		not specified	Likely benign (Jun 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DIO2	protein_coding	protein_coding	ENST00000555750	3	190228

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.620	0.379	124599	0	3	124602	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.935	137	171	0.799	0.00000981	1984
Missense in Polyphen		46	67.988	0.67659		772
Synonymous	0.987	58	68.4	0.848	0.00000380	627
Loss of Function	2.63	2	11.7	0.171	6.49e-7	136

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Responsible for the deiodination of T4 (3,5,3',5'- tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.
• Pathway: Thyroid hormone signaling pathway - Homo sapiens (human);Selenium Micronutrient Network;Selenium Metabolism and Selenoproteins;Angiopoietin Like Protein 8 Regulatory Pathway;Regulation of thyroid hormone activity;Metabolism of amino acids and derivatives;Metabolism;thyroid hormone metabolism II (via conjugation and/or degradation);thyroid hormone metabolism I (via deiodination);thyronamine and iodothyronamine metabolism;Thyroxine biosynthesis;Amine-derived hormones (Consensus)

Intolerance Scores

• loftool: 0.715
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.64

Haploinsufficiency Scores

• pHI: 0.125
• hipred: N
• hipred_score: 0.269
• ghis: 0.487

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.122

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dio2
• Phenotype: homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: dio2
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: orientation

Gene ontology

• Biological process: selenocysteine incorporation;thyroid hormone generation;thyroid hormone metabolic process;hormone biosynthetic process;oxidation-reduction process;positive regulation of cold-induced thermogenesis
• Cellular component: plasma membrane;membrane;integral component of membrane
• Molecular function: thyroxine 5'-deiodinase activity;selenium binding;ubiquitin protein ligase binding