DIO1

iodothyronine deiodinase 1, the group of Selenoproteins

Basic information

Region (hg38): 1:53891238-53911086

Previous symbols: [ "TXDI1" ]

Links

ENSG00000211452 ∙ NCBI:1733 ∙ OMIM:147892 ∙ HGNC:2883 ∙ Uniprot:P49895 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid hormone metabolism, abnormal, 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine	32718224; 34128397

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DIO1 gene.

• Inborn genetic diseases (7 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DIO1 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			5	1		6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	6	1	1

Variants in DIO1

This is a list of pathogenic ClinVar variants found in the DIO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-53894343-G-T		not specified	Uncertain significance (Feb 15, 2023)
1-53894346-G-A		not specified	Uncertain significance (Jan 08, 2024)
1-53894353-C-T		not specified	Uncertain significance (Feb 21, 2024)
1-53894391-T-C		not specified	Uncertain significance (Dec 13, 2021)
1-53894439-G-A		not specified	Uncertain significance (Oct 25, 2023)
1-53894442-C-T		not specified	Uncertain significance (Dec 15, 2022)
1-53894492-C-A		Thyroid hormone metabolism, abnormal, 2	Pathogenic (Apr 26, 2022)
1-53894498-G-A			Benign (Mar 29, 2018)
1-53904716-A-C		not specified	Likely benign (Jun 27, 2022)
1-53906119-T-C		not specified	Uncertain significance (Jun 03, 2022)
1-53906216-G-A		Thyroid hormone metabolism, abnormal, 2	Pathogenic (Apr 26, 2022)
1-53906283-A-G		not specified	Uncertain significance (Dec 16, 2022)
1-53909897-C-A		Levothyroxine response	drug response (-)
1-53909970-C-T		not specified	Uncertain significance (Jan 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DIO1	protein_coding	protein_coding	ENST00000361921	4	19848

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.584	0.414	125685	0	38	125723	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.479	127	143	0.887	0.00000773	1655
Missense in Polyphen		38	55.973	0.6789		710
Synonymous	0.198	52	53.8	0.966	0.00000290	473
Loss of Function	2.56	2	11.3	0.177	5.68e-7	112

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000272	0.000272
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000272	0.000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Responsible for the deiodination of T4 (3,5,3',5'- tetraiodothyronine) into T3 (3,5,3'-triiodothyronine) and of T3 into T2 (3,3'-diiodothyronine). Plays a role in providing a source of plasma T3 by deiodination of T4 in peripheral tissues such as liver and kidney.
• Pathway: Thyroid hormone signaling pathway - Homo sapiens (human);Selenium Micronutrient Network;Selenium Metabolism and Selenoproteins;Regulation of thyroid hormone activity;Metabolism of amino acids and derivatives;Tyrosine metabolism;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: 0.594
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.75

Haploinsufficiency Scores

• pHI: 0.230
• hipred: N
• hipred_score: 0.199
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0720

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dio1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: thyroid hormone generation;thyroid hormone metabolic process;hormone biosynthetic process;oxidation-reduction process
• Cellular component: endoplasmic reticulum membrane;plasma membrane;integral component of membrane
• Molecular function: thyroxine 5'-deiodinase activity;selenium binding