DIO1 iodothyronine deiodinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DIO1provided by HGNC
Official Full Name: iodothyronine deiodinase 1provided by HGNC
Primary source: HGNC:HGNC:2883
See related: Ensembl:ENSG00000211452 MIM:147892; AllianceGenome:HGNC:2883
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: 5DI; THMA2; TXDI1
Summary: The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the activation, as well as the inactivation of thyroid hormone by outer and inner ring deiodination, respectively. The activation reaction involves the conversion of the prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4), secreted by the thyroid gland, to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by 5'-deiodination. This protein provides most of the circulating T3, which is essential for growth, differentiation and basal metabolism in vertebrates. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2018]
Expression: Biased expression in thyroid (RPKM 180.4), kidney (RPKM 58.4) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 1p32.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (53894187..53911086)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (53777070..53793996)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (54359860..54376759)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A regulatory element associated to NAFLD in the promoter of DIO1 controls LDL-C, HDL-C and triglycerides in hepatic cells.
Title: A regulatory element associated to NAFLD in the promoter of DIO1 controls LDL-C, HDL-C and triglycerides in hepatic cells.
SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients.
Title: SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients.
Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes.
Title: Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes.
Novel DIO1 Gene Mutation Acting as Phenotype Modifier for Novel Compound Heterozygous TPO Gene Mutations Causing Congenital Hypothyroidism.
Title: Novel DIO1 Gene Mutation Acting as Phenotype Modifier for Novel Compound Heterozygous TPO Gene Mutations Causing Congenital Hypothyroidism.
Human Type 1 Iodothyronine Deiodinase (DIO1) Mutations Cause Abnormal Thyroid Hormone Metabolism.
Title: Human Type 1 Iodothyronine Deiodinase (DIO1) Mutations Cause Abnormal Thyroid Hormone Metabolism.
Deiodinases, organic anion transporter polypeptide polymorphisms and symptoms of anxiety and depression after ischemic stroke.
Title: Deiodinases, organic anion transporter polypeptide polymorphisms and symptoms of anxiety and depression after ischemic stroke.
Our results indicate that increased thyroidal D1 and D2 activities may be responsible for the higher serum FT3/FT4 ratio in patients with huge goitrous Hashimoto's thyroiditis.
Title: Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with huge goitrous Hashimoto's thyroiditis.
polymorphisms in DIO1 are associated with aerobic endurance performance
Title: [Association between DIO polymorphism and aerobic endurance].
this current study found that the serum DIO-1 concentration was inversely correlated with the concentration of TNF-alpha, which suggests that DIO-1 might inhibit the production of serum TNF-alpha in patients with chronic renal failure
Title: The relationship between inflammatory factors, oxidative stress and DIO-1 concentration in patients with chronic renal failure accompanied with or without euthyroid sick syndrome.
Multivariate linear regression analysis revealed that the DIO1 concentration and FT3 level were not associated with the concentration of serum 8-Isoprostane
Title: Investigation of the Oxidative Stress and DIO1 Expression in CRF Patients Accompanied With and Without Euthyroid Sick Syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (46)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Thyroid hormone metabolism, abnormal, 2 MedGen: C5676976 OMIM: 619855 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. EBI GWAS Catalog EBI GWAS CatalogPubMed
The CCND1 c.870G&gt;A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S3255 (e-PCR)
- UniSTS:64333

RH80009 (e-PCR)
- UniSTS:85589

NoName (e-PCR)
- UniSTS:489676

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables selenium binding	TAS Traceable Author Statement more info	PubMed
enables thyroxine 5'-deiodinase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in amino acid metabolic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in hormone biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in thyroid hormone generation	TAS Traceable Author Statement more info	PubMed
involved_in thyroid hormone metabolic process	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: type I iodothyronine deiodinase

Names: DIOI; deiodinase, iodothyronine type I; iodothyronine deiodinase type 1; selenoprotein DIO1; thyroxine 5'-deiodinase; thyroxine deiodinase type I (selenoprotein); type 1 DI; type-I 5'-deiodinase

NP_000783.2

EC 1.21.99.4

NP_001034804.1

EC 1.21.99.4

NP_001034805.1

EC 1.21.99.4

NP_001311245.1

EC 1.21.99.4

NP_998758.1

EC 1.21.99.4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023306.1 RefSeqGene

Range

5000..21899

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000792.7 → NP_000783.2 type I iodothyronine deiodinase isoform a

See identical proteins and their annotated locations for NP_000783.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).

Source sequence(s)

AK290780, BC017955, BE046205

Consensus CDS

CCDS41339.1

UniProtKB/Swiss-Prot

P49895, Q1RN02, Q3KNP8, Q6Q4C1, Q6Q4C2, Q6Q4C3, Q6Q4C4, Q6Q4C5, Q6Q4C6, Q6Q4C7, Q6Q4C9, Q8WWC6

Related

ENSP00000354643.4, ENST00000361921.8

Conserved Domains (1) summary

cl00388
Location:8 → 248

Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold
NM_001039715.3 → NP_001034804.1 type I iodothyronine deiodinase isoform c

See identical proteins and their annotated locations for NP_001034804.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame exon in the coding region compared to variant 1. The resulting isoform (c) is shorter, lacking an internal selenocysteine-containing protein segment compared to isoform a.

Source sequence(s)

AK290780, AY560377, BC017955, BE046205

Consensus CDS

CCDS30722.1

UniProtKB/Swiss-Prot

P49895

UniProtKB/TrEMBL

A8K415

Related

ENSP00000373528.3, ENST00000388876.3

Conserved Domains (1) summary

cl00388
Location:8 → 200

Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold
NM_001039716.3 → NP_001034805.1 type I iodothyronine deiodinase isoform d

See identical proteins and their annotated locations for NP_001034805.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an exon in the 3' coding region, which causes a frameshift compared to variant 1. The resulting isoform (d) is shorter, with a distinct C-terminus compared to isoform a.

Source sequence(s)

AK290780, BC017955, BE046205

Consensus CDS

CCDS41340.1

UniProtKB/Swiss-Prot

P49895

UniProtKB/TrEMBL

A8K415

Related

ENSP00000323198.6, ENST00000322679.10

Conserved Domains (1) summary

cl00388
Location:8 → 160

Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold
NM_001324316.2 → NP_001311245.1 type I iodothyronine deiodinase isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks two internal exons, which causes a frameshift compared to variant 1. The resulting shorter isoform (e) has the same N-terminus but a distinct C-terminus compared to isoform a.

Source sequence(s)

AK290780, AY560381, BC017955, BE046205

Consensus CDS

CCDS81328.1

UniProtKB/TrEMBL

C6ZRC2

Related

ENSP00000434758.1, ENST00000532493.5

Conserved Domains (1) summary

cl00388
Location:8 → 113

Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold
NM_213593.5 → NP_998758.1 type I iodothyronine deiodinase isoform b

See identical proteins and their annotated locations for NP_998758.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame donor splice site at the 5' terminal exon compared to variant 1. The resulting isoform (b) is shorter, lacking a 64 aa protein segment in the 5' coding region compared to isoform a.

Source sequence(s)

AK290780, AY560375, BC017955, BE046205

Consensus CDS

CCDS53320.1

UniProtKB/Swiss-Prot

P49895

UniProtKB/TrEMBL

A8K415

Related

ENSP00000435725.1, ENST00000525202.5

Conserved Domains (1) summary

cl00388
Location:8 → 184

Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

RNA

NR_136692.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses an alternate donor splice site at the 5' terminal exon compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon, as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK290780, AY560379, BC017955, BE046205
NR_136693.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) is alternatively spliced at the 5' end compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon, as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK290780, AY560382, BC017955, BE046205