DIO1

Chr 1AD

iodothyronine deiodinase 1

Also known as: 5DI, THMA2, TXDI1

NCBI Gene: 1733ENSG00000211452UniProt: P49895OMIM: 147892

The encoded protein is a selenoprotein deiodinase that catalyzes both activation and inactivation of thyroid hormones, converting thyroxine (T4) to the bioactive hormone triiodothyronine (T3) and providing most circulating T3 essential for growth, differentiation, and metabolism. Mutations cause abnormal thyroid hormone metabolism, type 2, inherited in an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.56), indicating some intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.561 OMIM phenotype
Clinical Summary— DIO1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.58) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 27 VUS of 47 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.584
Z-score 2.56
OE 0.18 (0.07–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.48Z-score
OE missense 0.89 (0.77–1.03)
127 obs / 143.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.07–0.56)
0≤0.351.4
Missense OE0.89 (0.77–1.03)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 2 / 11.3Missense obs/exp: 127 / 143.1Syn Z: 0.20
DN
0.6162th %ile
GOF
0.5660th %ile
LOF
0.3549th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic3
VUS27
Likely Benign3
Benign1
11
Pathogenic
3
Likely Pathogenic
27
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
9
0
11
Likely Pathogenic
0
0
3
0
3
VUS
0
23
4
0
27
Likely Benign
1
2
0
0
3
Benign
0
0
0
1
1
Total12716145

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DIO1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients