TXNDC11

Chr 16

thioredoxin domain containing 11

Also known as: EFP1

TXNDC11 encodes a protein that acts as a redox regulator involved in folding of DUOX1 and DUOX2 proteins, which are essential components of the thyroid hydrogen peroxide generating system required for thyroid hormone synthesis. Mutations cause congenital hypothyroidism with goiter, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants, and the thyroid dysfunction typically presents in the neonatal period.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.82
Clinical SummaryTXNDC11
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.000
Z-score 2.45
OE 0.57 (0.410.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.28Z-score
OE missense 1.16 (1.081.24)
593 obs / 511.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.410.82)
00.351.4
Missense OE1.16 (1.081.24)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 22 / 38.4Missense obs/exp: 593 / 511.5Syn Z: -2.57
DN
0.6550th %ile
GOF
0.7029th %ile
LOF
0.2776th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TXNDC11 · 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

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC