TXNDC11

Chr 16

thioredoxin domain containing 11

Also known as: EFP1

NCBI Gene: 51061 ENSG00000153066 UniProt: Q6PKC3

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.

ResearchSummary from RefSeq, UniProt

Predicted to be located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.82

Clinical Summary— TXNDC11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

164 VUS of 193 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.45

OE 0.57 (0.41–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.28Z-score

OE missense 1.16 (1.08–1.24)

593 obs / 511.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.57 (0.41–0.82)

0≤0.351.4

Missense OE?1.16 (1.08–1.24)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 22 / 38.4Missense obs/exp: 593 / 511.5Syn Z: -2.57

This gene — mechanism propensity

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

193 submitted variants in ClinVar

ClinVar

Classification Summary

VUS164

Likely Benign9

Benign3

164

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	164	0	164
Likely Benign	8	1	9
Benign	0	3	3
Total	172	4	176

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap TXNDC11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →