TXNDC17

Chr 17

thioredoxin domain containing 17

Also known as: TRP14, TXNL5

NCBI Gene: 84817 ENSG00000129235 UniProt: Q9BRA2

The protein functions as a disulfide reductase with peroxidase activity, catalyzing redox reactions and modulating TNF signaling pathways while helping eliminate cellular hydrogen peroxide. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. This condition primarily affects the central nervous system with developmental and neurological manifestations.

ResearchSummary from RefSeq, UniProt

Enables peroxidase activity and protein-disulfide reductase [NAD(P)H] activity. Involved in tumor necrosis factor-mediated signaling pathway. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.18

Clinical Summary— TXNDC17

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

20 VUS of 35 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?

1.18LOEUF

pLI 0.039

Z-score 1.28

OE 0.46 (0.21–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.16Z-score

OE missense 0.94 (0.77–1.17)

63 obs / 66.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.21–1.18)

0≤0.351.4

Missense OE?0.94 (0.77–1.17)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 3 / 6.5Missense obs/exp: 63 / 66.7Syn Z: -0.59

This gene — mechanism propensity

0.6743th %ile

GOF

0.5563th %ile

LOF

0.2582th %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

35 submitted variants in ClinVar

ClinVar

Classification Summary

VUS20

Benign2

VUS

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	20	0	20
Likely Benign	0	0	0
Benign	1	1	2
Total	21	1	22

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap TXNDC17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →