TXNDC15

Chr 5AR

thioredoxin domain containing 15

Also known as: BUG, C5orf14, MKS14, TMX5, UNQ335

NCBI Gene: 79770ENSG00000113621UniProt: Q96J42

This gene encodes a member of the thioredoxin superfamily. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. [provided by RefSeq, Apr 2017]

Primary Disease Associations & Inheritance

Meckel syndrome 14MIM #619879
AR
0
Active trials
21
Pathogenic / LP
96
ClinVar variants
5
Pubs (1 yr)
0.6
Missense Z
0.76
LOEUF
Clinical Summary— TXNDC15
🧬
Gene-Disease Validity (ClinGen)
ciliopathy · ARStrong

Strong evidence — appropriate for clinical testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 53 VUS of 96 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.010
Z-score 2.26
OE 0.38 (0.21–0.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.56Z-score
OE missense 0.89 (0.79–1.00)
185 obs / 207.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.21–0.76)
0≤0.351.4
Missense OE0.89 (0.79–1.00)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 6 / 15.7Missense obs/exp: 185 / 207.8Syn Z: 0.61
DN
DN
0.6260th %ile
GOF
0.5955th %ile
LOF
0.3551th %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

96 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS53
Likely Benign14
Benign6
Conflicting2
20
Pathogenic
1
Likely Pathogenic
53
VUS
14
Likely Benign
6
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
16
0
20
Likely Pathogenic
0
0
1
0
1
VUS
0
47
6
0
53
Likely Benign
0
3
2
9
14
Benign
0
1
3
2
6
Conflicting
—2
Total352281196

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

View in ClinVar →

TXNDC15 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 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