TXNL4A
Chr 18ARthioredoxin like 4A
Also known as: BMKS, DIB1, DIM1, SNRNP15, TXNL4, U5-15kD
The encoded protein is a component of the U5 small ribonucleoprotein particle that functions in pre-mRNA splicing as part of spliceosome assembly and the precatalytic spliceosome B complex. Mutations cause Burn-McKeown syndrome, a rare autosomal recessive disorder characterized by craniofacial dysmorphisms, cardiac defects, hearing loss, and bilateral choanal atresia. The gene shows low constraint against loss-of-function variants (pLI ~0, LOEUF 1.8), consistent with the recessive inheritance pattern.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Moderately missense-constrained (top ~2.5%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
231 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 0 | 164 | 0 | 166 |
Likely Pathogenic | 2 | 0 | 10 | 0 | 12 |
VUS | 1 | 10 | 18 | 0 | 29 |
Likely Benign | 0 | 0 | 4 | 3 | 7 |
Benign | 0 | 0 | 11 | 1 | 12 |
| Total | 5 | 10 | 207 | 4 | 226 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TXNL4A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools