# NM_006701.2:c.Exon 3 deletion

https://sugi.bio/variant/txnl4a-c-exon

## Summary

**TXNL4A c.Exon** is classified **Pathogenic** in TXNL4A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-03-28). Associated with choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome.

**At a glance:** Pathogenic · review: No assertion criteria · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the TXNL4A gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0010041/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [TXNL4A](https://sugi.bio/atlas/gene/TXNL4A/) |
| Coding change (HGVS c.) | c.Exon |
| MANE Select transcript | [NM_006701](https://www.ncbi.nlm.nih.gov/nuccore/NM_006701) |
| Variant type | Deletion |
| ClinVar | [VCV253189](https://www.ncbi.nlm.nih.gov/clinvar/variation/253189/) |

## Gene constraint & dosage {#gene-context}

**TXNL4A** population constraint: LOEUF 1.848, pLI 2.3119e-07, missense-Z 2.8181. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 88.21, 71% of residues very-high.

**32 experimental structure(s)** (PDB): [1PQN](https://www.rcsb.org/structure/1PQN), [1QGV](https://www.rcsb.org/structure/1QGV), [1SYX](https://www.rcsb.org/structure/1SYX), [3JCR](https://www.rcsb.org/structure/3JCR), [4BWQ](https://www.rcsb.org/structure/4BWQ), [4BWS](https://www.rcsb.org/structure/4BWS).

## What this gene does {#gene-function}

*Describes the biological roles of TXNL4A (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** TXNL4A participates in disease-associated pathways. In Reactome, TXNL4A is annotated in disease pathway(s) including **Dengue Virus-Host Interactions**.

**Disease mechanism (Reactome):** TXNL4A loss or alteration is curated in [Dengue Virus-Host Interactions](https://reactome.org/content/detail/R-HSA-9918481).

### Pathways affected {#pathways}

TXNL4A participates in **3 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Dengue Virus-Host Interactions](https://reactome.org/content/detail/R-HSA-9918481) | other |
| [mRNA Splicing - Major Pathway](https://reactome.org/content/detail/R-HSA-72163) | other |
| [mRNA Splicing - Minor Pathway](https://reactome.org/content/detail/R-HSA-72165) | other |

### Molecular function & processes (GO — experimentally supported) {#go}

**Biological process:** mRNA splicing, via spliceosome.

## Clinical significance {#significance}

**Pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2016-03-28.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| GeneReviews | Pathogenic | no assertion criteria provided | literature only | 2016-03-28 |

## Associated conditions {#conditions}

[choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome](https://sugi.bio/atlas/disease/choanal-atresia-hearing-loss-cardiac-defects-craniofacial-dysmorphism-syndrome/).

**Reported phenotype names (ClinVar):** Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome, OCULOOTOFACIAL DYSPLASIA, Branchio oculo facial syndrome Hing type, Burn-McKeown Syndrome (BMKS), Burn-McKeown syndrome.

## Similar variants {#similar}

Related TXNL4A variant pages (same residue, condition, or type): [TXNL4A p.Phe30fs](/variant/txnl4a-p-phe30fs), [TXNL4A p.Asn87Alafs](/variant/txnl4a-p-asn87alafs), [TXNL4A p.His32fs](/variant/txnl4a-p-his32fs), [TXNL4A p.Asn87Ser](/variant/txnl4a-p-asn87ser), [TXNL4A p.Val25Glu](/variant/txnl4a-p-val25glu), [TXNL4A p.Arg141=](/variant/txnl4a-p-arg141), [TXNL4A p.Gly97fs](/variant/txnl4a-p-gly97fs), [TXNL4A c.-61+1G>A](/variant/txnl4a-c-minus-61-plus-1g-a).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 253189). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*