Locus VACTERLX ZIC3
Disease ID
VACTERLX
Gene ID
ZIC3
Updated
Oct 2, 2026
v2.27.0
v2.27.0
Other gene loci
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Clinical Links
Disease
NameX-linked VACTERL syndrome
Inheritance
DescriptionVACTERL is an acronym for vertebral anomalies (similar to those of spondylocostal dysplasia), anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies (urethral atresia with hydronephrosis), and limb anomalies1 .
Age of Onset0
HPO Terms
HP:0000068 Urethral atresiaHP:0000105 Enlarged kidneyHP:0000126 HydronephrosisHP:0000238 HydrocephalusHP:0000925 Abnormality of the vertebral columnHP:0000960 Sacral dimpleHP:0001161 Hand polydactylyHP:0001561 PolyhydramniosHP:0001651 DextrocardiaHP:0001669 Transposition of the great arteriesHP:0002023 Anal atresiaHP:0002032 Esophageal atresiaHP:0002089 Pulmonary hypoplasiaHP:0002575 Tracheoesophageal fistulaHP:0003468 Abnormal vertebral morphologyHP:0003974 Absent radiusHP:0005301 Persistent left superior vena cavaHP:0005792 Short humerusHP:0006695 Atrioventricular canal defectHP:0008750 Laryngeal atresiaHP:0009623 Proximal placement of thumbHP:0010963 Absence of stomach bubble on fetal sonographyHP:0030680 Abnormal cardiovascular system morphologyHP:0031853 Isomerism
Association
Mendelian
Locus
DetailsFrequently genotyped as (NGC)*, although locus structure has been reported as (GCC)8(GCT)(GCC)4 . 1 patient with VACTERL died at birth with 12 repeats3 . 8 patients with X-linked oculo-auriculo-vertebral spectrum (OAVS) had 11 repeats (intermediate allele size); 1 individual in OAVS cohort with 12 repeats; likely phenotypic spectrum5 . Full-mutation alleles of 12 repeats were observed in three apparently unaffected individuals, two females and one male, from population long-read cohorts. One female showed skewed X-inactivation of the expanded allele6 .
MechanismPolyalanine expansion with unknown mechanism7 .
Unknown
Detection
Year
Year first published
20103
Location in Gene
Coding Exon 1
Gene Strand
Alleles
Ref. Motif Reference motif, reference orientation
GCN
Ranges
Benign (ref.) Benign motif, reference orientation
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Benign (gene) Benign motif, gene orientation
–
Pathogenic (ref.) Pathogenic motif, reference orientation
GCN
Pathogen. (gene) Pathogenic motif, gene orientation
GCN
Unknown (ref.) Unknown motif, reference orientation
–
Unknown (gene) Unknown motif, gene orientation
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Interruption (ref.) Interruption motif, reference orientation
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Interrup. (gene) Interruption motif, gene orientation
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gnomAD
References
Direct supporting references for info on this page.
2
Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions
Stephanie E.,Wallace, Lora JH,Bean
GeneReviews® [Internet] · 2022-10-20
genereviews:NBK5351483
Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder?
Marja W,Wessels, Brian,Kuchinka, Rogier,Heydanus, Bert J,Smit, Dennis,Dooijes, Ronald R,de Krijger, Maarten H,Lequin, Elisabeth M,de Jong, Margreet,Husen, Patrick J,Willems, Brett,Casey
Journal of medical genetics · 2010-05-01
pmid:204529984
Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.
Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman
Nature reviews. Genetics · 2024-03-11
pmid:384677845
Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3.
Aurélien,Trimouille, Angèle,Tingaud-Sequeira, Didier,Lacombe, Tina,Duelund Hjortshøj, Sven,Kreiborg, Hanne,Buciek Hove, Caroline,Rooryck
Clinical genetics · 2020-10-01
pmid:32639022Additional Literature
Additional literature related to this locus.
Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)
Reanalysis of Next-Generation Sequencing Data to Detect Tandem Repeat Expansions in 1,106 Czech Probands With Neurologic Disease.
Alena,Musilova, Petra,Lassuthova, Anna,Uhrova Meszarosova, Barbora,Straka, Jana,Krejcikova, Anna,Berounska, Marketa,Vlckova, Zuzana,Musova, Dana,Safka Brozkova
Neurology. Genetics · 2025-06-25
pmid:40585427