Curation VACTERLX ZIC3

Gene ZIC3

Disease VACTERLX

Inheritance XR

Score

3.5 + 0 = 3.5 / 18

Genetic + experimental = total

Classification

Limited

Refuted

Moderate

Definitive

Last Updated 08/18/2025

Pubs Reviewed 2

Publication Span 10.42 years

Publication Interval 10.42 years

Curator(s) Macayla Weiner, Laurel Hiatt

Description

ZIC3 VACTERLX is supported by two reports of N-terminal polyalanine repeat expansions: a de novo 10-to-12 alanine expansion in one male with VACTERL association overlapping X-linked heterotaxy, and a later report of a large X-linked OAVS family with segregation of a 10-to-11 alanine expansion plus one unrelated male OAVS case with a 10-to-12 alanine expansion. The evidence is locus-specific for the ZIC3 coding polyalanine tract and remains Limited based on available proband/family evidence.

All criTRia Curations Locus Page

Genetic evidence

Total: 3.5

Per page

Category	Type	Citation	Score	Details
Singular Evidence	Probands	PMID:20452998 PMID:32639022	3.5	PMID 20452998: one male neonate with VACTERL association/heterotaxy overlap carried a de novo ZIC3 c.165_166insGCCGCC polyalanine expansion (10 to 12 alanines), absent from the mother and 336 control X chromosomes. PMID 32639022: one X-linked OAVS family had eight affected males segregating ZIC3 c.159_161dup p.(Ala55dup) expansion (10 to 11 alanines), and one unrelated male OAVS case carried a 10-to-12 alanine expansion.

Experimental evidence

Total: 0

No experimental evidence details available.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.