ZRS ZPA regulatory sequence [Homo sapiens (human)] - Gene

Summary

Gene symbol: ZRS
Gene description: ZPA regulatory sequence
Primary source: MIM:620738
Gene type: biological region
Feature type(s): misc_feature: conserved_region
regulatory: enhancer, transcriptional_cis_regulatory_region
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: pZRS; MFCS1; ZRS/LMBR1
Summary: This locus represents a highly conserved functional element that is located in an intron of the limb development membrane protein 1 (LMBR1) gene. In the developing limb bud, this element functions as a long-range enhancer of the sonic hedgehog signaling molecule (SHH) gene, which is located approximately 1 Mb downstream. Mutations in this element disrupt limb patterning and can result in a range of congenital limb malformations, including preaxial polydactyly, triphalangeal thumbs, Werner mesomelic syndrome (WMS), polysyndactyly, or Laurin-Sandrow syndrome. [provided by RefSeq, Feb 2019]
Orthologs: mouse all
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Genomic context

Location:: 7q

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (156790708..156793079)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (157978491..157980862)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (156583402..156585773)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The heterozygous mutation of the ZRS (105C>G) probably underlies the congenital limb malformations in this family
Title: [Genetic analysis of one family with congenital limb malformations].
Our work describes the first mutation in the pZRS to be associated with triphalangeal thumb-polysyndactyly syndrome (TPT-PS)and provides functional evidence that this mutation leads to ectopic expression of this enhancer within the developing limb
Title: A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome.
71% of the index patients had a more severe phenotype compared to their great-grandparent. Although all family members share an identical mutation in the ZRS (105C>G), it does not explain the wide phenotypic range of anomalies. Our observational study provides better estimations for counseling and provides new insights in the long-range regulation of SHH by the ZRS-enhancer.
Title: Intrafamilial variability of the triphalangeal thumb phenotype in a Dutch population: Evidence for phenotypic progression over generations?
the first report of the assessment of the frequency of GLI3/SHH/preZRS/ZRS in Chinese polydactyly patients to show any higher possibility of mutations or variants for the 4 genes or sequences in China
Title: Mutational screening of GLI3, SHH, preZRS, and ZRS in 102 Chinese children with nonsyndromic polydactyly.

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Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Polydactyly of a triphalangeal thumb MedGen: C1868114 OMIM: 174500 GeneReviews: Not available	Compare labs
Tibia, hypoplasia or aplasia of, with polydactyly MedGen: C1861098 OMIM: 188740 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

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General gene information

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Other Names

VISTA enhancer hs2496
ZPA-specific enhancer
ZRS limb enhancer
ZRS/SHH enhancer
mammal-fish-conserved-sequence 1
zone of polarizing activity regulatory sequence

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.