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Official Full Name
hydrolethalus syndrome 1
Homo sapiens hydrolethalus syndrome 1 (HYLS1), transcript variant 2 as transfection-ready DNA NM_001134793.1

Recent Research Progress

HYLS1, hydrolethalus syndrome protein 1, is a protein that encoded by the HYLS1 gene. The HYLS1 gene consists of six exons spanning 17 KB of genomic regions with several alternative transcripts, which expresses HYLS1, a widely conserved protein. HYLS1a appears to be the longest isoform of this cDNA (2064 bp) consisting of exons 2, 4 and 6. On the basis of the observed EST homologies, this isoform could be identified in uterus, skin, kidney, brain, breast, liver, placenta, colon, lung, fetus, and pooled germ cell tumors, of which the length of exon 2 varies. There is also a variant HYLS1b consisting of exons 2 and 6 that exists. What's more, three other isoforms representing alternative splicing patterns were released in the Celera and NCBI databases with a comprehensive database search. However, none of these three isoforms can be experimentally verified by RT-PCR of RNA from fetal samples. Each transcript has the same conserved translation region encoded by exon 6 as HYLS1a and HYLS1b.

Due to its specific function, the highly conserved HYLS1 protein is inextricably linked to multiple lethal syndromes. According to some researches, transition fibres (TFs), together with the transition zone (TZ), are basal ciliary structures thought to be crucial for cilium biogenesis and function by acting as a ciliary gate to regulate selective protein entry and exit. Some studies demonstrated that the centriolar and basal body protein HYLS1, highly conserved in C. elegans, are essential for TF formation, TZ tissue and ciliary body gating. The absence of HYLS1 impairs the docking and entry of flagellar intra-transport (IFT) particles, ciliary gated membranes and soluble proteins, and axoneme assembly. Additional depletion of the TF component DYF-19 in HYLS1 mutants further exacerbates TZ anomalies and completely abrogates ciliogenesis. The data supported an important role for HYLS1 and TFs in establishment of the ciliary gate and underline the importance of selective protein entry for cilia assembly. It reported that stable incorporation of HYLS-1 into the outer centriole wall during centriole assembly confers on them the capacity to initiate ciliogenesis.

What’s more, as a research reported, Helix 9 of HYLS1 is stabilized by inter-residue electrostatic interaction and hydrogen bonding between Asp 211 and Arg 215. The stability is significantly disrupted by a D211G point mutation which may elicit random coil transition of an alpha helix, leading to the exposure of hydrophobic regions of the protein that aggregate to form nuclear inclusion bodies. This mutation causes hydrolethalus syndrome (HLS), a lethal malformation syndrome. However, the HYLS1 mutation is not just cause hydrolethalus syndrome. Oka M et al. recently reported living sibling patients with a homozygous no-stop mutation in exon 4 of HYLS1 in the second decade of life. The proband has joubert syndrome (JS). The younger brother also has JS and an enlarged posterior fossa that was initially diagnosed as Dandy Walker malformation. The mutation is unique as it affects the stop codon. Therefore we have reason to believe that HYLS1 plays an essential role in the formation of the primary cilium and cilium dysfunction or ciliopathy is closely related to various diseases of the line brain defect.


  1. Wei Q, et al. The hydrolethalus syndrome protein HYLS-1 regulates formation of the ciliary gate. Nature Communications, 2016, 7:12437.
  2. Oka M, et al. A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome. Clinical Genetics, 2016, 89(6):739-743.

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