HYLS1

Chr 11AR

HYLS1 centriolar and ciliogenesis associated

Also known as: HLS

NCBI Gene: 219844 ENSG00000198331 UniProt: Q96M11 OMIM: 610693

This gene encodes a cytoplasmic protein involved in ciliogenesis, the process of forming cellular cilia that are essential for normal development and cellular signaling. Mutations cause hydrolethalus syndrome, a severe autosomal recessive developmental disorder characterized by lethal congenital malformations. The gene shows low constraint against loss-of-function variants (pLI near zero), which is consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein localized to the cytoplasm. Mutations in this gene are associated with hydrolethalus syndrome. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.431 OMIM phenotype

Clinical Summary— HYLS1

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Gene-Disease Validity (ClinGen)

hydrolethalus syndrome · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score 0.30

OE 0.92 (0.60–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.96 (0.84–1.10)

161 obs / 167.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.60–1.43)

0≤0.351.4

Missense OE?0.96 (0.84–1.10)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 14 / 15.3Missense obs/exp: 161 / 167.4Syn Z: 0.15

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveHYLS1-related hydrolethalus syndromeOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6649th %ile

GOF

0.74top 25%

LOF

0.3842th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.