HAS2 encodes hyaluronan synthase 2, which catalyzes the synthesis of hyaluronan, a major extracellular matrix component essential for tissue architecture, cell adhesion, migration, and differentiation. Mutations cause syndromic short stature with joint and skin abnormalities, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants in the population, indicating its critical importance in human development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.28
Clinical SummaryHAS2
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.990
Z-score 4.03
OE 0.09 (0.040.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.79Z-score
OE missense 0.53 (0.470.61)
152 obs / 284.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.040.28)
00.351.4
Missense OE0.53 (0.470.61)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 2 / 22.7Missense obs/exp: 152 / 284.3Syn Z: -0.06

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HAS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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