HAS2

Chr 8

hyaluronan synthase 2

NCBI Gene: 3037 ENSG00000170961 UniProt: Q92819

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.

Summary from RefSeq, UniProt

P/LP submissions

P/LP missense

0.28

LOEUF· LoF intol.

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Mechanism

Clinical Summary— HAS2

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Gene-Disease Validity (ClinGen)

congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

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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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ClinVar Variants

50 unique Pathogenic / Likely Pathogenic· 32 VUS of 90 total submissions

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Clinical Trials

5 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.28LOEUF

pLI 0.990

Z-score 4.03

OE 0.09 (0.04–0.28)

Highly constrained

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

Missense Constraint

2.79Z-score

OE missense 0.53 (0.47–0.61)

152 obs / 284.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios

LoF OE0.09 (0.04–0.28)

0≤0.351.4

Missense OE0.53 (0.47–0.61)

0≤0.61.4

Synonymous OE1.01

0≤1.21.6

LoF obs/exp: 2 / 22.7Missense obs/exp: 152 / 284.3Syn Z: -0.06

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50

VUS32

Likely Benign1

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	50	0	50
Likely Pathogenic	0	0	0	0
VUS	30	2	0	32
Likely Benign	0	0	1	1
Benign	0	0	1	1
Total	30	52	2	84

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Neuroblastoma

Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma

ACTIVE NOT RECRUITING

NCT00911560Phase PHASE1, PHASE2Memorial Sloan Kettering Cancer CenterStarted 2009-05-27

adjuvant OPT-821 in a vaccine containing two antigens (GD2L and GD3L) covalently linked to KLHoral β-glucan

Neoplasm MetastasisNon-Small Cell Lung Cancer

Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)

ACTIVE NOT RECRUITING

NCT04886804Phase PHASE1Boehringer IngelheimStarted 2021-07-02

zongertinib

Fatty Liver Disease

The Role of Sugars in Fat Accumulation in the Liver

RECRUITING

NCT06751862Phase NAInstitute for Clinical and Experimental MedicineStarted 2024-06-20

150g of fat with glucose150g of fat with fructose150g of fat with sucrose

Increased Oocyte Deathin Vitro MaturationGREM1 Gene Mutation

GREM1, HAS2 and PTGS2 Gene Expression Following the in Vitro Maturation (IVM)

RECRUITING

NCT06315777Phase NANational University of MalaysiaStarted 2021-07-01