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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HAS1
hyaluronan synthase 1
Chromosome 19 · 19q13.41
NCBI Gene: 3036Ensembl: ENSG00000105509.12HGNC: HGNC:4818UniProt: D2N2G5
70PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingidentical protein bindingnegative regulation of fibroblast migrationhyaluronan biosynthetic processganglion or cyst of synovium/tendon/bursaAbnormality of the skeletal systemmusculoskeletal system diseasesynovial bursa disorder
✦AI Summary

HAS1 (hyaluronan synthase 1) catalyzes the synthesis of hyaluronan (HA) by adding GlcNAc and GlcUA monosaccharides to the nascent polymer 1. As one of three hyaluronan synthase isozymes, HAS1 is essential for extracellular matrix (ECM) assembly and regulates critical cellular processes including adhesion, migration, and differentiation 2. Beyond its canonical role in ECM synthesis, HAS1 localizes to both cytoplasmic and nuclear compartments, where it influences cell cycle progression, motility, and gene transcription 32. In wound healing, HAS1-expressing fibroblasts exhibit fetal-like phenotypes and enhanced migratory capacity through the PIEZO1-calcium-HIF1α pathway 4. Clinically, HAS1 dysregulation associates with multiple pathologies: aberrant splice variants promote B-lineage cancer through dominant-negative effects on wild-type HAS1 protein 5; elevated HAS1 expression in cancer-associated fibroblasts drives ECM remodeling and oral squamous cell carcinoma invasion 6; and reduced HAS1 transcription in Alzheimer's disease, mediated by phosphorylated tau-induced nuclear translocation, contributes to perineuronal net degradation 3. Therapeutically, apigenin induces HAS1 expression in keratinocytes, enhancing skin barrier function and offering potential benefits for inflammatory skin diseases 7.

Sources cited
1
Hyaluronan is synthesized at the cell membrane by hyaluronan synthase, with precursors UDP-glucuronic acid and UDP-N-acetylglucosamine
PMID: 3124495
2
HAS1 is one of three hyaluronan synthase family members; intracellular hyaluronan has regulatory roles in cell cycle, motility, RNA translation/splicing, and autophagy
PMID: 31276783
3
HAS1 is distributed in axon and nucleus; phosphorylated tau mediates cytosolic-nuclear translocation of HAS1 and negatively regulates its stability; non-ubiquitinated HAS1 translocates to nucleus forming nuclear speckles involved in gene transcription; HAS1 transcript levels are reduced in AD patients and AβPP/PS1 mice
PMID: 38518923
4
MMP13+ fibroblasts exhibit fetal-like HAS1 expression with heightened migratory activity activated through PIEZO1-calcium-HIF1α-VEGF-MMP13 pathway in wound healing
PMID: 38751164
5
Aberrant HAS1 splice variants in B-lineage cancers are dominant over full-length HAS1, showing different subcellular localization and enhanced intracellular HA synthesis; HAS1-Vc is transforming in vitro and tumorigenic in vivo
PMID: 19451652
6
HAS1 is significantly upregulated in cancer-associated fibroblasts at the invasion front of oral squamous cell carcinoma; HAS1 knockdown diminishes ECM remodeling and attenuates tumor invasion promotion
PMID: 40813707
7
Apigenin (20 μM) significantly induces HAS1 expression along with HAS2 and HAS3 in keratinocytes, promoting hyaluronic acid synthesis and enhancing skin barrier function
PMID: 32610574
Disease Associationsⓘ20
ganglion or cyst of synovium/tendon/bursaOpen Targets
0.38Weak
Abnormality of the skeletal systemOpen Targets
0.31Weak
musculoskeletal system diseaseOpen Targets
0.30Weak
synovial bursa disorderOpen Targets
0.25Weak
skin infectionOpen Targets
0.15Weak
myoepithelial tumorOpen Targets
0.11Weak
Miyoshi myopathyOpen Targets
0.09Suggestive
melanomaOpen Targets
0.08Suggestive
type 2 diabetes mellitusOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
immunodeficiency 88Open Targets
0.05Suggestive
eosinophil peroxidase deficiencyOpen Targets
0.05Suggestive
X-linked severe congenital neutropeniaOpen Targets
0.05Suggestive
gastric cancerOpen Targets
0.05Suggestive
Blackfan-Diamond anemiaOpen Targets
0.05Suggestive
neutropenia, severe congenital, 2, autosomal dominantOpen Targets
0.05Suggestive
nonimmune chronic idiopathic neutropenia of adultsOpen Targets
0.05Suggestive
linear and whorled nevoid hypermelanosisOpen Targets
0.05Suggestive
chronic myeloproliferative disorderOpen Targets
0.04Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
UGDHProtein interaction81%CD44Protein interaction76%HYAL1Protein interaction73%HAS3Shared pathway42%HAS2Shared pathway24%EXT2Shared pathway20%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
26%
Brain
7%
Lung
7%
Heart
5%
Liver
1%
Gene Interaction Network
Click a node to explore
HAS1UGDHCD44HYAL1HAS3HAS2EXT2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8IYH3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.25LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.90 [0.66–1.25]
RankingsWhere HAS1 stands among ~20K protein-coding genes
  • #6,722of 20,598
    Most Researched70
  • #13,174of 17,882
    Most Constrained (LOEUF)1.25
Genes detectedHAS1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Induce Fetal Wound Healing Features Revealed by Single-Cell RNA Sequencing.
PMID: 38751164
ACS Nano · 2024
1.00
2
AβPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease.
PMID: 38518923
Matrix Biol · 2024
0.90
3
Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-Allergic, Anti-Inflammatory, and Skin-Protective Activities.
PMID: 32610574
Int J Mol Sci · 2020
0.80
4
Hyaluronan synthases.
PMID: 9206724
J Biol Chem · 1997
0.70
5
Divide-and-conquer strategy with engineered ossification center organoids for rapid bone healing through developmental cell recruitment.
PMID: 40615395
Nat Commun · 2025
0.60