Details for: HAP1

Gene ID: 9001

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: HAP1

Ensembl ID: ENSG00000173805

Description: huntingtin associated protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pancreatic D cell CL0000173
    CSI 4.22
    rCSI 4.15%
    PRS 99.36
  • intestinal tuft cell CL0019032
    CSI 3.56
    rCSI 5.45%
    PRS 99.21
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 3.37
    rCSI 6.12%
    PRS 98.21
  • epithelial cell CL0000066
    CSI 3.06
    rCSI 4.69%
    PRS 97.08
  • brush cell CL0002204
    CSI 2.67
    rCSI 5.29%
    PRS 99.41
  • basal cell CL0000646
    CSI 2.59
    rCSI 3.47%
    PRS 99.3
  • tuft cell of colon CL0009041
    CSI 2.08
    rCSI 4.84%
    PRS 99.23

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [HAP1](/details-gene/9001) (Huntingtin Associated Protein 1) is a protein-coding gene located on chromosome 17q21.2. As its name suggests, it was first identified through its interaction with huntingtin, the protein implicated in Huntington's disease ([Link](https://doi.org/10.1038/378398a0)). Functionally, [HAP1](/details-gene/9001) is deeply involved in intracellular transport, particularly within the nervous system, where it facilitates the movement of vesicles, mitochondria, and signaling molecules along microtubules. Its roles extend to neurogenesis, synaptic transmission, and brain development. Expression data indicates that while its function is well-characterized in neurons, [HAP1](/details-gene/9001) also shows high significance in specialized secretory and sensory cell types outside the central nervous system, such as [pancreatic D cell](/details-cell/CL0000173) and [intestinal tuft cell](/details-cell/CL0019032), suggesting a broader role in regulating organized cellular transport and exocytosis. Its association with Huntington's disease is documented under OMIM entry [600947](https://omim.org/entry/600947). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [HAP1](/details-gene/9001) highlights its importance in specialized cells characterized by active transport and secretory functions. The gene shows the highest significance in [pancreatic D cell](/details-cell/CL0000173) (CSI: 4.22), a neuroendocrine cell type responsible for secreting somatostatin. This is consistent with its established role in vesicle transport and exocytosis. High significance is also observed in several chemosensory and epithelial cell types, including [intestinal tuft cell](/details-cell/CL0019032) (CSI: 3.56), [brush cell](/details-cell/CL0002204) (CSI: 2.67), and [tuft cell of colon](/details-cell/CL0009041) (CSI: 2.08). These cells utilize specialized signaling mechanisms, suggesting a role for [HAP1](/details-gene/9001) in the trafficking of receptors or signaling components. Furthermore, [HAP1](/details-gene/9001) is a significant marker in the central nervous system, particularly in [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059) (CSI: 3.37). This aligns with its known functions in neuronal development and maintenance. The broader significance in [epithelial cell](/details-cell/CL0000066) (CSI: 3.06) and [basal cell](/details-cell/CL0000646) (CSI: 2.59) suggests a fundamental role in organizing the cytoskeleton and intracellular transport machinery in a variety of cellular contexts. ## Pathways and Molecular Function The functions of [HAP1](/details-gene/9001) are predominantly centered on intracellular trafficking and neuronal processes. Gene Ontology annotations reveal its critical role in both [anterograde axonal transport](/details-link/GO:0008089) and [retrograde axonal transport](/details-link/GO:0008090). This includes the specific transport of organelles like mitochondria ([GO:0098957](/details-link/GO:0098957)) and vesicles ([GO:0047496](/details-link/GO:0047496)), which is consistent with its localization to the [axon cytoplasm](/details-link/GO:1904115), [cytoplasmic vesicle](/details-link/GO:0031410), and [cytoskeleton](/details-link/GO:0005856). Its involvement in neuronal function is extensive, contributing to [brain development](/details-link/GO:0007420), [neurogenesis](/details-link/GO:0022008), and [chemical synaptic transmission](/details-link/GO:0007268). At the molecular level, [HAP1](/details-gene/9001) participates in key signaling pathways, including the [neurotrophin trk receptor signaling pathway](/details-link/GO:0048011). This is supported by evidence that it binds brain-derived neurotrophic factor ([GO:0048403](/details-link/GO:0048403)) and mediates its transport and release ([Link](https://doi.org/10.1074/jbc.m109.073197)). Beyond its canonical neuronal roles, [HAP1](/details-gene/9001) is implicated in broader cellular maintenance processes such as [autophagy](/details-link/GO:0006914). It also plays a role in neurodegenerative disease pathways by negatively regulating amyloid-beta formation ([GO:1902430](/details-link/GO:1902430)), a function demonstrated by its ability to regulate the trafficking of the amyloid precursor protein ([Link](https://doi.org/10.1111/j.1471-4159.2012.07845.x)). ## Research Directions The diverse roles of [HAP1](/details-gene/9001) in both neuronal and non-neuronal secretory cells open several avenues for future investigation. Its function as a modifier of the age-at-onset for Huntington's disease suggests that its expression level or activity is clinically significant ([Link](https://doi.org/10.1093/hmg/ddn003)). **Proposed Hypotheses:** 1. Given its high significance in [pancreatic D cell](/details-cell/CL0000173) and its established role in [exocytosis](/details-link/GO:0006887), it is hypothesized that [HAP1](/details-gene/9001) is a key regulator of somatostatin vesicle trafficking to the plasma membrane and subsequent hormone release, thereby influencing glucose homeostasis. 2. The high expression of [HAP1](/details-gene/9001) in [intestinal tuft cell](/details-cell/CL0019032) and its annotated function in [positive regulation of non-motile cilium assembly](/details-link/GO:1902857) suggests that [HAP1](/details-gene/9001) is essential for the structural integrity or chemosensory function of the apical tuft in these cells, which is critical for detecting luminal contents and initiating mucosal immune responses. 3. Based on its interaction with huntingtin and its role in regulating amyloid-beta levels, it is hypothesized that [HAP1](/details-gene/9001) acts as a central node in a common pathway for managing proteopathic stress, and its dysfunction could be a contributing factor in a broader range of neurodegenerative disorders beyond Huntington's disease. **Experimental Approach for Hypothesis 1:** To test the role of [HAP1](/details-gene/9001) in somatostatin secretion, one could utilize a suitable pancreatic delta cell line (e.g., QGP-1) or primary mouse islets. [HAP1](/details-gene/9001) expression would be silenced using CRISPR-Cas9 or shRNA. The impact on hormone release would be assessed by stimulating the cells with secretagogues (e.g., high glucose, KCl) and measuring somatostatin levels in the supernatant via ELISA. Furthermore, immunofluorescence microscopy could be used to visualize the localization of somatostatin-containing granules, testing the hypothesis that [HAP1](/details-gene/9001) knockdown impairs their transport to the cell periphery. **Therapeutic Potential:** [HAP1](/details-gene/9001) presents a complex but compelling therapeutic target, primarily for Huntington's disease. Since its interaction with mutant huntingtin is a key pathogenic event, a therapeutic strategy aimed at **inhibition** of this specific protein-protein interaction, rather than modulating the overall level of [HAP1](/details-gene/9001), appears most promising. Developing small molecules or peptidomimetics that block the binding interface between [HAP1](/details-gene/9001) and mutant huntingtin could potentially mitigate toxicity without disrupting the essential physiological functions of [HAP1](/details-gene/9001) in cellular transport.

Genular Protein ID: 2924776516

Symbol: HAP1_HUMAN

Name: Huntingtin-associated protein 1

UniProtKB Accession Codes:

P54257 A8MQB5 O75358 Q59GK4 Q9H4G3 Q9HA98 Q9NY90

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 4 ExpressionAtlas 1 GO 48 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9668110

Title: A human HAP1 homologue. Cloning, expression, and interaction with huntingtin.

PubMed ID: 9668110

DOI: 10.1074/jbc.273.30.19220

PubMed ID: 10974549

Title: Human huntingtin-associated protein (HAP-1) gene: genomic organisation and an intragenic polymorphism.

PubMed ID: 10974549

DOI: 10.1016/s0378-1119(00)00269-9

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 7477378

Title: A huntingtin-associated protein enriched in brain with implications for pathology.

PubMed ID: 7477378

DOI: 10.1038/378398a0

PubMed ID: 9742138

Title: The cellular and subcellular localization of huntingtin-associated protein 1 (HAP1): comparison with huntingtin in rat and human.

PubMed ID: 9742138

DOI: 10.1523/jneurosci.18-19-07674.1998

PubMed ID: 18922795

Title: Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin p150 Glued.

PubMed ID: 18922795

DOI: 10.1074/jbc.m804183200

PubMed ID: 19996106

Title: Huntingtin-associated protein-1 interacts with pro-brain-derived neurotrophic factor and mediates its transport and release.

PubMed ID: 19996106

DOI: 10.1074/jbc.m109.073197

PubMed ID: 21386698

Title: Interaction of ataxin-3 with huntingtin-associated protein 1 through Josephin domain.

PubMed ID: 21386698

DOI: 10.1097/wnr.0b013e32834505f4

PubMed ID: 22731248

Title: Huntingtin associated protein 1 regulates trafficking of the amyloid precursor protein and modulates amyloid beta levels in neurons.

PubMed ID: 22731248

DOI: 10.1111/j.1471-4159.2012.07845.x

PubMed ID: 23532844

Title: The Joubert syndrome-associated missense mutation (V443D) in the Abelson-helper integration site 1 (AHI1) protein alters its localization and protein-protein interactions.

PubMed ID: 23532844

DOI: 10.1074/jbc.m112.420786

PubMed ID: 25074808

Title: Proteomic analysis of mammalian sperm cells identifies new components of the centrosome.

PubMed ID: 25074808

DOI: 10.1242/jcs.157008

PubMed ID: 18192679

Title: Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease.

PubMed ID: 18192679

DOI: 10.1093/hmg/ddn003

Sequence Information:

  • Length: 671
  • Mass: 75506
  • Checksum: 10971B807941B4EE
  • Sequence:
    • MRPKRLGRCC AGSRLGPGDP AALTCAPSPS ASPAPEPSAQ PQARGTGQRV GSRATSGSQF 
LSEARTGARP ASEAGAKAGA RRPSAFSAIQ GDVRSMPDNS DAPWTRFVFQ GPFGSRATGR 
GTGKAAGIWK TPAAYVGRRP GVSGPERAAF IRELEEALCP NLPPPVKKIT QEDVKVMLYL 
LEELLPPVWE SVTYGMVLQR ERDLNTAARI GQSLVKQNSV LMEENSKLEA LLGSAKEEIL 
YLRHQVNLRD ELLQLYSDSD EEDEDEEEEE EEKEAEEEQE EEEAEEDLQC AHPCDAPKLI 
SQEALLHQHH CPQLEALQEK LRLLEEENHQ LREEASQLDT LEDEEQMLIL ECVEQFSEAS 
QQMAELSEVL VLRLENYERQ QQEVARLQAQ VLKLQQRCRM YGAETEKLQK QLASEKEIQM 
QLQEESVWVG SQLQDLREKY MDCGGMLIEM QEEVKTLRQQ PPVSTGSATH YPYSVPLETL 
PGFQETLAEE LRTSLRRMIS DPVYFMERNY EMPRGDTSSL RYDFRYSEDR EQVRGFEAEE 
GLMLAADIMR GEDFTPAEEF VPQEELGAAK KVPAEEGVME EAELVSEETE GWEEVELELD 
EATRMNVVTS ALEASGLGPS HLDMNYVLQQ LANWQDAHYR RQLRWKMLQK GECPHGALPA 
ASRTSCRSSC R