HAP1
huntingtin associated protein 1
Basic information
Region (hg38): 17:41717742-41734644
Previous symbols: [ "HAP2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (100 variants)
- HAP1-related_disorder (19 variants)
- not_provided (8 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HAP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000177977.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 96 | 10 | 111 | |||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 99 | 14 | 9 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HAP1 | protein_coding | protein_coding | ENST00000347901 | 11 | 16903 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.35e-26 | 0.0000178 | 125375 | 1 | 372 | 125748 | 0.00148 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.0877 | 354 | 349 | 1.01 | 0.0000192 | 3931 |
| Missense in Polyphen | 20 | 23.997 | 0.83345 | 246 | ||
| Synonymous | -0.845 | 165 | 152 | 1.09 | 0.00000864 | 1229 |
| Loss of Function | -1.17 | 35 | 28.3 | 1.24 | 0.00000121 | 340 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00120 | 0.00118 |
| Ashkenazi Jewish | 0.00199 | 0.00199 |
| East Asian | 0.0112 | 0.0110 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000559 | 0.000536 |
| Middle Eastern | 0.0112 | 0.0110 |
| South Asian | 0.00206 | 0.00203 |
| Other | 0.000654 | 0.000652 |
dbNSFP
Source:
- Function
- FUNCTION: Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties. Both HTT and HAP1 are involved in intracellular trafficking and HAP1 is proposed to link HTT to motor proteins and/or transport cargos. Seems to play a role in vesicular transport within neurons and axons such as from early endosomes to late endocytic compartments and to promote neurite outgrowth. The vesicular transport function via association with microtubule-dependent transporters can be attenuated by association with mutant HTT. Involved in the axonal transport of BDNF and its activity-dependent secretion; the function seems to involve HTT, DCTN1 and a complex with SORT1. Involved in APP trafficking and seems to facilitate APP anterograde transport and membrane insertion thereby possibly reducing processing into amyloid beta. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptors to synapses; the function is dependent on kinesin motor protein KIF5 and is disrupted by HTT with expanded polyglutamine repeat. Involved in regulation of autophagosome motility by promoting efficient retrograde axonal transport. Seems to be involved in regulation of membrane receptor recycling and degradation, and respective signal transduction, including GABA(A) receptors, tyrosine kinase receptors, EGFR, IP3 receptor and androgen receptor. Among others suggested to be involved in control of feeding behavior (involving hypothalamic GABA(A) receptors), cerebellar and brainstem development (involving AHI1 and NTRK1/TrkA), postnatal neurogenesis (involving hypothalamic NTRK2/TrkB), and ITPR1/InsP3R1-mediated Ca(2+) release (involving HTT and possibly the effect of mutant HTT). Via association with DCTN1/dynactin p150-glued and HTT/huntingtin involved in cytoplasmic retention of REST in neurons. May be involved in ciliogenesis. Involved in regulation of exocytosis. Seems to be involved in formation of cytoplasmic inclusion bodies (STBs). In case of anomalous expression of TBP, can sequester a subset of TBP into STBs; sequestration is enhanced by an expanded polyglutamine repeat within TBP. HAP1-containing STBs have been proposed to play a protective role against neurodegeneration in Huntigton disease (HD) and spinocerebellar ataxia 17 (SCA17). {ECO:0000269|PubMed:18922795}.;
- Pathway
- GABAergic synapse - Homo sapiens (human);Huntington,s disease - Homo sapiens (human)
(Consensus)
Intolerance Scores
- loftool
- 0.998
- rvis_EVS
- 1.87
- rvis_percentile_EVS
- 97.21
Haploinsufficiency Scores
- pHI
- 0.114
- hipred
- N
- hipred_score
- 0.273
- ghis
- 0.433
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.350
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | High | Medium | High |
Mouse Genome Informatics
- Gene name
- Hap1
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Gene ontology
- Biological process
- protein targeting;exocytosis;autophagy;chemical synaptic transmission;brain development;anterograde axonal transport;retrograde axonal transport;protein localization;regulation of exocytosis;cerebellum development;hypothalamus cell differentiation;neurogenesis;cell projection organization;positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity;positive regulation of synaptic transmission, GABAergic;positive regulation of neurotrophin production;positive regulation of epidermal growth factor receptor signaling pathway;vesicle transport along microtubule;neurotrophin TRK receptor signaling pathway;mitochondrion distribution;positive regulation of neurogenesis;anterograde axonal transport of mitochondrion;negative regulation of amyloid-beta formation;regulation of organelle transport along microtubule;positive regulation of non-motile cilium assembly
- Cellular component
- nucleus;cytoplasm;mitochondrion;lysosome;autophagosome;endoplasmic reticulum;centrosome;centriole;cytoskeleton;synaptic vesicle;actin cytoskeleton;inclusion body;cell junction;dendrite;cytoplasmic vesicle;dendrite cytoplasm;axon cytoplasm
- Molecular function
- signaling receptor binding;protein binding;myosin binding;ion channel binding;brain-derived neurotrophic factor binding