HAP1

huntingtin associated protein 1

Basic information

Region (hg38): 17:41717742-41734644

Previous symbols: [ "HAP2" ]

Links

ENSG00000173805 ∙ NCBI:9001 ∙ OMIM:600947 ∙ HGNC:4812 ∙ Uniprot:P54257 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HAP1 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			66	4	5	75
nonsense					1	1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	67	4	7

Variants in HAP1

This is a list of pathogenic ClinVar variants found in the HAP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-41724711-G-A		not specified	Uncertain significance (Feb 01, 2025)
17-41724714-G-T			Benign (Jun 11, 2021)
17-41724747-G-GCC		HAP1-related disorder	Uncertain significance (May 31, 2023)
17-41724751-C-T			Benign (Apr 30, 2018)
17-41724757-GGCA-CCTTTCTGGAG		HAP1-related disorder	Uncertain significance (Aug 07, 2024)
17-41724780-T-G		not specified	Uncertain significance (Nov 29, 2023)
17-41724795-C-A		not specified	Uncertain significance (Mar 01, 2024)
17-41724796-G-A		not specified	Uncertain significance (Oct 05, 2023)
17-41724842-ATTCATGTCCAGGTG-A		HAP1-related disorder	Uncertain significance (Sep 19, 2024)
17-41724853-G-C		not specified	Uncertain significance (Feb 22, 2023)
17-41724871-C-T		not specified	Uncertain significance (Jan 03, 2025)
17-41724885-G-A		not specified	Uncertain significance (Oct 07, 2024)
17-41724900-T-G		not specified	Uncertain significance (Oct 30, 2023)
17-41724934-C-T		not specified	Uncertain significance (Mar 07, 2025)
17-41724998-C-T		HAP1-related disorder	Benign (Feb 28, 2019)
17-41724999-G-A		not specified	Uncertain significance (Aug 06, 2021)
17-41725036-C-A		not specified	Uncertain significance (Nov 13, 2024)
17-41725036-C-T		not specified	Uncertain significance (Feb 02, 2024)
17-41725047-G-A		HAP1-related disorder	Benign (Feb 28, 2019)
17-41725052-C-T		HAP1-related disorder	Likely benign (May 08, 2019)
17-41725053-G-A		not specified	Uncertain significance (Oct 24, 2024)
17-41725068-C-T		not specified	Uncertain significance (Apr 07, 2022)
17-41725069-G-A		not specified	Uncertain significance (Jul 30, 2024)
17-41725070-C-A		not specified	Uncertain significance (Jun 07, 2024)
17-41725075-T-C		HAP1-related disorder	Benign (Aug 01, 2018)

GnomAD

Source: gnomAD

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: dbNSFP

• 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