HOOK3

hook microtubule tethering protein 3, the group of FHF complex

Basic information

Region (hg38): 8:42896946-43030535

Links

ENSG00000168172 ∙ NCBI:84376 ∙ OMIM:607825 ∙ HGNC:23576 ∙ Uniprot:Q86VS8 ∙ 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 HOOK3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOOK3 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			29			29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	29	1	0

Variants in HOOK3

This is a list of pathogenic ClinVar variants found in the HOOK3 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-42897145-A-G		not specified	Uncertain significance (Sep 19, 2022)
8-42906188-G-A		not specified	Uncertain significance (Mar 18, 2024)
8-42906209-G-C		not specified	Uncertain significance (Dec 10, 2024)
8-42925567-T-C		not specified	Uncertain significance (Sep 22, 2023)
8-42925592-G-T		not specified	Uncertain significance (Jan 08, 2024)
8-42930130-T-G		Short stature	Likely pathogenic (Nov 18, 2001)
8-42930144-T-C		not specified	Uncertain significance (Jul 06, 2024)
8-42943352-G-A		not specified	Uncertain significance (Jul 20, 2022)
8-42943428-A-G		not specified	Uncertain significance (Mar 04, 2024)
8-42943429-C-T			Likely benign (Mar 01, 2023)
8-42950396-C-G		not specified	Uncertain significance (Jan 03, 2025)
8-42950408-A-T		not specified	Uncertain significance (Nov 03, 2022)
8-42957152-G-A		not specified	Uncertain significance (Nov 08, 2022)
8-42959307-A-T		not specified	Uncertain significance (Mar 03, 2025)
8-42964322-G-T		not specified	Uncertain significance (Dec 21, 2022)
8-42964378-A-G		not specified	Uncertain significance (Jul 13, 2022)
8-42964405-A-G		not specified	Uncertain significance (Dec 04, 2024)
8-42966515-G-C		not specified	Uncertain significance (Mar 07, 2024)
8-42966532-C-T		not specified	Uncertain significance (Aug 14, 2024)
8-42966583-A-G		not specified	Uncertain significance (Jun 03, 2024)
8-42966602-C-G		not specified	Uncertain significance (Feb 11, 2025)
8-42968096-G-A		not specified	Uncertain significance (Jan 01, 2025)
8-42968147-T-A		not specified	Uncertain significance (Apr 13, 2023)
8-42968179-G-A		not specified	Uncertain significance (Aug 10, 2021)
8-42973284-A-G			Benign (Mar 30, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOOK3	protein_coding	protein_coding	ENST00000307602	22	133608

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000192	125733	0	7	125740	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.36	230	355	0.648	0.0000181	4723
Missense in Polyphen		81	132.96	0.60923		1732
Synonymous	1.04	109	124	0.881	0.00000642	1238
Loss of Function	6.16	3	50.0	0.0600	0.00000270	616

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000449	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably serves as a target for the spiC protein from Salmonella typhimurium, which inactivates it, leading to a strong alteration in cellular trafficking (By similarity). Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). May regulate clearance of endocytosed receptors such as MSR1. Participates in defining the architecture and localization of the Golgi complex. Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non- processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (PubMed:25035494). {ECO:0000250|UniProtKB:Q8BUK6, ECO:0000269|PubMed:11238449, ECO:0000269|PubMed:17237231, ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:25035494}.

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.170
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.62

Haploinsufficiency Scores

• pHI: 0.181
• hipred: Y
• hipred_score: 0.728
• ghis: 0.643

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.508

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hook3
• Phenotype: skeleton phenotype; limbs/digits/tail phenotype; hematopoietic system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: endosome organization;lysosome organization;endosome to lysosome transport;protein transport;interkinetic nuclear migration;cytoskeleton-dependent intracellular transport;cytoplasmic microtubule organization;microtubule anchoring at centrosome;early endosome to late endosome transport;negative regulation of neurogenesis;Golgi localization;protein localization to centrosome;neuronal stem cell population maintenance
• Cellular component: pericentriolar material;cytoplasm;cis-Golgi network;centrosome;cytosol;microtubule;HOPS complex;centriolar satellite;FHF complex
• Molecular function: protein binding;microtubule binding;dynactin binding;identical protein binding;dynein light chain binding;dynein intermediate chain binding;dynein light intermediate chain binding