HOOK3

protein-coding

hook microtubule tethering protein 3, the group of FHF complex

Gene summary

Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

MANE transcript

NM_032410.4

Inheritance

—

ClinVar variants

P:1U:65B:1

Top phenotype

Short stature

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr8:42,896,946-43,030,535

External References & Databases

Ensembl (ENSG00000168172)

Transcript & Mutation Effects

hg38 • Region Span ~133.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HOOK3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 5

Short statureTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032410.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense		1 clinvar	56 clinvar			57
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	1	65	1	0	67

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032410.4	RefSeq	NP_115786.1	22	MANE Select
ENST00000307602.9	Ensembl	ENSP00000305699.3	22	MANE Select
ENST00000526882.5	Ensembl	ENSP00000435077.1	4	Standard
ENST00000533338.1	Ensembl	ENSP00000433813.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

endosome organization
lysosome organization
endosome to lysosome transport
protein transport
interkinetic nuclear migration

Molecular Function

protein binding
microtubule binding
dynactin binding
identical protein binding
dynein light chain binding

Cellular Component

pericentriolar material
cytoplasm
cis-Golgi network
centrosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307602
Coding exons: 22
Length: 133608
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125740
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.36	230	355	0.648	0.0000181	4723
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.508

Gene Damage Prediction

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