HOOK2

protein-coding

hook microtubule tethering protein 2, 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_013312.3

Inheritance

—

ClinVar variants

U:138B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr19:12,763,003-12,872,740

External References & Databases

Ensembl (ENSG00000095066)

Transcript & Mutation Effects

hg38 • Region Span ~109.7 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 HOOK2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013312.3. 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			1 clinvar	1 clinvar		2
missense			129 clinvar	4 clinvar	1 clinvar	134
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	138	5	1	144

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013312.3	RefSeq	NP_037444.2	23	MANE Select
ENST00000397668.8	Ensembl	ENSP00000380785.2	23	MANE Select
NM_001100176.2	RefSeq	NP_001093646.1	22	Standard
NM_001400041.1	RefSeq	NP_001386970.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

endocytosis
endosome organization
lysosome organization
endosome to lysosome transport
protein transport

Molecular Function

protein binding
microtubule binding
identical protein binding
dynein light intermediate chain binding

Cellular Component

cytoplasm
centrosome
cytosol
microtubule
HOPS complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397668
Coding exons: 23
Length: 109738
Individuals with no LoFs: 125481
Homozygous LoFs: 0
Heterozygous LoFs: 102
Defined: 125583
p: 0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.371	429	451	0.951	0.0000303	4578
Missense (PolyPhen)		113	103.32	1.0937		1224
Synonymous	0.794	174	188	0.926	0.0000118	1421
Loss of Function	1.98	35	50.2	0.698	0.00000265	528

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00052	0.00049	rare
Latino/Admixed American	0.00049	0.00049	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00089	0.00088	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00047	0.00046	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 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). Contributes to the establishment and maintenance of centrosome function. May function in the positioning or formation of aggresomes, which are pericentriolar accumulations of misfolded proteins, proteasomes and chaperones. {ECO:0000269|PubMed:17140400, ECO:0000269|PubMed:17540036, ECO:0000269|PubMed:18799622}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.932
RVIS EVS: 0.31
RVIS percentile EVS: 72.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.961

Gene Damage Prediction

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