HOOK1

protein-coding

hook microtubule tethering protein 1, the group of FHF complex

Gene summary

This gene encodes a member of the hook family of coiled-coil proteins, which bind to microtubules and organelles through their N- and C-terminal domains, respectively. The encoded protein localizes to discrete punctuate subcellular structures, and interacts with several members of the Rab GTPase family involved in endocytosis. It is thought to link endocytic membrane trafficking to the microtubule cytoskeleton. Several alternatively spliced transcript variants have been identified, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_015888.6

Inheritance

—

ClinVar variants

U:104B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr1:59,814,786-59,876,322

External References & Databases

Ensembl (ENSG00000134709)

Transcript & Mutation Effects

hg38 • Region Span ~61.5 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 HOOK1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 99

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015888.6. 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		2
missense			98 clinvar	3 clinvar		101
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	104	5	0	109

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015888.6	RefSeq	NP_056972.1	22	MANE Select
ENST00000371208.5	Ensembl	ENSP00000360252.3	22	MANE Select
ENST00000455990.5	Ensembl	ENSP00000398860.1	6	Standard
ENST00000685567.1	Ensembl	ENSP00000509959.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

Golgi organization
endosome organization
lysosome organization
multicellular organism development
endosome to lysosome transport

Molecular Function

actin binding
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: ENST00000371208
Coding exons: 22
Length: 61593
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125743
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.849	318	364	0.875	0.0000186	4842
Missense (PolyPhen)		130	146.28	0.88871		1967
Synonymous	0.514	115	122	0.941	0.00000624	1228
Loss of Function	3.66	21	48.5	0.433	0.00000228	601

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00025	0.00024	rare
South Asian	0.000075	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for spermatid differentiation. Probably involved in the positioning of the microtubules of the manchette and the flagellum in relation to the membrane skeleton (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) (PubMed:18799622). {ECO:0000250|UniProtKB:Q8BIL5, ECO:0000269|PubMed:18799622}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.811
RVIS EVS: -0.62
RVIS percentile EVS: 17.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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