CKAP5

protein-coding

cytoskeleton associated protein 5, the group of MicroRNA protein coding host genes|Small nucleolar RNA protein coding host genes|TOG domain containing

Gene summary

This gene encodes a cytoskeleton-associated protein which belongs to the TOG/XMAP215 family. The N-terminal half of this protein contains a microtubule-binding domain and the C-terminal half contains a KXGS motif for binding tubulin dimers. This protein has two distinct roles in spindle formation; it protects kinetochore microtubules from depolymerization and plays an essential role in centrosomal microtubule assembly. This protein may be necessary for the proper interaction of microtubules with the cell cortex for directional cell movement. It also plays a role in translation of the myelin basic protein (MBP) mRNA by interacting with heterogeneous nuclear ribonucleoprotein (hnRNP) A2, which associates with MBP. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001008938.4

Inheritance

—

ClinVar variants

U:213B:9

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr11:46,743,048-46,846,308

External References & Databases

Ensembl (ENSG00000175216)

Transcript & Mutation Effects

hg38 • Region Span ~103.3 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 CKAP5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 191

not providedTotal: 12

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001008938.4. 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			1 clinvar	6 clinvar		7
missense			197 clinvar	3 clinvar		200
nonsense			1 clinvar			1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	213	9	0	222

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001008938.4	RefSeq	NP_001008938.1	43	MANE Select
ENST00000529230.6	Ensembl	ENSP00000432768.1	43	MANE Select
NM_014756.4	RefSeq	NP_055571.2	42	Standard
ENST00000312055.10	Ensembl	ENSP00000310227.5	42	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
Amplification of signal from the kinetochores
Mitotic Spindle Checkpoint
Cell Cycle Checkpoints

Biological Process

G2/M transition of mitotic cell cycle
microtubule depolymerization
spindle organization
centrosome cycle
regulation of G2/M transition of mitotic cell cycle

Molecular Function

protein binding
cadherin binding
microtubule plus-end binding

Cellular Component

kinetochore
condensed chromosome kinetochore
spindle pole
gamma-tubulin complex
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000529230
Coding exons: 43
Length: 103250
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125747
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.78	722	1.07e+3	0.675	0.0000543	13388
Missense (PolyPhen)		165	317.49	0.5197		4144
Synonymous	1.79	335	379	0.883	0.0000190	3880
Loss of Function	8.59	10	105	0.0952	0.00000570	1296

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0.00013	0.00013	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch- TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments (PubMed:27156448). {ECO:0000269|PubMed:12569123, ECO:0000269|PubMed:18809577, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:21646404, ECO:0000269|PubMed:23532825, ECO:0000269|PubMed:27156448, ECO:0000269|PubMed:9570755}.;

Recessive Scores

pRec: 0.188

Intolerance Scores

LoFtool: 0.349
RVIS EVS: -1.61
RVIS percentile EVS: 2.98

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.850

Gene Damage Prediction

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