CKAP2L

protein-coding

cytoskeleton associated protein 2 like

Gene summary

The protein encoded by this gene is thought to be a mitotic spindle protein important to neural stem or progenitor cells. Mutations in this gene have been associated with spindle organization defects, including mitotic spindle defects, lagging chromosomes, and chromatin bridges. There is evidence that mutations in this gene are associated with Filippi syndrome, characterized by growth defects, microcephaly, intellectual disability, facial feature defects, and syndactyly. There is a pseudogene of this gene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MANE transcript

NM_152515.5

Inheritance

AD, AR

ClinVar variants

P:25U:150B:63

Top phenotype

Filippi syndrome

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr2:112,736,349-112,764,664

External References & Databases

Ensembl (ENSG00000169607)

Transcript & Mutation Effects

hg38 • Region Span ~28.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Filippi syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0010092

Submitter: Ambry Genetics

Filippi syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010092

Submitter: G2P

Filippi syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010092

Submitter: Orphanet

Filippi syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010092

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Filippi syndromeAR

Manifestation: Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 15365457; 18553552; 25439729

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CKAP2L variants in ClinVar

7 Conditions Cataloged

not providedTotal: 120

Inborn genetic diseasesTotal: 115

Filippi syndromeTotal: 30

not specifiedTotal: 18

CKAP2L-related disorderTotal: 17

Intellectual disabilityTotal: 1

HypogonadismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152515.5. 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	41 clinvar	3 clinvar	46
missense	1 clinvar	1 clinvar	143 clinvar	14 clinvar	5 clinvar	164
nonsense	2 clinvar	1 clinvar				3
start loss	1 clinvar	1 clinvar				2
frameshift	7 clinvar	10 clinvar	1 clinvar			18
splice donor/acceptor (+/-2bp)	1 clinvar		4 clinvar			5
Total	12	13	150	55	8	238

Highest pathogenic variant AF is 0.00010718499

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152515.5	RefSeq	NP_689728.3	9	MANE Select
ENST00000302450.11	Ensembl	ENSP00000305204.6	9	MANE Select
NM_001304361.2	RefSeq	NP_001291290.1	6	Standard
ENST00000435431.5	Ensembl	ENSP00000414834.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

spindle pole
centrosome
cytosol
mitotic spindle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302450
Coding exons: 9
Length: 28325
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125747
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0890	394	389	1.01	0.0000194	4873
Missense (PolyPhen)		92	88.152	1.0436		1127
Synonymous	1.15	127	145	0.879	0.00000754	1430
Loss of Function	3.17	12	31.1	0.386	0.00000154	407

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Microtubule-associated protein required for mitotic spindle formation and cell-cycle progression in neural progenitor cells. {ECO:0000269|PubMed:25439729}.;
Disease: DISEASE: Filippi syndrome (FLPIS) [MIM:272440]: A rare disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities. {ECO:0000269|PubMed:25439729}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0749

Intolerance Scores

LoFtool: 0.762
RVIS EVS: 1.38
RVIS percentile EVS: 94.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.107

Gene Damage Prediction

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