NCKAP5L

Summary

NCKAP5L (NCK associated protein 5 like, HGNC:29321) is a protein-coding gene on chromosome 12q13.12, encoding Nck-associated protein 5-like (Q9HCH0). Regulates microtubule organization and stabilization.

Involved in microtubule bundle formation and microtubule depolymerization. Located in centrosome and microtubule plus-end.

Source: NCBI Gene 57701 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 263 total
• MANE Select transcript: NM_001037806

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29321
Approved symbol	NCKAP5L
Name	NCK associated protein 5 like
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167566
Ensembl biotype	protein_coding
OMIM	615104
Entrez	57701

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000335999, ENST00000433948, ENST00000477361, ENST00000480927, ENST00000491441, ENST00000906698, ENST00000906699, ENST00000914431, ENST00000914432, ENST00000914433, ENST00000948982

RefSeq mRNA: 2 — MANE Select: NM_001037806 NM_001037806, NM_001368048

CCDS: CCDS41781

Canonical transcript exons

ENST00000335999 — 13 exons

Exon	Start	End
ENSE00001114474	49792678	49792986
ENSE00001114475	49793352	49793433
ENSE00001114478	49793734	49793896
ENSE00001163119	49792446	49792588
ENSE00001355695	49791152	49792051
ENSE00001355718	49794765	49797394
ENSE00001533455	49803922	49804080
ENSE00001551399	49828322	49828413
ENSE00001555335	49802958	49802996
ENSE00001557882	49805980	49806041
ENSE00001561708	49801848	49801967
ENSE00001562951	49798350	49798463
ENSE00003619220	49803097	49803165

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 92.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8354 / max 753.7421, expressed in 1758 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130858	11.4563	1754
130857	0.3145	131
130859	0.0646	27

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	92.32	gold quality
right adrenal gland cortex	UBERON:0035827	90.79	gold quality
right adrenal gland	UBERON:0001233	90.72	gold quality
left adrenal gland cortex	UBERON:0035825	89.79	gold quality
left adrenal gland	UBERON:0001234	89.66	gold quality
adrenal cortex	UBERON:0001235	89.22	gold quality
sural nerve	UBERON:0015488	87.87	gold quality
adrenal gland	UBERON:0002369	87.79	gold quality
tibial nerve	UBERON:0001323	87.12	gold quality
heart left ventricle	UBERON:0002084	87.07	gold quality
cardiac ventricle	UBERON:0002082	86.67	gold quality
right atrium auricular region	UBERON:0006631	86.51	gold quality
cardiac atrium	UBERON:0002081	85.94	gold quality
metanephros cortex	UBERON:0010533	85.11	gold quality
heart	UBERON:0000948	84.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.30	gold quality
right uterine tube	UBERON:0001302	84.09	gold quality
endocervix	UBERON:0000458	83.96	gold quality
granulocyte	CL:0000094	83.90	gold quality
right lobe of thyroid gland	UBERON:0001119	83.83	gold quality
left coronary artery	UBERON:0001626	83.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.65	gold quality
right coronary artery	UBERON:0001625	83.62	gold quality
right ovary	UBERON:0002118	83.61	gold quality
left lobe of thyroid gland	UBERON:0001120	83.45	gold quality
coronary artery	UBERON:0001621	83.31	gold quality
ascending aorta	UBERON:0001496	83.28	gold quality
spinal cord	UBERON:0002240	83.22	gold quality
adenohypophysis	UBERON:0002196	83.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting NCKAP5L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6879-5P	97.77	65.52	1521

Literature-anchored findings (GeneRIF, showing 3)

• These results show that Cep169 targets microtubule tips and regulates stability of microtubules with CDK5RAP2. (PMID:26485573)
• These data suggest that the dissociation of Cep169 from centrosomes is controlled by Cdk1/Cyclin B during mitosis, and that Cep169 might regulate MT dynamics of mitotic spindle. (PMID:26549230)
• Our findings suggest that Cep169 regulates cell growth by interacting with multiple proteins. (PMID:29269292)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nckap5l	ENSDARG00000079148
mus_musculus	Nckap5l	ENSMUSG00000023009
rattus_norvegicus	Nckap5l	ENSRNOG00000056678
drosophila_melanogaster	CG42663	FBGN0261545

Paralogs (1): NCKAP5 (ENSG00000176771)

Protein

Protein identifiers

Nck-associated protein 5-like — Q9HCH0 (reviewed: Q9HCH0)

Alternative names: Centrosomal protein of 169 kDa

All UniProt accessions (2): Q9HCH0, H7C1V4

UniProt curated annotations — full annotation on UniProt →

Function. Regulates microtubule organization and stabilization. Promotes microtubule growth and bundling formation and stabilizes microtubules by increasing intense acetylation of microtubules. Both tubulin-binding and homodimer formation are required for NCKAP5L-mediated microtubule bundle formation.

Subunit / interactions. Homodimer. Interacts with CDK5RAP2. Interacts with MAPRE1. Interacts with beta-tubulin.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Post-translational modifications. CDK1/Cyclin B-dependent phosphorylation mediates its dissociation from centrosomes during mitosis.

Miscellaneous. Dubious isoform produced through intron retention. Dubious isoform produced through intron retention.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HCH0-1	1	yes
Q9HCH0-2	2
Q9HCH0-4	4

RefSeq proteins (2): NP_001032895, NP_001354977 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026163	Nckap5l	Family
IPR032769	NCKAP5_C	Domain

Pfam: PF15246

UniProt features (51 total): compositionally biased region 14, region of interest 12, modified residue 12, short sequence motif 3, splice variant 3, mutagenesis site 3, coiled-coil region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCH0-F1	47.50	0.08

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (12): 440, 451, 470, 477, 493, 496, 498, 571, 577, 659, 767, 1194

Mutagenesis-validated functional residues (3):

Position	Phenotype
486–487	no decrease in localization to microtubule plus ends. loss of interaction with mapre1 and localization to microtubule pl
818–819	no decrease in localization to microtubule plus ends. loss of interaction with mapre1 and localization to microtubule pl
928–929	loss of interaction with mapre1 and significantly reduced localization to microtubule plus ends. loss of interaction wit

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_MICROTUBULE_DEPOLYMERIZATION, GOCC_CENTROSOME, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_PROTEIN_DEPOLYMERIZATION, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOCC_MICROTUBULE_PLUS_END, GOCC_MICROTUBULE_END, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, GOBP_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_SUPRAMOLECULAR_FIBER_ORGANIZATION, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GOCC_SUPRAMOLECULAR_POLYMER

GO Biological Process (2): microtubule bundle formation (GO:0001578), microtubule depolymerization (GO:0007019)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): centrosome (GO:0005813), microtubule plus-end (GO:0035371), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule (GO:0005874)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule cytoskeleton organization	1
microtubule polymerization or depolymerization	1
protein depolymerization	1
supramolecular fiber organization	1
binding	1
centriole	1
microtubule organizing center	1
microtubule end	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCKAP5L	ZNF18	P17022	667
NCKAP5L	CDK5RAP2	Q96SN8	601
NCKAP5L	UBE3B	Q7Z3V4	579
NCKAP5L	UBXN2B	Q14CS0	532
NCKAP5L	TEX2	Q8IWB9	509
NCKAP5L	DIP2B	Q9P265	489
NCKAP5L	DDX31	Q9H8H2	479
NCKAP5L	FAM186B	Q8IYM0	471
NCKAP5L	ZBED8L	Q8TCP9	447
NCKAP5L	C2orf15	Q8WU43	446
NCKAP5L	NCKIPSD	Q9NZQ3	433
NCKAP5L	RUVBL2	Q9Y230	405
NCKAP5L	ARFRP1	Q13795	387
NCKAP5L	RAD9A	Q99638	382
NCKAP5L	CLTCL1	P53675	376

IntAct

87 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
NCKAP5L	ATP1A1	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
TNIP2	CHUK	psi-mi:“MI:0914”(association)	0.350
TNIP2	TMEM178B	psi-mi:“MI:0914”(association)	0.350
MAPRE1	SCAMP1	psi-mi:“MI:0914”(association)	0.350
NCKAP5L	RCBTB2	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350
EXOC1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
NOL4	ZNF195	psi-mi:“MI:0914”(association)	0.350
NCKAP5	KIF3C	psi-mi:“MI:0914”(association)	0.350
FBXW11	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
OFD1	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
PCM1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
ODF2	DDX3X	psi-mi:“MI:2364”(proximity)	0.270
CEP128	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
CNTRL	ANKRD28	psi-mi:“MI:2364”(proximity)	0.270
NIN	AP3D1	psi-mi:“MI:2364”(proximity)	0.270
NINL	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
OFD1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (140): NCKAP5L (Affinity Capture-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Proximity Label-MS), NCKAP5L (Affinity Capture-MS), NCKAP5L (Affinity Capture-MS), NCKAP5L (Affinity Capture-MS), NCKAP5L (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2Z4LIS9, A2VE02, A4D1S0, A5PKC7, A5PL33, A6H7B4, A6NEL2, A6QP24, A6QPM6, A8MTW9, A8MYA2, D3ZAQ5, D4AAA5, E7EW31, O75474, O75638, O89113, O94850, P0C7X2, P14652, P50617, P70339, Q2KIS6, Q3UN58, Q5JPB2, Q5VZ46, Q6GQX2, Q6NZ36, Q6ZSJ8, Q6ZW13, Q76NI1, Q7TNS8, Q80TS7, Q86UU5, Q8IWN7, Q8N6K4, Q8N944

Diamond homologs: O14513, Q6GQX2, Q9HCH0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK1	“down-regulates activity”	NCKAP5L	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	76.1×	6e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	67.2×	1e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	67.2×	1e-10
Activation of BH3-only proteins	7	49.6×	1e-09
RHO GTPases activate PKNs	8	36.2×	1e-09
Intrinsic Pathway for Apoptosis	7	29.3×	8e-08
Loss of Nlp from mitotic centrosomes	12	27.2×	1e-12
Loss of proteins required for interphase microtubule organization from the centrosome	12	27.2×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
Golgi to plasma membrane transport	5	30.2×	9e-05
protein targeting	6	23.6×	4e-05
endocytic recycling	5	14.4×	3e-03
intracellular protein localization	11	12.4×	8e-07
protein transport	14	6.6×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

263 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	225
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2385 predictions. Top by Δscore:

Variant	Effect	Δscore
12:49792588:TCT:T	acceptor_loss	1.0000
12:49792589:C:CC	acceptor_gain	1.0000
12:49792589:C:CG	acceptor_loss	1.0000
12:49792590:T:G	acceptor_loss	1.0000
12:49792594:C:CT	acceptor_gain	1.0000
12:49792594:C:T	acceptor_gain	1.0000
12:49792595:A:T	acceptor_gain	1.0000
12:49792982:ACAGG:A	acceptor_gain	1.0000
12:49792983:CAGG:C	acceptor_gain	1.0000
12:49792983:CAGGC:C	acceptor_gain	1.0000
12:49792984:AGG:A	acceptor_gain	1.0000
12:49792985:GG:G	acceptor_gain	1.0000
12:49792986:GC:G	acceptor_loss	1.0000
12:49792987:C:CA	acceptor_loss	1.0000
12:49792987:C:CC	acceptor_gain	1.0000
12:49792988:T:G	acceptor_loss	1.0000
12:49793431:CGG:C	acceptor_gain	1.0000
12:49793434:C:CC	acceptor_gain	1.0000
12:49793436:G:GC	acceptor_gain	1.0000
12:49793730:TTACC:T	donor_loss	1.0000
12:49793731:TACC:T	donor_loss	1.0000
12:49793732:A:AC	donor_gain	1.0000
12:49793732:AC:A	donor_gain	1.0000
12:49793733:C:CG	donor_gain	1.0000
12:49793733:CC:C	donor_gain	1.0000
12:49793733:CCT:C	donor_gain	1.0000
12:49793733:CCTT:C	donor_gain	1.0000
12:49793733:CCTTT:C	donor_gain	1.0000
12:49793892:CCACC:C	acceptor_gain	1.0000
12:49793893:CACC:C	acceptor_gain	1.0000

AlphaMissense

8463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:49801942:A:G	L86P	1.000
12:49803104:A:G	L62P	1.000
12:49791864:A:G	L1327P	0.999
12:49791870:T:A	D1325V	0.999
12:49792940:G:C	F1129L	0.999
12:49792940:G:T	F1129L	0.999
12:49792942:A:G	F1129L	0.999
12:49792947:C:T	G1127E	0.999
12:49792955:A:C	S1124R	0.999
12:49792955:A:T	S1124R	0.999
12:49792957:T:G	S1124R	0.999
12:49794774:A:G	L1029P	0.999
12:49794927:A:G	L978P	0.999
12:49794948:A:G	L971P	0.999
12:49795188:A:C	I891S	0.999
12:49795188:A:T	I891N	0.999
12:49801921:A:G	L93P	0.999
12:49802968:A:G	L74P	0.999
12:49802971:A:G	L73S	0.999
12:49802975:C:G	A72P	0.999
12:49802983:A:T	V69E	0.999
12:49802992:G:T	A66D	0.999
12:49802993:C:G	A66P	0.999
12:49803125:C:G	R55P	0.999
12:49791856:A:G	C1330R	0.998
12:49791864:A:T	L1327Q	0.998
12:49791868:A:G	S1326P	0.998
12:49791870:T:C	D1325G	0.998
12:49791870:T:G	D1325A	0.998
12:49791876:A:T	L1323H	0.998

dbSNP variants (sampled 300 via entrez): RS1000010146 (12:49822848 A>C,G), RS1000055936 (12:49818100 C>G), RS1000209910 (12:49805886 C>G,T), RS1000345722 (12:49794110 A>G), RS1000397994 (12:49794360 A>G), RS1000466379 (12:49823236 G>A), RS1000498801 (12:49813056 T>A,C), RS1000499417 (12:49818464 C>T), RS1000511914 (12:49818287 C>A), RS1000706935 (12:49807173 T>G), RS1000813378 (12:49801089 G>A), RS1000858403 (12:49830124 A>G), RS1000902007 (12:49825371 G>A), RS1000918310 (12:49795257 G>A,C), RS1000952402 (12:49825608 C>T)

Disease associations

OMIM: gene MIM:615104 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008154_14	Trunk fat mass	1.000000e-06
GCST008157_46	Body fat mass	1.000000e-06
GCST009702_6	Body mass index	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Ozone	increases abundance, affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.