CTTNBP2NL

Summary

CTTNBP2NL (CTTNBP2 N-terminal like, HGNC:25330) is a protein-coding gene on chromosome 1p13.2, encoding CTTNBP2 N-terminal-like protein (Q9P2B4). Regulates lamellipodial actin dynamics in a CTTN-dependent manner.

Enables protein phosphatase 2A binding activity. Acts upstream of or within negative regulation of transmembrane transport; negative regulation of transporter activity; and protein dephosphorylation. Located in actin cytoskeleton. Part of FAR/SIN/STRIPAK complex.

Source: NCBI Gene 55917 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_018704

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25330
Approved symbol	CTTNBP2NL
Name	CTTNBP2 N-terminal like
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547A023
Ensembl gene	ENSG00000143079
Ensembl biotype	protein_coding
OMIM	615100
Entrez	55917

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000271277, ENST00000441739, ENST00000502356, ENST00000607039, ENST00000862867, ENST00000862868, ENST00000862869, ENST00000862870, ENST00000918267, ENST00000918268, ENST00000967295, ENST00000967296, ENST00000967297

RefSeq mRNA: 1 — MANE Select: NM_018704 NM_018704

CCDS: CCDS845

Canonical transcript exons

ENST00000271277 — 6 exons

Exon	Start	End
ENSE00000957960	112448942	112449172
ENSE00000957961	112454449	112454556
ENSE00001159793	112416157	112416264
ENSE00001450658	112455931	112461164
ENSE00001450660	112412194	112412317
ENSE00001450661	112396214	112396272

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5681 / max 166.9396, expressed in 1654 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4663	3.9817	1486
4664	3.4434	1409
4665	1.8698	993
4666	0.2733	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.20	gold quality
esophagus squamous epithelium	UBERON:0006920	97.16	gold quality
upper arm skin	UBERON:0004263	97.08	gold quality
amniotic fluid	UBERON:0000173	96.90	gold quality
epithelial cell of pancreas	CL:0000083	96.36	gold quality
sural nerve	UBERON:0015488	95.50	gold quality
skin of hip	UBERON:0001554	95.02	gold quality
upper leg skin	UBERON:0004262	93.57	gold quality
gingiva	UBERON:0001828	93.39	gold quality
gingival epithelium	UBERON:0001949	93.22	gold quality
visceral pleura	UBERON:0002401	93.06	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.02	gold quality
endothelial cell	CL:0000115	92.95	gold quality
colonic mucosa	UBERON:0000317	92.86	gold quality
cartilage tissue	UBERON:0002418	92.86	gold quality
penis	UBERON:0000989	92.59	gold quality
cauda epididymis	UBERON:0004360	92.43	gold quality
oral cavity	UBERON:0000167	92.42	gold quality
mammalian vulva	UBERON:0000997	92.38	gold quality
cortical plate	UBERON:0005343	92.13	gold quality
kidney epithelium	UBERON:0004819	91.82	silver quality
oocyte	CL:0000023	91.37	gold quality
parietal pleura	UBERON:0002400	91.14	gold quality
lower lobe of lung	UBERON:0008949	91.01	gold quality
colonic epithelium	UBERON:0000397	90.92	gold quality
pharyngeal mucosa	UBERON:0000355	90.56	gold quality
placenta	UBERON:0001987	90.47	gold quality
vena cava	UBERON:0004087	90.02	gold quality
saphenous vein	UBERON:0007318	89.60	gold quality
germinal epithelium of ovary	UBERON:0001304	89.11	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	38.98
E-CURD-112	yes	13.81
E-ANND-3	yes	10.24
E-GEOD-99795	no	86.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

216 targeting CTTNBP2NL, 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-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4692	100.00	67.32	2066
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4534	99.99	66.58	1907
HSA-LET-7F-2-3P	99.98	70.98	2588

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cttnbp2nla	ENSDARG00000053179
danio_rerio	cttnbp2nlb	ENSDARG00000056091
mus_musculus	Cttnbp2nl	ENSMUSG00000062127
rattus_norvegicus	Cttnbp2nl	ENSRNOG00000014479
drosophila_melanogaster	Naus	FBGN0034308

Paralogs (3): FILIP1 (ENSG00000118407), FILIP1L (ENSG00000168386), LUZP1 (ENSG00000169641)

Protein

Protein identifiers

CTTNBP2 N-terminal-like protein — Q9P2B4 (reviewed: Q9P2B4)

All UniProt accessions (2): Q9P2B4, B1AMN7

UniProt curated annotations — full annotation on UniProt →

Function. Regulates lamellipodial actin dynamics in a CTTN-dependent manner. Associates with core striatin-interacting phosphatase and kinase (STRIPAK) complex to form CTTNBP2NL-STRIPAK complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation.

Subunit / interactions. Interacts with CTTN/cortactin; this interaction may redistribute CTTN to stress fibers. May form homomers. Associates with the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26.

Subcellular location. Cell projection. Lamellipodium. Cytoplasm. Cytoskeleton. Stress fiber.

RefSeq proteins (1): NP_061174* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019131	Cortactin-binding_p2_N	Domain
IPR050719	Cortactin-Actin_Reg	Family

Pfam: PF09727

UniProt features (24 total): modified residue 12, compositionally biased region 4, region of interest 3, sequence variant 2, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2B4-F1	67.43	0.35

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): 285, 481, 488, 523, 527, 560, 563, 568, 570, 590, 592, 284

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 204 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, AP1_01, AAGCAAT_MIR137, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, MODULE_522, HNF1_Q6, SP1_Q2_01, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, ZIC1_01, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, ACATTCC_MIR1_MIR206

GO Biological Process (4): protein dephosphorylation (GO:0006470), negative regulation of transporter activity (GO:0032410), negative regulation of transmembrane transport (GO:0034763), protein localization to actin cytoskeleton (GO:1903119)

GO Molecular Function (2): protein phosphatase 2A binding (GO:0051721), protein binding (GO:0005515)

GO Cellular Component (7): stress fiber (GO:0001725), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), FAR/SIN/STRIPAK complex (GO:0090443), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of transport	2
cellular anatomical structure	2
dephosphorylation	1
protein modification process	1
transporter activity	1
negative regulation of molecular function	1
regulation of transmembrane transport	1
negative regulation of cellular process	1
transmembrane transport	1
protein localization to cytoskeleton	1
protein phosphatase binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
cytoskeleton	1
cell leading edge	1
plasma membrane bounded cell projection	1
protein-containing complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTTNBP2NL	STRN3	Q13033	877
CTTNBP2NL	STRIP1	Q5VSL9	864
CTTNBP2NL	MOB4	Q9Y3A3	807
CTTNBP2NL	SLMAP	Q14BN4	718
CTTNBP2NL	SIKE1	Q9BRV8	718
CTTNBP2NL	STRN4	Q9NRL3	690
CTTNBP2NL	PDCD10	Q9BUL8	685
CTTNBP2NL	FGFR1OP2	Q9NVK5	677
CTTNBP2NL	STK24	Q9Y6E0	667
CTTNBP2NL	STRN	O43815	629
CTTNBP2NL	STRIP2	Q9ULQ0	612
CTTNBP2NL	PPP2R1A	P30153	567
CTTNBP2NL	MAP2K3	P46734	519
CTTNBP2NL	STK26	Q9P289	481
CTTNBP2NL	WIPF2	Q8TF74	469

IntAct

133 interactions, top by confidence:

A	B	Type	Score
PDCD10	STK25	psi-mi:“MI:0914”(association)	0.980
STRN3	PPP2R1A	psi-mi:“MI:0914”(association)	0.920
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
STK24	STK25	psi-mi:“MI:0914”(association)	0.890
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
STRN3	STK25	psi-mi:“MI:0914”(association)	0.880
CTTNBP2NL	STK25	psi-mi:“MI:0914”(association)	0.880
STRN3	STRN	psi-mi:“MI:0914”(association)	0.880
STRN3	STRN	psi-mi:“MI:2364”(proximity)	0.880
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
STRIP1	PPP2CB	psi-mi:“MI:0914”(association)	0.870
STK26	STRN	psi-mi:“MI:0914”(association)	0.860
PRDM14	CBFA2T2	psi-mi:“MI:0914”(association)	0.860
PPP2CA	STRN	psi-mi:“MI:0914”(association)	0.840
STRIP1	STK25	psi-mi:“MI:0914”(association)	0.840

BioGRID (167): CTTNBP2NL (Two-hybrid), USHBP1 (Two-hybrid), CTTNBP2NL (Affinity Capture-MS), CTTNBP2NL (Affinity Capture-MS), CTTNBP2NL (Affinity Capture-MS), CTTNBP2NL (Affinity Capture-MS), STRN (Co-fractionation), CTTNBP2NL (Affinity Capture-MS), CTTNBP2NL (Proximity Label-MS), CTTNBP2NL (Proximity Label-MS), CTTNBP2NL (Affinity Capture-MS), CTTNBP2NL (Affinity Capture-MS), CTTNBP2NL (Affinity Capture-MS), CTTNBP2NL (Affinity Capture-MS), CTTNBP2NL (Affinity Capture-MS)

ESM2 similar proteins: A0M8S4, A0M8T5, A1X157, B9EJA2, O35867, P0C6C1, P39880, P53564, P53565, Q00PJ1, Q02225, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07DZ5, Q07E15, Q07E28, Q07E41, Q09YG9, Q09YI1, Q09YJ3, Q09YK4, Q09YM8, Q108T9, Q13625, Q2IBA2, Q2IBB2, Q2IBD4, Q2IBE6, Q2IBF7, Q2IBF8, Q2QL82, Q2QLA2, Q2QLB3, Q2QLF8, Q2QLG9, Q53HC0, Q5RDH2, Q5T1M5

Diamond homologs: A0M8S4, A0M8T5, A1X157, B9EJA2, Q00PJ1, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07DZ5, Q07E15, Q07E28, Q07E41, Q09YG9, Q09YI1, Q09YJ3, Q09YK4, Q09YM8, Q108T9, Q2IBA2, Q2IBB2, Q2IBD4, Q2IBE6, Q2IBF7, Q2IBF8, Q2QL82, Q2QLA2, Q2QLB3, Q2QLF8, Q2QLG9, Q4L180, Q5RDH2, Q6P6L0, Q8SX68, Q8WZ74, Q99LJ0, Q9P2B4, Q8IVL1, A3KNA5, Q7Z7B0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CTTNBP2NL	“up-regulates activity”	STRN4	binding
CTTNBP2NL	“up-regulates activity”	STRN	binding
CTTNBP2NL	up-regulates	Actin_cytoskeleton_reorganization
CTTNBP2NL	“up-regulates activity”	CTTN	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	5	13.2×	6e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	11.0×	1e-03
RHO GTPases Activate Formins	6	10.6×	5e-04
EML4 and NUDC in mitotic spindle formation	5	10.6×	1e-03
Resolution of Sister Chromatid Cohesion	5	9.8×	2e-03
Mitotic Prometaphase	6	9.4×	6e-04
Separation of Sister Chromatids	5	6.9×	7e-03
Diseases of signal transduction by growth factor receptors and second messengers	5	6.5×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of hippo signaling	7	72.3×	2e-09
neuron projection morphogenesis	5	20.3×	1e-03
protein autophosphorylation	5	10.7×	8e-03
protein phosphorylation	7	7.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1374 predictions. Top by Δscore:

Variant	Effect	Δscore
1:112396272:GGTA:G	donor_loss	1.0000
1:112396273:GTAGG:G	donor_loss	1.0000
1:112396274:T:A	donor_loss	1.0000
1:112416149:T:TA	acceptor_gain	1.0000
1:112416153:TCA:T	acceptor_loss	1.0000
1:112416154:CA:C	acceptor_loss	1.0000
1:112416155:A:AG	acceptor_gain	1.0000
1:112416155:AG:A	acceptor_gain	1.0000
1:112416156:G:GT	acceptor_gain	1.0000
1:112416156:GG:G	acceptor_gain	1.0000
1:112416156:GGC:G	acceptor_gain	1.0000
1:112416156:GGCT:G	acceptor_gain	1.0000
1:112416260:TAAAG:T	donor_loss	1.0000
1:112416261:AAAG:A	donor_loss	1.0000
1:112416262:AAGG:A	donor_loss	1.0000
1:112416263:AGGT:A	donor_loss	1.0000
1:112416265:G:GG	donor_gain	1.0000
1:112416266:T:A	donor_loss	1.0000
1:112448940:A:AG	acceptor_gain	1.0000
1:112448940:AG:A	acceptor_gain	1.0000
1:112448941:G:GG	acceptor_gain	1.0000
1:112448941:GG:G	acceptor_gain	1.0000
1:112448941:GGC:G	acceptor_gain	1.0000
1:112448941:GGCC:G	acceptor_gain	1.0000
1:112448941:GGCCC:G	acceptor_gain	1.0000
1:112449168:GAAAG:G	donor_gain	1.0000
1:112449170:AAG:A	donor_gain	1.0000
1:112449171:AG:A	donor_gain	1.0000
1:112449172:GG:G	donor_gain	1.0000
1:112449172:GGTA:G	donor_loss	1.0000

AlphaMissense

4174 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:112416197:T:C	L11P	1.000
1:112416218:T:C	L18P	1.000
1:112416223:G:A	G20R	1.000
1:112416223:G:C	G20R	1.000
1:112416230:T:C	L22P	1.000
1:112416235:G:C	A24P	1.000
1:112449012:T:C	L57P	1.000
1:112449144:T:C	L101P	1.000
1:112454462:T:C	L115P	1.000
1:112454503:G:A	G129R	1.000
1:112454503:G:C	G129R	1.000
1:112454525:T:C	L136P	1.000
1:112454546:T:C	L143P	1.000
1:112456238:T:C	L249P	1.000
1:112457006:T:A	V505D	1.000
1:112416200:T:C	L12P	0.999
1:112416206:T:C	L14P	0.999
1:112416224:G:A	G20E	0.999
1:112416230:T:A	L22H	0.999
1:112416248:T:A	V28D	0.999
1:112416256:G:C	A31P	0.999
1:112449018:G:C	R59T	0.999
1:112449019:A:C	R59S	0.999
1:112449019:A:T	R59S	0.999
1:112449021:A:T	D60V	0.999
1:112449090:T:C	L83P	0.999
1:112449152:G:C	A104P	0.999
1:112454480:G:C	R121P	0.999
1:112454497:G:C	A127P	0.999
1:112454525:T:A	L136Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000028394 (1:112410087 A>G,T), RS1000117710 (1:112439208 G>A,T), RS1000121557 (1:112456799 G>A), RS1000218693 (1:112453184 T>G), RS1000224854 (1:112460359 A>C), RS1000277966 (1:112398848 A>G), RS1000308092 (1:112393461 T>C), RS1000338718 (1:112393852 A>G), RS1000408911 (1:112449015 A>G), RS1000456120 (1:112459445 T>A), RS1000459996 (1:112403625 T>C), RS1000473218 (1:112422224 T>C,G), RS1000501862 (1:112408287 T>G), RS1000549502 (1:112453563 G>A), RS1000558739 (1:112458781 C>T)

Disease associations

OMIM: gene MIM:615100 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006979_998	Heel bone mineral density	3.000000e-09
GCST011176_11	Stroke	9.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cyclosporine	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cadmium	increases abundance, decreases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

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