CPLANE2

Summary

CPLANE2 (ciliogenesis and planar polarity effector complex subunit 2, HGNC:28127) is a protein-coding gene on chromosome 1p36.13, encoding Ciliogenesis and planar polarity effector 2 (Q9BU20). Required for efficient primary cilia initiation, regulating a late step in cilia initiation.

Predicted to enable GTP binding activity. Predicted to be involved in cilium assembly; protein localization; and regulation of vesicle-mediated transport. Predicted to act upstream of or within several processes, including axoneme assembly; endocardial cushion fusion; and regulation of smoothened signaling pathway. Located in centriole; ciliary basal body; and ciliary transition zone.

Source: NCBI Gene 79363 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_030907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28127
Approved symbol	CPLANE2
Name	ciliogenesis and planar polarity effector complex subunit 2
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC10731
Ensembl gene	ENSG00000132881
Ensembl biotype	protein_coding
OMIM	620487
Entrez	79363

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000375599, ENST00000434014, ENST00000945441

RefSeq mRNA: 1 — MANE Select: NM_030907 NM_030907

CCDS: CCDS171

Canonical transcript exons

ENST00000375599 — 5 exons

Exon	Start	End
ENSE00000906126	16232893	16233017
ENSE00001161042	16231692	16232297
ENSE00001679186	16232510	16232646
ENSE00001819719	16236631	16237183
ENSE00003605348	16233612	16233764

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 88.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.2237 / max 43.4608, expressed in 1190 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10532	2.2237	1190

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.88	gold quality
anterior cingulate cortex	UBERON:0009835	78.66	gold quality
cingulate cortex	UBERON:0003027	78.65	gold quality
stromal cell of endometrium	CL:0002255	78.64	gold quality
prefrontal cortex	UBERON:0000451	78.45	gold quality
type B pancreatic cell	CL:0000169	78.07	gold quality
olfactory bulb	UBERON:0002264	77.87	gold quality
right adrenal gland	UBERON:0001233	76.93	gold quality
right adrenal gland cortex	UBERON:0035827	76.65	gold quality
right uterine tube	UBERON:0001302	76.23	gold quality
right frontal lobe	UBERON:0002810	75.95	gold quality
left adrenal gland cortex	UBERON:0035825	75.73	gold quality
adenohypophysis	UBERON:0002196	75.67	gold quality
left adrenal gland	UBERON:0001234	75.63	gold quality
amygdala	UBERON:0001876	75.43	gold quality
nucleus accumbens	UBERON:0001882	75.13	gold quality
left ovary	UBERON:0002119	73.72	gold quality
right lobe of thyroid gland	UBERON:0001119	73.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.55	gold quality
caudate nucleus	UBERON:0001873	73.50	gold quality
adrenal cortex	UBERON:0001235	73.44	gold quality
right ovary	UBERON:0002118	73.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	73.05	gold quality
apex of heart	UBERON:0002098	73.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	73.03	gold quality
lower esophagus	UBERON:0013473	73.02	gold quality
mucosa of stomach	UBERON:0001199	73.01	gold quality
adrenal gland	UBERON:0002369	72.97	gold quality
left lobe of thyroid gland	UBERON:0001120	72.94	gold quality
neocortex	UBERON:0001950	72.80	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting CPLANE2, 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-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-4661-3P	96.81	66.02	342
HSA-MIR-3918	96.13	64.65	1300

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cplane2	ENSDARG00000028442
mus_musculus	Cplane2	ENSMUSG00000073733
rattus_norvegicus	LOC120103024	ENSRNOG00000023346

Protein

Protein identifiers

Ciliogenesis and planar polarity effector 2 — Q9BU20 (reviewed: Q9BU20)

Alternative names: REM2- and Rab-like small GTPase 1

All UniProt accessions (2): Q9BU20, H0Y6L8

UniProt curated annotations — full annotation on UniProt →

Function. Required for efficient primary cilia initiation, regulating a late step in cilia initiation. Plays a role in the final maturation of the mother centriole and ciliary vesicle that allows extension of the ciliary axoneme.

Subunit / interactions. Interacts with FUZ. Associates with the CPLANE (ciliogenesis and planar polarity effectors) complex via its interaction with FUZ.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body. Microtubule organizing center. Centrosome. Centriole.

Similarity. Belongs to the small GTPase superfamily. Rab family.

RefSeq proteins (1): NP_112169* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR039677	RSG1	Family

Pfam: PF00071

UniProt features (16 total): binding site 12, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BU20-F1	90.38	0.71

Functional residue map

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

Ligand- & substrate-binding residues (12): 87; 176; 178; 206; 64; 65; 67; 68; 69; 70; 82; 84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_VESICLE_ORGANIZATION, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ENDOCARDIAL_CUSHION_MORPHOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_ADHESION, GOBP_EXOCYTOSIS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_PROTEIN_MATURATION, GOBP_ORGANELLE_MEMBRANE_FUSION, GOBP_HEART_MORPHOGENESIS

GO Biological Process (15): endocardial cushion fusion (GO:0003274), exocytosis (GO:0006887), smoothened signaling pathway (GO:0007224), intracellular protein localization (GO:0008104), regulation of smoothened signaling pathway (GO:0008589), protein transport (GO:0015031), protein processing (GO:0016485), regulation of exocytosis (GO:0017157), dorsal/ventral neural tube patterning (GO:0021904), regulation of vesicle fusion (GO:0031338), axoneme assembly (GO:0035082), limb development (GO:0060173), cilium assembly (GO:0060271), cranial skeletal system development (GO:1904888), cell projection organization (GO:0030030)

GO Molecular Function (4): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (8): centriole (GO:0005814), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), ciliary base (GO:0097546), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cilium	3
regulation of vesicle-mediated transport	2
microtubule organizing center	2
intracellular membraneless organelle	2
endocardial cushion morphogenesis	1
cell adhesion involved in heart morphogenesis	1
cell-cell adhesion	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
cell surface receptor signaling pathway	1
macromolecule localization	1
smoothened signaling pathway	1
regulation of signal transduction	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
proteolysis	1
protein maturation	1
exocytosis	1
regulation of secretion by cell	1
dorsal/ventral pattern formation	1
neural tube patterning	1
vesicle fusion	1
regulation of organelle organization	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
appendage development	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
anatomical structure development	1
cellular component organization	1

Protein interactions and networks

STRING

1345 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPLANE2	INTU	Q9ULD6	918
CPLANE2	WDPCP	O95876	858
CPLANE2	FUZ	Q9BT04	785
CPLANE2	RAB23	Q9ULC3	608
CPLANE2	IFT43	Q96FT9	578
CPLANE2	ARL13B	Q3SXY8	574
CPLANE2	IFT27	Q9BW83	560
CPLANE2	IFT22	Q9H7X7	547
CPLANE2	ARL3	P36405	503
CPLANE2	KIF9	Q9HAQ2	473
CPLANE2	DNAJC27	Q9NZQ0	466
CPLANE2	TTBK2	Q6IQ55	464
CPLANE2	TBC1D32	Q96NH3	464
CPLANE2	RAB8A	P24407	456
CPLANE2	KIF24	Q5T7B8	446

IntAct

27 interactions, top by confidence:

A	B	Type	Score
FUZ	CPLANE2	psi-mi:“MI:0915”(physical association)	0.800
CPLANE2	FUZ	psi-mi:“MI:0915”(physical association)	0.800
IMPDH2	CPLANE2	psi-mi:“MI:0915”(physical association)	0.720
CPLANE2	IMPDH2	psi-mi:“MI:0915”(physical association)	0.720
RND3	CPLANE2	psi-mi:“MI:0915”(physical association)	0.560
MSLN	CPLANE2	psi-mi:“MI:0915”(physical association)	0.370
CPLANE2	TMEM14C	psi-mi:“MI:0915”(physical association)	0.370
CPLANE2	FUZ	psi-mi:“MI:0914”(association)	0.350
INTU	CCNA2	psi-mi:“MI:0914”(association)	0.350
CPLANE2	PKP1	psi-mi:“MI:0914”(association)	0.350
CPLANE2	HSPA8	psi-mi:“MI:0914”(association)	0.350
FUZ	UBL4A	psi-mi:“MI:0914”(association)	0.350
FUZ	HSPA8	psi-mi:“MI:0914”(association)	0.350
FUZ	PRORP	psi-mi:“MI:0914”(association)	0.350
CPLANE2	IMPDH2	psi-mi:“MI:0915”(physical association)	0.000
FUZ	CPLANE2	psi-mi:“MI:0915”(physical association)	0.000
CPLANE2	RND3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): RSG1 (Two-hybrid), INTU (Affinity Capture-MS), CDC37 (Affinity Capture-MS), PKP1 (Affinity Capture-MS), FUZ (Affinity Capture-MS), FUZ (Two-hybrid), FUZ (Affinity Capture-MS), INTU (Affinity Capture-MS), RSG1 (Two-hybrid), RSG1 (Two-hybrid), IMPDH2 (Two-hybrid), PKP1 (Affinity Capture-MS), FUZ (Affinity Capture-MS), RSG1 (Affinity Capture-MS), RSG1 (Affinity Capture-MS)

ESM2 similar proteins: A1L1L6, A2A825, A6QL63, C9J798, O14908, O43374, O94844, O95278, O95294, Q0P5N6, Q15126, Q1LVW0, Q2HJF8, Q2TBH1, Q3UMR5, Q3UNW5, Q4R4U1, Q5E9M9, Q5R5F8, Q5ZIW1, Q5ZM73, Q5ZM83, Q66JN8, Q6DFV5, Q6GQW0, Q6IE70, Q6NVC5, Q6NYU2, Q7TSA0, Q7Z6G3, Q8BG51, Q8BGF7, Q8BHT7, Q8CIW5, Q8IXI1, Q8IXI2, Q8JZN7, Q8VCX6, Q91XQ2, Q923S8

Diamond homologs: A2A825, B7ZTR0, Q66JN8, Q6GNL4, Q8IYK8, Q9BU20, Q9WTY2, P55041, Q8VEL9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“CPLANE complex”	“up-regulates activity”	CPLANE2	binding
CPLANE2	up-regulates	Cilium_assembly

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

799 predictions. Top by Δscore:

Variant	Effect	Δscore
1:16232598:CAG:C	acceptor_gain	1.0000
1:16232599:A:T	acceptor_gain	1.0000
1:16232642:CAAGC:C	acceptor_gain	1.0000
1:16232643:AAGC:A	acceptor_gain	1.0000
1:16232645:GC:G	acceptor_gain	1.0000
1:16232646:CC:C	acceptor_gain	1.0000
1:16232646:CCTGG:C	acceptor_loss	1.0000
1:16232647:C:CC	acceptor_gain	1.0000
1:16232648:T:C	acceptor_loss	1.0000
1:16232650:G:C	acceptor_gain	1.0000
1:16232653:A:AC	acceptor_gain	1.0000
1:16232653:A:C	acceptor_gain	1.0000
1:16232892:CCAG:C	donor_gain	1.0000
1:16233015:TGC:T	acceptor_gain	1.0000
1:16233608:TCA:T	donor_loss	1.0000
1:16233610:A:AC	donor_gain	1.0000
1:16233610:AC:A	donor_gain	1.0000
1:16233611:C:CC	donor_gain	1.0000
1:16233611:CC:C	donor_gain	1.0000
1:16233611:CCG:C	donor_gain	1.0000
1:16233611:CCGG:C	donor_gain	1.0000
1:16233611:CCGGT:C	donor_gain	1.0000
1:16233760:CAGCC:C	acceptor_gain	1.0000
1:16233761:AGCC:A	acceptor_gain	1.0000
1:16233762:GCC:G	acceptor_gain	1.0000
1:16233763:CC:C	acceptor_gain	1.0000
1:16233763:CCC:C	acceptor_gain	1.0000
1:16233763:CCCT:C	acceptor_loss	1.0000
1:16233764:CC:C	acceptor_gain	1.0000
1:16233764:CCTAG:C	acceptor_loss	1.0000

AlphaMissense

1668 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:16232908:G:C	F125L	0.985
1:16232908:G:T	F125L	0.985
1:16232910:A:G	F125L	0.985
1:16232608:G:C	F143L	0.983
1:16232608:G:T	F143L	0.983
1:16232610:A:G	F143L	0.983
1:16232994:A:G	W97R	0.982
1:16232994:A:T	W97R	0.982
1:16232510:T:A	K176I	0.979
1:16232516:C:T	G174D	0.977
1:16233673:C:A	K68N	0.977
1:16233673:C:G	K68N	0.977
1:16233706:C:A	K57N	0.977
1:16233706:C:G	K57N	0.977
1:16233674:T:A	K68M	0.976
1:16233674:T:G	K68T	0.975
1:16232607:A:G	S144P	0.974
1:16233698:A:T	V60E	0.974
1:16233692:C:T	G62E	0.973
1:16233711:A:C	Y56D	0.973
1:16236700:A:G	W15R	0.973
1:16236700:A:T	W15R	0.973
1:16232624:G:T	A138D	0.969
1:16232625:C:G	A138P	0.969
1:16233692:C:A	G62V	0.969
1:16233693:C:A	G62W	0.969
1:16233660:C:G	A73P	0.968
1:16232522:A:T	V172D	0.967
1:16232576:A:G	L154P	0.967
1:16232609:A:G	F143S	0.967

dbSNP variants (sampled 300 via entrez): RS1000774406 (1:16233069 G>A), RS1002216153 (1:16238719 A>T), RS1002548132 (1:16234911 A>C,T), RS1003222729 (1:16237203 C>T), RS1003253844 (1:16237398 C>G), RS1003620441 (1:16236721 C>A,G,T), RS1003804787 (1:16236254 TG>T), RS1004811596 (1:16237590 A>T), RS1005297324 (1:16231356 C>T), RS1006013203 (1:16232599 A>G), RS1006077833 (1:16238646 G>A,T), RS1006499222 (1:16239038 T>C,G), RS1006698518 (1:16238034 A>C), RS1007023294 (1:16237578 C>T), RS1007079833 (1:16237692 C>T)

Disease associations

OMIM: gene MIM:620487 | 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
GCST001277_7	Liver enzyme levels (gamma-glutamyl transferase)	3.000000e-19
GCST008058_42	Estimated glomerular filtration rate	1.000000e-10
GCST008059_245	Estimated glomerular filtration rate	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
beauvericin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
enniatins	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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