CDC42SE1

Summary

CDC42SE1 (CDC42 small effector 1, HGNC:17719) is a protein-coding gene on chromosome 1q21.3, encoding CDC42 small effector protein 1 (Q9NRR8). Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly.

Predicted to enable GTPase inhibitor activity. Predicted to be involved in signal transduction. Located in cell junction.

Source: NCBI Gene 56882 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 17 total
• Druggable target: yes
• MANE Select transcript: NM_020239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17719
Approved symbol	CDC42SE1
Name	CDC42 small effector 1
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	SCIP1, SPEC1
Ensembl gene	ENSG00000197622
Ensembl biotype	protein_coding
OMIM	619456
Entrez	56882

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 21 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000357235, ENST00000439374, ENST00000470278, ENST00000483763, ENST00000491825, ENST00000492796, ENST00000540998, ENST00000890174, ENST00000890175, ENST00000890176, ENST00000890177, ENST00000890178, ENST00000890179, ENST00000890180, ENST00000890181, ENST00000890182, ENST00000919198, ENST00000919199, ENST00000919200, ENST00000919201, ENST00000919202, ENST00000919203, ENST00000919204, ENST00000963038, ENST00000963039

RefSeq mRNA: 2 — MANE Select: NM_020239 NM_001038707, NM_020239

CCDS: CCDS981

Canonical transcript exons

ENST00000357235 — 5 exons

Exon	Start	End
ENSE00003519252	151055677	151055993
ENSE00003604581	151055016	151055126
ENSE00003684539	151054231	151054321
ENSE00003841658	151050985	151053327
ENSE00003849571	151059479	151059622

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 103.0574 / max 1732.7762, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14402	99.9918	1827
14401	1.4135	694
14399	1.0693	95
14398	0.4361	81
14397	0.1297	55
14396	0.0170	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.27	gold quality
blood	UBERON:0000178	98.79	gold quality
lower esophagus mucosa	UBERON:0035834	98.21	gold quality
monocyte	CL:0000576	98.17	gold quality
leukocyte	CL:0000738	98.09	gold quality
mononuclear cell	CL:0000842	97.99	gold quality
epithelium of nasopharynx	UBERON:0001951	97.97	gold quality
lymph node	UBERON:0000029	97.89	gold quality
spleen	UBERON:0002106	97.66	gold quality
esophagus mucosa	UBERON:0002469	97.61	gold quality
tibial nerve	UBERON:0001323	97.51	gold quality
vagina	UBERON:0000996	97.34	gold quality
left uterine tube	UBERON:0001303	97.18	gold quality
right lung	UBERON:0002167	97.16	gold quality
upper lobe of left lung	UBERON:0008952	96.98	gold quality
gall bladder	UBERON:0002110	96.97	gold quality
minor salivary gland	UBERON:0001830	96.96	gold quality
esophagus	UBERON:0001043	96.79	gold quality
tonsil	UBERON:0002372	96.78	gold quality
skin of abdomen	UBERON:0001416	96.76	gold quality
vermiform appendix	UBERON:0001154	96.72	gold quality
ascending aorta	UBERON:0001496	96.71	gold quality
thoracic aorta	UBERON:0001515	96.68	gold quality
skin of leg	UBERON:0001511	96.52	gold quality
right lobe of thyroid gland	UBERON:0001119	96.51	gold quality
saliva-secreting gland	UBERON:0001044	96.48	gold quality
descending thoracic aorta	UBERON:0002345	96.46	gold quality
mouth mucosa	UBERON:0003729	96.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.40	gold quality
left lobe of thyroid gland	UBERON:0001120	96.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	246.21
E-ANND-3	yes	9.48
E-CURD-112	yes	3.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GRHL2

miRNA regulators (miRDB)

121 targeting CDC42SE1, 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-6127	100.00	66.76	2188
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4779	99.86	66.50	1583

Literature-anchored findings (GeneRIF, showing 2)

• Overexpression studies of the related SPEC1 showed that it also was recruited to the activated TCR. Mutational analysis revealed that localization of SPEC1 to the TCR required two N-terminal cysteine residues (PMID:15840583)
• CDC42SE1 is downregulated in skin cancer to promote tumorigenesis. (PMID:30717410)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc42se1	ENSDARG00000023724
mus_musculus	Cdc42se1	ENSMUSG00000046722
rattus_norvegicus	Cdc42se1	ENSRNOG00000060538

Paralogs (1): CDC42SE2 (ENSG00000158985)

Protein

Protein identifiers

CDC42 small effector protein 1 — Q9NRR8 (reviewed: Q9NRR8)

Alternative names: CDC42-binding protein SCIP1, Small effector of CDC42 protein 1

All UniProt accessions (1): Q9NRR8

UniProt curated annotations — full annotation on UniProt →

Function. Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly. Alters CDC42-induced cell shape changes. In activated T-cells, may play a role in CDC42-mediated F-actin accumulation at the immunological synapse. May play a role in early contractile events in phagocytosis in macrophages.

Subunit / interactions. Interacts with CDC42 (in GTP-bound form). Interacts weakly with RAC1 and not at all with RHOA.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane.

Tissue specificity. Widely expressed. Expressed at higher level in T-lymphocytes, dendritic and whole blood cells.

Domain organisation. The CRIB domain mediates interaction with CDC42.

Similarity. Belongs to the CDC42SE/SPEC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRR8-1	1, Alpha	yes
Q9NRR8-2	2, Beta

RefSeq proteins (2): NP_001033796, NP_064624* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000095	CRIB_dom	Domain
IPR036936	CRIB_dom_sf	Homologous_superfamily
IPR039056	SPEC	Family

UniProt features (14 total): mutagenesis site 6, region of interest 2, lipid moiety-binding region 2, chain 1, domain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRR8-F1	69.54	0.10

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 (2): 10, 11

Mutagenesis-validated functional residues (6):

Position	Phenotype
38	abolishes interaction with cdc42, induces a decrease in blocking cdc42-induced jnk activation but does not affect target
41	abolishes interaction with cdc42, induces a decrease in blocking cdc42-induced jnk activation but does not affect target
62	abolishes interaction with cdc42 and induces a decrease in blocking cdc42-induced jnk activation; when associated with a
66	abolishes interaction with cdc42 and induces a decrease in blocking cdc42-induced jnk activation; when associated with a
10–11	prevents targeting to the activated tcr.
33	abolishes interaction with cdc42, induces a decrease in blocking cdc42-induced jnk activation but does not affect target

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 274 (showing top): CREL_01, WANG_CLIM2_TARGETS_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GCANCTGNY_MYOD_Q6, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, SP1_Q2_01, NFKB_Q6, PATIL_LIVER_CANCER, CAGCAGG_MIR370, SOX9_B1

GO Biological Process (4): phagocytosis (GO:0006909), signal transduction (GO:0007165), regulation of cell shape (GO:0008360), regulation of Rho protein signal transduction (GO:0035023)

GO Molecular Function (3): GTPase inhibitor activity (GO:0005095), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (5): cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell junction (GO:0030054), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endocytosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of cell morphogenesis	1
regulation of biological quality	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
GTPase activity	1
enzyme inhibitor activity	1
GTPase regulator activity	1
GTPase binding	1
binding	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

280 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC42SE1	CDC42	P21181	573
CDC42SE1	CDC42EP4	Q9H3Q1	473
CDC42SE1	PNPLA4	P41247	457
CDC42SE1	CDC42BPB	Q9Y5S2	447
CDC42SE1	ARHGEF19	Q8IW93	437
CDC42SE1	C1orf56	Q9BUN1	433
CDC42SE1	TMED2	Q15363	423
CDC42SE1	BAIAP2L1	Q9UHR4	421
CDC42SE1	BAIAP2	Q9UQB8	405
CDC42SE1	FLII	Q13045	383
CDC42SE1	SYNGAP1	Q96PV0	369
CDC42SE1	CDC42BPA	Q5VT25	343
CDC42SE1	GRHL3	Q8TE85	340
CDC42SE1	ATP6V1F	Q16864	333
CDC42SE1	CREB3	O43889	329

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CDC42SE1	EIF5B	psi-mi:“MI:0914”(association)	0.530
CDC42SE1	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
CDC42SE1	CDC42	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): CDC42SE1 (Affinity Capture-RNA), CDC42SE1 (Affinity Capture-RNA), CDC42SE1 (Affinity Capture-RNA), MIPEP (Affinity Capture-MS), EIF5B (Affinity Capture-MS), CDC42 (Affinity Capture-MS), BTBD1 (Affinity Capture-MS), CDC42SE1 (Reconstituted Complex), CDC42SE1 (Two-hybrid), CDC42SE1 (Two-hybrid), CDC42SE1 (Affinity Capture-RNA), FHL2 (Affinity Capture-MS), EIF5B (Affinity Capture-MS), MIPEP (Affinity Capture-MS), CDC42 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUV1, A0A1B0GVM6, A6NIU2, B9VXI8, C0HLZ6, C9J3V5, D3ZF18, F1MQW7, G3UWD5, J3QM76, O70738, P03294, P0DXO0, P0DXO1, P12064, P22962, P27070, P27982, P31628, P33460, P50892, P53186, P61580, P61581, P61582, P61583, Q04221, Q10027, Q16048, Q1T7F1, Q3E795, Q494R0, Q5BIS3, Q5BKH3, Q5K130, Q5YCU8, Q5ZKB1, Q67BS9, Q6ZSB3, Q6ZUT4

Diamond homologs: A1L1K4, A6QLJ4, A9JR56, Q28EW5, Q28GG3, Q4V853, Q5BIS3, Q5BJM7, Q5BKH3, Q5FVD7, Q5R4F8, Q5RDD6, Q5ZKB1, Q66KZ1, Q6AX78, Q6GPV4, Q6TEL3, Q8BGH7, Q8BHL7, Q9NRR3, Q9NRR8, Q9VNE7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1764 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151055046:C:A	donor_gain	0.9900
1:151055849:G:C	donor_gain	0.9900
1:151055890:A:C	donor_gain	0.9900
1:151055915:AGAG:A	donor_gain	0.9900
1:151067255:T:TA	donor_gain	0.9900
1:151067267:T:TA	acceptor_gain	0.9900
1:151070214:A:AC	donor_gain	0.9900
1:151070215:G:C	donor_gain	0.9900
1:151057932:G:GG	donor_gain	0.9800
1:151070236:A:AC	donor_gain	0.9800
1:151070237:C:CC	donor_gain	0.9800
1:151055831:C:CT	donor_gain	0.9700
1:151057908:G:T	donor_gain	0.9700
1:151057928:GTCA:G	donor_gain	0.9700
1:151063964:C:CC	acceptor_gain	0.9700
1:151067217:A:AG	acceptor_gain	0.9700
1:151067218:G:GG	acceptor_gain	0.9700
1:151067218:GGAA:G	acceptor_gain	0.9700
1:151067268:G:A	acceptor_gain	0.9700
1:151053325:AACCT:A	acceptor_loss	0.9600
1:151053326:ACCTG:A	acceptor_loss	0.9600
1:151053327:CCTGA:C	acceptor_loss	0.9600
1:151053329:T:A	acceptor_loss	0.9600
1:151057881:G:GT	donor_gain	0.9600
1:151070241:CAG:C	donor_gain	0.9600
1:151070262:A:AC	donor_gain	0.9600
1:151070263:C:CC	donor_gain	0.9600
1:151053333:A:C	acceptor_loss	0.9500
1:151057885:C:G	donor_gain	0.9500
1:151067213:TTCTA:T	acceptor_loss	0.9500

AlphaMissense

520 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151055073:A:C	F36L	1.000
1:151055073:A:T	F36L	1.000
1:151055075:A:G	F36L	1.000
1:151055058:G:C	H41Q	0.999
1:151055058:G:T	H41Q	0.999
1:151055074:A:C	F36C	0.999
1:151055074:A:G	F36S	0.999
1:151055092:A:T	I30N	0.999
1:151055059:T:A	H41L	0.998
1:151055059:T:C	H41R	0.998
1:151055060:G:C	H41D	0.998
1:151055060:G:T	H41N	0.998
1:151055067:G:C	H38Q	0.998
1:151055067:G:T	H38Q	0.998
1:151055068:T:C	H38R	0.998
1:151055069:G:C	H38D	0.998
1:151055069:G:T	H38N	0.998
1:151055083:G:T	P33Q	0.998
1:151055084:G:A	P33S	0.998
1:151055060:G:A	H41Y	0.997
1:151055065:A:G	L39P	0.997
1:151055077:T:A	N35I	0.997
1:151055083:G:A	P33L	0.997
1:151055089:C:T	G31E	0.997
1:151055092:A:C	I30S	0.997
1:151055107:A:C	I25S	0.997
1:151054299:A:G	M63T	0.996
1:151055075:A:T	F36I	0.996
1:151055076:A:C	N35K	0.996
1:151055076:A:T	N35K	0.996

dbSNP variants (sampled 300 via entrez): RS1000487622 (1:151053455 C>A), RS1000737106 (1:151057297 G>A), RS1000895962 (1:151061342 C>T), RS1001518189 (1:151059272 C>A,T), RS1001569194 (1:151058874 G>A,C), RS1001756962 (1:151051659 G>C), RS1001793301 (1:151057682 T>C), RS1001929024 (1:151057437 C>T), RS1002669524 (1:151052337 G>A), RS1002863352 (1:151059515 T>A), RS1003198660 (1:151057607 T>C,G), RS1003208437 (1:151057431 G>A), RS1003213808 (1:151052029 A>G,T), RS1003814087 (1:151053653 T>C), RS1004082629 (1:151053158 G>A)

Disease associations

OMIM: gene MIM:619456 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3308925 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
glycidyl methacrylate	increases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Acetaminophen	decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Silver	increases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Thiram	increases expression	1
Vincristine	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Lithium Chloride	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
tert-Butylhydroperoxide	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1212031	Binding	Inhibition of GTPase activity of Cdc42	Synthesis of potent chemical inhibitors of dynamin GTPase. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1MY	Abcam HeLa CDC42SE1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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