CTXN2

Summary

CTXN2 (cortexin 2, HGNC:31109) is a protein-coding gene on chromosome 15q21.1, encoding Cortexin-2 (P0C2S0).

Predicted to be located in membrane.

Source: NCBI Gene 399697 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 14 total — 2 pathogenic
• MANE Select transcript: NM_001145668

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31109
Approved symbol	CTXN2
Name	cortexin 2
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000233932
Ensembl biotype	protein_coding
Entrez	399697

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000417307, ENST00000644354, ENST00000645050, ENST00000647363, ENST00000901547, ENST00000901548, ENST00000941635, ENST00000941636

RefSeq mRNA: 3 — MANE Select: NM_001145668 NM_001145668, NM_001370415, NM_001370416

CCDS: CCDS45254

Canonical transcript exons

ENST00000417307 — 2 exons

Exon	Start	End
ENSE00001629931	48201244	48203758
ENSE00002564103	48191665	48191853

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 67.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1469 / max 11.6531, expressed in 70 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146539	0.1469	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	67.12	gold quality
frontal cortex	UBERON:0001870	65.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.88	gold quality
superior frontal gyrus	UBERON:0002661	65.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.53	gold quality
quadriceps femoris	UBERON:0001377	65.49	gold quality
hypothalamus	UBERON:0001898	65.42	gold quality
cerebellar vermis	UBERON:0004720	64.61	gold quality
right frontal lobe	UBERON:0002810	64.11	gold quality
cerebral cortex	UBERON:0000956	63.79	gold quality
nucleus accumbens	UBERON:0001882	63.67	gold quality
anterior cingulate cortex	UBERON:0009835	63.41	gold quality
primary visual cortex	UBERON:0002436	62.34	gold quality
islet of Langerhans	UBERON:0000006	62.04	gold quality
brain	UBERON:0000955	61.66	gold quality
putamen	UBERON:0001874	60.85	gold quality
temporal lobe	UBERON:0001871	60.68	gold quality
amygdala	UBERON:0001876	60.61	gold quality
cerebellum	UBERON:0002037	60.08	gold quality
cerebellar cortex	UBERON:0002129	60.01	gold quality
cerebellar hemisphere	UBERON:0002245	59.98	gold quality
caudate nucleus	UBERON:0001873	59.71	gold quality
substantia nigra	UBERON:0002038	59.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	59.26	gold quality
thymus	UBERON:0002370	58.00	silver quality
pituitary gland	UBERON:0000007	57.64	gold quality
cortical plate	UBERON:0005343	57.57	gold quality
adenohypophysis	UBERON:0002196	56.98	gold quality
Ammon’s horn	UBERON:0001954	56.36	gold quality
spinal cord	UBERON:0002240	51.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting CTXN2, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ctxn2	ENSMUSG00000074872
rattus_norvegicus	Ctxn2	ENSRNOG00000037146

Paralogs (2): CTXN1 (ENSG00000178531), CTXN3 (ENSG00000205279)

Protein

Protein identifiers

Cortexin-2 — P0C2S0 (reviewed: P0C2S0)

All UniProt accessions (1): P0C2S0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the cortexin family.

RefSeq proteins (3): NP_001139140, NP_001357344, NP_001357345 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020066	Cortexin	Family

Pfam: PF11057

UniProt features (2 total): chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C2S0-F1	70.79	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): NOUZOVA_METHYLATED_IN_APL, HMG20B_TARGET_GENES, KMT2D_TARGET_GENES, MIER1_TARGET_GENES, ZNF7_TARGET_GENES, MIR548D_3P, MIR548H_3P_MIR548Z, MIR548BB_3P, MIR548AC, MIR6875_3P, MIR3978, MIR181B_2_3P_MIR181B_3P, MIR4420, MIR12122, MIR133A_3P_MIR133B

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTXN2	MYEF2	Q9P2K5	744
CTXN2	SLC24A5	Q71RS6	616
CTXN2	SLC12A1	Q13621	593
CTXN2	TRPV6	Q9H1D0	452
CTXN2	NT5DC1	Q5TFE4	444
CTXN2	ACKR1	Q16570	437
CTXN2	AMER3	Q8N944	417
CTXN2	ZMYM6	O95789	398
CTXN2	ABTB2	Q8N961	397
CTXN2	LRRC55	Q6ZSA7	393
CTXN2	SVIP	Q8NHG7	383
CTXN2	RUNDC3A	Q59EK9	375
CTXN2	SLC12A2	P55011	368
CTXN2	PGPEP1	Q9NXJ5	357
CTXN2	SLC45A2	Q9UMX9	357

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GST9, A0A1B0GTU2, A0A1B0GV90, A0A590UK83, A2RRL7, A7S641, A8WG88, A9JTJ0, B9X187, K7EJ46, O00168, O08589, O13001, P0C2S0, P15383, P41237, P56513, P60606, P63160, P63161, Q04645, Q04646, Q04679, Q04680, Q0P467, Q28EH9, Q3SZX0, Q3UJ81, Q3URE8, Q3ZBP2, Q4LDR2, Q4R6L9, Q502I1, Q592E4, Q5XF36, Q6AXF6, Q6NWH5, Q6PBK8, Q6Q3F5, Q71RC9

Diamond homologs: A0A1B0GQX3, A0A1B0GST9, A0A1B0GTU2, A0A1B0GV90, P0C2S0, P41237, P60606, Q3URE8, Q4LDR2, Q8K129, Q592E4, Q8BXZ0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1341108	GRCh37/hg19 15q21.1(chr15:48179968-48727846)x1	Pathogenic
832299	NC_000015.10:g.(?48134288)(48644779_?)del	Pathogenic

SpliceAI

311 predictions. Top by Δscore:

Variant	Effect	Δscore
15:48178078:TTTTA:T	donor_gain	0.9900
15:48178082:AACG:A	donor_gain	0.9900
15:48178086:C:CA	donor_gain	0.9900
15:48191850:GAAGG:G	donor_loss	0.9900
15:48191851:A:T	donor_gain	0.9900
15:48191851:AAGG:A	donor_loss	0.9900
15:48191854:G:T	donor_loss	0.9900
15:48191855:T:A	donor_loss	0.9900
15:48191873:G:GT	donor_gain	0.9900
15:48191876:G:GG	donor_gain	0.9900
15:48195699:A:AG	donor_gain	0.9900
15:48178076:CATTT:C	donor_gain	0.9800
15:48178083:A:C	donor_gain	0.9800
15:48192931:TAGTA:T	acceptor_gain	0.9800
15:48192932:AGTAA:A	acceptor_gain	0.9800
15:48192933:GTAAG:G	acceptor_gain	0.9800
15:48191850:G:GT	donor_gain	0.9700
15:48191875:A:AG	donor_gain	0.9700
15:48191880:C:G	donor_gain	0.9700
15:48178075:A:AC	donor_gain	0.9600
15:48178076:C:CC	donor_gain	0.9600
15:48191849:GGAAG:G	donor_gain	0.9600
15:48191850:GAAG:G	donor_gain	0.9500
15:48191854:G:GG	donor_gain	0.9400
15:48191933:A:G	donor_gain	0.9400
15:48192281:GAT:G	donor_gain	0.9300
15:48199759:A:AG	donor_gain	0.9300
15:48178094:G:C	donor_gain	0.9100
15:48192933:GTAA:G	acceptor_gain	0.9100
15:48191928:TCCAG:T	donor_gain	0.9000

AlphaMissense

529 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:48201412:T:C	C38R	0.992
15:48201442:T:C	C48R	0.990
15:48201401:T:A	V34D	0.988
15:48201403:G:A	G35R	0.988
15:48201403:G:C	G35R	0.988
15:48201431:T:A	L44H	0.987
15:48201424:G:A	G42R	0.986
15:48201424:G:C	G42R	0.986
15:48201395:C:A	A32D	0.985
15:48201431:T:C	L44P	0.985
15:48201425:G:A	G42E	0.983
15:48201444:C:G	C48W	0.983
15:48201455:T:C	L52P	0.981
15:48201440:G:C	R47P	0.978
15:48201464:C:A	P55Q	0.978
15:48201463:C:T	P55S	0.977
15:48201492:G:C	W64C	0.977
15:48201492:G:T	W64C	0.977
15:48201404:G:A	G35E	0.976
15:48201431:T:G	L44R	0.976
15:48201389:G:A	G30D	0.974
15:48201410:T:G	L37W	0.974
15:48201422:T:C	L41S	0.974
15:48201455:T:A	L52Q	0.974
15:48201443:G:A	C48Y	0.972
15:48201458:T:C	L53P	0.972
15:48201464:C:T	P55L	0.972
15:48201466:T:G	Y56D	0.970
15:48201388:G:C	G30R	0.968
15:48201410:T:C	L37S	0.965

dbSNP variants (sampled 300 via entrez): RS1000006277 (15:48188583 A>C,G), RS1000125990 (15:48196367 C>T), RS1000303635 (15:48185358 A>G), RS1000308712 (15:48203930 A>G), RS1000402693 (15:48177765 G>A), RS1000403268 (15:48188848 T>C), RS1000567308 (15:48193390 A>G), RS1000743929 (15:48201387 T>C,G), RS1000799937 (15:48192995 A>G), RS1000834612 (15:48188376 A>G), RS1000940659 (15:48183238 A>G), RS1001029800 (15:48201176 T>C), RS1001120747 (15:48203594 G>A), RS1001160341 (15:48197735 A>C), RS1001209885 (15:48177434 A>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:154700, MIM:607086

GenCC curated gene-disease

Mondo (2): Marfan syndrome (MONDO:0007947), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625)

Orphanet (3): Marfan syndrome type 1 (Orphanet:284963), Marfan syndrome (Orphanet:558), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008382	Marfan Syndrome	C05.116.099.674; C14.240.400.725; C14.280.400.725; C16.131.077.550; C16.131.240.400.720; C16.320.540; C17.300.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01295047	PHASE4	COMPLETED	Comparison of Medical Therapies in Marfan Syndrome.
NCT00429364	PHASE3	COMPLETED	Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome
NCT00485368	PHASE3	COMPLETED	Angiotensin Converting Enzyme Inhibitors in Marfan Syndrome
NCT00683124	PHASE3	UNKNOWN	Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients
NCT00723801	PHASE3	COMPLETED	Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
NCT00763893	PHASE3	TERMINATED	Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome
NCT00782327	PHASE3	COMPLETED	Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers
NCT01145612	PHASE3	UNKNOWN	Atenolol Versus Losartan in the Prevention of Progressive Dilation of the Aorta in Marfan Syndrome
NCT01361087	PHASE3	WITHDRAWN	Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With Marfan Syndrome
NCT01715207	PHASE3	COMPLETED	Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS
NCT00593710	PHASE2	COMPLETED	Losartan Versus Atenolol for the Treatment of Marfan Syndrome
NCT00651235	PHASE2	UNKNOWN	A Randomized, Open-label, LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome
NCT01949233	PHASE2	UNKNOWN	The Oxford Marfan Trial
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00270686	Not specified	COMPLETED	Studies of Heritable Disorders of Connective Tissue
NCT01322165	Not specified	COMPLETED	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
NCT01707563	Not specified	COMPLETED	Clinical Variability in Marfan Syndrome
NCT01760668	Not specified	COMPLETED	Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome
NCT02050113	Not specified	RECRUITING	Complex Aortic Aneurysm Repair Using Physician Modified Endografts and Custom Made Devices
NCT02111668	Not specified	COMPLETED	Thoracic Aortic Dilatation Syndromes
NCT02148900	Not specified	UNKNOWN	Development of a Blood Test for Marfan Syndrome
NCT02213484	Not specified	COMPLETED	Micro RNAs as a Marker of Aortic Aneurysm in Hereditary Aortopathy Syndromes
NCT02815072	Not specified	UNKNOWN	Generation of Marfan Syndrome and Fontan Cardiovascular Models Using Patient-specific Induced Pluripotent Stem Cells
NCT03236571	Not specified	COMPLETED	Cardiorespiratory and Muscular Rehabilitation of Children and Young Adults With Marfan Syndrome.
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT03567460	Not specified	COMPLETED	Children and Adolescents With Marfan Syndrome: 10,000 Healthy Steps and Beyond
NCT03581682	Not specified	COMPLETED	Tele-Clinic Visits in Pediatric Marfan Patients Using Parental Echo: The Future?
NCT04194619	Not specified	RECRUITING	Pregnancy in Women With Rare Multisystemic Vascular Diseases: COGRare5 Study
NCT04319107	Not specified	COMPLETED	Classifying Ectopia Lentis in Marfan Syndrome Into Five Grades of Increasing Severity
NCT04553094	Not specified	COMPLETED	Effects of Personalized Training at Home Combining Endurance and Resistance in Patients Suffering From Marfan Syndrome
NCT04641325	Not specified	COMPLETED	Marfan Syndrome Moderate Exercise Pilot
NCT04731493	Not specified	UNKNOWN	Effect on the Quality of Life of a Therapeutic Education Program in Patients With Marfan Syndrome
NCT04774172	Not specified	COMPLETED	Mortality and Morbidity Outcomes in Marfans
NCT04776668	Not specified	COMPLETED	Living With Marfan Syndrome and Your Aorta
NCT04776681	Not specified	COMPLETED	Living With Marfans and Your Aorta: Surgical Outcomes Study
NCT04970459	Not specified	RECRUITING	Biological Collection for Marfan and Related Syndromes
NCT05123339	Not specified	COMPLETED	Clinical Signs and Activity Limitations Associated With Dural Ectasia in Patients With Marfan Disease
NCT05389865	Not specified	ACTIVE_NOT_RECRUITING	Proximal Aortopathy in Scotland - Epidemiology and Surgical Outcomes
NCT05516043	Not specified	COMPLETED	Safety and Performance of POLYTHESE® Vascular Prosthesis
NCT05578469	Not specified	UNKNOWN	Surgical Treatment of Marfan Syndrome With Subluxation Lens