CNST

Summary

CNST (consortin, connexin sorting protein, HGNC:26486) is a protein-coding gene on chromosome 1q44, encoding Consortin (Q6PJW8). Required for targeting of connexins to the plasma membrane.

Targeting of numerous transmembrane proteins to the cell surface is thought to depend on their recognition by cargo receptors that interact with the adaptor machinery for anterograde traffic at the distal end of the Golgi complex. Consortin (CNST) is an integral membrane protein that acts as a binding partner of connexins, the building blocks of gap junctions, and acts as a trans-Golgi network (TGN) receptor involved in connexin targeting to the plasma membrane and recycling from the cell surface (del Castillo et al., 2010 [PubMed 19864490]).

Source: NCBI Gene 163882 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 140 total — 1 likely-pathogenic
• MANE Select transcript: NM_152609

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26486
Approved symbol	CNST
Name	consortin, connexin sorting protein
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32001, PPP1R64
Ensembl gene	ENSG00000162852
Ensembl biotype	protein_coding
OMIM	613439
Entrez	163882

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000366511, ENST00000366512, ENST00000366513, ENST00000483271, ENST00000857030, ENST00000857031, ENST00000857032, ENST00000857033, ENST00000857034, ENST00000857035, ENST00000857036, ENST00000857037, ENST00000857038, ENST00000857039, ENST00000857040, ENST00000920406, ENST00000963608, ENST00000963609, ENST00000963610, ENST00000963611

RefSeq mRNA: 2 — MANE Select: NM_152609 NM_001139459, NM_152609

CCDS: CCDS1628, CCDS44343

Canonical transcript exons

ENST00000366513 — 11 exons

Exon	Start	End
ENSE00001069230	246634473	246634587
ENSE00001069233	246633924	246634010
ENSE00001125864	246660199	246660334
ENSE00001125874	246647139	246648037
ENSE00001441892	246665700	246668595
ENSE00001834878	246566456	246566663
ENSE00003475396	246591512	246591941
ENSE00003575104	246641941	246642037
ENSE00003583891	246641749	246641770
ENSE00003598786	246631894	246631924
ENSE00003660300	246621429	246621634

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 95.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.2913 / max 270.4276, expressed in 1791 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9543	5.5494	1622
9540	5.4586	1622
9539	4.1713	1200
9542	1.4522	900
9541	1.1928	710
9548	1.0595	301
9549	0.2699	73
9550	0.0827	33
202037	0.0548	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	95.35	gold quality
dorsal root ganglion	UBERON:0000044	94.52	gold quality
secondary oocyte	CL:0000655	92.06	gold quality
vastus lateralis	UBERON:0001379	91.95	gold quality
deltoid	UBERON:0001476	91.17	gold quality
quadriceps femoris	UBERON:0001377	90.99	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.83	gold quality
trigeminal ganglion	UBERON:0001675	90.60	gold quality
skeletal muscle tissue	UBERON:0001134	90.41	gold quality
visceral pleura	UBERON:0002401	89.89	gold quality
gastrocnemius	UBERON:0001388	89.83	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.63	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.59	gold quality
muscle of leg	UBERON:0001383	89.58	gold quality
left ventricle myocardium	UBERON:0006566	89.53	silver quality
substantia nigra pars compacta	UBERON:0001965	89.46	gold quality
biceps brachii	UBERON:0001507	89.42	gold quality
muscle tissue	UBERON:0002385	89.40	gold quality
calcaneal tendon	UBERON:0003701	89.27	gold quality
parietal pleura	UBERON:0002400	89.13	gold quality
primary visual cortex	UBERON:0002436	89.02	gold quality
endothelial cell	CL:0000115	88.75	gold quality
oocyte	CL:0000023	88.60	gold quality
occipital lobe	UBERON:0002021	88.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.33	silver quality
monocyte	CL:0000576	88.12	gold quality
leukocyte	CL:0000738	87.87	gold quality
epithelial cell of pancreas	CL:0000083	87.74	gold quality
tendon	UBERON:0000043	87.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.48	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ANND-5	yes	524.95
E-CURD-112	yes	34.79
E-MTAB-9067	yes	10.94
E-ANND-3	yes	9.43
E-MTAB-5061	yes	5.97
E-MTAB-7606	no	1247.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

157 targeting CNST, 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-5692A	100.00	74.40	6850
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-335-3P	99.93	73.36	4958

Literature-anchored findings (GeneRIF, showing 2)

• Consortin is a trans-Golgi network cargo receptor for the plasma membrane targeting and recycling of connexins. (PMID:19864490)
• Circular RNA_CNST Promotes the Tumorigenesis of Osteosarcoma Cells by Sponging miR-421. (PMID:32693639)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnstb	ENSDARG00000042759
danio_rerio	cnsta	ENSDARG00000086283
mus_musculus	Cnst	ENSMUSG00000038949
rattus_norvegicus	Cnst	ENSRNOG00000002710

Protein

Protein identifiers

Consortin — Q6PJW8 (reviewed: Q6PJW8)

All UniProt accessions (2): B1AQM9, Q6PJW8

UniProt curated annotations — full annotation on UniProt →

Function. Required for targeting of connexins to the plasma membrane.

Subunit / interactions. Interacts with connexins GJA1/CX43, GJB1/CX32, GJB2/CX26, GJB3/CX31, GJB6/CX30 and GJC1/CX45. Also interacts with GGA1 and GGA2. Does not interact with PANX1.

Subcellular location. Cell membrane. Golgi apparatus. trans-Golgi network membrane. Cytoplasmic vesicle. Secretory vesicle.

Similarity. Belongs to the CNST family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6PJW8-1	1	yes
Q6PJW8-2	2
Q6PJW8-3	3

RefSeq proteins (2): NP_001132931, NP_689822* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028129	Consortin_C	Domain
IPR042318	Consortin	Family
IPR054132	Consortin_N	Domain

Pfam: PF15281, PF22883

UniProt features (26 total): compositionally biased region 5, region of interest 5, splice variant 4, sequence variant 4, sequence conflict 4, topological domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PJW8-F1	52.99	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 198 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_VESICLE_MEDIATED_TRANSPORT, CHANDRAN_METASTASIS_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GGCNKCCATNK_UNKNOWN, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOCC_TRANS_GOLGI_NETWORK, GGAANCGGAANY_UNKNOWN, WCTCNATGGY_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_GOLGI_TO_PLASMA_MEMBRANE_PROTEIN_TRANSPORT

GO Biological Process (1): positive regulation of Golgi to plasma membrane protein transport (GO:0042998)

GO Molecular Function (3): phosphatase binding (GO:0019902), connexin binding (GO:0071253), protein binding (GO:0005515)

GO Cellular Component (7): trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), membrane (GO:0016020), transport vesicle (GO:0030133), protein-containing complex (GO:0032991), Golgi apparatus (GO:0005794), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
cytoplasm	2
regulation of Golgi to plasma membrane protein transport	1
Golgi to plasma membrane protein transport	1
positive regulation of protein transport	1
positive regulation of protein localization to plasma membrane	1
enzyme binding	1
protein binding	1
binding	1
Golgi apparatus subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cytoplasmic vesicle	1
cellular_component	1
intracellular membrane-bounded organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNST	GGA2	Q9UJY4	819
CNST	GGA1	Q9UJY5	763
CNST	GJB6	O95452	739
CNST	GJC1	P36383	730
CNST	GJB2	P29033	695
CNST	GJB1	P08034	664
CNST	GJA1	P17302	576
CNST	SORT1	Q99523	536
CNST	SORL1	Q92673	485
CNST	LRP3	O75074	457
CNST	GJB4	Q9NTQ9	417
CNST	GGA3	Q9NZ52	409
CNST	BACE1	P56817	391
CNST	STAB1	Q9NY15	372
CNST	ATP6V1H	Q9UI12	349
CNST	ATP6V1F	Q16864	349

IntAct

30 interactions, top by confidence:

A	B	Type	Score
CNST	PPP1CA	psi-mi:“MI:0915”(physical association)	0.800
PPP1CA	CNST	psi-mi:“MI:0407”(direct interaction)	0.800
CNST	ROPN1	psi-mi:“MI:0915”(physical association)	0.740
ROPN1	CNST	psi-mi:“MI:0915”(physical association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CC	CNST	psi-mi:“MI:0915”(physical association)	0.550
POT1	CNST	psi-mi:“MI:0915”(physical association)	0.510
CNST	AHNAK	psi-mi:“MI:0915”(physical association)	0.400
CNST	Gja1	psi-mi:“MI:0915”(physical association)	0.400
EWSR1	CNST	psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MAGEA9	MED19	psi-mi:“MI:0914”(association)	0.350
PPP1CC	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CNST	Gga1	psi-mi:“MI:0403”(colocalization)	0.270
Gga2	CNST	psi-mi:“MI:0403”(colocalization)	0.270
CNST	POT1	psi-mi:“MI:0915”(physical association)	0.000
CNST		psi-mi:“MI:0915”(physical association)	0.000
PIGP	CNST	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): CNST (Two-hybrid), CNST (Affinity Capture-MS), CNST (Affinity Capture-MS), CNST (Two-hybrid), CNST (Affinity Capture-MS), CNST (Affinity Capture-MS), CNST (Affinity Capture-MS), CNST (Affinity Capture-RNA), CNST (Affinity Capture-RNA), CNST (Affinity Capture-MS), CNST (Affinity Capture-MS), CNST (Proximity Label-MS), CNST (Proximity Label-MS), CNST (Proximity Label-MS), CNST (Proximity Label-MS)

ESM2 similar proteins: A0P8Z5, B0KYV5, B1WC58, B2RYR0, F1LR10, F6SNN2, O75128, O75410, P51826, P61590, P61591, P61592, P61593, P61594, Q3USH1, Q501R9, Q5IFK1, Q5PQK4, Q5R8C5, Q5SU73, Q5SWA1, Q5U5Q9, Q6NZF1, Q6P1D7, Q6P7W0, Q6PJW8, Q6Y685, Q6ZSG2, Q6ZVT6, Q7TT79, Q80XI1, Q80XJ2, Q80YR6, Q86T90, Q8BFU3, Q8C9B9, Q8IY92, Q8IYW5, Q8ND24, Q8NEM0

Diamond homologs: Q6PJW8, Q8CBC4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	113
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
561259	46,XX,der(1)(q44,q44).seq[GRCh37/hg19]der(1)(1pter->1q44(+)(244867200)::TCGCC{5}::q44(-)(246816211),q44(-)(2460642{39-40})::CGG…CCC{49}::q44(+)(246569872)->1qter)	Likely pathogenic

SpliceAI

3145 predictions. Top by Δscore:

Variant	Effect	Δscore
1:246631946:G:GT	donor_gain	1.0000
1:246642033:GTCAG:G	donor_gain	1.0000
1:246642034:TCAGG:T	donor_loss	1.0000
1:246642038:GTAT:G	donor_loss	1.0000
1:246642039:T:G	donor_loss	1.0000
1:246647138:GAGA:G	acceptor_gain	1.0000
1:246648035:GAG:G	donor_gain	1.0000
1:246648051:G:GT	donor_gain	1.0000
1:246665698:A:AG	acceptor_gain	1.0000
1:246665699:G:GG	acceptor_gain	1.0000
1:246591510:A:AG	acceptor_gain	0.9900
1:246591511:G:GG	acceptor_gain	0.9900
1:246591511:GAC:G	acceptor_gain	0.9900
1:246613414:G:GT	donor_gain	0.9900
1:246613414:G:T	donor_gain	0.9900
1:246621425:AAAG:A	acceptor_gain	0.9900
1:246621427:A:G	acceptor_gain	0.9900
1:246621428:GGA:G	acceptor_gain	0.9900
1:246621428:GGAC:G	acceptor_gain	0.9900
1:246631992:G:GT	donor_gain	0.9900
1:246634586:GA:G	donor_gain	0.9900
1:246634588:G:GG	donor_gain	0.9900
1:246641747:A:AG	acceptor_gain	0.9900
1:246641748:G:GG	acceptor_gain	0.9900
1:246641748:GT:G	acceptor_gain	0.9900
1:246641932:A:G	acceptor_gain	0.9900
1:246641933:C:G	acceptor_gain	0.9900
1:246641939:A:AG	acceptor_gain	0.9900
1:246641939:A:AT	acceptor_loss	0.9900
1:246641940:G:GA	acceptor_gain	0.9900

AlphaMissense

4792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:246665762:A:C	S679R	0.998
1:246665764:T:A	S679R	0.998
1:246665764:T:G	S679R	0.998
1:246660304:T:C	F648L	0.997
1:246660306:C:A	F648L	0.997
1:246660306:C:G	F648L	0.997
1:246633951:T:C	L215P	0.996
1:246660305:T:C	F648S	0.996
1:246665741:T:C	C672R	0.996
1:246633955:A:C	E216D	0.995
1:246633955:A:T	E216D	0.995
1:246634007:T:A	W234R	0.995
1:246634007:T:C	W234R	0.995
1:246660227:T:A	I622K	0.995
1:246660230:T:C	L623S	0.995
1:246621629:C:G	H194D	0.994
1:246633954:A:T	E216V	0.994
1:246633957:G:C	R217P	0.994
1:246633987:T:C	L227P	0.994
1:246660227:T:C	I622T	0.994
1:246660305:T:G	F648C	0.994
1:246634009:G:C	W234C	0.993
1:246634009:G:T	W234C	0.993
1:246621627:T:C	L193P	0.992
1:246633941:T:C	F212L	0.991
1:246633943:C:A	F212L	0.991
1:246633943:C:G	F212L	0.991
1:246665754:T:A	V676D	0.991
1:246665786:T:C	C687R	0.991
1:246631897:G:C	A197P	0.990

dbSNP variants (sampled 300 via entrez): RS1000012700 (1:246586494 A>C), RS1000023305 (1:246598047 C>T), RS1000052529 (1:246599696 G>A), RS1000130580 (1:246651272 C>A,G,T), RS1000138294 (1:246590529 T>G), RS1000143870 (1:246567011 C>T), RS1000176466 (1:246621270 A>G,T), RS1000190400 (1:246660237 G>C), RS1000207196 (1:246604388 T>C), RS1000218053 (1:246616238 A>G), RS1000228877 (1:246586377 CTATATCAAAGA>C), RS1000266435 (1:246566272 C>A,T), RS1000300786 (1:246590949 A>C), RS1000302004 (1:246655217 A>AT), RS1000303785 (1:246576734 TCCAC>T)

Disease associations

OMIM: gene MIM:613439 | disease phenotypes: MIM:617391

GenCC curated gene-disease

Mondo (1): developmental and epileptic encephalopathy, 54 (MONDO:0033363)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009312_6	Antisaccade task score	9.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007969	cognitive inhibition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	4
sodium arsenite	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
fenvalerate	increases expression	1
butyraldehyde	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
enzacamene	increases expression	1
avobenzone	increases expression	1
octylmethoxycinnamate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
torcetrapib	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethoate	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Iopanoic Acid	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SJ44	HAP1 CNST (-) 1	Cancer cell line	Male
CVCL_SJ45	HAP1 CNST (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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