SCG5

Summary

SCG5 (secretogranin V, HGNC:10816) is a protein-coding gene on chromosome 15q13.3, encoding Neuroendocrine protein 7B2 (P05408). Acts as a molecular chaperone for PCSK2/PC2, preventing its premature activation in the regulated secretory pathway.

This gene encodes a secreted chaperone protein that prevents the aggregation of other secreted proteins, including proteins that are associated with neurodegenerative and metabolic disease. The encoded protein may be best known for its role in the trafficking and activation of prohormone convertase PC2 (encoded by Gene ID: 5126). Phosphorylation of the encoded protein has been shown to have an inhibitory effect on its chaperone function. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein.

Source: NCBI Gene 6447 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001144757

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10816
Approved symbol	SCG5
Name	secretogranin V
Location	15q13.3
Locus type	gene with protein product
Status	Approved
Aliases	7B2, SgV
Ensembl gene	ENSG00000166922
Ensembl biotype	protein_coding
OMIM	173120
Entrez	6447

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000300175, ENST00000413748, ENST00000470349, ENST00000471027, ENST00000475752, ENST00000494364, ENST00000497208, ENST00000498069, ENST00000498607, ENST00000925874, ENST00000943780

RefSeq mRNA: 4 — MANE Select: NM_001144757 NM_001144757, NM_001394278, NM_001394279, NM_003020

CCDS: CCDS45207, CCDS45208, CCDS91974, CCDS91975

Canonical transcript exons

ENST00000300175 — 6 exons

Exon	Start	End
ENSE00001107798	32684557	32684669
ENSE00001210922	32643586	32643818
ENSE00003476047	32691710	32691763
ENSE00003492281	32679766	32679915
ENSE00003924654	32641710	32641778
ENSE00003931146	32696514	32697092

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.9554 / max 937.6021, expressed in 1138 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145693	19.5949	863
145703	3.9716	417
145702	2.3527	360
145707	1.8413	250
145701	0.3268	119
145706	0.2330	97
145705	0.1940	82
145700	0.1563	84
145696	0.1291	33
145699	0.0576	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	99.82	gold quality
superior frontal gyrus	UBERON:0002661	99.39	gold quality
primary visual cortex	UBERON:0002436	99.25	gold quality
prefrontal cortex	UBERON:0000451	99.24	gold quality
cortical plate	UBERON:0005343	99.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.19	gold quality
adenohypophysis	UBERON:0002196	99.15	gold quality
pituitary gland	UBERON:0000007	99.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.01	gold quality
frontal cortex	UBERON:0001870	98.97	gold quality
cerebral cortex	UBERON:0000956	98.71	gold quality
hypothalamus	UBERON:0001898	98.61	gold quality
cerebellum	UBERON:0002037	98.61	gold quality
cerebellar cortex	UBERON:0002129	98.61	gold quality
nucleus accumbens	UBERON:0001882	98.60	gold quality
cerebellar hemisphere	UBERON:0002245	98.60	gold quality
right frontal lobe	UBERON:0002810	98.53	gold quality
brain	UBERON:0000955	98.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.43	gold quality
Ammon’s horn	UBERON:0001954	98.26	gold quality
anterior cingulate cortex	UBERON:0009835	98.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.14	gold quality
putamen	UBERON:0001874	98.08	gold quality
caudate nucleus	UBERON:0001873	97.95	gold quality
substantia nigra	UBERON:0002038	97.95	gold quality
corpus callosum	UBERON:0002336	97.73	gold quality
temporal lobe	UBERON:0001871	97.71	gold quality
amygdala	UBERON:0001876	97.71	gold quality
stromal cell of endometrium	CL:0002255	97.16	gold quality
pancreas	UBERON:0001264	96.65	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	7964.72
E-MTAB-5061	yes	5066.37
E-GEOD-83139	yes	4063.04
E-GEOD-93593	yes	762.04
E-MTAB-9154	yes	558.11
E-CURD-10	yes	266.71
E-HCAD-56	yes	153.63
E-HCAD-31	yes	49.75
E-HCAD-10	yes	40.19
E-CURD-114	yes	12.71
E-GEOD-125970	yes	9.86
E-HCAD-25	yes	9.76
E-ENAD-27	no	9.68
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, MAF, NEUROD1, PAX6

miRNA regulators (miRDB)

29 targeting SCG5, 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-5193	100.00	67.26	1744
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-7978	99.86	66.90	856
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-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-4327	97.21	67.71	676
HSA-MIR-6767-3P	93.99	66.01	204

Literature-anchored findings (GeneRIF, showing 10)

• SGNE1 was overexpressed in gastrointestinal peptide-independent ACTH-independent macronodular adrenal hyperplasia. hyperplasia (PMID:14767469)
• SGNE1 identified as a novel epigenetically silenced gene in medulloblastomas and its inactivation, as well as its inhibitory effect on tumor cell proliferation and focus formation strongly argues for a significant role in medulloblastoma development. (PMID:17334394)
• SGNE1 genetic variation does not contribute to obesity and common forms of Type 2 diabetes but may worsen glucose intolerance and insulin resistance, especially in the background of severe and early onset obesity (PMID:17617923)
• Secretogranins V assays failed to detect increased concentrations in any of the patients with neuroendocrine tumours. (PMID:18448176)
• the significant effects of SGNE1/7B2 on the growth and apoptosis of glioblastoma cells provide a first proof for a functional implication of SGNE1/7B2 inactivation in the molecular pathology of gliomas. (PMID:21901745)
• conclude that 7B2 is a natively disordered protein whose function as an antiaggregant chaperone is likely facilitated by its lack of appreciable secondary structure and tendency to form oligomers (PMID:22947085)
• data provide insight into novel functions of 7B2 and establish this neural protein as an anti-aggregation chaperone associated with neurodegenerative disease (PMID:23172224)
• 7B2 chaperones blocked the cytotoxic effects of exogenous hIAPP (PMID:24042052)
• FAM20C plays a role in 7B2-mediated proPC2 activation by phosphorylating residue Thr111; and that 7B2 function is regulated by alternative splicing. (PMID:25811241)
• Describe a hereditary mixed polyposis syndrome in which is characterized by SCG5-GREM1 duplication. (PMID:27984123)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	scg5	ENSDARG00000032126
danio_rerio	scg5	ENSDARG00000077045
mus_musculus	Scg5	ENSMUSG00000023236
rattus_norvegicus	Scg5	ENSRNOG00000007542
drosophila_melanogaster	7B2	FBGN0041707
caenorhabditis_elegans		WBGENE00011392

Protein

Protein identifiers

Neuroendocrine protein 7B2 — P05408 (reviewed: P05408)

Alternative names: Pituitary polypeptide, Secretogranin V, Secretogranin-5, Secretory granule endocrine protein I

All UniProt accessions (4): P05408, C9J650, C9JNY7, H7C4X7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a molecular chaperone for PCSK2/PC2, preventing its premature activation in the regulated secretory pathway. Binds to inactive PCSK2 in the endoplasmic reticulum and facilitates its transport from there to later compartments of the secretory pathway where it is proteolytically matured and activated. Also required for cleavage of PCSK2 but does not appear to be involved in its folding. Plays a role in regulating pituitary hormone secretion. The C-terminal peptide inhibits PCSK2 in vitro.

Subunit / interactions. Interacts with PCSK2/PC2 early in the secretory pathway. Dissociation occurs at later stages.

Subcellular location. Secreted.

Post-translational modifications. Proteolytically cleaved in the Golgi by a furin-like convertase to generate bioactive peptides. Sulfated on tyrosine residues.

Similarity. Belongs to the 7B2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P05408-1	1	yes
P05408-2	2

RefSeq proteins (4): NP_001138229, NP_001381207, NP_001381208, NP_003011 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007945	Secretogranin_V	Family

Pfam: PF05281

UniProt features (10 total): chain 2, modified residue 2, signal peptide 1, peptide 1, region of interest 1, disulfide bond 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05408-F1	62.49	0.00

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): 141, 205

Disulfide bonds (1): 120–130

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 243 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_SECRETORY_GRANULE, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, chr15q13, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_CELL_CELL_SIGNALING, MODULE_66, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, AMIT_EGF_RESPONSE_480_MCF10A, GOBP_PROTEIN_MATURATION, MODULE_289, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (4): intracellular protein transport (GO:0006886), neuropeptide signaling pathway (GO:0007218), peptide hormone processing (GO:0016486), regulation of hormone secretion (GO:0046883)

GO Molecular Function (5): enzyme inhibitor activity (GO:0004857), GTP binding (GO:0005525), enzyme regulator activity (GO:0030234), obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), nucleus (GO:0005634), secretory granule (GO:0030141)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
G protein-coupled receptor signaling pathway	1
hormone metabolic process	1
signaling receptor ligand precursor processing	1
regulation of cell communication	1
regulation of hormone levels	1
regulation of signaling	1
hormone secretion	1
regulation of secretion by cell	1
enzyme regulator activity	1
molecular function inhibitor activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
molecular function regulator activity	1
binding	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
endomembrane system	1
secretory vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

25 interactions, top by confidence:

A	B	Type	Score
UBQLN1	SCG5	psi-mi:“MI:0915”(physical association)	0.560
SCG5	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
SCG5	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
SCG5	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SCG5		psi-mi:“MI:0915”(physical association)	0.560
SCG5	CSH2	psi-mi:“MI:0915”(physical association)	0.400
SCG5	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
SCG5	CCR2	psi-mi:“MI:0915”(physical association)	0.370
SCG5	KHDRBS1	psi-mi:“MI:0915”(physical association)	0.370
SCG5	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
SCG5	APOD	psi-mi:“MI:0914”(association)	0.350
PSTPIP1	SCG5	psi-mi:“MI:0915”(physical association)	0.000
SCG5	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
SCG5	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
SCG5	UBQLN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): UBQLN1 (Two-hybrid), CSH2 (Affinity Capture-MS), UBQLN4 (Two-hybrid), SCG5 (Two-hybrid), UBQLN2 (Two-hybrid), SCG5 (Two-hybrid), SCG5 (Two-hybrid), SCG5 (Two-hybrid), SCG5 (Affinity Capture-MS), CSH2 (Affinity Capture-MS), FABP4 (Affinity Capture-MS), H2AFY (Affinity Capture-MS), CRYAB (Affinity Capture-MS), CHAC1 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS)

ESM2 similar proteins: A0JMK6, A5A6J6, B9WZ56, C0HKY1, C0HM54, E1ZXU8, O12956, O35314, O35417, O70176, P01165, P01282, P01362, P05060, P05408, P06300, P06308, P10362, P12285, P12961, P13521, P13589, P16014, P16613, P17685, P17686, P18509, P18844, P20616, P23389, P27682, P30945, P41534, P41535, P41585, P45644, P48143, P48144, P81401, P85799

Diamond homologs: A5A6J6, P01165, P05408, P12961, P18844, P27682, Q59E04

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1253 predictions. Top by Δscore:

Variant	Effect	Δscore
15:32641776:TCGGT:T	donor_loss	1.0000
15:32641777:CGG:C	donor_loss	1.0000
15:32641780:T:A	donor_loss	1.0000
15:32679760:TCGCA:T	acceptor_loss	1.0000
15:32679761:CGCA:C	acceptor_loss	1.0000
15:32679762:GCAG:G	acceptor_loss	1.0000
15:32679763:CAG:C	acceptor_loss	1.0000
15:32679764:AGG:A	acceptor_loss	1.0000
15:32679765:G:A	acceptor_loss	1.0000
15:32684666:GTGG:G	donor_gain	1.0000
15:32696513:GA:G	acceptor_gain	1.0000
15:32696513:GAGT:G	acceptor_gain	1.0000
15:32641779:G:GG	donor_gain	0.9900
15:32641781:GAG:G	donor_loss	0.9900
15:32643581:TGCA:T	acceptor_loss	0.9900
15:32643582:GCAG:G	acceptor_loss	0.9900
15:32643583:CAG:C	acceptor_loss	0.9900
15:32643584:A:AG	acceptor_gain	0.9900
15:32643584:A:G	acceptor_loss	0.9900
15:32643585:G:GG	acceptor_gain	0.9900
15:32643814:TGAAG:T	donor_loss	0.9900
15:32643815:GAAGG:G	donor_loss	0.9900
15:32643816:AAG:A	donor_loss	0.9900
15:32643817:AG:A	donor_loss	0.9900
15:32643818:GG:G	donor_loss	0.9900
15:32643819:G:A	donor_loss	0.9900
15:32643820:T:A	donor_loss	0.9900
15:32679764:A:AG	acceptor_gain	0.9900
15:32679765:G:GG	acceptor_gain	0.9900
15:32679765:GGT:G	acceptor_gain	0.9900

AlphaMissense

1392 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:32684568:T:A	C130S	0.998
15:32684569:G:C	C130S	0.998
15:32696564:G:C	K198N	0.998
15:32696564:G:T	K198N	0.998
15:32679897:T:A	C120S	0.997
15:32679897:T:C	C120R	0.997
15:32679898:G:C	C120S	0.997
15:32684568:T:C	C130R	0.996
15:32679780:G:A	G81R	0.995
15:32679780:G:C	G81R	0.995
15:32679899:T:G	C120W	0.995
15:32696567:G:C	K199N	0.995
15:32696567:G:T	K199N	0.995
15:32679793:T:C	L85S	0.994
15:32679818:C:A	N93K	0.994
15:32679818:C:G	N93K	0.994
15:32679898:G:A	C120Y	0.994
15:32684598:T:C	F140L	0.994
15:32684600:C:A	F140L	0.994
15:32684600:C:G	F140L	0.994
15:32684570:T:G	C130W	0.993
15:32684601:A:C	S141R	0.993
15:32684603:T:A	S141R	0.993
15:32684603:T:G	S141R	0.993
15:32696557:T:A	V196D	0.993
15:32679788:G:C	Q83H	0.992
15:32679788:G:T	Q83H	0.992
15:32696526:T:G	Y186D	0.991
15:32696563:A:C	K198T	0.991
15:32643818:G:C	G76R	0.990

dbSNP variants (sampled 300 via entrez): RS1000105728 (15:32673039 T>G), RS1000227557 (15:32666913 C>T), RS1000314072 (15:32653812 A>G), RS1000347790 (15:32640591 G>A,C), RS1000377706 (15:32687277 C>G,T), RS1000387087 (15:32660317 C>A), RS1000474578 (15:32673499 A>G), RS1000509456 (15:32691224 G>C), RS1000543971 (15:32681620 T>C), RS1000594946 (15:32654265 G>C), RS1000596551 (15:32681141 G>C), RS1000669647 (15:32641734 C>G,T), RS1000825718 (15:32648255 T>C), RS1000854466 (15:32645138 A>G), RS1000856525 (15:32678715 C>A,T)

Disease associations

OMIM: gene MIM:173120 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001161_3	Colorectal cancer	2.000000e-08
GCST001762_916	Obesity-related traits	5.000000e-08
GCST002411_3	Colorectal cancer	1.000000e-11
GCST002919_15	Colorectal cancer	3.000000e-11
GCST003989_5	Chin dimples	6.000000e-45
GCST007552_22	Colorectal cancer	1.000000e-08
GCST009869_62	Colorectal cancer	7.000000e-08
GCST90020024_478	A body shape index	1.000000e-08
GCST90020029_281	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
(+)-JQ1 compound	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	2
mono-(2-ethylhexyl)phthalate	decreases expression	2
3,4,5,3’,4’-pentachlorobiphenyl	affects expression, increases expression	2
Acetaminophen	affects expression, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Silicon Dioxide	affects expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
afuresertib	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	increases abundance, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
3,4-dichloroaniline	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
cupric chloride	increases expression	1
hydroquinone	increases expression	1
diallyl trisulfide	increases expression	1
seocalcitol	decreases expression	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
PCB 180	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1

Clinical trials (associated diseases)

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