SPRING1

Summary

SPRING1 (SREBF pathway regulator in golgi 1, HGNC:26128) is a protein-coding gene on chromosome 12q24.22, encoding SREBP regulating gene protein (Q9H741). Positively regulates hepatic SREBP signaling pathway by modulating the proper localization of SCAP (SREBP cleavage-activating protein) to the endoplasmic reticulum, thereby controlling the level of functional SCAP. It is a selective cancer dependency (DepMap: 12.1% of cell lines).

Involved in positive regulation of SREBP signaling pathway. Located in Golgi membrane.

Source: NCBI Gene 79794 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 13 total
• Cancer dependency (DepMap): dependent in 12.1% of screened cell lines
• MANE Select transcript: NM_024738

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26128
Approved symbol	SPRING1
Name	SREBF pathway regulator in golgi 1
Location	12q24.22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21415, SPRING, POST1, LUR1
Ensembl gene	ENSG00000111412
Ensembl biotype	protein_coding
Entrez	79794

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000261318, ENST00000547606, ENST00000547630, ENST00000548356

RefSeq mRNA: 4 — MANE Select: NM_024738 NM_001353623, NM_001353624, NM_001353625, NM_024738

CCDS: CCDS9179

Canonical transcript exons

ENST00000261318 — 5 exons

Exon	Start	End
ENSE00001092224	116723067	116723223
ENSE00001259546	116710171	116717893
ENSE00001259553	116737790	116738069
ENSE00003504206	116720296	116720447
ENSE00003626780	116719763	116719876

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 97.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8725 / max 225.8831, expressed in 1797 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133478	15.4207	1796
133477	0.4518	238

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.43	gold quality
visceral pleura	UBERON:0002401	96.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.53	gold quality
pons	UBERON:0000988	95.25	gold quality
substantia nigra pars compacta	UBERON:0001965	94.24	gold quality
superior vestibular nucleus	UBERON:0007227	94.23	gold quality
lower lobe of lung	UBERON:0008949	93.98	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.81	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.65	gold quality
middle temporal gyrus	UBERON:0002771	93.29	gold quality
adult organism	UBERON:0007023	93.27	gold quality
entorhinal cortex	UBERON:0002728	93.11	gold quality
lateral globus pallidus	UBERON:0002476	92.74	gold quality
postcentral gyrus	UBERON:0002581	92.63	gold quality
parietal lobe	UBERON:0001872	92.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.24	gold quality
pleura	UBERON:0000977	91.88	gold quality
ventral tegmental area	UBERON:0002691	91.76	gold quality
colonic mucosa	UBERON:0000317	91.47	gold quality
oocyte	CL:0000023	91.32	gold quality
amniotic fluid	UBERON:0000173	91.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.25	gold quality
esophagus squamous epithelium	UBERON:0006920	91.14	gold quality
corpus epididymis	UBERON:0004359	91.12	gold quality
subthalamic nucleus	UBERON:0001906	90.93	gold quality
secondary oocyte	CL:0000655	90.78	gold quality
tibia	UBERON:0000979	90.60	gold quality
dorsal root ganglion	UBERON:0000044	90.57	gold quality
germinal epithelium of ovary	UBERON:0001304	90.44	gold quality
superior frontal gyrus	UBERON:0002661	90.37	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.36
E-HCAD-13	yes	7.33
E-MTAB-4850	no	378.35
E-HCAD-5	no	2.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

120 targeting SPRING1, 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-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-613	99.91	71.50	1710

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Sterol-regulatory element binding proteins (SREBP) regulating gene (SPRING/C12ORF49) is a glycosylated Golgi membrane protein and its ablation reduces SREBP signaling. Attenuated SREBP signaling in SPRING(KO) cells results from reduced SREBP cleavage-activating protein (SCAP) and its mislocalization to Golgi irrespective of cellular sterol status. A wide range of tumor cell lines display dependency on SPRING expression. (PMID:32111832)
• POST1/C12ORF49 regulates the SREBP pathway by promoting site-1 protease maturation. (PMID:32666500)
• Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism. (PMID:32694731)
• Metabolic coessentiality mapping identifies C12orf49 as a regulator of SREBP processing and cholesterol metabolism. (PMID:32694732)
• Chromosome 12 Open Reading Frame 49 Promotes Tumor Growth and Predicts Poor Prognosis in Colorectal Cancer. (PMID:36348128)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	spring1	ENSDARG00000078315
mus_musculus	Spring1	ENSMUSG00000032840
rattus_norvegicus	Spring1	ENSRNOG00000001123
drosophila_melanogaster	CG15643	FBGN0030654

Protein

Protein identifiers

SREBP regulating gene protein — Q9H741 (reviewed: Q9H741)

Alternative names: SREBF pathway regulator in Golgi 1

All UniProt accessions (4): Q9H741, F8VPB4, F8VVN2, H0YHS8

UniProt curated annotations — full annotation on UniProt →

Function. Positively regulates hepatic SREBP signaling pathway by modulating the proper localization of SCAP (SREBP cleavage-activating protein) to the endoplasmic reticulum, thereby controlling the level of functional SCAP.

Subunit / interactions. Interacts with SCAP.

Subcellular location. Golgi apparatus membrane.

Similarity. Belongs to the SPRING family.

RefSeq proteins (4): NP_001340552, NP_001340553, NP_001340554, NP_079014* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019352	SPRING1	Family

Pfam: PF10218

UniProt features (19 total): helix 5, strand 5, topological domain 2, chain 1, turn 1, transmembrane region 1, glycosylation site 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8UW8	ELECTRON MICROSCOPY	2.3
9CSD	ELECTRON MICROSCOPY	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H741-F1	80.98	0.46

Functional residue map

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

Glycosylation sites (1): 67

Mutagenesis-validated functional residues (1):

Position	Phenotype
67	loss of glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 118 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_ER_NUCLEUS_SIGNALING_PATHWAY, MCAATNNNNNGCG_UNKNOWN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, LIAO_METASTASIS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, DOUGLAS_BMI1_TARGETS_UP, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, chr12q24, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, STAMBOLSKY_BOUND_BY_MUTATED_TP53

GO Biological Process (1): positive regulation of SREBP signaling pathway (GO:2000640)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
SREBP signaling pathway	1
positive regulation of intracellular signal transduction	1
regulation of SREBP signaling pathway	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRING1	MBTPS1	Q14703	751
SPRING1	TMEM41A	Q96HV5	538
SPRING1	RGL4	Q8IZJ4	415
SPRING1	SOWAHC	Q53LP3	400
SPRING1	RABL3	Q5HYI8	396
SPRING1	MBTPS2	O43462	392
SPRING1	RAB3GAP2	Q9H2M9	389
SPRING1	GNPTAB	Q3T906	388
SPRING1	MPC2	O95563	370
SPRING1	TM9SF3	Q9HD45	370
SPRING1	NANS	Q9NR45	360
SPRING1	C5orf22	Q49AR2	350
SPRING1	LANCL1	O43813	348
SPRING1	UBIAD1	Q9Y5Z9	348
SPRING1	SNRNP25	Q9BV90	347

IntAct

19 interactions, top by confidence:

A	B	Type	Score
SPRING1	KRT31	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	SPRING1	psi-mi:“MI:0915”(physical association)	0.560
KRT31	SPRING1	psi-mi:“MI:0915”(physical association)	0.560
SPRING1	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
TTMP	SPRING1	psi-mi:“MI:0915”(physical association)	0.560
SPRING1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
TCEANC2	SPRING1	psi-mi:“MI:0915”(physical association)	0.400
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
SPRING1	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC2A7	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTMP	SPRING1	psi-mi:“MI:0915”(physical association)	0.000
	SPRING1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (277): C12orf49 (Two-hybrid), C12orf49 (Two-hybrid), C12orf49 (Synthetic Growth Defect), PLSCR1 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), HTRA1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), ZWILCH (Affinity Capture-MS), KIAA1715 (Affinity Capture-MS), SCCPDH (Affinity Capture-MS), ACP2 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), CANX (Affinity Capture-MS), SLC30A7 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IKU3, A0A4Y5X186, A4IIA2, O35118, O35251, O42493, O42499, O73824, P01180, P01181, P01183, P01185, P01186, P05486, P08162, P08163, P08833, P0DN42, P0DN43, P0DTJ2, P10769, P11858, P15210, P15211, P16041, P16042, P16229, P17668, P19630, P21916, P24787, P35455, Q00945, Q07662, Q07663, Q17QN8, Q32L50, Q3UPR9, Q503V3, Q56R10

Diamond homologs: Q17QN8, Q503V3, Q5ZJE4, Q6GNT2, Q8BTG6, Q9H741

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1343 predictions. Top by Δscore:

Variant	Effect	Δscore
12:116719874:TTG:T	acceptor_gain	1.0000
12:116719875:TG:T	acceptor_gain	1.0000
12:116719877:C:CC	acceptor_gain	1.0000
12:116720290:CCATA:C	donor_loss	1.0000
12:116720291:CATAC:C	donor_loss	1.0000
12:116720293:TA:T	donor_loss	1.0000
12:116720294:A:AG	donor_loss	1.0000
12:116723061:CCTCA:C	donor_loss	1.0000
12:116723062:CTCA:C	donor_loss	1.0000
12:116723063:TCA:T	donor_loss	1.0000
12:116723064:CAC:C	donor_loss	1.0000
12:116723065:ACCGA:A	donor_loss	1.0000
12:116723066:C:CT	donor_loss	1.0000
12:116723091:T:TA	donor_gain	1.0000
12:116723092:C:A	donor_gain	1.0000
12:116723224:CTGCA:C	acceptor_loss	1.0000
12:116723225:T:G	acceptor_loss	1.0000
12:116737785:CTGA:C	donor_loss	1.0000
12:116737787:GACCT:G	donor_loss	1.0000
12:116737789:C:CT	donor_loss	1.0000
12:116737789:CCTG:C	donor_gain	1.0000
12:116717697:CG:C	donor_gain	0.9900
12:116717890:CGCT:C	acceptor_gain	0.9900
12:116717892:CT:C	acceptor_gain	0.9900
12:116717894:C:CC	acceptor_gain	0.9900
12:116719709:T:A	donor_gain	0.9900
12:116719759:TGA:T	donor_loss	0.9900
12:116719760:GAC:G	donor_loss	0.9900
12:116719762:CCTG:C	donor_loss	0.9900
12:116719872:AGTTG:A	acceptor_gain	0.9900

AlphaMissense

1364 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:116717871:T:C	Y186C	1.000
12:116719776:C:A	R174M	1.000
12:116719776:C:G	R174T	1.000
12:116719778:G:C	C173W	1.000
12:116719779:C:G	C173S	1.000
12:116719780:A:G	C173R	1.000
12:116719780:A:T	C173S	1.000
12:116719788:A:G	L170P	1.000
12:116719790:G:C	C169W	1.000
12:116719792:A:G	C169R	1.000
12:116719800:A:C	F166C	1.000
12:116720309:A:G	L136P	1.000
12:116720323:A:C	C131W	1.000
12:116717846:G:C	C194W	0.999
12:116717847:C:T	C194Y	0.999
12:116717848:A:G	C194R	0.999
12:116717868:C:G	R187P	0.999
12:116717872:A:C	Y186D	0.999
12:116717872:A:G	Y186H	0.999
12:116717876:G:C	N184K	0.999
12:116717876:G:T	N184K	0.999
12:116717891:G:C	S179R	0.999
12:116717891:G:T	S179R	0.999
12:116717893:T:G	S179R	0.999
12:116719767:G:C	S177C	0.999
12:116719771:A:G	S176P	0.999
12:116719775:C:A	R174S	0.999
12:116719775:C:G	R174S	0.999
12:116719777:T:C	R174G	0.999
12:116719779:C:A	C173F	0.999

dbSNP variants (sampled 300 via entrez): RS1000244233 (12:116738242 C>G,T), RS1000319004 (12:116738454 C>A), RS1000580260 (12:116739522 C>G), RS1000653651 (12:116739745 A>C,G,T), RS1000653913 (12:116732402 C>T), RS1000807966 (12:116733760 A>G), RS1000875594 (12:116732537 G>A,T), RS1001232821 (12:116713644 T>C), RS1001264955 (12:116733977 A>C), RS1001575794 (12:116732892 G>T), RS1001596419 (12:116739123 G>A), RS1001649195 (12:116733167 G>A), RS1001686051 (12:116719595 T>C), RS1001706880 (12:116713264 T>C), RS1001738495 (12:116719912 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002875_60	Diisocyanate-induced asthma	2.000000e-06
GCST005232_6	Neuroticism	8.000000e-10
GCST006611_99	HDL cholesterol	2.000000e-08
GCST006940_114	Neurociticism	4.000000e-08
GCST010241_47	Apolipoprotein A1 levels	5.000000e-15
GCST90006990_10	Gut microbiota relative abundance (Prevotella)	3.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0007660	neuroticism measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
Leflunomide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Calcitriol	affects cotreatment, increases expression	1
Carbamazepine	affects expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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