SCRG1

Summary

SCRG1 (stimulator of chondrogenesis 1, HGNC:17036) is a protein-coding gene on chromosome 4q34.1, encoding Scrapie-responsive protein 1 (O75711).

Scrapie-responsive gene 1 is associated with neurodegenerative changes observed in transmissible spongiform encephalopathies. It may play a role in host response to prion-associated infections. The scrapie responsive protein 1 may be partly included in the membrane or secreted by the cells due to its hydrophobic N-terminus. In addition, the encoded protein can interact with bone marrow stromal cell antigen 1 (BST1) to enhance the differentiation potentials of human mesenchymal stem cells during tissue and bone regeneration.

Source: NCBI Gene 11341 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_007281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17036
Approved symbol	SCRG1
Name	stimulator of chondrogenesis 1
Location	4q34.1
Locus type	gene with protein product
Status	Approved
Aliases	SCRG-1, lincSCRG1
Ensembl gene	ENSG00000164106
Ensembl biotype	protein_coding
OMIM	603163
Entrez	11341

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000296506, ENST00000512188, ENST00000883955

RefSeq mRNA: 2 — MANE Select: NM_007281 NM_001329597, NM_007281

CCDS: CCDS3818

Canonical transcript exons

ENST00000296506 — 3 exons

Exon	Start	End
ENSE00001081475	173391173	173391428
ENSE00001081476	173399068	173399116
ENSE00001081477	173384701	173388395

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 99.55.

FANTOM5 (CAGE): breadth broad, TPM avg 14.0520 / max 887.6662, expressed in 529 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54866	7.6707	425
54864	3.4064	264
54865	1.7659	244
54867	0.8626	222
54868	0.1834	74
54869	0.0576	21
54870	0.0501	19
54871	0.0299	6
54872	0.0254	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.55	gold quality
lateral globus pallidus	UBERON:0002476	98.73	gold quality
subthalamic nucleus	UBERON:0001906	98.46	gold quality
saphenous vein	UBERON:0007318	98.33	gold quality
inferior vagus X ganglion	UBERON:0005363	97.97	gold quality
cranial nerve II	UBERON:0000941	97.84	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.84	gold quality
cartilage tissue	UBERON:0002418	97.66	gold quality
superior vestibular nucleus	UBERON:0007227	97.57	gold quality
pons	UBERON:0000988	97.55	gold quality
blood vessel layer	UBERON:0004797	97.30	gold quality
globus pallidus	UBERON:0001875	97.27	gold quality
medulla oblongata	UBERON:0001896	97.26	gold quality
ventral tegmental area	UBERON:0002691	97.18	gold quality
medial globus pallidus	UBERON:0002477	96.94	gold quality
substantia nigra pars compacta	UBERON:0001965	96.74	gold quality
pericardium	UBERON:0002407	96.64	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.62	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.26	gold quality
adult organism	UBERON:0007023	96.08	gold quality
postcentral gyrus	UBERON:0002581	96.00	gold quality
CA1 field of hippocampus	UBERON:0003881	95.94	gold quality
parietal lobe	UBERON:0001872	95.84	gold quality
tendon of biceps brachii	UBERON:0008188	95.54	gold quality
cauda epididymis	UBERON:0004360	95.45	gold quality
descending thoracic aorta	UBERON:0002345	95.44	gold quality
dorsal root ganglion	UBERON:0000044	95.42	gold quality
spinal cord	UBERON:0002240	95.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.07	gold quality
vena cava	UBERON:0004087	95.00	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	1542.93
E-HCAD-56	yes	476.28
E-MTAB-11121	yes	354.34
E-HCAD-5	yes	351.90
E-GEOD-134144	yes	35.27
E-GEOD-84465	yes	24.24
E-HCAD-25	yes	19.67
E-ANND-3	yes	6.75
E-CURD-112	yes	6.17
E-GEOD-93593	yes	5.21
E-GEOD-124858	no	94.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting SCRG1, 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-3925-3P	100.00	69.95	1237
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-200C-5P	97.71	67.73	596
HSA-MIR-708-3P	97.50	68.67	1082

Literature-anchored findings (GeneRIF, showing 6)

• Aomatsu et al. identified a novel SCRG1/BST1 (CD157) ligand-receptor combination that maintains human mesenchymal stem cells expressions of stem cell markers Oct-4 and CD271 (LNGFR), as well as self-renewal, migration, and osteogenic differentiation potentials during ex vivo expansion. (PMID:24413464)
• Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells. (PMID:24413464)
• High lncRNA in SCRG1 gene expression is associated with liver fibrosis. (PMID:30226813)
• Haploinsufficiency of the basic helix-loop-helix transcription factor HAND2 causes congenital heart defects. (PMID:32134193)
• Identification of SCRG1 as a Potential Therapeutic Target for Human Synovial Inflammation. (PMID:35720295)
• Identification of a Novel Angiogenesis Signalling circSCRG1/miR-1268b/NR4A1 Pathway in Atherosclerosis and the Regulatory Effects of TMP-PF In Vitro. (PMID:36770940)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scrg1	ENSMUSG00000031610
rattus_norvegicus	Scrg1	ENSRNOG00000069516

Protein

Protein identifiers

Scrapie-responsive protein 1 — O75711 (reviewed: O75711)

Alternative names: Scrapie-responsive gene 1 protein

All UniProt accessions (3): D6RD99, O75711, Q6FGG5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Expressed abundantly in the central nervous system of adult, but not at all in fetal brain. High levels of SCRG1 transcripts are also observed in testis and aorta.

Similarity. Belongs to the SCRG1 family.

RefSeq proteins (2): NP_001316526, NP_009212* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028063	SCRG1	Family

Pfam: PF15224

UniProt features (4 total): signal peptide 1, chain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75711-F1	79.80	0.11

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): 72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, XU_GH1_AUTOCRINE_TARGETS_UP, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, chr4q34, COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP, RIGGI_EWING_SARCOMA_PROGENITOR_DN, MODULE_99, SMID_BREAST_CANCER_RELAPSE_IN_BRAIN_UP, GOCC_NEURON_PROJECTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, GOCC_NEURON_PROJECTION_TERMINUS, SMID_BREAST_CANCER_LUMINAL_B_DN, BLALOCK_ALZHEIMERS_DISEASE_DN

GO Biological Process (2): nervous system development (GO:0007399), mesenchymal stem cell proliferation (GO:0097168)

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

GO Cellular Component (5): obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), neuron projection terminus (GO:0044306), extracellular region (GO:0005576), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
system development	1
stem cell proliferation	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
neuron projection	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCRG1	BST1	Q10588	741
SCRG1	ZFP36	P26651	542
SCRG1	FAM229B	Q4G0N7	392
SCRG1	CD38	P28907	377
SCRG1	CNMD	O75829	369
SCRG1	ROPN1L	Q96C74	368
SCRG1	TBC1D30	Q9Y2I9	360
SCRG1	VTN	P01141	353
SCRG1	H0YJW9	H0YJW9	353
SCRG1	GUSB	P08236	353
SCRG1	MANBA	O00462	349
SCRG1	EPYC	Q99645	344
SCRG1	CILP	O75339	340
SCRG1	UCMA	Q8WVF2	340
SCRG1	LHFPL2	Q6ZUX7	333

IntAct

13 interactions, top by confidence:

A	B	Type	Score
SCRG1	CATSPER1	psi-mi:“MI:0915”(physical association)	0.560
CATSPER1	SCRG1	psi-mi:“MI:0915”(physical association)	0.560
SCRG1	MANBAL	psi-mi:“MI:0915”(physical association)	0.560
SCRG1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SCRG1	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
SCRG1	MANBAL	psi-mi:“MI:0915”(physical association)	0.000
SCRG1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000
SCRG1	FAM209A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): CATSPER1 (Two-hybrid), SCRG1 (Two-hybrid), SCRG1 (Two-hybrid), SCRG1 (Two-hybrid), CD36 (Reconstituted Complex)

ESM2 similar proteins: A0A384E0Y8, A0JNQ7, A9JSD6, A9XFZ7, D2Y2C0, D2Y2E1, D2Y2E2, D2Y2E3, D2Y2E4, D2Y2E5, D3ZVN1, O75711, O96049, P02703, P02704, P02705, P04118, P08162, P0CJ14, P0DQT9, P0DQU0, P0DQU1, P0DRJ0, P11858, P17084, P19090, P42889, P42890, P80407, P83668, Q07663, Q27023, Q3UW21, Q5BQU9, Q5BQX9, Q5D231, Q5D232, Q5D233, Q5W280, Q6UWE3

Diamond homologs: O75711, O88745, Q9Z0K6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

491 predictions. Top by Δscore:

Variant	Effect	Δscore
4:173388280:A:AC	donor_gain	1.0000
4:173388281:C:CC	donor_gain	1.0000
4:173391171:A:AC	donor_gain	1.0000
4:173391172:C:CC	donor_gain	1.0000
4:173391224:C:A	donor_gain	1.0000
4:173391245:T:TA	donor_gain	1.0000
4:173388548:G:A	donor_gain	0.9900
4:173391166:T:TA	donor_gain	0.9900
4:173391220:ACATC:A	donor_gain	0.9900
4:173391221:CATCC:C	donor_gain	0.9900
4:173391287:T:TA	donor_gain	0.9900
4:173391429:C:CC	acceptor_gain	0.9900
4:173388284:A:AC	donor_gain	0.9800
4:173391229:C:A	donor_gain	0.9800
4:173391424:TGGCC:T	acceptor_gain	0.9800
4:173391426:GCCCT:G	acceptor_loss	0.9800
4:173391427:CC:C	acceptor_gain	0.9800
4:173391427:CCCTG:C	acceptor_loss	0.9800
4:173391428:CC:C	acceptor_gain	0.9800
4:173391428:CCTGA:C	acceptor_loss	0.9800
4:173391429:CTGAA:C	acceptor_loss	0.9800
4:173391430:T:G	acceptor_loss	0.9800
4:173399064:ATAC:A	donor_loss	0.9800
4:173399067:C:A	donor_loss	0.9800
4:173388285:T:C	donor_gain	0.9700
4:173391216:T:TA	donor_gain	0.9700
4:173391284:C:CA	donor_gain	0.9700
4:173388331:A:C	donor_gain	0.9600
4:173391167:CCT:C	donor_loss	0.9600
4:173391168:CTT:C	donor_loss	0.9600

AlphaMissense

655 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:173391235:C:A	W60C	0.979
4:173391235:C:G	W60C	0.979
4:173391188:A:G	L76S	0.971
4:173391208:A:C	C69W	0.967
4:173391180:A:G	C79R	0.966
4:173391210:A:G	C69R	0.966
4:173391203:C:T	C71Y	0.960
4:173391183:A:G	C78R	0.959
4:173391202:G:C	C71W	0.959
4:173391178:G:C	C79W	0.958
4:173391333:A:G	C28R	0.957
4:173388386:G:C	F84L	0.954
4:173388386:G:T	F84L	0.954
4:173388388:A:G	F84L	0.954
4:173391181:G:C	C78W	0.954
4:173391209:C:T	C69Y	0.952
4:173391179:C:G	C79S	0.951
4:173391180:A:T	C79S	0.951
4:173391182:C:G	C78S	0.951
4:173391183:A:T	C78S	0.951
4:173391203:C:G	C71S	0.951
4:173391204:A:T	C71S	0.951
4:173391203:C:A	C71F	0.949
4:173388383:A:C	F85L	0.948
4:173388383:A:T	F85L	0.948
4:173388385:A:G	F85L	0.948
4:173388387:A:C	F84C	0.948
4:173391179:C:T	C79Y	0.947
4:173391332:C:T	C28Y	0.947
4:173391209:C:G	C69S	0.946

dbSNP variants (sampled 300 via entrez): RS1000008031 (4:173444010 G>A), RS1000022037 (4:173440448 G>C), RS1000032859 (4:173396271 G>A), RS1000050817 (4:173441146 G>A), RS1000054753 (4:173397820 T>C), RS1000111786 (4:173447286 C>A), RS1000147014 (4:173500873 A>C), RS1000160065 (4:173479483 T>C), RS1000194834 (4:173490992 T>G), RS1000216482 (4:173482359 A>G), RS10002252 (4:173411464 G>A,C,T), RS1000227356 (4:173491338 G>A), RS1000243655 (4:173519094 G>C,T), RS1000268600 (4:173518565 T>A), RS1000273532 (4:173398348 T>G)

Disease associations

OMIM: gene MIM:603163 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003989_35	Chin dimples	2.000000e-11
GCST004735_40	Epstein-Barr virus copy number in lymphoblastoid cell lines	5.000000e-06
GCST006479_60	Diverticular disease	3.000000e-07
GCST010002_20	Refractive error	2.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	5
trichostatin A	affects cotreatment, increases expression	3
Vorinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	increases abundance, increases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Carbamazepine	affects expression	1
Copper	increases expression, affects cotreatment	1
Dust	increases abundance, decreases expression	1
Indomethacin	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Selenium	decreases expression	1
Silicon Dioxide	decreases expression	1
Tretinoin	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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