SDF2L1

Summary

SDF2L1 (stromal cell derived factor 2 like 1, HGNC:10676) is a protein-coding gene on chromosome 22q11.21, encoding Stromal cell-derived factor 2-like protein 1 (Q9HCN8).

Enables misfolded protein binding activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. Part of protein folding chaperone complex.

Source: NCBI Gene 23753 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_022044

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10676
Approved symbol	SDF2L1
Name	stromal cell derived factor 2 like 1
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	AP000553.C22.4, OTTHUMT00000075032
Ensembl gene	ENSG00000128228
Ensembl biotype	protein_coding
OMIM	607551
Entrez	23753

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000248958, ENST00000466935, ENST00000927919

RefSeq mRNA: 1 — MANE Select: NM_022044 NM_022044

CCDS: CCDS13792

Canonical transcript exons

ENST00000248958 — 3 exons

Exon	Start	End
ENSE00000879336	21642302	21642523
ENSE00000879337	21642862	21643058
ENSE00000879338	21643894	21644299

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 96.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5006 / max 261.1019, expressed in 1787 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191193	15.4875	1775
191192	1.3132	701
191194	0.6999	264

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.38	gold quality
adenohypophysis	UBERON:0002196	96.15	gold quality
right lobe of liver	UBERON:0001114	95.84	gold quality
pituitary gland	UBERON:0000007	95.28	gold quality
right lobe of thyroid gland	UBERON:0001119	94.97	gold quality
left lobe of thyroid gland	UBERON:0001120	94.53	gold quality
body of pancreas	UBERON:0001150	94.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.27	gold quality
thyroid gland	UBERON:0002046	93.25	gold quality
pericardium	UBERON:0002407	92.78	gold quality
spleen	UBERON:0002106	92.41	gold quality
corpus epididymis	UBERON:0004359	91.72	gold quality
stromal cell of endometrium	CL:0002255	91.47	gold quality
minor salivary gland	UBERON:0001830	91.30	gold quality
body of stomach	UBERON:0001161	91.28	gold quality
ascending aorta	UBERON:0001496	91.07	gold quality
right testis	UBERON:0004534	90.88	gold quality
granulocyte	CL:0000094	90.81	gold quality
thoracic aorta	UBERON:0001515	90.81	gold quality
right atrium auricular region	UBERON:0006631	90.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.63	gold quality
monocyte	CL:0000576	90.38	gold quality
saliva-secreting gland	UBERON:0001044	90.19	gold quality
apex of heart	UBERON:0002098	90.08	gold quality
mononuclear cell	CL:0000842	90.04	gold quality
leukocyte	CL:0000738	89.94	gold quality
left testis	UBERON:0004533	89.94	gold quality
pancreas	UBERON:0001264	89.91	gold quality
left adrenal gland	UBERON:0001234	89.86	gold quality
transverse colon	UBERON:0001157	89.82	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	1644.41
E-CURD-88	yes	520.48
E-MTAB-9467	yes	64.52
E-HCAD-1	yes	62.15
E-HCAD-4	yes	61.18
E-CURD-46	yes	55.02
E-CURD-122	yes	53.07
E-MTAB-8410	yes	46.10
E-HCAD-6	yes	40.37
E-CURD-112	yes	34.73
E-HCAD-11	yes	27.13
E-HCAD-9	yes	25.60
E-MTAB-9067	yes	15.40
E-MTAB-10553	yes	12.04
E-MTAB-8060	no	1081.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting SDF2L1, 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-548AN	99.97	70.91	2817
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-6728-3P	98.63	67.63	1534

Literature-anchored findings (GeneRIF, showing 6)

• SDF2L1 increases the time that misfolded proteins have to achieve a correctly folded conformation and thus that SDF2L1 can act as a buffer for substrate availability for ERAD in pancreatic beta-cells. (PMID:23444373)
• SDF2L1 associates with ERdj3 and acts as a component in the BiP chaperone cycle to prevent the aggregation of misfolded proteins. (PMID:28597544)
• In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker. (PMID:30814508)
• The ERdj3-SDF2L1 complex suppressed ER protein aggregation, and this suppression did not require substrate transfer to BiP. (PMID:31624144)
• Expression profiles of PRKG1, SDF2L1 and PPP1R12A are predictive and prognostic factors for therapy response and survival in high-grade serous ovarian cancer. (PMID:32096871)
• SDF2L1 Inhibits Cell Proliferation, Migration, and Invasion in Nasopharyngeal Carcinoma. (PMID:33134371)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sdf2l1	ENSDARG00000035631
mus_musculus	Sdf2l1	ENSMUSG00000022769
rattus_norvegicus	Sdf2l1	ENSRNOG00000001859
drosophila_melanogaster	CG11999	FBGN0037312

Paralogs (3): POMT2 (ENSG00000009830), POMT1 (ENSG00000130714), SDF2 (ENSG00000132581)

Protein

Protein identifiers

Stromal cell-derived factor 2-like protein 1 — Q9HCN8 (reviewed: Q9HCN8)

Alternative names: PWP1-interacting protein 8

All UniProt accessions (1): Q9HCN8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Part of a large chaperone multiprotein complex comprising CABP1, DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX.

Subcellular location. Endoplasmic reticulum lumen.

Tissue specificity. Ubiquitously expressed with high expression in testis, moderate expression in the pancreas, spleen, prostate, small intestine and colon. Very low expression is seen in brain and skeletal muscle.

RefSeq proteins (1): NP_071327* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016093	MIR_motif	Domain
IPR036300	MIR_dom_sf	Homologous_superfamily

Pfam: PF02815

UniProt features (9 total): domain 3, sequence conflict 2, signal peptide 1, chain 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCN8-F1	89.30	0.79

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 (1): 215

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 177 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, ELVIDGE_HYPOXIA_DN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, BOYAULT_LIVER_CANCER_SUBCLASS_G2, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, RACCACAR_AML_Q6, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GTGCCTT_MIR506, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_PROTEIN_MATURATION, AML_Q6, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_PROTEIN_FOLDING

GO Biological Process (5): ERAD pathway (GO:0036503), protein refolding (GO:0042026), regulation of apoptotic process (GO:0042981), cellular response to misfolded protein (GO:0071218), response to endoplasmic reticulum stress (GO:0034976)

GO Molecular Function (4): protein-folding chaperone binding (GO:0051087), ATPase binding (GO:0051117), misfolded protein binding (GO:0051787), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), membrane (GO:0016020), endoplasmic reticulum chaperone complex (GO:0034663), protein folding chaperone complex (GO:0101031)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
protein folding	1
apoptotic process	1
regulation of programmed cell death	1
cellular response to topologically incorrect protein	1
response to misfolded protein	1
cellular response to stress	1
enzyme binding	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cellular anatomical structure	1
endoplasmic reticulum protein-containing complex	1
intracellular protein-containing complex	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDF2L1	HSP90B1	P14625	890
SDF2L1	KDELR1	P24390	866
SDF2L1	DNAJB11	Q9UBS4	853
SDF2L1	HYOU1	Q9Y4L1	829
SDF2L1	PDIA4	P13667	767
SDF2L1	CRELD2	Q6UXH1	619
SDF2L1	PDIA6	Q15084	602
SDF2L1	PPIB	P23284	601
SDF2L1	CALR	P27797	582
SDF2L1	UGGT1	Q9NYU2	572
SDF2L1	IQCC	Q4KMZ1	534
SDF2L1	SDF4	Q9BRK5	522
SDF2L1	HERPUD1	Q15011	513
SDF2L1	HSPA5	P11021	499
SDF2L1	PWP1	Q13610	491

IntAct

133 interactions, top by confidence:

A	B	Type	Score
TCTN2	CLGN	psi-mi:“MI:0914”(association)	0.780
BRAF	KRAS	psi-mi:“MI:0914”(association)	0.680
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
POMK	LRP5	psi-mi:“MI:0914”(association)	0.640
SDF2L1	OLFM2	psi-mi:“MI:0914”(association)	0.640
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
SGTA	SDF2L1	psi-mi:“MI:0915”(physical association)	0.560
SGTB	SDF2L1	psi-mi:“MI:0915”(physical association)	0.560
SNX5	SNX2	psi-mi:“MI:0914”(association)	0.550
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
SDF2L1	CLIC1	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530
ADAM33	LRP5	psi-mi:“MI:0914”(association)	0.530
NRROS	NDUFA3	psi-mi:“MI:0914”(association)	0.530
WNT7A	LDLR	psi-mi:“MI:0914”(association)	0.530
B4GALT4	HSPA5	psi-mi:“MI:0914”(association)	0.530
WNT3A	CANX	psi-mi:“MI:0914”(association)	0.530
CTSG	MANBA	psi-mi:“MI:0914”(association)	0.530
POGLUT1	CLGN	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530
GALNS	FBXO21	psi-mi:“MI:0914”(association)	0.530
env	PSMD11	psi-mi:“MI:0914”(association)	0.460
env	APP	psi-mi:“MI:0914”(association)	0.460
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
ALK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
MET	NDUFA4	psi-mi:“MI:0914”(association)	0.420

BioGRID (361): SDF2L1 (Affinity Capture-MS), SDF2L1 (Affinity Capture-MS), DNAJB11 (Affinity Capture-MS), VWA1 (Affinity Capture-MS), EMC3 (Affinity Capture-MS), PDIA5 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), SDF2L1 (Affinity Capture-MS), SDF2L1 (Proximity Label-MS), SDF2L1 (Affinity Capture-MS), SDF2L1 (Affinity Capture-MS), SDF2L1 (Affinity Capture-MS), SDF2L1 (Affinity Capture-MS), SDF2L1 (Affinity Capture-MS)

ESM2 similar proteins: B0LPN4, E9PZQ0, E9Q401, F1LMY4, O14926, O18728, O95834, P10767, P11403, P11716, P16960, P21658, P21817, P30957, P47823, P55075, P85845, Q13144, Q16658, Q24498, Q24524, Q32M02, Q3U7R1, Q4R4H3, Q5CZL1, Q5E9M9, Q5XGM5, Q61553, Q64350, Q6P6T4, Q6P9Z4, Q6PFQ7, Q6SZW1, Q7TNG5, Q7TSA0, Q7Z6L1, Q8CHW4, Q8IXI1, Q8JZN7, Q8K2J0

Diamond homologs: O13898, O74189, P33775, P47190, P52867, Q3SZ45, Q3T083, Q54P23, Q5ACU3, Q8BGQ4, Q99470, Q9DCT5, Q9ESP1, Q9HCN8, Q9UKY4, F1Q8R9, P31382, P42934, Q29IL2, Q5A688, Q5ADM9, Q9C100, Q9W5D4, Q59X23, Q8R2R1, Q99PR0, Q9VTK2, Q9Y6A1, F1QF89, Q93ZE8, O42933, P46971

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SDF2L1	“up-regulates activity”	LRP4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
cell surface receptor protein tyrosine kinase signaling pathway	8	8.8×	5e-03
protein autophosphorylation	8	7.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

366 predictions. Top by Δscore:

Variant	Effect	Δscore
22:21643889:TATAG:T	acceptor_loss	1.0000
22:21643892:AGGAG:A	acceptor_gain	1.0000
22:21643893:GGAGG:G	acceptor_gain	1.0000
22:21642519:ATCCG:A	donor_gain	0.9900
22:21642520:TCCG:T	donor_gain	0.9900
22:21642522:CGG:C	donor_loss	0.9900
22:21642524:G:GC	donor_loss	0.9900
22:21642524:G:GG	donor_gain	0.9900
22:21642857:CTCA:C	acceptor_loss	0.9900
22:21642858:TCA:T	acceptor_loss	0.9900
22:21642860:AGG:A	acceptor_loss	0.9900
22:21642861:GGCA:G	acceptor_gain	0.9900
22:21643057:AGGTG:A	donor_loss	0.9900
22:21643058:GGT:G	donor_loss	0.9900
22:21643059:GTG:G	donor_loss	0.9900
22:21643060:T:A	donor_loss	0.9900
22:21643883:T:A	acceptor_gain	0.9900
22:21643886:A:AG	acceptor_gain	0.9900
22:21643890:ATAGG:A	acceptor_gain	0.9900
22:21643891:TAGG:T	acceptor_gain	0.9900
22:21643892:A:AG	acceptor_gain	0.9900
22:21643892:AG:A	acceptor_gain	0.9900
22:21643892:AGGA:A	acceptor_gain	0.9900
22:21643893:G:GG	acceptor_gain	0.9900
22:21643893:GG:G	acceptor_gain	0.9900
22:21643893:GGAG:G	acceptor_gain	0.9900
22:21642522:CG:C	donor_gain	0.9800
22:21642523:GG:G	donor_gain	0.9800
22:21642544:G:GT	donor_gain	0.9800
22:21642546:A:T	donor_gain	0.9800

AlphaMissense

1424 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:21643942:T:A	W145R	1.000
22:21643942:T:C	W145R	1.000
22:21643944:G:C	W145C	1.000
22:21643944:G:T	W145C	1.000
22:21643971:G:C	W154C	1.000
22:21643971:G:T	W154C	1.000
22:21643994:T:C	F162S	1.000
22:21644107:T:A	W200R	1.000
22:21644107:T:C	W200R	1.000
22:21644109:G:C	W200C	1.000
22:21644109:G:T	W200C	1.000
22:21642514:T:C	Y60H	0.999
22:21642515:A:G	Y60C	0.999
22:21642912:A:C	S80R	0.999
22:21642914:C:A	S80R	0.999
22:21642914:C:G	S80R	0.999
22:21642918:T:A	W82R	0.999
22:21642918:T:C	W82R	0.999
22:21642920:G:C	W82C	0.999
22:21642920:G:T	W82C	0.999
22:21643018:T:C	L115P	0.999
22:21643020:C:G	H116D	0.999
22:21643900:A:C	S131R	0.999
22:21643902:T:A	S131R	0.999
22:21643902:T:G	S131R	0.999
22:21643906:T:C	F133L	0.999
22:21643908:T:A	F133L	0.999
22:21643908:T:G	F133L	0.999
22:21643943:G:C	W145S	0.999
22:21644108:G:C	W200S	0.999

dbSNP variants (sampled 300 via entrez): RS1000056378 (22:21640882 G>T), RS1001585621 (22:21642173 A>C,T), RS1001630409 (22:21642182 C>T), RS1001637826 (22:21642313 A>C), RS1001725339 (22:21642355 G>A,C,T), RS1001831822 (22:21643125 G>C), RS1001967614 (22:21643324 C>T), RS1001974832 (22:21640972 G>A,C), RS1002062166 (22:21643675 G>C), RS1003511694 (22:21644404 T>C), RS1003982725 (22:21641377 C>T), RS1004334788 (22:21641013 A>G), RS1005772176 (22:21641813 C>T), RS1005972003 (22:21642755 TG>T,TGG), RS1008291156 (22:21642076 C>A,T)

Disease associations

OMIM: gene MIM:607551 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004131_48	Inflammatory bowel disease	4.000000e-15
GCST004132_118	Crohn’s disease	1.000000e-15
GCST004133_48	Ulcerative colitis	9.000000e-06
GCST007827_18	Alzheimer’s disease or HDL levels (pleiotropy)	4.000000e-12
GCST007843_30	Rheumatoid arthritis	6.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	10
Cyclosporine	increases expression	7
Cisplatin	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
Nickel	increases expression	2
Oxygen	decreases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	increases expression	2
Thapsigargin	increases expression	2
beauvericin	affects cotreatment, decreases expression	1
chloroacetaldehyde	increases expression	1
bisphenol A	increases expression	1
lead acetate	increases expression	1
arsenite	affects binding, increases reaction	1
sodium bichromate	decreases expression	1
afimoxifene	decreases reaction, increases expression	1
manganese chloride	increases expression, increases abundance	1
ochratoxin A	affects cotreatment, decreases expression	1
cupric chloride	increases expression	1
diallyl trisulfide	decreases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	decreases expression	1
enniatins	decreases expression, affects cotreatment	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3GJ	Abcam HEK293T SDF2L1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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