SDF4

Summary

SDF4 (stromal cell derived factor 4, HGNC:24188) is a protein-coding gene on chromosome 1p36.33, encoding 45 kDa calcium-binding protein (Q9BRK5). May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.

This gene encodes a stromal cell derived factor that is a member of the CREC protein family. The encoded protein contains six EF-hand motifs and calcium-binding motifs. This protein localizes to the Golgi lumen and may be involved in regulating calcium dependent cellular activities.

Source: NCBI Gene 51150 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 89 total
• GTEx eGene: eQTL in 28 tissues, sQTL in 50 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.88 (unconstrained)
• MANE Select transcript: NM_016176
• Notable: 89 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24188
Approved symbol	SDF4
Name	stromal cell derived factor 4
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	Cab45
Ensembl gene	ENSG00000078808
Ensembl biotype	protein_coding
OMIM	614282
Entrez	51150

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 24 protein_coding, 14 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000360001

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 1, TSL 5: 1

ENST00000360001, ENST00000263741, ENST00000403997, ENST00000459994, ENST00000465727, ENST00000478938, ENST00000494748, ENST00000900948, ENST00000900949, ENST00000900950, ENST00000900951, ENST00000900952, ENST00000900953, ENST00000900954, ENST00000900955, ENST00000921530, ENST00000921531, ENST00000921532, ENST00000921533, ENST00000969251, ENST00000969252, ENST00000995091, ENST00000995092, ENST00000995093, ENST00000995094, ENST00000995097, ENST00000995098, ENST00000995099, ENST00000995100, ENST00001030276, ENST00001030277, ENST00001030279, ENST00001030280, ENST00001030283, ENST00001062478, ENST00001062479, ENST00001062480, ENST00001062481, ENST00001062483, ENST00001119783, ENST00001142921

RefSeq mRNA: 2 — MANE Select: NM_016176 NM_016176, NM_016547

CCDS: CCDS12, CCDS30553

Canonical transcript exons

ENST00000360001 — 7 exons

Exon	Start	End
ENSE00000869639	1223244	1223357
ENSE00000869640	1223832	1223968
ENSE00001131112	1218769	1218927
ENSE00001480105	1216931	1217688
ENSE00001945650	1231892	1232001
ENSE00003459646	1228468	1228946
ENSE00003628628	1218458	1218633

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.8581 / max 796.8220, expressed in 1825 samples.

Highest expression (Bgee): stromal cell of endometrium, hemisphere of cerebellum, cartilage tissue, cerebellar hemisphere, cerebellar cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SDF4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 50 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 78 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	5.9e-219	+1.68	1:1231507:T:C
Thyroid	sqtl	6.7e-201	+1.58	1:1231507:T:C
Muscle Skeletal	sqtl	4.3e-199	+1.53	1:1231507:T:C
Whole Blood	sqtl	9.5e-197	-1.71	1:1231507:T:C
Artery Tibial	sqtl	1.1e-190	-1.75	1:1231507:T:C
Nerve Tibial	sqtl	1.5e-185	-1.79	1:1231507:T:C
Adipose Visceral Omentum	sqtl	2.7e-183	+1.73	1:1231507:T:C
Skin Sun Exposed Lower leg	sqtl	3.0e-179	-1.62	1:1231507:T:C
Lung	sqtl	4.8e-170	-1.70	1:1231507:T:C
Esophagus Mucosa	sqtl	5.4e-161	-1.63	1:1231507:T:C
Heart Atrial Appendage	sqtl	6.7e-151	+1.71	1:1231507:T:C
Esophagus Muscularis	sqtl	6.1e-150	-1.68	1:1231507:T:C
Breast Mammary Tissue	sqtl	2.9e-127	-1.74	1:1231507:T:C
Brain Cerebellar Hemisphere	sqtl	4.6e-126	+1.99	1:1231507:T:C
Colon Transverse	sqtl	6.1e-126	+1.54	1:1231507:T:C
Heart Left Ventricle	sqtl	6.0e-119	+1.77	1:1231507:T:C
Artery Aorta	sqtl	3.3e-118	-1.70	1:1231507:T:C
Cells EBV-transformed lymphocytes	sqtl	3.0e-111	+1.71	1:1231507:T:C
Colon Sigmoid	sqtl	1.4e-106	-1.69	1:1231507:T:C
Pituitary	sqtl	6.7e-104	+1.78	1:1231507:T:C

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
9734	80.3108	1825
9737	4.5528	1624
9736	4.3465	1640
9733	3.7074	1578
201310	3.6870	1589
9735	2.3581	1335
9732	0.5873	312
9731	0.3081	132

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.27	gold quality
cartilage tissue	UBERON:0002418	98.05	gold quality
cerebellar hemisphere	UBERON:0002245	97.98	gold quality
cerebellar cortex	UBERON:0002129	97.96	gold quality
mucosa of transverse colon	UBERON:0004991	97.94	gold quality
thoracic aorta	UBERON:0001515	97.91	gold quality
ascending aorta	UBERON:0001496	97.90	gold quality
descending thoracic aorta	UBERON:0002345	97.88	gold quality
cardia of stomach	UBERON:0001162	97.84	gold quality
right atrium auricular region	UBERON:0006631	97.84	gold quality
right coronary artery	UBERON:0001625	97.82	gold quality
cardiac atrium	UBERON:0002081	97.77	gold quality
apex of heart	UBERON:0002098	97.71	gold quality
ileal mucosa	UBERON:0000331	97.69	gold quality
cerebellum	UBERON:0002037	97.58	gold quality
transverse colon	UBERON:0001157	97.50	gold quality
body of stomach	UBERON:0001161	97.49	gold quality
trachea	UBERON:0003126	97.44	gold quality
pylorus	UBERON:0001166	97.43	gold quality
aorta	UBERON:0000947	97.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.37	gold quality
coronary artery	UBERON:0001621	97.33	gold quality
nipple	UBERON:0002030	97.33	gold quality
fundus of stomach	UBERON:0001160	97.31	gold quality
parotid gland	UBERON:0001831	97.31	gold quality
left coronary artery	UBERON:0001626	97.30	gold quality
endocervix	UBERON:0000458	97.29	gold quality
small intestine	UBERON:0002108	97.28	gold quality
right ovary	UBERON:0002118	97.26	gold quality
right lobe of liver	UBERON:0001114	97.24	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.24	gold quality
colonic mucosa	UBERON:0000317	97.23	gold quality
right lobe of thyroid gland	UBERON:0001119	97.20	gold quality
jejunal mucosa	UBERON:0000399	97.18	gold quality
pituitary gland	UBERON:0000007	97.14	gold quality
left adrenal gland	UBERON:0001234	97.14	gold quality
renal medulla	UBERON:0000362	97.13	gold quality
adenohypophysis	UBERON:0002196	97.13	gold quality
heart left ventricle	UBERON:0002084	97.08	gold quality
left ovary	UBERON:0002119	97.06	gold quality
left adrenal gland cortex	UBERON:0035825	97.05	gold quality
lower lobe of lung	UBERON:0008949	97.04	gold quality
tibia	UBERON:0000979	97.03	gold quality
cardiac ventricle	UBERON:0002082	97.03	gold quality
popliteal artery	UBERON:0002250	97.03	gold quality
tibial artery	UBERON:0007610	97.03	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.00	gold quality
body of uterus	UBERON:0009853	96.98	gold quality
adrenal cortex	UBERON:0001235	96.97	gold quality
granulocyte	CL:0000094	96.96	gold quality
colon	UBERON:0001155	96.96	gold quality
left lobe of thyroid gland	UBERON:0001120	96.95	gold quality
left ventricle myocardium	UBERON:0006566	96.94	gold quality
upper lobe of lung	UBERON:0008948	96.94	gold quality
right adrenal gland	UBERON:0001233	96.93	gold quality
duodenum	UBERON:0002114	96.93	gold quality
left uterine tube	UBERON:0001303	96.92	gold quality
upper lobe of left lung	UBERON:0008952	96.90	gold quality
large intestine	UBERON:0000059	96.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.87	gold quality
metanephros cortex	UBERON:0010533	96.85	gold quality
vena cava	UBERON:0004087	96.82	gold quality
saliva-secreting gland	UBERON:0001044	96.81	gold quality
body of pancreas	UBERON:0001150	96.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.80	gold quality
right lung	UBERON:0002167	96.78	gold quality
lower esophagus	UBERON:0013473	96.78	gold quality
heart	UBERON:0000948	96.77	gold quality
type B pancreatic cell	CL:0000169	96.74	silver quality
omental fat pad	UBERON:0010414	96.74	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.74	gold quality
gall bladder	UBERON:0002110	96.73	gold quality
peritoneum	UBERON:0002358	96.72	gold quality
saphenous vein	UBERON:0007318	96.71	gold quality
right adrenal gland cortex	UBERON:0035827	96.71	gold quality
minor salivary gland	UBERON:0001830	96.70	gold quality
stomach	UBERON:0000945	96.68	gold quality
intestine	UBERON:0000160	96.67	gold quality
pericardium	UBERON:0002407	96.67	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.66	gold quality
thyroid gland	UBERON:0002046	96.61	gold quality
nasal cavity epithelium	UBERON:0005384	96.60	gold quality
mucosa of stomach	UBERON:0001199	96.58	gold quality
adrenal gland	UBERON:0002369	96.56	gold quality
ectocervix	UBERON:0012249	96.52	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.50	gold quality
right testis	UBERON:0004534	96.49	gold quality
nasal cavity mucosa	UBERON:0001826	96.48	gold quality
placenta	UBERON:0001987	96.48	gold quality
olfactory bulb	UBERON:0002264	96.48	silver quality
spleen	UBERON:0002106	96.46	gold quality
left testis	UBERON:0004533	96.46	gold quality
adult mammalian kidney	UBERON:0000082	96.41	gold quality
adipose tissue	UBERON:0001013	96.36	gold quality
skin of leg	UBERON:0001511	96.35	gold quality
urethra	UBERON:0000057	96.34	gold quality
superior surface of tongue	UBERON:0007371	96.32	gold quality
corpus epididymis	UBERON:0004359	96.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.29	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	220.3
Frontal cortex	tissue	206.6
Choroid plexus	tissue	128.8
Duodenum	tissue	110.2	high
Small intestine	tissue	109.9	high
Heart muscle	tissue	93.8	not detected
Pancreas	tissue	93.0	medium
Liver	tissue	90.8	medium
Spinal cord	tissue	88.8
Colon	tissue	84.3	high
Adipose tissue	tissue	80.9	not detected
Superior colliculi	tissue	79.3
Appendix	tissue	74.3	high
Stomach 1	tissue	72.7	low
Ovary	tissue	71.8	not detected
Pituitary gland	tissue	70.4
Salivary gland	tissue	70.1	low
Skeletal muscle	tissue	69.6	not detected
Placenta	tissue	68.9	high
Adrenal gland	tissue	66.6	medium
Hippocampus	tissue	66.2	low
Locus coeruleus	tissue	65.7
Prostate	tissue	65.7	high
Vagina	tissue	65.3	low
Postcentral gyrus	tissue	65.2
Cervix	tissue	63.1	medium
Gallbladder	tissue	62.0	high
Thyroid gland	tissue	61.8	low
Spleen	tissue	61.4	low
Pons	tissue	60.1
Substantia nigra	tissue	59.3
Urinary bladder	tissue	59.1	not detected
Hypothalamus	tissue	58.3
Nucleus accumbens	tissue	58.2
Medulla oblongata	tissue	58.0
Parathyroid gland	tissue	57.7	medium
Midbrain	tissue	57.1
Rectum	tissue	56.7	high
Thalamus	tissue	56.5
Kidney	tissue	56.4	high
Lung	tissue	56.0	not detected
Smooth muscle	tissue	54.3	not detected
Bone marrow	tissue	53.1	not detected
Skin 1	tissue	52.0	not detected
Septum	tissue	51.3
Hippocampal formation	tissue	50.7
Lymph node	tissue	50.0	not detected
Esophagus	tissue	49.5	low
Seminal vesicle	tissue	49.2	low
Basal ganglia	tissue	48.6	medium
Putamen	tissue	47.7
Cerebral cortex	tissue	47.4	medium
Endometrium 1	tissue	47.4	high
Somatosensory cortex	tissue	47.4
Periaqueductal gray	tissue	47.2
Fallopian tube	tissue	46.0	not detected
Ventral forebrain	tissue	45.6
Entorhinal cortex	tissue	45.0
Prefrontal cortex	tissue	44.9
Testis	tissue	44.4	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (130.4), Dorsal spinal cord (88.8), Nucleus ambiguus (85.4), Anterior thalamic nucleus, ventral (83.8), Area postrema (78.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting SDF4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 34 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-5003-5P	99.61	69.13	1624

Functional genomics

gnomAD constraint: pLI 0.000299, LOEUF 0.875, missense Z 1.18 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000360001 — one region, missense o/e 0.89.

Literature-anchored findings (GeneRIF, showing 11)

• In a yeast two-hybrid screen the EF-hand Ca(2+)-binding protein Cab45 was identified as an interaction partner of Munc18b. (PMID:17442889)
• SDF-2, SDF-4 and SDF-5 are expressed in mammary tissues and cells and that a reduced level of SDF-2 and SDF-4 are associated with a poor clinical outcome. (PMID:19513569)
• Calcium is required for the retention of Cab45 in the Golgi membranes, where Cab45 binds secretory cargo in a calcium-dependent reaction. (PMID:23266954)
• Cab45S, a novel regulator of GRP78/BiP, suppresses endoplasmic reticulum stress-induced IRE1 activation and apoptosis by binding to and elevating GRP78/BiP, and has a role in the inhibition of ER stress-induced apoptosis. (PMID:24810055)
• The obtained results indicate that the changes in gene expression in bone marrow progenitor cells can be involved into space flight-induced osteopenia. (PMID:25509878)
• Data reveal that the ability of Cab45S to inhibit SERCA2b activity is crucial for its role as a modulator of cell proliferation and tumor growth. (PMID:25772237)
• Ca(2+)-dependent changes in Cab45 mediate sorting of specific cargo molecules at the trans-Golgi network. (PMID:27138253)
• Fam20C regulates protein secretion by Cab45 phosphorylation. (PMID:32422653)
• SDF4 Is a Prognostic Factor for 28-Days Mortality in Patients With Sepsis via Negatively Regulating ER Stress. (PMID:34326834)
• Cab45 deficiency leads to the mistargeting of progranulin and prosaposin and aberrant lysosomal positioning. (PMID:36398980)
• LINC00173 facilitates tumor progression by stimulating RAB1B-mediated PA2G4 and SDF4 secretion in nasopharyngeal carcinoma. (PMID:36606322)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sdf4	ENSDARG00000070682
mus_musculus	Sdf4	ENSMUSG00000029076
rattus_norvegicus	Sdf4	ENSRNOG00000019981
drosophila_melanogaster	myd	FBGN0051475
caenorhabditis_elegans		WBGENE00016965

Paralogs (4): RCN1 (ENSG00000049449), RCN2 (ENSG00000117906), CALU (ENSG00000128595), RCN3 (ENSG00000142552)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Capra hircus	A5YVD9	99.2%	Diamond
Bos taurus	Q3ZBZ1	99.2%	Diamond
Xenopus tropicalis	Q5BKL9	94.4%	Diamond
Xenopus laevis	Q66JA6	94.4%	Diamond
Gallus gallus	Q5ZKE5	88.6%	Diamond
Macaca fascicularis	Q4R585	87.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
UBE2J2	protein-coding	118424
C1QTNF12	protein-coding	388581
TNFRSF4	protein-coding	7293
TTLL10-AS1	ncRNA	100506376
TTLL10	protein-coding	254173
TNFRSF18	protein-coding	8784
B3GALT6	protein-coding	126792
LINC01786	ncRNA	101928895
SCNN1D	protein-coding	6339
MIR200BHG	ncRNA	124903818
MIR429	ncRNA	554210

Protein

Protein identifiers

45 kDa calcium-binding protein — Q9BRK5 (reviewed: Q9BRK5)

Alternative names: Stromal cell-derived factor 4

All UniProt accessions (4): A0A5F9UJX7, A0A5F9UP49, G3V1E2, H0Y3T6

UniProt curated annotations — full annotation on UniProt →

Function. May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment. Isoform 5 may be involved in the exocytosis of zymogens by pancreatic acini.

Subunit / interactions. Isoform 5 interacts with STXBP1; the interaction is enhanced in presence of calcium. Isoform 5 interacts with STX3.

Subcellular location. Golgi apparatus lumen Cytoplasm. Cell membrane. Cell projection. Bleb.

Tissue specificity. Ubiquitous. Isoform 5 is expressed in pancreas.

Domain organisation. Binds calcium via its EF-hands. Isoform 5 binds calcium.

Similarity. Belongs to the CREC family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9BRK5-1	1, Cab45a, Cab45-G	yes
Q9BRK5-2	2
Q9BRK5-3	3
Q9BRK5-4	4
Q9BRK5-5	5, Cab45b, Cab45-C
Q9BRK5-6	6

RefSeq proteins (2): NP_057260, NP_057631 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR027240	CAB45_EFh	Domain

Pfam: PF13202, PF13499

UniProt features (69 total): binding site 26, sequence conflict 16, splice variant 7, domain 6, modified residue 5, mutagenesis site 3, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRK5-F1	81.03	0.60

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IH supported · IF supported

Functional residue map

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

Ligand- & substrate-binding residues (26)

Position	Role
113	Ca(2+)
115	Ca(2+)
117	Ca(2+)
122	Ca(2+)
150	Ca(2+)
152	Ca(2+)
154	Ca(2+)
156	Ca(2+)
161	Ca(2+)
213	Ca(2+)
220	Ca(2+)
246	Ca(2+)
248	Ca(2+)
250	Ca(2+)
252	Ca(2+)
257	Ca(2+)
291	Ca(2+)
293	Ca(2+)
295	Ca(2+)
302	Ca(2+)
327	Ca(2+)
329	Ca(2+)
331	Ca(2+)
333	Ca(2+)
338	Ca(2+)
111	Ca(2+)

Post-translational modifications (5)

Type	Positions
Phosphoserine	99
Phosphothreonine	193, 217, 265, 299

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	40

Mutagenesis-validated functional residues (3)

Position	Phenotype
257	does not affect calcium-binding.
302	inhibits calcium-binding.
338	does not affect calcium-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 175 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_ETHANOL, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_UV_PROTECTION, GOBP_EXOCYTOSIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_UV, GOBP_SECRETION, GOBP_RESPONSE_TO_RADIATION, GOBP_CALCIUM_ION_REGULATED_EXOCYTOSIS, GOBP_FAT_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS

GO Biological Process (7): UV protection (GO:0009650), calcium-ion regulated exocytosis (GO:0017156), cerebellum development (GO:0021549), fat cell differentiation (GO:0045444), response to ethanol (GO:0045471), zymogen granule exocytosis (GO:0070625), maintenance of synapse structure (GO:0099558)

GO Molecular Function (3): calcium ion binding (GO:0005509), identical protein binding (GO:0042802), metal ion binding (GO:0046872)

GO Cellular Component (9): cytoplasm (GO:0005737), late endosome (GO:0005770), endoplasmic reticulum (GO:0005783), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), membrane (GO:0016020), bleb (GO:0032059), extracellular exosome (GO:0070062), Golgi apparatus (GO:0005794)

GO top-level categories

24 GO namespaces:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
response to UV	1
regulated exocytosis	1
metencephalon development	1
animal gross anatomical part developmental process	1
cell differentiation	1
response to alcohol	1
calcium-ion regulated exocytosis	1
cell junction maintenance	1
synapse organization	1
metal ion binding	1
protein binding	1
cation binding	1
intracellular anatomical structure	1
endosome	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
maintenance of synapse structure	BP	genetic interaction
extracellular exosome	CC	high-throughput assay
membrane	CC	high-throughput assay
calcium ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,270 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDF4	S100B	P04271	897
SDF4	PVALB	P20472	849
SDF4	CALB1	P05937	849
SDF4	CALB2	P22676	779
SDF4	S100G	P29377	770
SDF4	S100A6	P06703	701
SDF4	CALML4	Q96GE6	685
SDF4	S100A4	P26447	683
SDF4	CALM1	P02593	677
SDF4	CALML3	P27482	650
SDF4	CALML5	Q9NZT1	650
SDF4	CALML6	Q8TD86	622
SDF4	S100A1	P23297	615
SDF4	GFAP	P14136	549
SDF4	SRI	P30626	522

IntAct

Human interaction partners of SDF4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
ACAD11	association	0.640	2
CASP6	physical association	0.560	3
LAMP2	physical association	0.560	3
PRPF40A	physical association	0.560	3
SH3GLB1	physical association	0.560	3
GTPBP6	association	0.530	2
MOK	physical association	0.400	1
ANXA7	physical association	0.370	1
CDKN1A	physical association	0.370	1
NR1I2	physical association	0.370	1
RAP1B	physical association	0.370	1
RCC1	physical association	0.370	1
RPA2	physical association	0.370	1
SMN1	physical association	0.370	1
SNCA	physical association	0.370	1
TK1	physical association	0.370	1
TTR	physical association	0.370	1
ZNF512B	physical association	0.370	1

BioGRID (250 interactions; top human partners by supporting records): ACAD11 (Affinity Capture-MS; 3 records), ARL8B (Affinity Capture-MS; 3 records), ATP2B2 (Affinity Capture-MS; 3 records), CHST11 (Affinity Capture-MS; 3 records), CHST12 (Affinity Capture-MS; 3 records), ERF (Affinity Capture-MS; 3 records), FHL2 (Affinity Capture-MS; 3 records), FOXF2 (Affinity Capture-MS; 3 records), GALNT11 (Affinity Capture-MS; 3 records), GPRIN1 (Affinity Capture-MS; 3 records), GTPBP6 (Affinity Capture-MS; 3 records), ILK (Affinity Capture-MS; 3 records), IQGAP2 (Affinity Capture-MS; 3 records), KIAA1671 (Affinity Capture-MS; 3 records), MTFR1L (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
FAM20C	“up-regulates activity”	SDF4	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for SDF4: 89 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	5
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 996):

Position(s)	Effect	Δscore	Sites
1:1217689–1217690	acceptor_loss	1.0000	6
1:1218456–1218457	donor_loss	1.0000	5
1:1223246	donor_gain	1.0000
1:1223830–1223831	donor_loss	1.0000	4
1:1223835	donor_gain	1.0000
1:1223873	donor_gain	1.0000
1:1223969	acceptor_loss	1.0000
1:1223978	acceptor_gain	1.0000
1:1218634–1218635	acceptor_loss	0.9900	6
1:1223830–1223831	donor_loss	0.9900	2

AlphaMissense

843 missense substitutions predicted likely pathogenic (of 2,400 scored), across 197 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M233	9	0.856	0.984
D246	8	0.978	0.991
D291	8	0.972	0.989
D111	8	0.970	0.987
D327	8	0.968	0.992
F224	8	0.952	0.995
F346	8	0.951	0.995
D150	8	0.948	0.975
H226	8	0.935	0.991
F362	8	0.929	0.996
H134	8	0.923	0.972
H359	8	0.912	0.966
F82	8	0.896	0.990
D70	8	0.879	0.963
S349	8	0.877	0.994
D208	8	0.848	0.947
H61	8	0.836	0.934
D244	8	0.778	0.875
W204	7	0.993	0.998
F258	7	0.990	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	3.81e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000418
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000716

Disease associations

OMIM: gene MIM:614282 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST005537_224	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2e-10
GCST006988_164	Blond vs. brown/black hair color	2e-9
GCST007932_108	Medication use (thyroid preparations)	3e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0003924	hair color
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4742317 (PROTEIN-PROTEIN INTERACTION), CHEMBL6067531 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.29	Kd	518.7	nM	CHEMBL3752910
6.29	ED50	518.7	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149932: Binding affinity to human SDF4 incubated for 45 mins by Kinobead based pull down assay	kd	0.5187	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	decreases expression, affects expression, affects cotreatment	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Tobacco Smoke Pollution	affects expression, decreases methylation	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
salinomycin	decreases expression	1
tris(2-butoxyethyl) phosphate	affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
2-ethylhexyldiphenylphosphate	decreases expression, affects cotreatment	1
perfluorooctanoic acid	decreases expression	1
tris(chloroethyl)phosphate	affects cotreatment, decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
santicizer 148	affects cotreatment, decreases expression	1
tri-(2-chloroisopropyl)phosphate	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Methotrexate	affects response to substance	1
Silicon Dioxide	decreases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713769	Binding	Protac activity at CRBN/SDF4 in human BxPC-3 cells assessed as SDF4 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — *J Med Chem*

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3GK	Abcam HEK293T SDF4 KO	Transformed cell line	Female
CVCL_E2JR	HAP1 SDF4 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SDF4 across ~30M SureChEMBL compounds — explore on Sugi Predict.