SPOCK2

Summary

SPOCK2 (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 2, HGNC:13564) is a protein-coding gene on chromosome 10q22.1, encoding Testican-2 (Q92563). May participate in diverse steps of neurogenesis.

This gene encodes a protein which binds with glycosaminoglycans to form part of the extracellular matrix. The protein contains thyroglobulin type-1, follistatin-like, and calcium-binding domains, and has glycosaminoglycan attachment sites in the acidic C-terminal region. Three alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Source: NCBI Gene 9806 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 75 total
• GTEx eGene: eQTL in 29 tissues, sQTL in 13 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.90 (unconstrained)
• MANE Select transcript: NM_001244950
• Notable: 75 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13564
Approved symbol	SPOCK2
Name	SPARC (osteonectin), cwcv and kazal like domains proteoglycan 2
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0275, testican-2
Ensembl gene	ENSG00000107742
Ensembl biotype	protein_coding
OMIM	607988
Entrez	9806

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 5 protein_coding_CDS_not_defined

MANE Select: ENST00000373109

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

ENST00000373109, ENST00000317376, ENST00000412663, ENST00000460053, ENST00000463279, ENST00000469121, ENST00000483699, ENST00000495888, ENST00000885192, ENST00001141921

RefSeq mRNA: 3 — MANE Select: NM_001244950 NM_001134434, NM_001244950, NM_014767

CCDS: CCDS44431, CCDS7313

Canonical transcript exons

ENST00000373109 — 11 exons

Exon	Start	End
ENSE00000708564	72070312	72070426
ENSE00000708566	72072144	72072258
ENSE00000708569	72072503	72072548
ENSE00002496406	72072902	72072910
ENSE00003497999	72064178	72064240
ENSE00003621083	72063025	72063162
ENSE00003682718	72068187	72068301
ENSE00003689100	72066902	72067120
ENSE00003691013	72067613	72067732
ENSE00003845917	72059034	72062905
ENSE00004799866	72088140	72088551

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 99.61.

FANTOM5 (CAGE): breadth broad, TPM avg 45.5254 / max 1785.9832, expressed in 568 samples.

Highest expression (Bgee): paraflocculus, lateral nuclear group of thalamus, cerebellar cortex, cerebellar hemisphere, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SPOCK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 13 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 42 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	3.7e-47	+0.55	10:72082931:G:GAGAAAAGCGTAA
Adrenal Gland	eqtl	3.7e-46	-0.78	10:72073597:C:T
Heart Left Ventricle	eqtl	1.0e-37	+0.56	10:72082931:G:GAGAAAAGCGTAA
Whole Blood	sqtl	5.7e-26	-0.40	10:72086583:A:G
Brain Cerebellar Hemisphere	eqtl	4.5e-22	-0.34	10:72086583:A:G
Lung	sqtl	5.8e-22	-0.54	10:72087068:C:T
Brain Cerebellum	eqtl	2.3e-20	-0.30	10:72086583:A:G
Adipose Visceral Omentum	eqtl	4.9e-18	+0.37	10:72082931:G:GAGAAAAGCGTAA
Testis	sqtl	4.9e-15	-0.64	10:72085663:G:A
Ovary	eqtl	3.6e-14	-0.57	10:72074150:C:A
Esophagus Muscularis	eqtl	1.4e-13	+0.28	10:72082931:G:GAGAAAAGCGTAA
Adipose Subcutaneous	eqtl	2.2e-10	+0.26	10:72082931:G:GAGAAAAGCGTAA
Breast Mammary Tissue	eqtl	4.9e-10	+0.34	10:72082931:G:GAGAAAAGCGTAA
Brain Cerebellum	sqtl	9.0e-10	-0.57	10:72084088:G:A
Thyroid	eqtl	9.6e-10	+0.27	10:72088347:TG:T
Brain Spinal cord cervical c-1	sqtl	2.2e-06	-0.57	10:72083700:T:C
Pancreas	eqtl	4.1e-06	+0.36	10:72083700:T:C
Brain Cortex	sqtl	1.6e-05	-0.48	10:72086126:G:A
Heart Atrial Appendage	eqtl	1.8e-05	+0.29	10:72082931:G:GAGAAAAGCGTAA
Nerve Tibial	eqtl	5.1e-05	+0.22	10:72097226:A:G

FANTOM5 promoters

showing 10 of 17 alternative TSS:

Promoter ID	TPM avg	Samples expressed
109971	26.3155	453
109970	7.5927	395
109972	6.5676	324
109978	1.0919	222
109973	0.9146	195
109969	0.7013	208
109968	0.6433	205
109974	0.5566	173
109979	0.3458	147
109967	0.3112	131

Top tissues by expression

showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	99.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.33	gold quality
cerebellar cortex	UBERON:0002129	98.94	gold quality
cerebellar hemisphere	UBERON:0002245	98.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.92	gold quality
cerebellum	UBERON:0002037	98.91	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.84	gold quality
dorsal root ganglion	UBERON:0000044	98.74	gold quality
cerebellar vermis	UBERON:0004720	98.72	gold quality
middle frontal gyrus	UBERON:0002702	98.59	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.59	gold quality
substantia nigra pars compacta	UBERON:0001965	98.48	gold quality
pons	UBERON:0000988	98.42	gold quality
superior vestibular nucleus	UBERON:0007227	98.42	gold quality
inferior olivary complex	UBERON:0002127	98.41	gold quality
lateral globus pallidus	UBERON:0002476	98.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.20	gold quality
nucleus accumbens	UBERON:0001882	98.12	gold quality
ventral tegmental area	UBERON:0002691	98.06	gold quality
frontal pole	UBERON:0002795	98.06	gold quality
hypothalamus	UBERON:0001898	98.01	gold quality
medulla oblongata	UBERON:0001896	97.95	gold quality
right frontal lobe	UBERON:0002810	97.74	gold quality
cingulate cortex	UBERON:0003027	97.70	gold quality
anterior cingulate cortex	UBERON:0009835	97.68	gold quality
primary visual cortex	UBERON:0002436	97.58	gold quality
caudate nucleus	UBERON:0001873	97.53	gold quality
occipital lobe	UBERON:0002021	97.53	gold quality
prefrontal cortex	UBERON:0000451	97.47	gold quality
postcentral gyrus	UBERON:0002581	97.45	gold quality
superior frontal gyrus	UBERON:0002661	97.45	gold quality
putamen	UBERON:0001874	97.39	gold quality
frontal cortex	UBERON:0001870	97.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.31	gold quality
parietal lobe	UBERON:0001872	97.30	gold quality
amygdala	UBERON:0001876	97.27	gold quality
middle temporal gyrus	UBERON:0002771	97.20	gold quality
temporal lobe	UBERON:0001871	97.19	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.16	gold quality
entorhinal cortex	UBERON:0002728	97.14	gold quality
thymus	UBERON:0002370	97.12	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.93	gold quality
medial globus pallidus	UBERON:0002477	96.80	gold quality
telencephalon	UBERON:0001893	96.77	gold quality
globus pallidus	UBERON:0001875	96.71	gold quality
neocortex	UBERON:0001950	96.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.64	gold quality
midbrain	UBERON:0001891	96.63	gold quality
brain	UBERON:0000955	96.61	gold quality
central nervous system	UBERON:0001017	96.59	gold quality
substantia nigra	UBERON:0002038	96.49	gold quality
cerebral cortex	UBERON:0000956	96.48	gold quality
forebrain	UBERON:0001890	96.48	gold quality
Ammon’s horn	UBERON:0001954	96.46	gold quality
lymph node	UBERON:0000029	96.45	gold quality
inferior vagus X ganglion	UBERON:0005363	96.22	gold quality
granulocyte	CL:0000094	96.18	gold quality
orbitofrontal cortex	UBERON:0004167	96.14	gold quality
metanephric glomerulus	UBERON:0004736	96.09	gold quality
trigeminal ganglion	UBERON:0001675	96.06	gold quality
spinal cord	UBERON:0002240	96.02	gold quality
right lung	UBERON:0002167	95.99	gold quality
renal glomerulus	UBERON:0000074	95.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.90	gold quality
subthalamic nucleus	UBERON:0001906	95.30	gold quality
CA1 field of hippocampus	UBERON:0003881	94.47	gold quality
upper lobe of left lung	UBERON:0008952	94.32	gold quality
cranial nerve II	UBERON:0000941	94.22	gold quality
decidua	UBERON:0002450	94.14	gold quality
upper lobe of lung	UBERON:0008948	93.97	gold quality
germinal epithelium of ovary	UBERON:0001304	93.60	gold quality
vermiform appendix	UBERON:0001154	93.53	gold quality
adenohypophysis	UBERON:0002196	93.08	gold quality
blood	UBERON:0000178	93.00	gold quality
adult mammalian kidney	UBERON:0000082	92.91	gold quality
pituitary gland	UBERON:0000007	92.41	gold quality
adult organism	UBERON:0007023	91.93	gold quality
caecum	UBERON:0001153	91.71	gold quality
lung	UBERON:0002048	91.70	gold quality
renal medulla	UBERON:0000362	91.05	gold quality
metanephros	UBERON:0000081	90.55	gold quality
lower lobe of lung	UBERON:0008949	90.22	gold quality
corpus callosum	UBERON:0002336	90.17	gold quality
gall bladder	UBERON:0002110	89.85	gold quality
kidney	UBERON:0002113	89.47	gold quality
cortex of kidney	UBERON:0001225	88.92	gold quality
right testis	UBERON:0004534	88.55	gold quality
right adrenal gland cortex	UBERON:0035827	88.17	gold quality
spleen	UBERON:0002106	88.04	gold quality
left testis	UBERON:0004533	87.84	gold quality
olfactory bulb	UBERON:0002264	87.65	silver quality
kidney epithelium	UBERON:0004819	87.45	gold quality
left adrenal gland	UBERON:0001234	87.20	gold quality
adrenal gland	UBERON:0002369	87.16	gold quality
apex of heart	UBERON:0002098	87.12	gold quality
testis	UBERON:0000473	87.05	gold quality
adrenal cortex	UBERON:0001235	87.00	gold quality
ileal mucosa	UBERON:0000331	86.94	gold quality
left adrenal gland cortex	UBERON:0035825	86.59	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	467.27
E-MTAB-6678	yes	398.61
E-MTAB-9221	yes	383.04
E-MTAB-7381	yes	332.11
E-CURD-112	yes	226.74
E-CURD-6	yes	110.84
E-HCAD-4	yes	62.30
E-CURD-88	yes	55.25
E-MTAB-8142	yes	39.98
E-HCAD-1	yes	36.41
E-HCAD-10	yes	36.06
E-MTAB-8410	yes	34.74
E-GEOD-135922	yes	25.48
E-CURD-46	yes	21.55
E-ANND-3	yes	11.91

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	392.7
Cerebellum	tissue	379.3	high
Superior colliculi	tissue	377.7
Thalamus	tissue	344.3
Pons	tissue	337.7
Postcentral gyrus	tissue	310.7
Basal ganglia	tissue	304.6	high
Midbrain	tissue	297.8
Caudate putamen	tissue	266.6
Putamen	tissue	257.6
Ventral forebrain	tissue	253.1
Nucleus accumbens	tissue	252.3
Hippocampus	tissue	245.7	medium
Septum	tissue	245.5
Frontal cortex	tissue	244.3
Hippocampal formation	tissue	243.7
Hypothalamus	tissue	243.2
Substantia nigra	tissue	242.3
Cerebral cortex	tissue	233.1	medium
Somatosensory cortex	tissue	233.1
Spinal cord	tissue	229.1
Amygdala	tissue	228.2
Prefrontal cortex	tissue	220.1
Motor cortex	tissue	216.3
Medulla oblongata	tissue	209.0
Occipital cortex	tissue	202.7
Entorhinal cortex	tissue	201.7
Retrosplenial and cingulate cortex	tissue	199.4
Temporal cortex	tissue	193.6
Insular cortex	tissue	193.5
Retrosplenial cortex	tissue	187.1
Periaqueductal gray	tissue	183.9
Olfactory bulb	tissue	127.1
Thymus	tissue	106.6
Lung	tissue	81.6	medium
Lymph node	tissue	63.0	medium
Corpus callosum	tissue	60.6
Bone marrow	tissue	54.4	low
Adrenal gland	tissue	43.9	medium
Tonsil	tissue	42.5	medium
Appendix	tissue	41.7	medium
Pituitary gland	tissue	40.8
Choroid plexus	tissue	32.7
Retina	tissue	31.1
Kidney	tissue	28.0	medium
Spleen	tissue	27.1	medium
Testis	tissue	18.9	high
Gallbladder	tissue	14.3	medium
Small intestine	tissue	11.9	medium
Stomach 1	tissue	11.8	medium
Urinary bladder	tissue	9.2	medium
Duodenum	tissue	8.7	medium
Heart muscle	tissue	6.2	not detected
Tongue	tissue	6.2
Fallopian tube	tissue	5.9	low
Colon	tissue	5.5	low
Adipose tissue	tissue	5.4	not detected
Seminal vesicle	tissue	5.3	low
Rectum	tissue	5.0	low
Skeletal muscle	tissue	4.7	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Nuclei of the trapezoid body (494.6), Nucleus raphe magnus (477.5), Habenula (474.2), Pulvinar (446.5), Medial dorsal thalamic nucleus (445.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EZH2

miRNA regulators (miRDB)

Targeting SPOCK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 39 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-6080	99.43	69.43	373
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-6842-3P	98.07	66.33	1325

Functional genomics

gnomAD constraint: pLI 1.5e-09, LOEUF 0.9, missense Z 0.223 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000373109 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 14)

• Neurons are a major source of all of the testican family members in the normal brain. Abundant distribution of testican 2 may contribute to glioma invasion by inactivating other testican family members including N-Tes, which all inhibit MT-MMPs. (PMID:12810672)
• purification and characterization of a recombinant testican-2 expressed in insect cells; the C1q subcomponent of complement component C1 was identified as a potential interacting partner of testican-2 (PMID:17950619)
• candidate susceptibility gene for bronchopulmonary dysplasia; lung expression pattern indicates potential role in alveolarization (PMID:21836138)
• The upregulation of SPOCK2-encoded Testican2 proteoglycan and of ectodysplasin (EDA) protein was coupled with a down-regulation of EDA2 receptor (EDA2R). (PMID:29708036)
• Dysregulation of pseudogene/lncRNA-hsa-miR-363-3p-SPOCK2 pathway fuels stage progression of ovarian cancer. (PMID:31794425)
• SPOCK2 Affects the Biological Behavior of Endometrial Cancer Cells by Regulation of MT1-MMP and MMP2. (PMID:32430715)
• Downregulation of SPOCK2 promotes the proliferation, adhesion, and invasion of endometrial epithelial cells. (PMID:32851893)
• Circulating testican-2 is a podocyte-derived marker of kidney health. (PMID:32958645)
• Testican-2 Is Associated with Reduced Risk of Incident ESKD. (PMID:36288905)
• SPOCK2 and SPRED1 function downstream of EZH2 to impede the malignant progression of lung adenocarcinoma in vitro and in vivo. (PMID:36629984)
• Integrated bulk and single-cell RNA-sequencing reveals SPOCK2 as a novel biomarker gene in the development of congenital pulmonary airway malformation. (PMID:37165378)
• SPOCK2 gene expression is downregulated in pancreatic ductal adenocarcinoma cells and correlates with prognosis of patients with pancreatic cancer. (PMID:37188984)
• The novel prognostic marker SPOCK2 regulates tumour progression in melanoma. (PMID:38888196)
• SPOCK: Master regulator of malignant tumors (Review). (PMID:39392048)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spock2	ENSMUSG00000058297
rattus_norvegicus	Spock2	ENSRNOG00000061544
drosophila_melanogaster	Cow	FBGN0039054
caenorhabditis_elegans		WBGENE00016918

Paralogs (3): SPOCK1 (ENSG00000152377), SPOCK3 (ENSG00000196104), KIAA1210 (ENSG00000250423)

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
Pongo abelii	Q5RD69	97.6%	Diamond
Sus scrofa	P16611	90.1%	Diamond
Bos taurus	P20959	90.1%	Diamond
Aquarana catesbeiana	P31226	57.1%	Diamond
Actinia equina	P81439	56.1%	Diamond
Hadronyche infensa	A0A1D0C023	47.4%	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
DDIT4-AS1	ncRNA	110806271
ANAPC16	protein-coding	119504
ASCC1	protein-coding	51008
LINC03139	ncRNA	124902447
CHST3	protein-coding	9469
PSAP	protein-coding	5660
DDIT4	protein-coding	54541

Protein

Protein identifiers

Testican-2 — Q92563 (reviewed: Q92563)

Alternative names: SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2

All UniProt accessions (1): Q92563

UniProt curated annotations — full annotation on UniProt →

Function. May participate in diverse steps of neurogenesis. Binds calcium.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Highly expressed in brain. Also found in lung and testis.

Post-translational modifications. Contains chondroitin sulfate and heparan sulfate O-linked oligosaccharides.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92563-1	1	yes
Q92563-2	2

RefSeq proteins (3): NP_001127906, NP_001231879, NP_055582 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR002350	Kazal_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR019577	SPARC/Testican_Ca-bd-dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily

Pfam: PF00086, PF07648, PF10591

UniProt features (22 total): disulfide bond 8, glycosylation site 3, splice variant 2, domain 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92563-F1	67.37	0.09

Human Protein Atlas

Protein class: Predicted secreted proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Type	Positions
Phosphoserine	72

Disulfide bonds (8)

Type	Positions
Disulfide bond	90–101, 95–111, 136–166, 139–159, 148–180, 313–337, 348–355, 357–376

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	225
O-linked (xyl…) (glycosaminoglycan) serine	383, 388

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: 294 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, AHRARNT_01, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GAANYNYGACNY_UNKNOWN, GOBP_SYNAPSE_ASSEMBLY, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, AP4_Q6, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, MODULE_66, GTGCCTT_MIR506, TCF4_Q5

GO Biological Process (5): synapse assembly (GO:0007416), regulation of cell-substrate adhesion (GO:0010810), extracellular matrix organization (GO:0030198), regulation of cell differentiation (GO:0045595), positive regulation of cell motility (GO:2000147)

GO Molecular Function (5): calcium ion binding (GO:0005509), glycosaminoglycan binding (GO:0005539), metalloendopeptidase inhibitor activity (GO:0008191), extracellular matrix binding (GO:0050840), protein binding (GO:0005515)

GO Cellular Component (2): extracellular matrix (GO:0031012), gel phase of interstitial matrix (GO:0140150)

GO top-level categories

21 GO namespaces:

Category	Terms
binding	2
external encapsulating structure	2
nervous system development	1
cell junction assembly	1
synapse organization	1
regulation of cell adhesion	1
cell-substrate adhesion	1
extracellular structure organization	1
external encapsulating structure organization	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
positive regulation of locomotion	1
positive regulation of cellular process	1
cell motility	1
regulation of cell motility	1
metal ion binding	1
carbohydrate derivative binding	1
metalloendopeptidase activity	1
endopeptidase inhibitor activity	1
interstitial matrix	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
calcium ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 700 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPOCK2	MMP16	P51512	788
SPOCK2	FST	P19883	734
SPOCK2	TG	P01266	709
SPOCK2	MMP14	P50281	586
SPOCK2	MMP2	P08253	455
SPOCK2	SS18L2	Q9UHA2	439
SPOCK2	MMP1	P03956	427
SPOCK2	SFTPC	P11686	384
SPOCK2	FMOD	Q06828	372
SPOCK2	MRPL51	Q4U2R6	366
SPOCK2	SPOUT1	Q5T280	366
SPOCK2	DMTF1	Q9Y222	366
SPOCK2	VMA22	Q96NT0	359
SPOCK2	RPL35A	P18077	358
SPOCK2	ERBB2	P04626	345

IntAct

Human interaction partners of SPOCK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
ENKD1	physical association	0.560	3
UBA52	physical association	0.400	1
PLXNB3	physical association	0.370	1
VPS4B	association	0.350	1
DSCR9	physical association	0.000	1

BioGRID (21 interactions; top human partners by supporting records): SPOCK3 (Affinity Capture-Western; 2 records), COL14A1 (Affinity Capture-MS), DDX58 (Affinity Capture-RNA), DSCR9 (Two-hybrid), EME1 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), PLXNB3 (Two-hybrid), POP4 (Affinity Capture-MS), RPL23 (Affinity Capture-MS), RPS14 (Affinity Capture-MS), SENP5 (Affinity Capture-MS), SLC25A14 (Affinity Capture-MS), SLC25A16 (Affinity Capture-MS), TEX15 (Affinity Capture-MS), TPRKB (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for SPOCK2: 75 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	3
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 784):

Position(s)	Effect	Δscore	Sites
10:72063163	acceptor_loss	1.0000
10:72066900–72066901	donor_loss	1.0000	5
10:72066904	donor_gain	1.0000
10:72066931	donor_gain	1.0000
10:72067121	acceptor_gain	1.0000
10:72067122	acceptor_loss	1.0000	2
10:72067611	donor_loss	1.0000
10:72067733–72067734	acceptor_loss	1.0000	5
10:72068185–72068186	donor_loss	1.0000	5
10:72072142–72072143	donor_loss	1.0000	5

AlphaMissense

1,133 missense substitutions predicted likely pathogenic (of 2,814 scored), across 238 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
M253	9	0.961	0.995
D258	8	0.989	0.996
D290	8	0.984	0.995
D63	8	0.982	0.996
F215	8	0.982	0.999
F254	8	0.980	1.000
F306	8	0.980	0.999
D151	8	0.973	0.997
F61	8	0.972	0.999
D294	8	0.968	0.994
D213	8	0.967	0.987
F285	8	0.965	0.998
D88	8	0.964	0.993
F286	8	0.954	0.995
D262	8	0.923	0.989
D206	8	0.913	0.965
D68	8	0.910	0.975
D385	8	0.906	0.960
D84	8	0.889	0.963
D67	8	0.858	0.980

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.46e-05
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	3.56e-05
Ovary Serous Cystadenocarcinoma (TCGA)	unfavorable	0.000324
Breast Invasive Carcinoma (TCGA)	favorable	0.000892

Disease associations

OMIM: gene MIM:607988 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST006585_2351	Blood protein levels	3e-17
GCST010796_2786	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8
GCST000937_5	Insulin-like growth factors	5e-7
GCST001539_5	Smoking behavior	8e-7
GCST012255_1	Response to antioxidants and zinc in age-related macular degeneration (disease progression)	3e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004627	IGF-1 measurement
EFO:0004318	smoking behavior
EFO:0004327	electrocardiography
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
bufotalin	decreases expression	1
propionaldehyde	increases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
arsenic disulfide	affects expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzene	increases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Paclitaxel	affects cotreatment, increases expression	1
Antirheumatic Agents	decreases expression	1
Acrylamide	decreases expression	1
p-Chloromercuribenzoic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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