SPINK8

Summary

SPINK8 (serine peptidase inhibitor Kazal type 8 (putative), HGNC:33160) is a protein-coding gene on chromosome 3p21.31, encoding Serine protease inhibitor Kazal-type 8 (P0C7L1). Probable serine protease inhibitor.

Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be located in extracellular region.

Source: NCBI Gene 646424 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_001080525

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33160
Approved symbol	SPINK8
Name	serine peptidase inhibitor Kazal type 8 (putative)
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000229453
Ensembl biotype	protein_coding
Entrez	646424

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000434006, ENST00000944525

RefSeq mRNA: 1 — MANE Select: NM_001080525 NM_001080525

CCDS: CCDS46822

Canonical transcript exons

ENST00000434006 — 8 exons

Exon	Start	End
ENSE00001607892	48319497	48319618
ENSE00001647485	48328275	48328354
ENSE00001705286	48321025	48321074
ENSE00001724206	48306842	48307003
ENSE00001784716	48309904	48309946
ENSE00003924019	48333535	48333661
ENSE00003927527	48332366	48332471
ENSE00003931667	48329153	48329274

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 93.52.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.21	gold quality
lower esophagus mucosa	UBERON:0035834	76.76	gold quality
ganglionic eminence	UBERON:0004023	68.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	67.53	gold quality
ventricular zone	UBERON:0003053	66.77	gold quality
esophagus mucosa	UBERON:0002469	66.61	gold quality
bone marrow	UBERON:0002371	65.17	gold quality
blood	UBERON:0000178	64.86	gold quality
Ammon’s horn	UBERON:0001954	64.23	gold quality
granulocyte	CL:0000094	62.28	gold quality
hypothalamus	UBERON:0001898	60.77	gold quality
substantia nigra	UBERON:0002038	60.35	gold quality
amygdala	UBERON:0001876	60.16	gold quality
temporal lobe	UBERON:0001871	59.69	gold quality
primary visual cortex	UBERON:0002436	57.53	gold quality
spleen	UBERON:0002106	56.33	gold quality
putamen	UBERON:0001874	54.34	gold quality
anterior cingulate cortex	UBERON:0009835	53.62	gold quality
cerebellar hemisphere	UBERON:0002245	53.56	gold quality
cerebellar cortex	UBERON:0002129	53.08	gold quality
brain	UBERON:0000955	53.07	gold quality
cerebellum	UBERON:0002037	53.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	52.93	gold quality
caudate nucleus	UBERON:0001873	52.74	gold quality
cerebral cortex	UBERON:0000956	52.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	52.24	gold quality
corpus callosum	UBERON:0002336	51.54	gold quality
bone marrow cell	CL:0002092	51.33	silver quality
body of pancreas	UBERON:0001150	50.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting SPINK8, 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-5696	99.98	72.36	4487
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-640	98.44	66.93	644
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-15B-3P	97.85	66.68	974

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spink8	ENSMUSG00000050074
rattus_norvegicus	Spink8	ENSRNOG00000037199

Paralogs (5): SPINK2 (ENSG00000128040), SPINK7 (ENSG00000145879), SPINK14 (ENSG00000196800), SPINK9 (ENSG00000204909), SPINK13 (ENSG00000214510)

Protein

Protein identifiers

Serine protease inhibitor Kazal-type 8 — P0C7L1 (reviewed: P0C7L1)

All UniProt accessions (1): P0C7L1

UniProt curated annotations — full annotation on UniProt →

Function. Probable serine protease inhibitor.

Subcellular location. Secreted.

RefSeq proteins (1): NP_001073994* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002350	Kazal_dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily

Pfam: PF00050

UniProt features (9 total): disulfide bond 3, signal peptide 1, chain 1, domain 1, site 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C7L1-F1	80.58	0.41

Functional residue map

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

Catalytic / active sites (1): 51–52 (reactive bond)

Disulfide bonds (3): 42–76, 49–73, 62–94

Glycosylation sites (1): 85

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, chr3p21, MIR5696, MIR4729, MIR4709_3P, MIR222_5P, MIR329_5P, MIR516B_5P, MIR10526_3P, MIR15B_3P

GO Biological Process (0):

GO Molecular Function (3): serine-type endopeptidase inhibitor activity (GO:0004867), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPINK8	SPINK7	P58062	509
SPINK8	PNOC	Q13519	476
SPINK8	CAMSAP2	Q08AD1	456
SPINK8	SPINK14	Q6IE38	454
SPINK8	USP43	Q70EL4	439
SPINK8	REG4	Q9BYZ8	426
SPINK8	CC2D1B	Q5T0F9	406
SPINK8	KRT73	Q86Y46	398
SPINK8	VWC2	Q2TAL6	384
SPINK8	SPINK6	Q6UWN8	378
SPINK8	ARAP2	Q8WZ64	373
SPINK8	SPINK9	Q5DT21	372
SPINK8	ADAMTS14	Q8WXS8	368
SPINK8	MAB21L4	Q08AI8	368
SPINK8	CRCT1	Q9UGL9	365
SPINK8	DBNDD1	Q9H9R9	365

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A3G5BID2, B4QW11, B5M0W4, D0MVC9, D2CFI7, D3GGZ8, D3ZVP0, E9Q6D8, F5GTK6, O54819, O62247, O97176, P01002, P01003, P01005, P04542, P07701, P08481, P09036, P09655, P09656, P0C7L1, P0DN15, P0DN16, P0DQG8, P10646, P13671, P15358, P19761, P26461, P61134, P61135, P83579, Q02445, Q09TK7, Q11101, Q177W0, Q18206, Q1W4C9, Q20930

Diamond homologs: A2ASQ1, A5YT95, D3ZVP0, O35679, O60575, O62650, O95633, P00995, P00996, P00997, P00998, P01003, P01005, P04542, P05560, P09036, P09655, P09656, P0C7L1, P0DKM8, P0DKM9, P0DKT1, P0DKT2, P0DKT3, P0DKT4, P0DKT5, P10184, P10669, P11706, P16226, P19883, P20155, P21674, P25304, P31514, P31696, P34953, P37109, P47931, P50291

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

847 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48328269:A:C	donor_gain	0.9900
3:48328271:TCA:T	donor_loss	0.9900
3:48328272:CA:C	donor_loss	0.9900
3:48328273:A:AC	donor_gain	0.9900
3:48328273:A:C	donor_loss	0.9900
3:48328274:C:CC	donor_gain	0.9900
3:48309903:C:CC	donor_gain	0.9800
3:48328269:ACTC:A	donor_loss	0.9800
3:48328274:CCA:C	donor_gain	0.9800
3:48328274:CCAA:C	donor_gain	0.9800
3:48319495:A:AC	donor_gain	0.9600
3:48319496:C:CC	donor_gain	0.9600
3:48328273:AC:A	donor_gain	0.9600
3:48328274:CC:C	donor_gain	0.9600
3:48309903:CACA:C	donor_gain	0.9200
3:48314185:C:A	donor_gain	0.9200
3:48328274:CCAAT:C	donor_gain	0.9200
3:48321023:A:AC	donor_gain	0.9000
3:48321024:CTA:C	donor_gain	0.8900
3:48321024:CTATT:C	donor_gain	0.8900
3:48309947:C:CC	acceptor_gain	0.8600
3:48319464:T:C	acceptor_gain	0.8600
3:48316352:A:AC	donor_gain	0.8500
3:48307014:AGTAT:A	acceptor_gain	0.8200
3:48319496:CAGA:C	donor_gain	0.8100
3:48321732:TGA:T	donor_gain	0.8100
3:48307001:TTCC:T	acceptor_loss	0.7900
3:48307006:G:C	acceptor_loss	0.7900
3:48309895:TTTAC:T	donor_loss	0.7900
3:48309899:CTTA:C	donor_loss	0.7900

AlphaMissense

646 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48319551:C:G	C62S	0.973
3:48319552:A:T	C62S	0.973
3:48309905:C:G	C94S	0.964
3:48309906:A:T	C94S	0.964
3:48319548:C:T	G63D	0.947
3:48319518:C:G	C73S	0.944
3:48319519:A:T	C73S	0.944
3:48319512:A:G	L75P	0.940
3:48319509:C:G	C76S	0.936
3:48319510:A:T	C76S	0.936
3:48319551:C:T	C62Y	0.931
3:48319610:G:C	C42W	0.929
3:48319519:A:G	C73R	0.927
3:48319542:T:G	D65A	0.926
3:48319550:A:C	C62W	0.926
3:48319611:C:G	C42S	0.922
3:48319612:A:T	C42S	0.922
3:48319552:A:G	C62R	0.921
3:48319543:C:G	D65H	0.917
3:48319531:A:C	Y69D	0.912
3:48319552:A:C	C62G	0.910
3:48319508:G:C	C76W	0.909
3:48319542:T:A	D65V	0.909
3:48309904:A:C	C94W	0.908
3:48319510:A:G	C76R	0.908
3:48319517:G:C	C73W	0.908
3:48309906:A:G	C94R	0.907
3:48319530:T:C	Y69C	0.906
3:48319612:A:G	C42R	0.906
3:48319518:C:T	C73Y	0.904

dbSNP variants (sampled 300 via entrez): RS1000086144 (3:48318574 C>T), RS1000153344 (3:48317263 C>A,T), RS1000196982 (3:48311703 A>C), RS1000429565 (3:48314394 C>T), RS1000476068 (3:48330465 G>A), RS1000521238 (3:48335501 G>A), RS1000532727 (3:48313420 T>C), RS1000921719 (3:48320150 A>C,G), RS1001107280 (3:48325752 C>A,G), RS1001297037 (3:48329694 T>C), RS1001442564 (3:48327559 G>C), RS1001515326 (3:48310550 T>G), RS1001554965 (3:48327869 A>G), RS1002070919 (3:48321816 A>G), RS1002358113 (3:48321584 G>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
GCST010242_31	HDL cholesterol levels	7.000000e-16
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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