SPINK13

Summary

SPINK13 (serine peptidase inhibitor Kazal type 13, HGNC:27200) is a protein-coding gene on chromosome 5q32, encoding Serine protease inhibitor Kazal-type 13 (Q1W4C9). May be a serine protease inhibitor.

Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of acrosome reaction. Predicted to be located in extracellular region.

Source: NCBI Gene 153218 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001040129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27200
Approved symbol	SPINK13
Name	serine peptidase inhibitor Kazal type 13
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	SPINK5L3, LiESP6, HESPINTOR, MGC149260
Ensembl gene	ENSG00000214510
Ensembl biotype	protein_coding
OMIM	615205
Entrez	153218

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000398450, ENST00000511106, ENST00000512953

RefSeq mRNA: 1 — MANE Select: NM_001040129 NM_001040129

CCDS: CCDS43383

Canonical transcript exons

ENST00000398450 — 5 exons

Exon	Start	End
ENSE00003488626	148270040	148270142
ENSE00003841549	148268794	148268888
ENSE00003848588	148286000	148286255
ENSE00003889602	148274347	148274384
ENSE00003890942	148282104	148282231

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 97.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.3025 / max 238.2065, expressed in 60 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59309	1.0173	57
59307	0.1660	16
59310	0.0692	18
59308	0.0500	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	97.04	gold quality
seminal vesicle	UBERON:0000998	94.10	gold quality
cauda epididymis	UBERON:0004360	90.94	gold quality
adrenal tissue	UBERON:0018303	86.29	gold quality
caput epididymis	UBERON:0004358	76.98	gold quality
sperm	CL:0000019	76.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.67	gold quality
left coronary artery	UBERON:0001626	71.32	gold quality
right adrenal gland	UBERON:0001233	70.18	gold quality
right adrenal gland cortex	UBERON:0035827	69.82	gold quality
left adrenal gland cortex	UBERON:0035825	69.72	gold quality
left adrenal gland	UBERON:0001234	69.32	gold quality
coronary artery	UBERON:0001621	68.69	gold quality
metanephros	UBERON:0000081	68.10	gold quality
adrenal cortex	UBERON:0001235	67.69	gold quality
adrenal gland	UBERON:0002369	67.01	gold quality
popliteal artery	UBERON:0002250	67.00	gold quality
tibial artery	UBERON:0007610	66.96	gold quality
metanephros cortex	UBERON:0010533	66.48	gold quality
mucosa of stomach	UBERON:0001199	65.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	60.20	gold quality
right ovary	UBERON:0002118	59.93	gold quality
right coronary artery	UBERON:0001625	59.31	gold quality
corpus callosum	UBERON:0002336	59.29	gold quality
right testis	UBERON:0004534	58.88	gold quality
body of stomach	UBERON:0001161	58.08	gold quality
cortex of kidney	UBERON:0001225	57.58	gold quality
left ovary	UBERON:0002119	57.22	gold quality
right atrium auricular region	UBERON:0006631	57.01	gold quality
cardiac atrium	UBERON:0002081	56.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.78

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• SPINK13 inhibited cell migration and epithelial to mesenchymal transition (EMT). SPINK13 was found to inhibit the expression of urokinase-type plasminogen activator (uPA), while recombinant uPA protein could reverse the inhibitory effect of SPINK13 on OC metastasis. (PMID:29439245)
• The results of the study indicated that SPINK13 could function as a promising therapeutic approach for patients with advanced hepatocellular carcinoma. (PMID:30862605)
• Gene set enrichment analysis (GSEA) showed that SPINK13 expression was involved in complement, apical junction, epithelial-mesenchymal transition (EMT), glycolysis, hypoxia, and inflammation signaling pathways. (PMID:31825950)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spink13	ENSMUSG00000073551
rattus_norvegicus	Spink13	ENSRNOG00000038793

Paralogs (5): SPINK2 (ENSG00000128040), SPINK7 (ENSG00000145879), SPINK14 (ENSG00000196800), SPINK9 (ENSG00000204909), SPINK8 (ENSG00000229453)

Protein

Protein identifiers

Serine protease inhibitor Kazal-type 13 — Q1W4C9 (reviewed: Q1W4C9)

Alternative names: Hepatitis B virus DNA polymerase transactivated serine protease inhibitor, Hespintor, Serine protease inhibitor Kazal-type 5-like 3

All UniProt accessions (2): A0A9E8LN18, Q1W4C9

UniProt curated annotations — full annotation on UniProt →

Function. May be a serine protease inhibitor. Essential for sperm maturation and fertility. Inhibits sperm acrosome reaction, protecting sperm from premature reaction.

Subcellular location. Secreted.

Isoforms (2)

UniProt ID	Names	Canonical?
Q1W4C9-1	1	yes
Q1W4C9-2	2

RefSeq proteins (1): NP_001035218* (*=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, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q1W4C9-F1	87.17	0.50

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): 55–56 (reactive bond)

Disulfide bonds (3): 39–75, 53–72, 61–93

Glycosylation sites (1): 55

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_ACROSOME_REACTION, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_ACROSOME_REACTION, GOBP_FERTILIZATION, chr5q32, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, CEBPE_TARGET_GENES

GO Biological Process (1): negative regulation of acrosome reaction (GO:1902225)

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
acrosome reaction	1
regulation of acrosome reaction	1
negative regulation of reproductive process	1
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

312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPINK13	D6RI10	D6RI10	629
SPINK13	SPINK14	Q6IE38	607
SPINK13	SPINK7	P58062	571
SPINK13	SPINK9	Q5DT21	542
SPINK13	OR1E1	P30953	520
SPINK13	WFDC8	Q8IUA0	519
SPINK13	SPINK1	P00995	507
SPINK13	SPINK6	Q6UWN8	504
SPINK13	SPINK4	O60575	492
SPINK13	SPATA18	Q8TC71	468
SPINK13	UNC45B	Q8IWX7	460
SPINK13	SPINK5	Q9NQ38	434
SPINK13	FXYD4	P59646	389
SPINK13	SPINK8	P0C7L1	363
SPINK13	COXFA4L2	Q9NRX3	349

IntAct

4 interactions, top by confidence:

A	B	Type	Score
HTT	SPINK13	psi-mi:“MI:0915”(physical association)	0.560

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: D3ZVP0, O35679, P01003, P83579, Q1W4C9, Q3UTS8, Q5DT21, A2ASQ1, A5YT95, D0NJ41, O00468, O60575, O62650, O96790, P00995, P00996, P00997, P00998, P00999, P01000, P01001, P01002, P01005, P04542, P05560, P05561, P05594, P05595, P05596, P05601, P05605, P05617, P08479, P08480, P08481, P09036, P09655, P09656, P0DKM7, P0DKM8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

606 predictions. Top by Δscore:

Variant	Effect	Δscore
5:148282229:GAG:G	donor_gain	0.9800
5:148282103:GCCCC:G	acceptor_gain	0.9700
5:148282102:A:AG	acceptor_gain	0.9500
5:148282103:G:GG	acceptor_gain	0.9500
5:148268884:TCCAG:T	donor_loss	0.8900
5:148268885:CCAG:C	donor_loss	0.8900
5:148268886:CAGG:C	donor_loss	0.8900
5:148268887:AGG:A	donor_loss	0.8900
5:148268888:GGTAA:G	donor_loss	0.8900
5:148268889:GT:G	donor_loss	0.8900
5:148268890:T:G	donor_loss	0.8900
5:148268961:G:GG	donor_gain	0.8900
5:148268960:A:AG	donor_gain	0.8700
5:148282228:AGAG:A	donor_loss	0.8700
5:148282229:GAGG:G	donor_loss	0.8700
5:148282230:AG:A	donor_loss	0.8700
5:148282231:GGTAA:G	donor_loss	0.8700
5:148282232:G:GC	donor_loss	0.8700
5:148282233:TA:T	donor_loss	0.8700
5:148282234:A:AG	donor_loss	0.8700
5:148282236:G:C	donor_loss	0.8700
5:148282098:TTGCA:T	acceptor_loss	0.8600
5:148282099:TGCA:T	acceptor_loss	0.8600
5:148282100:GCA:G	acceptor_loss	0.8600
5:148282101:C:CG	acceptor_loss	0.8600
5:148282102:A:AC	acceptor_loss	0.8600
5:148282235:AG:A	donor_loss	0.8600
5:148280711:GTC:G	donor_gain	0.8500
5:148282092:AT:A	acceptor_loss	0.8500
5:148282093:T:TA	acceptor_loss	0.8500

AlphaMissense

629 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:148282204:A:T	N70I	0.987
5:148282205:T:A	N70K	0.987
5:148282205:T:G	N70K	0.987
5:148282209:T:A	C72S	0.986
5:148282210:G:C	C72S	0.986
5:148282174:T:A	V60D	0.985
5:148282176:T:A	C61S	0.984
5:148282177:G:C	C61S	0.984
5:148282152:T:A	C53S	0.983
5:148282153:G:C	C53S	0.983
5:148282218:T:A	C75S	0.980
5:148282219:G:C	C75S	0.980
5:148286022:T:C	F87L	0.978
5:148286024:T:A	F87L	0.978
5:148286024:T:G	F87L	0.978
5:148282197:T:C	F68L	0.977
5:148282199:C:A	F68L	0.977
5:148282199:C:G	F68L	0.977
5:148286040:T:A	C93S	0.977
5:148286041:G:C	C93S	0.977
5:148286023:T:G	F87C	0.972
5:148282110:T:A	C39S	0.969
5:148282111:G:C	C39S	0.969
5:148282209:T:C	C72R	0.967
5:148282219:G:A	C75Y	0.965
5:148282152:T:C	C53R	0.964
5:148282203:A:T	N70Y	0.958
5:148282218:T:C	C75R	0.953
5:148282176:T:C	C61R	0.950
5:148282198:T:G	F68C	0.950

dbSNP variants (sampled 300 via entrez): RS1000064734 (5:148282744 C>T), RS1000320367 (5:148276346 T>C), RS1000338907 (5:148274561 A>C,T), RS1000494825 (5:148280454 T>A,G), RS1000544760 (5:148278596 A>C,G), RS1000613200 (5:148280211 C>G), RS1000675118 (5:148273125 T>G), RS1000722111 (5:148272758 C>T), RS1000768206 (5:148271538 T>C), RS1001017640 (5:148284734 T>A), RS1001429844 (5:148268709 G>T), RS1001616478 (5:148269326 C>A,T), RS1001672291 (5:148269071 T>C), RS1001895793 (5:148273671 C>A,T), RS1002007315 (5:148267655 G>T)

Disease associations

OMIM: gene MIM:615205 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
NSC 689534	affects binding, increases expression	1
Arsenic	affects methylation	1
Copper	affects binding, increases expression	1
Malathion	decreases expression	1
Progesterone	increases expression	1
Valproic Acid	decreases methylation	1
Cyclosporine	decreases expression	1
Asbestos, Serpentine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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