SPINT3

Summary

SPINT3 (serine peptidase inhibitor, Kunitz type 3, HGNC:11248) is a protein-coding gene on chromosome 20q13.12, encoding Kunitz-type protease inhibitor 3 (P49223).

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

Source: NCBI Gene 10816 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_006652

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11248
Approved symbol	SPINT3
Name	serine peptidase inhibitor, Kunitz type 3
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	HKIB9
Ensembl gene	ENSG00000101446
Ensembl biotype	protein_coding
OMIM	613941
Entrez	10816

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000217428

RefSeq mRNA: 1 — MANE Select: NM_006652 NM_006652

CCDS: CCDS46608

Canonical transcript exons

ENST00000217428 — 2 exons

Exon	Start	End
ENSE00001458359	45515533	45515622
ENSE00001458362	45512461	45512844

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 99.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2612 / max 381.1553, expressed in 6 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187447	0.2555	6
187448	0.0057	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.78	gold quality
sperm	CL:0000019	85.38	gold quality
male germ cell	CL:0000015	84.32	gold quality
seminal vesicle	UBERON:0000998	75.35	gold quality
corpus epididymis	UBERON:0004359	74.99	gold quality
cervix squamous epithelium	UBERON:0006922	69.90	gold quality
caput epididymis	UBERON:0004358	68.03	gold quality
cardiac muscle of right atrium	UBERON:0003379	65.72	gold quality
left ventricle myocardium	UBERON:0006566	65.49	gold quality
myocardium	UBERON:0002349	58.67	gold quality
skin of abdomen	UBERON:0001416	55.74	gold quality
cervix epithelium	UBERON:0004801	54.14	gold quality
endothelial cell	CL:0000115	52.94	gold quality
oviduct epithelium	UBERON:0004804	51.75	gold quality
pancreatic ductal cell	CL:0002079	50.58	silver quality
hair follicle	UBERON:0002073	50.04	gold quality
thymus	UBERON:0002370	49.94	gold quality
epithelial cell of pancreas	CL:0000083	49.57	gold quality
quadriceps femoris	UBERON:0001377	49.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
zone of skin	UBERON:0000014	49.17	gold quality
vastus lateralis	UBERON:0001379	49.13	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
kidney epithelium	UBERON:0004819	47.93	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting SPINT3, 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-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-6796-5P	95.37	66.08	1120

Literature-anchored findings (GeneRIF, showing 1)

• Identifies genes on chromosome 20q12-13.1, including the gene encoding this kunitz domain-containing serine protease inhibitor. (PMID:17589793)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spint3	ENSMUSG00000074596
rattus_norvegicus	Spint3	ENSRNOG00000052294

Protein

Protein identifiers

Kunitz-type protease inhibitor 3 — P49223 (reviewed: P49223)

Alternative names: HKIB9

All UniProt accessions (1): P49223

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

RefSeq proteins (1): NP_006643* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002223	Kunitz_BPTI	Domain
IPR020901	Prtase_inh_Kunz-CS	Conserved_site
IPR036880	Kunitz_BPTI_sf	Homologous_superfamily
IPR050098	TFPI/VKTCI-like	Family

Pfam: PF00014

UniProt features (7 total): disulfide bond 3, signal peptide 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49223-F1	93.13	0.76

Functional residue map

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

Disulfide bonds (3): 36–86, 45–69, 61–82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MARTENS_TRETINOIN_RESPONSE_UP, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, MIR8485, MIR4447, MIR4441, MIR6715B_5P, MIR4270, MIR4269, MIR4472, MIR6754_5P, GSE9946_IMMATURE_VS_PROSTAGLANDINE2_TREATED_MATURE_DC_DN

GO Biological Process (0):

GO Molecular Function (2): serine-type endopeptidase inhibitor activity (GO:0004867), 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
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPINT3	SPINT4	Q6UDR6	587
SPINT3	GLYATL3	Q5SZD4	577
SPINT3	WFDC9	Q8NEX5	542
SPINT3	TEDDM1	Q5T9Z0	514
SPINT3	THAP4	Q8WY91	479
SPINT3	WFDC13	Q8IUB5	434
SPINT3	WFDC10A	Q9H1F0	432
SPINT3	WASHC2C	Q9Y4E1	418
SPINT3	MRTO4	Q9UKD2	380
SPINT3	EMC1	Q8N766	366
SPINT3	RGL1	Q9NZL6	358
SPINT3	WFDC6	Q9BQY6	355
SPINT3	WFDC8	Q8IUA0	329
SPINT3	FARP1	Q9Y4F1	325
SPINT3	CPA2	P48052	323

IntAct

0 interactions, top by confidence:

BioGRID (1): SPINT3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D0BND9, A0A6B7FBD3, A6MFL4, B2G331, B5KL27, B5KL28, B5KL29, B5KL30, B5KL32, B5KL33, B5KL34, B5KL35, B5KL37, B5KL38, B5KL39, B5KL40, B5KL41, B5L5Q1, B5L5Q3, B5L5Q6, E7FL13, G9I929, O35536, P0DJ45, P0DJ50, P0DJ80, P0DJ85, P0DMJ1, P0DMJ5, P0DN06, P0DN07, P0DN09, P0DN10, P0DN11, P0DN12, P0DN13, P0DN14, P0DN15, P0DN16, P0DN17

Diamond homologs: A0A1Z0YU59, A0A6P8HC43, A5X2X1, A6MFL1, A6MFL2, A6MFL3, A6MFL4, A6MGX9, A6MGY1, A7X3V4, A7X3V7, A8Y7N4, A8Y7N5, A8Y7N7, A8Y7N8, A8Y7P0, A8Y7P2, A8Y7P3, A8Y7P4, A8Y7P6, B2KTG1, B4ESA3, B4ESA4, B5G6G6, B5KF94, B5KF95, B5KF96, B5KL30, B5KL33, B5KL34, B5KL35, B5KL36, B5KL39, B5L5M7, B5L5R0, B5L5R4, B5L5R7, B6RLX2, B7S4N9, C0HLA5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

184 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45515529:CAA:C	donor_loss	0.9500
20:45515529:CAACC:C	donor_gain	0.9500
20:45515530:AACCT:A	donor_loss	0.9500
20:45515532:C:CG	donor_loss	0.9500
20:45515528:CCAA:C	donor_gain	0.8900
20:45515530:AACC:A	donor_gain	0.8900
20:45515531:A:T	donor_gain	0.8900
20:45515532:C:G	donor_gain	0.8800
20:45515533:C:G	donor_gain	0.8800
20:45515532:CCT:C	donor_gain	0.8700
20:45512845:C:CC	acceptor_gain	0.8400
20:45512841:GTGT:G	acceptor_gain	0.7500
20:45512842:TGT:T	acceptor_gain	0.6900
20:45513912:T:C	acceptor_gain	0.6500
20:45513912:T:TC	acceptor_gain	0.6500
20:45515531:A:AC	donor_gain	0.6400
20:45515532:C:CC	donor_gain	0.6400
20:45515527:A:AC	donor_gain	0.6200
20:45515528:C:CC	donor_gain	0.6200
20:45515523:T:A	donor_gain	0.6100
20:45512722:C:CT	acceptor_gain	0.5800
20:45512747:A:T	acceptor_gain	0.5500
20:45512843:GTC:G	acceptor_loss	0.5500
20:45512844:TC:T	acceptor_loss	0.5500
20:45512845:C:CA	acceptor_loss	0.5500
20:45512846:T:C	acceptor_loss	0.5500
20:45515534:T:A	donor_gain	0.5500
20:45512847:G:C	acceptor_loss	0.5400
20:45514218:C:CT	acceptor_gain	0.5400
20:45515525:A:T	donor_gain	0.5400

AlphaMissense

581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45512693:A:C	F76L	0.995
20:45512693:A:T	F76L	0.995
20:45512694:A:C	F76C	0.995
20:45512695:A:G	F76L	0.995
20:45512729:A:C	F64L	0.994
20:45512729:A:T	F64L	0.994
20:45512731:A:G	F64L	0.994
20:45512769:C:G	R51P	0.994
20:45512730:A:C	F64C	0.993
20:45512762:A:C	F53L	0.993
20:45512762:A:T	F53L	0.993
20:45512764:A:G	F53L	0.993
20:45512700:T:A	N74I	0.992
20:45512739:C:G	C61S	0.992
20:45512740:A:T	C61S	0.992
20:45512794:C:A	G43C	0.992
20:45512694:A:G	F76S	0.991
20:45512699:G:C	N74K	0.990
20:45512699:G:T	N74K	0.990
20:45512765:C:A	W52C	0.988
20:45512765:C:G	W52C	0.988
20:45512814:C:G	C36S	0.988
20:45512815:A:T	C36S	0.988
20:45512664:C:G	C86S	0.987
20:45512665:A:T	C86S	0.987
20:45512759:G:C	F54L	0.987
20:45512759:G:T	F54L	0.987
20:45512761:A:G	F54L	0.987
20:45512676:C:G	C82S	0.986
20:45512677:A:T	C82S	0.986

dbSNP variants (sampled 300 via entrez): RS1000320754 (20:45516317 C>A), RS1000395980 (20:45516566 G>A), RS1000660171 (20:45514886 A>T), RS1002207839 (20:45515315 G>C), RS1003292956 (20:45517004 A>G), RS1003861967 (20:45513078 T>C), RS1004570130 (20:45514308 G>A), RS1004624060 (20:45515844 T>C), RS1005218325 (20:45517320 C>A,T), RS1005505683 (20:45514355 G>A), RS1006650302 (20:45517449 T>A,C), RS1006755437 (20:45515274 G>A,T), RS1008825005 (20:45516899 A>G,T), RS1009315647 (20:45516348 T>C), RS1009759396 (20:45516605 C>T)

Disease associations

OMIM: gene MIM:613941 | disease phenotypes: MIM:600057

GenCC curated gene-disease

Mondo (1): bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039)

Orphanet (1): Classic bladder exstrophy (Orphanet:93930)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000597_8	Brain structure	9.000000e-07
GCST006585_1566	Blood protein levels	3.000000e-76

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
2-palmitoylglycerol	increases expression	1
Acetaminophen	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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