SPINT4

Summary

SPINT4 (serine peptidase inhibitor, Kunitz type 4, HGNC:16130) is a protein-coding gene on chromosome 20q13.12, encoding Kunitz-type protease inhibitor 4 (Q6UDR6).

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

Source: NCBI Gene 391253 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_178455

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16130
Approved symbol	SPINT4
Name	serine peptidase inhibitor, Kunitz type 4
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ601O1.1
Ensembl gene	ENSG00000149651
Ensembl biotype	protein_coding
OMIM	619430
Entrez	391253

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000279058

RefSeq mRNA: 1 — MANE Select: NM_178455 NM_178455

CCDS: CCDS33477

Canonical transcript exons

ENST00000279058 — 3 exons

Exon	Start	End
ENSE00000991809	45722347	45722482
ENSE00000991810	45723880	45724057
ENSE00001401484	45725629	45725830

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 40.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3351 / max 537.0920, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184936	0.3351	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
urinary bladder	UBERON:0001255	40.98	gold quality
calcaneal tendon	UBERON:0003701	40.09	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
corpus callosum	UBERON:0002336	36.51	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
sural nerve	UBERON:0015488	36.36	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
right coronary artery	UBERON:0001625	31.21	silver quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
skin of leg	UBERON:0001511	29.68	silver quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
liver	UBERON:0002107	28.95	silver quality
zone of skin	UBERON:0000014	28.71	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
skin of abdomen	UBERON:0001416	27.30	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
blood	UBERON:0000178	26.47	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
leukocyte	CL:0000738	25.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.46

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• We propose that the evolution of WFDC8 and SPINT4 has been shaped by complex selective scenarios due to the interdependence of variant fitness and ecological variables. (PMID:21536719)

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	spint1b	ENSDARG00000012467
danio_rerio	lrp11	ENSDARG00000034076
danio_rerio	tfpil	ENSDARG00000089361
danio_rerio	si:dkeyp-73b11.8	ENSDARG00000090185
danio_rerio	wfikkn1	ENSDARG00000101364
danio_rerio	spint1a	ENSDARG00000102332
mus_musculus	Spint4	ENSMUSG00000017310
rattus_norvegicus	Spint4	ENSRNOG00000014794
drosophila_melanogaster	CG7565	FBGN0035833
caenorhabditis_elegans		WBGENE00008304
caenorhabditis_elegans		WBGENE00008449
caenorhabditis_elegans		WBGENE00009386
caenorhabditis_elegans		WBGENE00010792
caenorhabditis_elegans		WBGENE00012186
caenorhabditis_elegans		WBGENE00012814
caenorhabditis_elegans		WBGENE00015355
caenorhabditis_elegans		WBGENE00020648
caenorhabditis_elegans		WBGENE00021939

Paralogs (13): TFPI (ENSG00000003436), EPPIN (ENSG00000101448), TFPI2 (ENSG00000105825), AMBP (ENSG00000106927), LRP11 (ENSG00000120256), WFIKKN1 (ENSG00000127578), KIAA0319 (ENSG00000137261), KIAA0319L (ENSG00000142687), WFDC8 (ENSG00000158901), SPINT1 (ENSG00000166145), SPINT2 (ENSG00000167642), WFIKKN2 (ENSG00000173714), WFDC6 (ENSG00000243543)

Protein

Protein identifiers

Kunitz-type protease inhibitor 4 — Q6UDR6 (reviewed: Q6UDR6)

All UniProt accessions (2): Q6UDR6, A0A384P5R1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

RefSeq proteins (1): NP_848550* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002223	Kunitz_BPTI	Domain
IPR036880	Kunitz_BPTI_sf	Homologous_superfamily
IPR042943	SPINT4	Family

Pfam: PF00014

UniProt features (7 total): disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UDR6-F1	91.38	0.68

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 (2): 41–91, 50–74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, DELACROIX_RAR_BOUND_ES, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, GSE7596_AKT_TRANSD_VS_CTRL_CD4_TCONV_WITH_TGFB_DN, GOMF_MOLECULAR_FUNCTION_INHIBITOR_ACTIVITY, GOMF_PEPTIDASE_INHIBITOR_ACTIVITY, GSE2770_TGFB_AND_IL4_VS_IL4_TREATED_ACT_CD4_TCELL_2H_DN, chr20q13, GSE3203_WT_VS_IFNAR1_KO_INFLUENZA_INFECTED_LN_BCELL_UP, GSE23505_IL6_IL1_VS_IL6_IL1_IL23_TREATED_CD4_TCELL_UP, GSE32986_GMCSF_VS_GMCSF_AND_CURDLAN_HIGHDOSE_STIM_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

212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPINT4	WFDC6	Q9BQY6	810
SPINT4	WFDC8	Q8IUA0	809
SPINT4	EPPIN	O95925	717
SPINT4	WFDC13	Q8IUB5	715
SPINT4	WFDC10B	Q8IUB3	642
SPINT4	WFDC10A	Q9H1F0	620
SPINT4	SEMG1	P04279	595
SPINT4	SPINT3	P49223	587
SPINT4	LCN9	Q8WX39	582
SPINT4	WFDC9	Q8NEX5	571
SPINT4	SEMG2	Q02383	568
SPINT4	WFDC3	Q8IUB2	544
SPINT4	PP2D1	A8MPX8	507
SPINT4	CES5A	Q6NT32	449
SPINT4	DEFB128	Q7Z7B8	447
SPINT4	DEFB127	Q9H1M4	447

IntAct

0 interactions, top by confidence:

BioGRID (1): SPINT4 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1Q1NL17, A0A346CIA0, A7X3V0, B6DCX0, B6DCX1, C0HMD5, C5H8E7, C9X4K7, C9X4K8, D3GGZ8, D5HR51, D9U298, D9U2A5, E7D082, H1ZZI3, P01484, P01491, P04815, P0CI54, P0CI82, P0DN01, P0DQG2, P0DQG5, P0DUI2, P15223, P45665, P56637, P82628, P84688, P86404, P86405, Q09JW3, Q09TK7, Q1I180, Q29143, Q68PG3, Q6UDR6, Q7Z096, Q8MVC4, Q8MVZ2

Diamond homologs: A0A1D0BND9, A0A6P8HC43, A5X2X1, A7X3V7, B2KTG1, B5G6G6, B5KL37, B5L5M7, B5L5R0, B6ZIW0, B7S4N9, C0HLB2, C1IBY4, C1IC53, C8YJ94, C8YJ95, D5J9Q8, E5AJX3, F5GTK6, F6ULY1, I2G9B4, O35536, O54819, O62845, O76840, O95925, P00976, P00978, P00979, P00980, P00992, P00993, P02760, P04365, P04366, P0DJ48, P0DJ50, P0DKL8, P0DMJ2, P0DMJ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

272 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45722483:G:T	donor_loss	0.9900
20:45722491:C:G	donor_gain	0.9900
20:45724025:TG:T	donor_gain	0.9900
20:45724058:G:GG	donor_gain	0.9900
20:45724026:G:GT	donor_gain	0.9800
20:45724026:GA:G	donor_gain	0.9800
20:45724027:AA:A	donor_gain	0.9800
20:45724053:CCACC:C	donor_gain	0.9700
20:45724056:CC:C	donor_gain	0.9700
20:45725626:CAGG:C	acceptor_gain	0.9700
20:45725627:AGGA:A	acceptor_gain	0.9700
20:45725628:GGAG:G	acceptor_gain	0.9700
20:45725628:GGA:G	acceptor_gain	0.9500
20:45722440:G:GA	donor_gain	0.9400
20:45724023:C:G	donor_gain	0.9400
20:45724093:T:TA	donor_gain	0.9300
20:45724094:A:AA	donor_gain	0.9300
20:45725618:T:TA	acceptor_gain	0.9300
20:45725627:A:AG	acceptor_gain	0.9300
20:45725628:G:GG	acceptor_gain	0.9300
20:45724063:G:GT	donor_gain	0.9100
20:45725624:A:G	acceptor_gain	0.9100
20:45725627:AGGAG:A	acceptor_gain	0.8900
20:45725628:GGAGG:G	acceptor_gain	0.8900
20:45722464:A:G	donor_gain	0.8800
20:45722483:G:GG	donor_gain	0.8800
20:45724055:ACC:A	donor_gain	0.8700
20:45725623:A:AG	acceptor_gain	0.8700
20:45724054:CACC:C	donor_gain	0.8600
20:45725627:AG:A	acceptor_gain	0.8600

AlphaMissense

656 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45723975:T:C	F71L	0.976
20:45723977:C:A	F71L	0.976
20:45723977:C:G	F71L	0.976
20:45723969:T:C	F69L	0.955
20:45723971:T:A	F69L	0.955
20:45723971:T:G	F69L	0.955
20:45723936:T:C	F58L	0.952
20:45723938:C:A	F58L	0.952
20:45723938:C:G	F58L	0.952
20:45724005:T:C	F81L	0.944
20:45724007:C:A	F81L	0.944
20:45724007:C:G	F81L	0.944
20:45723976:T:G	F71C	0.870
20:45724006:T:G	F81C	0.841
20:45723975:T:A	F71I	0.839
20:45723975:T:G	F71V	0.829
20:45723970:T:G	F69C	0.817
20:45723976:T:C	F71S	0.816
20:45723932:A:C	R56S	0.803
20:45723932:A:T	R56S	0.803
20:45724006:T:C	F81S	0.798
20:45724000:A:T	N79I	0.779
20:45723927:T:C	F55L	0.762
20:45723929:T:A	F55L	0.762
20:45723929:T:G	F55L	0.762
20:45724001:C:A	N79K	0.746
20:45724001:C:G	N79K	0.746
20:45723951:T:C	S63P	0.742
20:45723907:G:A	G48E	0.735
20:45723984:T:A	C74S	0.699

dbSNP variants (sampled 300 via entrez): RS1000264752 (20:45724182 A>G,T), RS1001296615 (20:45724887 G>A), RS1001702050 (20:45722125 C>G,T), RS1001767368 (20:45724560 A>T), RS1004040410 (20:45720918 G>A), RS1004050211 (20:45720671 C>T), RS1005977511 (20:45721525 G>T), RS1006384020 (20:45722467 T>C), RS1006394144 (20:45722140 T>G), RS1007637767 (20:45722615 C>G,T), RS1008101515 (20:45725422 T>G), RS1008172477 (20:45725129 G>A,C), RS1008674736 (20:45726099 C>T), RS1009937074 (20:45724528 A>C), RS1009958315 (20:45721683 G>T)

Disease associations

OMIM: gene MIM:619430 | 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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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