SPINK14

Summary

SPINK14 (serine peptidase inhibitor Kazal type 14 (putative), HGNC:33825) is a protein-coding gene on chromosome 5q32, encoding Serine protease inhibitor Kazal-type 14 (Q6IE38). May be a serine protease inhibitor.

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

Source: NCBI Gene 408187 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_001001325

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33825
Approved symbol	SPINK14
Name	serine peptidase inhibitor Kazal type 14 (putative)
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	SPINK5L2
Ensembl gene	ENSG00000196800
Ensembl biotype	protein_coding
Entrez	408187

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000356972, ENST00000562793

RefSeq mRNA: 1 — MANE Select: NM_001001325 NM_001001325

CCDS: CCDS4288

Canonical transcript exons

ENST00000356972 — 5 exons

Exon	Start	End
ENSE00001408596	148170930	148170973
ENSE00001428035	148174234	148174370
ENSE00003574452	148175353	148175619
ENSE00003923533	148168546	148168567
ENSE00003926433	148169661	148169799

Expression profiles

Bgee: expression breadth broad, 72 present calls, max score 83.94.

Top tissues by expression

121 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	83.94	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.06	gold quality
corpus callosum	UBERON:0002336	64.71	gold quality
mucosa of transverse colon	UBERON:0004991	60.36	gold quality
rectum	UBERON:0001052	60.03	gold quality
lower esophagus mucosa	UBERON:0035834	58.11	gold quality
sural nerve	UBERON:0015488	44.02	gold quality
minor salivary gland	UBERON:0001830	42.46	gold quality
saliva-secreting gland	UBERON:0001044	41.91	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
adrenal tissue	UBERON:0018303	37.08	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
prostate gland	UBERON:0002367	34.46	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
body of stomach	UBERON:0001161	32.62	gold quality
liver	UBERON:0002107	32.36	gold quality
transverse colon	UBERON:0001157	32.30	gold quality
stomach	UBERON:0000945	32.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
gall bladder	UBERON:0002110	31.85	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
right lobe of thyroid gland	UBERON:0001119	31.40	gold quality
urinary bladder	UBERON:0001255	31.22	gold quality
monocyte	CL:0000576	31.18	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
upper lobe of left lung	UBERON:0008952	31.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting SPINK14, 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-4533	100.00	69.48	2758
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-7705	98.69	67.47	543
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-3162-5P	95.67	67.53	794
HSA-MIR-518A-3P	93.85	64.90	108
HSA-MIR-518B	93.85	64.62	111
HSA-MIR-518C-3P	93.85	64.62	111
HSA-MIR-518D-3P	93.85	64.59	111
HSA-MIR-518F-3P	93.85	64.93	108
HSA-MIR-526A-3P	93.85	65.32	108

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spink14	ENSMUSG00000051050
rattus_norvegicus	Spink14	ENSRNOG00000028902

Paralogs (5): SPINK2 (ENSG00000128040), SPINK7 (ENSG00000145879), SPINK9 (ENSG00000204909), SPINK13 (ENSG00000214510), SPINK8 (ENSG00000229453)

Protein

Protein identifiers

Serine protease inhibitor Kazal-type 14 — Q6IE38 (reviewed: Q6IE38)

All UniProt accessions (2): Q6IE38, H3BT63

UniProt curated annotations — full annotation on UniProt →

Function. May be a serine protease inhibitor.

Subcellular location. Secreted.

RefSeq proteins (1): NP_001001325* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002350	Kazal_dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR050159	Kazal-type_SerProtInhib	Family

Pfam: PF00050

UniProt features (8 total): disulfide bond 3, signal peptide 1, chain 1, domain 1, site 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IE38-F1	81.44	0.38

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): 59–60 (reactive bond)

Disulfide bonds (3): 40–79, 57–76, 65–97

Glycosylation sites (1): 51

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 26 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_REGULATION_OF_PROTEOLYSIS, chr5q32, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, MIR4533, MIR766_5P

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

266 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPINK14	SPINK9	Q5DT21	729
SPINK14	OR1E1	P30953	648
SPINK14	SPINK13	Q1W4C9	607
SPINK14	SPINK6	Q6UWN8	599
SPINK14	FXYD4	P59646	594
SPINK14	PILRA	Q9UKJ1	541
SPINK14	COXFA4L2	Q9NRX3	532
SPINK14	SPATA18	Q8TC71	527
SPINK14	DSTYK	Q6XUX3	524
SPINK14	UNC45B	Q8IWX7	515
SPINK14	TTC23L	Q6PF05	506
SPINK14	GLB1L3	Q8NCI6	481
SPINK14	KCNMB3	Q9NPA1	464
SPINK14	SPINK8	P0C7L1	454
SPINK14	CIBAR2	Q6ZTR7	443

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SPINK14	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): UBR3 (Affinity Capture-MS), PLTP (Affinity Capture-MS), WDR60 (Affinity Capture-MS), FAM175B (Affinity Capture-MS), RNF123 (Affinity Capture-MS), ZER1 (Affinity Capture-MS), BRE (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), PPM1A (Affinity Capture-MS), IDE (Affinity Capture-MS), PITRM1 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), SPINK14 (Positive Genetic)

ESM2 similar proteins: A0A384E0Y8, A0A6I8RMG7, A0JNQ7, A9JSD6, A9XFZ7, B3F211, B7XFU7, D3ZVN1, O70367, O75711, O88745, O96049, P02703, P02704, P02705, P04118, P08162, P08163, P0DQT9, P0DQU0, P11858, P15211, P17084, P18313, P19090, P30970, P35455, P42889, P42890, P51499, P53542, Q07663, Q27023, Q3UW21, Q3YC03, Q5BQU9, Q5D231, Q6DDW2, Q6IE38, Q6UWE3

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

411 predictions. Top by Δscore:

Variant	Effect	Δscore
5:148170927:TA:T	acceptor_loss	0.9900
5:148170928:A:AG	acceptor_gain	0.9900
5:148170929:G:GG	acceptor_gain	0.9900
5:148174003:GC:G	donor_gain	0.9900
5:148170970:TAAG:T	donor_loss	0.9800
5:148170970:TAAGG:T	acceptor_loss	0.9800
5:148170971:AAG:A	donor_loss	0.9800
5:148170973:GG:G	donor_loss	0.9800
5:148170971:AAGGT:A	acceptor_loss	0.9700
5:148170972:AGGTA:A	acceptor_loss	0.9700
5:148170974:G:T	acceptor_loss	0.9700
5:148171855:C:G	donor_gain	0.9700
5:148170973:GGTAA:G	acceptor_loss	0.9600
5:148174228:TTTCA:T	acceptor_loss	0.9500
5:148174229:TTCAG:T	acceptor_loss	0.9500
5:148174230:TCAGG:T	acceptor_loss	0.9500
5:148174231:CAGGT:C	acceptor_loss	0.9500
5:148174232:AG:A	acceptor_loss	0.9500
5:148174233:G:T	acceptor_loss	0.9500
5:148169799:GGT:G	donor_loss	0.9400
5:148169800:G:T	donor_loss	0.9400
5:148169801:T:A	donor_loss	0.9400
5:148170975:T:G	acceptor_loss	0.9400
5:148171895:GA:G	donor_gain	0.9400
5:148169802:GAG:G	donor_loss	0.9300
5:148170969:TTAAG:T	acceptor_loss	0.9300
5:148169803:AGT:A	donor_loss	0.9100
5:148169800:G:GG	donor_gain	0.9000
5:148174367:GCTT:G	donor_gain	0.8600
5:148173938:TC:T	donor_gain	0.8500

AlphaMissense

628 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:148175393:T:A	C97S	0.972
5:148175394:G:C	C97S	0.972
5:148175393:T:C	C97R	0.965
5:148174315:T:A	C65S	0.958
5:148174316:G:C	C65S	0.958
5:148174344:T:A	N74K	0.957
5:148174344:T:G	N74K	0.957
5:148174357:T:A	C79S	0.955
5:148174358:G:C	C79S	0.955
5:148174291:T:A	C57S	0.953
5:148174292:G:C	C57S	0.953
5:148175395:T:G	C97W	0.951
5:148174240:T:A	C40S	0.945
5:148174241:G:C	C40S	0.945
5:148174357:T:C	C79R	0.945
5:148174316:G:A	C65Y	0.938
5:148174348:T:A	C76S	0.938
5:148174349:G:C	C76S	0.938
5:148174291:T:C	C57R	0.933
5:148174366:A:C	S82R	0.932
5:148174368:C:A	S82R	0.932
5:148174368:C:G	S82R	0.932
5:148175357:T:C	S85P	0.931
5:148174315:T:C	C65R	0.929
5:148174355:T:C	L78P	0.928
5:148174319:G:A	G66D	0.927
5:148174240:T:C	C40R	0.924
5:148174336:T:G	Y72D	0.924
5:148174348:T:C	C76R	0.924
5:148174358:G:A	C79Y	0.924

dbSNP variants (sampled 300 via entrez): RS1000078784 (5:148171058 G>A), RS1000998913 (5:148172651 T>C), RS1001196909 (5:148169552 A>G), RS1001355724 (5:148171777 T>C), RS1001670897 (5:148169918 GTA>G,GTATA), RS1001831085 (5:148172125 A>G), RS1003377170 (5:148175987 C>T), RS1003754131 (5:148167031 C>T), RS1003771430 (5:148175418 G>A,T), RS1005168563 (5:148167094 T>A,C), RS10052031 (5:148175326 A>C,T), RS1005675185 (5:148173063 G>A,C), RS1005760776 (5:148166773 G>C), RS1006121954 (5:148173375 G>A,T), RS1006188927 (5:148167442 T>C)

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

2 associations (top):

Study	Trait	p-value
GCST003265_226	Post bronchodilator FEV1/FVC ratio in COPD	5.000000e-06
GCST003265_338	Post bronchodilator FEV1/FVC ratio in COPD	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9285669	SPINK14	3	0.00	1	hydrochlorothiazide

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
CGP 52608	increases reaction, affects binding	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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