ZG16

Summary

ZG16 (zymogen granule protein 16, HGNC:30961) is a protein-coding gene on chromosome 16p11.2, encoding Zymogen granule membrane protein 16 (O60844). May play a role in protein trafficking.

Predicted to enable carbohydrate binding activity and peptidoglycan binding activity. Predicted to be involved in protein transport. Predicted to act upstream of or within defense response to Gram-positive bacterium and suppression of symbiont entry into host. Located in Golgi lumen and collagen-containing extracellular matrix.

Source: NCBI Gene 653808 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total — 1 pathogenic
• MANE Select transcript: NM_152338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30961
Approved symbol	ZG16
Name	zymogen granule protein 16
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	hZG16, JCLN1, ZG16A
Ensembl gene	ENSG00000174992
Ensembl biotype	protein_coding
OMIM	617311
Entrez	653808

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000400752, ENST00000897713, ENST00000897714, ENST00000897715, ENST00000953902, ENST00000953903, ENST00000953904, ENST00000953905

RefSeq mRNA: 1 — MANE Select: NM_152338 NM_152338

CCDS: CCDS54000

Canonical transcript exons

ENST00000400752 — 4 exons

Exon	Start	End
ENSE00001618235	29778256	29778306
ENSE00001631391	29779505	29779637
ENSE00001707900	29780104	29782973
ENSE00001794000	29779260	29779321

Expression profiles

Bgee: expression breadth broad, 92 present calls, max score 99.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1841 / max 101.9681, expressed in 19 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153486	0.1841	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	99.79	gold quality
ileal mucosa	UBERON:0000331	99.76	gold quality
colonic mucosa	UBERON:0000317	99.71	gold quality
jejunal mucosa	UBERON:0000399	98.84	gold quality
mucosa of transverse colon	UBERON:0004991	98.34	gold quality
rectum	UBERON:0001052	97.15	gold quality
duodenum	UBERON:0002114	94.96	gold quality
transverse colon	UBERON:0001157	90.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.33	gold quality
small intestine	UBERON:0002108	86.64	gold quality
jejunum	UBERON:0002115	82.99	gold quality
intestine	UBERON:0000160	82.30	gold quality
caecum	UBERON:0001153	81.81	gold quality
large intestine	UBERON:0000059	81.51	gold quality
colon	UBERON:0001155	80.70	gold quality
vermiform appendix	UBERON:0001154	78.87	gold quality
liver	UBERON:0002107	77.30	gold quality
colonic epithelium	UBERON:0000397	74.12	gold quality
right lobe of liver	UBERON:0001114	73.71	gold quality
tendon of biceps brachii	UBERON:0008188	70.50	gold quality
body of pancreas	UBERON:0001150	69.68	gold quality
buccal mucosa cell	CL:0002336	69.11	gold quality
triceps brachii	UBERON:0001509	67.62	gold quality
gluteal muscle	UBERON:0002000	67.19	gold quality
sigmoid colon	UBERON:0001159	66.74	gold quality
epithelial cell of pancreas	CL:0000083	64.50	gold quality
biceps brachii	UBERON:0001507	62.99	gold quality
amniotic fluid	UBERON:0000173	62.53	gold quality
endometrium epithelium	UBERON:0004811	61.77	gold quality
superficial temporal artery	UBERON:0001614	61.16	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	115747.81
E-GEOD-125970	yes	85916.20
E-CURD-88	yes	18242.32
E-MTAB-9543	yes	9229.75
E-ANND-3	yes	5.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting ZG16, 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-4753-3P	99.90	71.03	3786
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-6807-5P	97.51	64.25	1046

Literature-anchored findings (GeneRIF, showing 8)

• hZG16 was markedly down-regulated in hepatocellular carcinoma (HCC) as indicated by RT-PCR. (PMID:17307141)
• the sugar-binding site and the adjacent basic patch of ZG16p and ZG16b cooperatively form a functional glycosaminoglycan-binding site. (PMID:21110947)
• Human ZG16p recognizes pathogenic fungi through non-self polyvalent mannose in the digestive system. (PMID:21893569)
• Pathogen-related glycan microarray analysis identified phosphatidylinositol mono- and di-mannosides (PIM1 and PIM2) as novel ligand candidates of ZG16p. (PMID:25919894)
• Data show that an upstream regulator of zymogen granule protein 16 (ZG16), miR-196a, which was significantly overexpressed in colorectal cancer (CRC) and promotes cell growth and stemness. (PMID:27880730)
• our study demonstrated that ZG16 expression was sequentially reduced from normal, adenoma, to carcinoma. Association with multiple clinicopathological features indicates that ZG16 may play an important role in cancer initiation and progression. ZG16 may serve as a potential biomarker for diagnosis and prognosis of colorectal cancer (PMID:29661177)
• Conformational switches and redox properties of the colon cancer-associated human lectin ZG16. (PMID:34077620)
• ZG16 enhances the maturation of dendritic cells via induction of CD40 and contributes to the antitumor immunity in pancreatic cancer. (PMID:39261658)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zg16	ENSMUSG00000049350
rattus_norvegicus	Zg16	ENSRNOG00000016857

Protein

Protein identifiers

Zymogen granule membrane protein 16 — O60844 (reviewed: O60844)

Alternative names: Secretory lectin ZG16

All UniProt accessions (1): O60844

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in protein trafficking. May act as a linker molecule between the submembranous matrix on the luminal side of zymogen granule membrane (ZGM) and aggregated secretory proteins during granule formation in the TGN.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Zymogen granule lumen. Golgi apparatus lumen.

Tissue specificity. Highly expressed in liver. Detected at lower levels in colon, ileum and jejunum.

Similarity. Belongs to the jacalin lectin family.

RefSeq proteins (1): NP_689551* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001229	Jacalin-like_lectin_dom	Domain
IPR036404	Jacalin-like_lectin_dom_sf	Homologous_superfamily
IPR052321	PolyBind_ProtTraffic	Family

Pfam: PF01419

UniProt features (16 total): strand 9, sequence variant 3, signal peptide 1, chain 1, domain 1, helix 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7O4P	X-RAY DIFFRACTION	1.08
7O88	X-RAY DIFFRACTION	1.2
7O3I	X-RAY DIFFRACTION	1.5
3APA	X-RAY DIFFRACTION	1.65
3VZE	X-RAY DIFFRACTION	1.9
3VY6	X-RAY DIFFRACTION	2
3VY7	X-RAY DIFFRACTION	2.14
3VZG	X-RAY DIFFRACTION	2.7
3VZF	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60844-F1	91.83	0.84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): HNF3ALPHA_Q6, GOCC_SECRETORY_GRANULE, GNF2_HPN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GROSS_HYPOXIA_VIA_ELK3_UP, chr16p11, GNF2_LCAT, CAIRO_HEPATOBLASTOMA_DN, GNF2_HPX, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, SANSOM_APC_TARGETS_DN, SABATES_COLORECTAL_ADENOMA_DN, LEE_LIVER_CANCER_E2F1_DN

GO Biological Process (3): protein transport (GO:0015031), defense response to Gram-positive bacterium (GO:0050830), suppression of symbiont entry into host (GO:0052373)

GO Molecular Function (3): carbohydrate binding (GO:0030246), peptidoglycan binding (GO:0042834), protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), zymogen granule membrane (GO:0042589), mucus layer (GO:0070701), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
cytoplasm	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
defense response to bacterium	1
defense response to symbiont	1
glycosaminoglycan binding	1
Golgi apparatus	1
intracellular organelle lumen	1
secretory granule membrane	1
zymogen granule	1
extracellular region	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZG16	MS4A12	Q9NXJ0	744
ZG16	FCGBP	Q9Y6R7	741
ZG16	CLCA1	A8K7I4	698
ZG16	HORMAD1	Q86X24	694
ZG16	TFF3	Q07654	656
ZG16	AGR2	O95994	631
ZG16	LYPD8	Q6UX82	595
ZG16	SYCN	Q0VAF6	584
ZG16	HIRIP3	Q9BW71	570
ZG16	CLCA4	Q14CN2	555
ZG16	ASPHD1	Q5U4P2	543
ZG16	GUCA2A	Q02747	506
ZG16	FIMP1	Q96LL3	479
ZG16	C16orf54	Q6UWD8	479
ZG16	TMIGD1	Q6UXZ0	479

IntAct

57 interactions, top by confidence:

A	B	Type	Score
SGTA	ZG16	psi-mi:“MI:0915”(physical association)	0.780
ZG16	UBQLN1	psi-mi:“MI:0915”(physical association)	0.780
UBQLN1	ZG16	psi-mi:“MI:0915”(physical association)	0.780
ZG16	PUF60	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	ZG16	psi-mi:“MI:0915”(physical association)	0.560
PUF60	ZG16	psi-mi:“MI:0915”(physical association)	0.560
ZG16	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
ZG16	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
ZG16	SGTB	psi-mi:“MI:0915”(physical association)	0.560
ZG16	CTNNA3	psi-mi:“MI:0915”(physical association)	0.560
ZG16	GLYCTK	psi-mi:“MI:0915”(physical association)	0.560
ZG16	ASPH	psi-mi:“MI:0915”(physical association)	0.560
ZG16	KCNIP3	psi-mi:“MI:0915”(physical association)	0.560
ZG16	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
ZG16		psi-mi:“MI:0915”(physical association)	0.370
ZG16	UBQLN1	psi-mi:“MI:0915”(physical association)	0.000
ZG16	SGTB	psi-mi:“MI:0915”(physical association)	0.000
ZG16	SGTA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): ZG16 (Two-hybrid), ZG16 (Two-hybrid), ZG16 (Two-hybrid), ZG16 (Two-hybrid), ZG16 (Two-hybrid), ZG16 (Two-hybrid), ZG16 (Two-hybrid), ZG16 (Two-hybrid), PUF60 (Two-hybrid), CTNNA3 (Two-hybrid), UBQLN2 (Two-hybrid), SGTB (Two-hybrid), ASPH (Two-hybrid), ZG16 (Two-hybrid), ZG16 (Two-hybrid)

ESM2 similar proteins: A2WMH2, A2WPN7, C0HK14, C0HLR9, C0HM44, D9UBG0, D9UBI3, F4IB94, F4IB95, H3JUC3, O04310, O04311, O04312, O04313, O04314, O04316, O04318, O49326, O60844, O65187, O80948, O80950, O80998, P0C5C6, P18670, P18674, P82859, P82953, P83304, P84801, P93114, P93193, Q0JMY8, Q5U9T2, Q5XF82, Q8CJD3, Q8GWI7, Q8K0C5, Q9FFW6, Q9FFW7

Diamond homologs: O60844, P08723, Q8CJD3, Q8K0C5, Q9SAV1, P15501, Q96DA0, C0HLR9, F4HQX1, P93193

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1180509	GRCh37/hg19 16p11.2(chr16:29615859-30199454)x1	Pathogenic

SpliceAI

471 predictions. Top by Δscore:

Variant	Effect	Δscore
16:29779636:GG:G	donor_gain	1.0000
16:29779637:GG:G	donor_gain	1.0000
16:29780102:A:AG	acceptor_gain	1.0000
16:29780103:G:GA	acceptor_gain	1.0000
16:29780103:GT:G	acceptor_gain	1.0000
16:29780103:GTCT:G	acceptor_gain	1.0000
16:29779503:A:AG	acceptor_gain	0.9900
16:29779504:G:GG	acceptor_gain	0.9900
16:29779528:A:AG	acceptor_gain	0.9900
16:29779529:G:GG	acceptor_gain	0.9900
16:29779529:GTGGA:G	acceptor_gain	0.9900
16:29779633:GTAGG:G	donor_gain	0.9900
16:29779635:AGGGT:A	donor_loss	0.9900
16:29779636:GGGT:G	donor_loss	0.9900
16:29779637:GGTA:G	donor_loss	0.9900
16:29779638:GTAAG:G	donor_loss	0.9900
16:29779639:T:A	donor_loss	0.9900
16:29780103:GTC:G	acceptor_gain	0.9900
16:29779504:GTTCA:G	acceptor_gain	0.9800
16:29779528:AGT:A	acceptor_gain	0.9800
16:29779529:GTG:G	acceptor_gain	0.9800
16:29779322:G:GG	donor_gain	0.9700
16:29780103:GTCTT:G	acceptor_gain	0.9700
16:29778304:CAG:C	donor_loss	0.9600
16:29778305:AGGT:A	donor_loss	0.9600
16:29778307:GTG:G	donor_loss	0.9600
16:29778308:T:G	donor_loss	0.9600
16:29779504:GTT:G	acceptor_gain	0.9600
16:29779529:GT:G	acceptor_gain	0.9600
16:29779638:G:GG	donor_gain	0.9600

AlphaMissense

1068 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:29780369:G:C	A152P	0.992
16:29779561:T:C	F38L	0.991
16:29779563:C:A	F38L	0.991
16:29779563:C:G	F38L	0.991
16:29780386:G:C	W157C	0.991
16:29780386:G:T	W157C	0.991
16:29779600:G:C	A51P	0.990
16:29779607:G:C	R53P	0.990
16:29780129:T:A	W72R	0.989
16:29780129:T:C	W72R	0.989
16:29780131:G:C	W72C	0.989
16:29780131:G:T	W72C	0.989
16:29780132:A:C	S73R	0.988
16:29780134:C:A	S73R	0.988
16:29780134:C:G	S73R	0.988
16:29780331:T:A	L139H	0.986
16:29780384:T:A	W157R	0.986
16:29780384:T:C	W157R	0.986
16:29780297:T:C	F128L	0.983
16:29780299:C:A	F128L	0.983
16:29780299:C:G	F128L	0.983
16:29779613:G:C	R55P	0.982
16:29780277:G:A	G121E	0.980
16:29780115:G:C	R67P	0.979
16:29780298:T:C	F128S	0.979
16:29779541:G:A	G31E	0.978
16:29779562:T:G	F38C	0.978
16:29780205:T:A	V97D	0.977
16:29779562:T:C	F38S	0.976
16:29780106:T:C	L64P	0.976

dbSNP variants (sampled 300 via entrez): RS1001099486 (16:29779180 T>G), RS1001706314 (16:29779313 G>T), RS1002086226 (16:29783216 C>T), RS1002393962 (16:29776456 T>C), RS1002856198 (16:29777782 C>T), RS1002991959 (16:29777980 T>TG), RS1003160779 (16:29781054 A>G), RS1003383810 (16:29780640 A>G,T), RS1004729387 (16:29781693 C>T), RS1005214936 (16:29777928 C>A,T), RS1005432080 (16:29779963 C>A), RS1005842292 (16:29777588 G>A,C), RS1006409334 (16:29783065 A>C), RS1006625544 (16:29776305 A>G), RS1006728545 (16:29778358 G>T)

Disease associations

OMIM: gene MIM:617311 | 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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
methyleugenol	decreases expression	1
sodium arsenite	decreases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Hydrogen Peroxide	affects expression	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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