ZNG1C

Summary

ZNG1C (Zn regulated GTPase metalloprotein activator 1C, HGNC:18519) is a protein-coding gene on chromosome 9q21.11, encoding Zinc-regulated GTPase metalloprotein activator 1C (Q5JTY5). Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them.

Predicted to enable GTP binding activity; hydrolase activity; and metal ion binding activity. Predicted to be located in nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 445571 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_201453

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18519
Approved symbol	ZNG1C
Name	Zn regulated GTPase metalloprotein activator 1C
Location	9q21.11
Locus type	gene with protein product
Status	Approved
Aliases	bA561O23.1
Ensembl gene	ENSG00000196873
Ensembl biotype	protein_coding
OMIM	611080
Entrez	445571

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 19 protein_coding, 8 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000360171, ENST00000377342, ENST00000377344, ENST00000377349, ENST00000469687, ENST00000478048, ENST00000611426, ENST00000612050, ENST00000614377, ENST00000614398, ENST00000615061, ENST00000616550, ENST00000618217, ENST00000618921, ENST00000619322, ENST00000621396, ENST00000621474, ENST00000622755, ENST00000622817, ENST00000890596, ENST00000890597, ENST00000890598, ENST00000890599, ENST00000890600, ENST00000937634, ENST00000937635, ENST00000937636, ENST00000956223, ENST00000956224, ENST00000956225, ENST00000956226, ENST00000956227, ENST00000956228

RefSeq mRNA: 7 — MANE Select: NM_201453 NM_001291821, NM_001378113, NM_001378114, NM_001378115, NM_001378116, NM_001378117, NM_201453

CCDS: CCDS35038

Canonical transcript exons

ENST00000360171 — 15 exons

Exon	Start	End
ENSE00001694232	68247613	68247709
ENSE00001919062	68241983	68242185
ENSE00001931319	68299481	68300035
ENSE00003299788	68248806	68248897
ENSE00003461068	68297752	68297817
ENSE00003482697	68256921	68256980
ENSE00003517114	68297580	68297648
ENSE00003521900	68268934	68268978
ENSE00003562988	68245213	68245299
ENSE00003626055	68258532	68258569
ENSE00003630427	68274882	68274938
ENSE00003630488	68298964	68299093
ENSE00003633718	68264468	68264514
ENSE00003635966	68266220	68266306
ENSE00003657818	68285989	68286040

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.22.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	93.22	gold quality
calcaneal tendon	UBERON:0003701	93.22	gold quality
leukocyte	CL:0000738	92.47	gold quality
islet of Langerhans	UBERON:0000006	91.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.49	gold quality
sural nerve	UBERON:0015488	91.06	gold quality
vermiform appendix	UBERON:0001154	89.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.87	gold quality
pancreas	UBERON:0001264	89.75	gold quality
cerebellar cortex	UBERON:0002129	89.67	gold quality
cerebellum	UBERON:0002037	89.66	gold quality
cerebellar hemisphere	UBERON:0002245	89.65	gold quality
tonsil	UBERON:0002372	89.50	gold quality
adenohypophysis	UBERON:0002196	89.42	gold quality
liver	UBERON:0002107	89.41	gold quality
body of pancreas	UBERON:0001150	89.19	gold quality
pituitary gland	UBERON:0000007	88.96	gold quality
right adrenal gland	UBERON:0001233	88.90	gold quality
nucleus accumbens	UBERON:0001882	88.71	gold quality
adult mammalian kidney	UBERON:0000082	88.61	gold quality
granulocyte	CL:0000094	88.59	gold quality
left adrenal gland cortex	UBERON:0035825	88.49	gold quality
left adrenal gland	UBERON:0001234	88.41	gold quality
right adrenal gland cortex	UBERON:0035827	88.29	gold quality
hypothalamus	UBERON:0001898	88.24	gold quality
anterior cingulate cortex	UBERON:0009835	88.04	gold quality
Ammon’s horn	UBERON:0001954	88.03	gold quality
adrenal gland	UBERON:0002369	87.99	gold quality
superior frontal gyrus	UBERON:0002661	87.96	gold quality
right frontal lobe	UBERON:0002810	87.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	20.82
E-ENAD-20	no	62.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting ZNG1C, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-221-3P	99.86	71.56	1329

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbwd	ENSDARG00000004318
mus_musculus	Zng1	ENSMUSG00000024878
rattus_norvegicus	Zng1a	ENSRNOG00000015516

Paralogs (4): ZNG1B (ENSG00000136682), ZNG1E (ENSG00000147996), ZNG1A (ENSG00000172785), ZNG1F (ENSG00000215126)

Protein

Protein identifiers

Zinc-regulated GTPase metalloprotein activator 1C — Q5JTY5 (reviewed: Q5JTY5)

Alternative names: Cobalamin synthase W domain-containing protein 3

All UniProt accessions (8): A0A087WWG3, A0A087WYD2, A0A0A0MRU4, A0A0B4J2E3, Q5JTY5, F2Z3P0, Q5JTY2, Q5RIB5

UniProt curated annotations — full annotation on UniProt →

Function. Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them. Catalyzes zinc insertion into the active site of methionine aminopeptidase METAP1, which function to cleave the initiator methionine from polypeptides during or after protein translation. Mechanistically, the N-terminal psi-PxLVp motif binds to the C6H2-type zinc finger of inactive form of METAP1. After formation of the docked complex, zinc is transferred from the CXCC motif in the GTPase domain of ZNG1C to the zinc binding site in the peptidase domain of METAP1 in a process requiring GTP hydrolysis. GTP/GDP exchange is required for release of active METAP1.

Subcellular location. Nucleus.

Similarity. Belongs to the SIMIBI class G3E GTPase family. ZNG1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JTY5-1	1	yes
Q5JTY5-2	2

RefSeq proteins (7): NP_001278750, NP_001365042, NP_001365043, NP_001365044, NP_001365045, NP_001365046, NP_958861* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003495	CobW/HypB/UreG_nucleotide-bd	Domain
IPR011629	CobW-like_C	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036627	CobW-likC_sf	Homologous_superfamily
IPR051316	Zinc-reg_GTPase_activator	Family

Pfam: PF02492, PF07683

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (14 total): binding site 6, short sequence motif 2, chain 1, domain 1, splice variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JTY5-F1	75.73	0.36

Functional residue map

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

Ligand- & substrate-binding residues (6): 110; 203–206; 49–56; 107; 109; 110–114

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): GOBP_PROTEIN_MATURATION, SANSOM_APC_TARGETS, chr9q21, GOMF_METALLOCHAPERONE_ACTIVITY, GOMF_MOLECULAR_CARRIER_ACTIVITY, MIR559, MIR548Y, MIR548BB_5P, MIR548AR_5P, MIR548AD_5P_MIR548AE_5P_MIR548AY_5P_MIR548B_5P_MIR548D_5P, MIR548AK_MIR548AM_5P_MIR548C_5P_MIR548H_5P_MIR548O_5P_MIR548AU_5P, MIR548O_5P_MIR548W, MIR548AB, MIR548AS_5P, MIR548A_5P

GO Biological Process (0):

GO Molecular Function (5): GTP binding (GO:0005525), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNG1C	SETD2	Q9BYW2	549
ZNG1C	ANKRD20A3P	Q5VUR7	544
ZNG1C	FAM72C	H0Y354	490
ZNG1C	FAM72B	Q86X60	484
ZNG1C	ANKRD20A2P	Q5SQ80	478
ZNG1C	ANKRD20A4P	Q4UJ75	477
ZNG1C	TRIM49C	P0CI26	471
ZNG1C	HSPB3	Q12988	469
ZNG1C	FAM72D	Q6L9T8	449
ZNG1C	ANKRD20A1	Q5TYW2	435
ZNG1C	FAM72A	Q5TYM5	426
ZNG1C	DHRS4L2	Q6PKH6	399
ZNG1C	B8ZZ87	B8ZZ87	378
ZNG1C	POTEJ	P0CG39	371
ZNG1C	TBC1D19	Q8N5T2	370

IntAct

144 interactions, top by confidence:

A	B	Type	Score
DNAJB11	HSPA5	psi-mi:“MI:0914”(association)	0.830
ARPC5	ARPC3	psi-mi:“MI:0914”(association)	0.730
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
ZNG1C	ZMYND19	psi-mi:“MI:0915”(physical association)	0.560
ZNG1C	APBB2	psi-mi:“MI:0915”(physical association)	0.560
CASP6	ZNG1C	psi-mi:“MI:0915”(physical association)	0.560
ZNG1C	DNM2	psi-mi:“MI:0915”(physical association)	0.560
ZNG1C	TOR1A	psi-mi:“MI:0915”(physical association)	0.560
ZNG1C		psi-mi:“MI:0915”(physical association)	0.560
ZNG1C	HIP1	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	ZNG1C	psi-mi:“MI:0915”(physical association)	0.560
RAN	ZNG1C	psi-mi:“MI:0915”(physical association)	0.560
PEX26	ZNG1C	psi-mi:“MI:0915”(physical association)	0.560
HTT	ZNG1C	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (133): CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS)

ESM2 similar proteins: A0A078BQP2, A0A131MCZ8, A0JN54, A3KGB4, A3QM97, A8WPG9, G5ED05, O16715, O88673, P11528, P20192, P23743, P23897, P25092, P30733, P33530, P49619, P49620, P49621, P51556, P55141, P55204, P70106, P90895, P91550, Q03603, Q09435, Q0IIM8, Q10029, Q17586, Q19954, Q22949, Q23681, Q3UWA6, Q4V339, Q4V3C7, Q5JTY5, Q5RIA9, Q618H8, Q67XQ0

Diamond homologs: B0R0B1, O74310, P24203, P31521, P33030, P53729, P94400, Q4V339, Q5JTY5, Q5RIA9, Q8IUF1, Q8VEH6, Q99MB4, Q9BRT8, P22042, P29937, Q869Q0, Q9HZQ2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2981 predictions. Top by Δscore:

Variant	Effect	Δscore
9:68245207:TTATA:T	acceptor_loss	1.0000
9:68245208:TATAG:T	acceptor_loss	1.0000
9:68245209:ATAGG:A	acceptor_loss	1.0000
9:68245210:TA:T	acceptor_loss	1.0000
9:68245211:AGGTG:A	acceptor_loss	1.0000
9:68245212:G:T	acceptor_loss	1.0000
9:68245295:GGAAG:G	donor_gain	1.0000
9:68245296:GAAG:G	donor_gain	1.0000
9:68245296:GAAGG:G	donor_gain	1.0000
9:68245300:G:GG	donor_gain	1.0000
9:68245300:GT:G	donor_loss	1.0000
9:68245301:T:G	donor_loss	1.0000
9:68247705:GTGAA:G	donor_gain	1.0000
9:68247707:G:GT	donor_gain	1.0000
9:68247707:GAA:G	donor_gain	1.0000
9:68247710:G:GG	donor_gain	1.0000
9:68247715:G:GT	donor_gain	1.0000
9:68247716:A:T	donor_gain	1.0000
9:68248897:GG:G	donor_loss	1.0000
9:68258526:TTGTA:T	acceptor_loss	1.0000
9:68258527:TGTA:T	acceptor_loss	1.0000
9:68258528:GTAG:G	acceptor_loss	1.0000
9:68258529:TAG:T	acceptor_loss	1.0000
9:68258530:A:AG	acceptor_gain	1.0000
9:68258530:A:T	acceptor_loss	1.0000
9:68258531:G:GA	acceptor_loss	1.0000
9:68258531:G:GG	acceptor_gain	1.0000
9:68258570:G:GG	donor_gain	1.0000
9:68261002:G:GG	donor_gain	1.0000
9:68266219:GGCAA:G	acceptor_gain	1.0000

AlphaMissense

2597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:68299481:G:A	G361D	0.995
9:68299093:G:C	G361R	0.991
9:68299481:G:T	G361V	0.990
9:68299088:T:C	L359P	0.988
9:68299004:T:A	V331D	0.982
9:68297590:C:T	T276I	0.981
9:68297813:T:C	L316P	0.981
9:68299505:T:C	L369P	0.981
9:68266255:A:T	K204I	0.979
9:68297756:T:C	L297P	0.977
9:68297817:G:C	K317N	0.976
9:68297817:G:T	K317N	0.976
9:68299490:T:C	L364S	0.976
9:68299093:G:T	G361C	0.974
9:68297590:C:A	T276K	0.972
9:68298964:G:A	G318R	0.971
9:68298964:G:C	G318R	0.971
9:68299088:T:G	L359R	0.966
9:68274916:T:C	F248L	0.964
9:68274918:T:A	F248L	0.964
9:68274918:T:G	F248L	0.964
9:68297810:G:C	R315T	0.963
9:68299009:G:C	G333R	0.962
9:68299505:T:A	L369H	0.961
9:68298965:G:A	G318E	0.959
9:68297590:C:G	T276R	0.958
9:68299010:G:A	G333D	0.956
9:68297811:G:C	R315S	0.954
9:68297811:G:T	R315S	0.954
9:68297632:T:C	L290P	0.953

dbSNP variants (sampled 300 via entrez): RS10083632 (9:68277578 C>G), RS10114848 (9:68276781 G>A,C,T), RS10115438 (9:68250261 A>T), RS10115441 (9:68250290 A>G), RS10117536 (9:68250374 G>A), RS10117571 (9:68250531 G>A), RS10121742 (9:68277420 C>A,T), RS10124324 (9:68277839 T>C), RS10124919 (9:68276831 A>G,T), RS10125095 (9:68277379 A>C,G), RS10125718 (9:68277570 A>G), RS10125892 (9:68280766 G>A), RS1025464039 (9:68278092 G>A), RS10429494 (9:68296015 C>T), RS1043609 (9:68299025 A>G)

Disease associations

OMIM: gene MIM:611080 | 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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	increases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	increases abundance, increases expression	1
Testosterone	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Volatile Organic Compounds	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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