ZNG1E

Summary

ZNG1E (Zn regulated GTPase metalloprotein activator 1E, HGNC:24584) is a protein-coding gene on chromosome 9q21.11, encoding Zinc-regulated GTPase metalloprotein activator 1E (Q5RIA9). Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them.

Predicted to enable GTPase activity and zinc chaperone activity. Predicted to be involved in protein maturation. Predicted to be located in nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 220869 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_001330668

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24584
Approved symbol	ZNG1E
Name	Zn regulated GTPase metalloprotein activator 1E
Location	9q21.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147996
Ensembl biotype	protein_coding
Entrez	220869

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 16 protein_coding, 12 retained_intron, 7 nonsense_mediated_decay, 7 protein_coding_CDS_not_defined

ENST00000377380, ENST00000377384, ENST00000377389, ENST00000377392, ENST00000377395, ENST00000382404, ENST00000382405, ENST00000429800, ENST00000430059, ENST00000441808, ENST00000461932, ENST00000463075, ENST00000464913, ENST00000465474, ENST00000468066, ENST00000468198, ENST00000469921, ENST00000471620, ENST00000472916, ENST00000476161, ENST00000476797, ENST00000478650, ENST00000480229, ENST00000480819, ENST00000485088, ENST00000486191, ENST00000486221, ENST00000486466, ENST00000489273, ENST00000491485, ENST00000495615, ENST00000496364, ENST00000497250, ENST00000857329, ENST00000857330, ENST00000857331, ENST00000857332, ENST00000937662, ENST00000937663, ENST00000937664, ENST00000957196, ENST00000957197

RefSeq mRNA: 6 — MANE Select: NM_001330668 NM_001024916, NM_001286835, NM_001286836, NM_001330668, NM_001363751, NM_001410971

CCDS: CCDS75841, CCDS75843, CCDS75844, CCDS83367, CCDS87654, CCDS94413

Canonical transcript exons

ENST00000382405 — 15 exons

Exon	Start	End
ENSE00001863167	65675928	65676130
ENSE00001930390	65733510	65734041
ENSE00003471707	65698515	65698561
ENSE00003496926	65720041	65720092
ENSE00003518263	65731802	65731867
ENSE00003557862	65690967	65691026
ENSE00003595647	65702970	65703014
ENSE00003600211	65681574	65681670
ENSE00003612415	65692571	65692608
ENSE00003620028	65708902	65708958
ENSE00003646673	65732993	65733122
ENSE00003664227	65682766	65682857
ENSE00003664279	65731630	65731698
ENSE00003683726	65679166	65679252
ENSE00003684089	65700251	65700337

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.16.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	97.16	gold quality
cerebellar cortex	UBERON:0002129	97.15	gold quality
cerebellum	UBERON:0002037	97.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.80	gold quality
calcaneal tendon	UBERON:0003701	96.33	gold quality
adenohypophysis	UBERON:0002196	96.00	gold quality
bone marrow cell	CL:0002092	95.87	gold quality
lower esophagus mucosa	UBERON:0035834	95.86	gold quality
pituitary gland	UBERON:0000007	95.81	gold quality
body of pancreas	UBERON:0001150	95.79	gold quality
right lobe of liver	UBERON:0001114	95.53	gold quality
Ammon’s horn	UBERON:0001954	95.48	gold quality
nucleus accumbens	UBERON:0001882	95.32	gold quality
caudate nucleus	UBERON:0001873	95.28	gold quality
hypothalamus	UBERON:0001898	95.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.19	gold quality
right lobe of thyroid gland	UBERON:0001119	95.11	gold quality
right frontal lobe	UBERON:0002810	95.09	gold quality
putamen	UBERON:0001874	95.06	gold quality
right uterine tube	UBERON:0001302	94.92	gold quality
monocyte	CL:0000576	94.90	gold quality
superior frontal gyrus	UBERON:0002661	94.90	gold quality
anterior cingulate cortex	UBERON:0009835	94.82	gold quality
primary visual cortex	UBERON:0002436	94.79	gold quality
thyroid gland	UBERON:0002046	94.78	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.78	gold quality
left lobe of thyroid gland	UBERON:0001120	94.74	gold quality
liver	UBERON:0002107	94.70	gold quality
skin of abdomen	UBERON:0001416	94.69	gold quality
zone of skin	UBERON:0000014	94.64	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	20.27
E-MTAB-7606	no	663.03
E-MTAB-5061	no	3.43
E-HCAD-31	no	2.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting ZNG1E, 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), ZNG1A (ENSG00000172785), ZNG1C (ENSG00000196873), ZNG1F (ENSG00000215126)

Protein

Protein identifiers

Zinc-regulated GTPase metalloprotein activator 1E — Q5RIA9 (reviewed: Q5RIA9)

Alternative names: Cobalamin synthase W domain-containing protein 5

All UniProt accessions (10): Q5RIA9, A0A0A6YYH9, E7EUZ7, F2Z3P0, H0Y857, Q5JTY2, Q5RIB0, Q5RIB3, Q5RIB5, Q6NVZ8

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 ZNG1E 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 (3)

UniProt ID	Names	Canonical?
Q5RIA9-1	1	yes
Q5RIA9-2	2
Q5RIA9-3	3

RefSeq proteins (6): NP_001020087, NP_001273764, NP_001273765, NP_001317597, NP_001350680, NP_001397900 (=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 (18 total): binding site 6, splice variant 3, sequence variant 2, short sequence motif 2, chain 1, domain 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-Q5RIA9-F1	75.43	0.40

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: 44 (showing top): GOBP_PROTEIN_MATURATION, chr9q21, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_METALLOCHAPERONE_ACTIVITY, GOMF_MOLECULAR_CARRIER_ACTIVITY, COBLL1_TARGET_GENES, HMGA1_TARGET_GENES, LHX9_TARGET_GENES, 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

GO Biological Process (1): protein maturation (GO:0051604)

GO Molecular Function (7): GTPase activity (GO:0003924), GTP binding (GO:0005525), metal ion binding (GO:0046872), zinc chaperone activity (GO:0140827), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	1
protein metabolic process	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
zinc ion binding	1
metallochaperone activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNG1E	SETD2	Q9BYW2	549
ZNG1E	HSPB3	Q12988	469
ZNG1E	FUNDC2	Q9BWH2	431
ZNG1E	MRPS15	P82914	418
ZNG1E	NXT2	Q9NPJ8	396
ZNG1E	TMEM107	Q6UX40	377
ZNG1E	TBC1D19	Q8N5T2	371
ZNG1E	CLRN3	Q8NCR9	370
ZNG1E	CNTNAP3B	Q96NU0	370
ZNG1E	KANSL1L	A0AUZ9	359
ZNG1E	ZNF429	Q86V71	358
ZNG1E	ENY2	Q9NPA8	358
ZNG1E	MSANTD4	Q8NCY6	349
ZNG1E	ZNF260	Q3ZCT1	348
ZNG1E	FBXO8	Q9NRD0	348

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ECE1	ZNG1E	psi-mi:“MI:0915”(physical association)	0.370
ELK1	TPP1	psi-mi:“MI:0914”(association)	0.350
ELK1	PPP6C	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZNG1E		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): CBWD5 (Affinity Capture-RNA), CBWD5 (Two-hybrid), ZMYND19 (Two-hybrid), CBWD5 (Affinity Capture-MS), CBWD5 (Proximity Label-MS), CBWD5 (Negative Genetic), CBWD5 (Negative Genetic), CBWD5 (Negative Genetic), CBWD5 (Affinity Capture-MS), CBWD5 (Affinity Capture-MS), CBWD5 (Proximity Label-MS), CBWD5 (Affinity Capture-MS), CBWD5 (Proximity Label-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2574 predictions. Top by Δscore:

Variant	Effect	Δscore
9:65679163:C:A	acceptor_loss	1.0000
9:65679163:C:CC	acceptor_gain	1.0000
9:65679167:GCACC:G	acceptor_loss	1.0000
9:65679251:C:CC	donor_gain	1.0000
9:65679251:C:CG	donor_loss	1.0000
9:65679251:CCTT:C	donor_gain	1.0000
9:65679251:CCTTC:C	donor_gain	1.0000
9:65679252:A:AC	donor_gain	1.0000
9:65679252:ACCT:A	donor_loss	1.0000
9:65679252:ACCTT:A	donor_gain	1.0000
9:65679253:TA:T	donor_loss	1.0000
9:65679254:TTA:T	donor_loss	1.0000
9:65679255:CTTA:C	donor_loss	1.0000
9:65679256:ACTT:A	donor_loss	1.0000
9:65681660:A:C	donor_gain	1.0000
9:65681664:C:CC	donor_gain	1.0000
9:65681665:A:AC	donor_gain	1.0000
9:65681667:T:TA	donor_gain	1.0000
9:65681669:C:CT	donor_gain	1.0000
9:65681669:CTT:C	donor_gain	1.0000
9:65681669:CTTCA:C	donor_gain	1.0000
9:65681670:A:AC	donor_gain	1.0000
9:65681675:T:A	donor_gain	1.0000
9:65681677:ATT:A	donor_gain	1.0000
9:65682858:TACCA:T	donor_loss	1.0000
9:65682859:TTACC:T	donor_loss	1.0000
9:65682860:CTTA:C	donor_loss	1.0000
9:65682861:TCTTA:T	donor_loss	1.0000
9:65692567:T:C	acceptor_loss	1.0000
9:65692568:C:CA	acceptor_loss	1.0000

AlphaMissense

2597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:65731806:T:C	L297P	0.982
9:65733117:T:C	L359P	0.978
9:65731863:T:C	L316P	0.972
9:65733033:T:A	V331D	0.972
9:65700286:A:T	K204I	0.968
9:65733510:G:A	G361D	0.965
9:65733534:T:C	L369P	0.964
9:65732993:G:A	G318R	0.963
9:65732993:G:C	G318R	0.963
9:65733519:T:C	L364S	0.958
9:65731867:G:C	K317N	0.955
9:65731867:G:T	K317N	0.955
9:65732994:G:A	G318E	0.952
9:65733108:G:C	R356P	0.952
9:65731640:C:T	T276I	0.947
9:65733510:G:T	G361V	0.945
9:65733038:G:C	G333R	0.942
9:65708936:T:C	F248L	0.941
9:65708938:T:A	F248L	0.941
9:65708938:T:G	F248L	0.941
9:65731860:G:C	R315T	0.941
9:65682815:T:C	F130L	0.940
9:65682817:T:A	F130L	0.940
9:65682817:T:G	F130L	0.940
9:65733117:T:G	L359R	0.939
9:65733122:G:C	G361R	0.939
9:65733106:T:A	N355K	0.935
9:65733106:T:G	N355K	0.935
9:65733114:T:A	V358D	0.933
9:65731861:G:C	R315S	0.932

dbSNP variants (sampled 300 via entrez): RS1000645646 (9:65687839 T>C,G), RS1000676818 (9:65682095 C>T), RS1002905309 (9:65678626 T>C), RS1003209341 (9:65675630 T>C), RS1003651170 (9:65671026 C>G), RS1004413247 (9:65676869 G>A), RS1004640087 (9:65668212 A>C,G,T), RS1006278830 (9:65660152 A>G), RS1007996464 (9:65687995 C>G), RS1010681239 (9:65687604 A>G,T), RS1011421380 (9:65667115 C>A,G), RS10114440 (9:65705748 T>C,G), RS1011496986 (9:65666107 G>A), RS10115527 (9:65689491 C>T), RS10115528 (9:65721922 G>A)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
titanium dioxide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
pyrachlostrobin	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Antimycin A	decreases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Cisplatin	decreases expression	1
Folic Acid	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	decreases expression, decreases reaction	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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