ZNG1B

Summary

ZNG1B (Zn regulated GTPase metalloprotein activator 1B, HGNC:17907) is a protein-coding gene on chromosome 2q14.1, encoding Zinc-regulated GTPase metalloprotein activator 1B (Q8IUF1). Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them. It is a selective cancer dependency (DepMap: 68.4% of cell lines).

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 150472 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 65 total
• Cancer dependency (DepMap): dependent in 68.4% of screened cell lines
• MANE Select transcript: NM_172003

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17907
Approved symbol	ZNG1B
Name	Zn regulated GTPase metalloprotein activator 1B
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000136682
Ensembl biotype	protein_coding
OMIM	611079
Entrez	150472

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 22 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000259199, ENST00000358604, ENST00000416503, ENST00000456188, ENST00000463627, ENST00000468417, ENST00000479583, ENST00000490323, ENST00000490446, ENST00000492566, ENST00000883248, ENST00000883249, ENST00000883250, ENST00000883251, ENST00000883252, ENST00000883253, ENST00000883254, ENST00000883255, ENST00000883256, ENST00000883257, ENST00000920858, ENST00000920859, ENST00000920860, ENST00000920861, ENST00000920862, ENST00000920863, ENST00000920864, ENST00000947888, ENST00000947889, ENST00000947890

RefSeq mRNA: 6 — MANE Select: NM_172003 NM_001330336, NM_001330337, NM_001330339, NM_001330340, NM_001330342, NM_172003

CCDS: CCDS2116, CCDS82502

Canonical transcript exons

ENST00000259199 — 15 exons

Exon	Start	End
ENSE00001819931	113437691	113438022
ENSE00001890971	113495637	113496204
ENSE00003465194	113471033	113471089
ENSE00003466437	113460673	113460719
ENSE00003468609	113462408	113462494
ENSE00003469465	113482177	113482228
ENSE00003478365	113454741	113454778
ENSE00003503231	113441351	113441437
ENSE00003505939	113495120	113495249
ENSE00003510213	113493757	113493825
ENSE00003565995	113444964	113445055
ENSE00003587219	113443767	113443863
ENSE00003629624	113453139	113453198
ENSE00003679802	113465129	113465173
ENSE00003692444	113493929	113493994

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.85.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	95.85	gold quality
leukocyte	CL:0000738	95.39	gold quality
islet of Langerhans	UBERON:0000006	94.66	gold quality
adenohypophysis	UBERON:0002196	93.71	gold quality
pancreas	UBERON:0001264	93.39	gold quality
right adrenal gland cortex	UBERON:0035827	93.20	gold quality
body of pancreas	UBERON:0001150	93.17	gold quality
pituitary gland	UBERON:0000007	93.14	gold quality
right adrenal gland	UBERON:0001233	93.09	gold quality
left adrenal gland	UBERON:0001234	93.06	gold quality
adrenal tissue	UBERON:0018303	93.06	gold quality
left adrenal gland cortex	UBERON:0035825	92.87	gold quality
left lobe of thyroid gland	UBERON:0001120	92.75	gold quality
gastrocnemius	UBERON:0001388	92.72	gold quality
adrenal gland	UBERON:0002369	92.67	gold quality
thyroid gland	UBERON:0002046	92.64	gold quality
muscle of leg	UBERON:0001383	92.61	gold quality
heart left ventricle	UBERON:0002084	92.35	gold quality
nucleus accumbens	UBERON:0001882	92.24	gold quality
lower esophagus	UBERON:0013473	92.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.20	gold quality
endometrium	UBERON:0001295	92.18	gold quality
skeletal muscle tissue	UBERON:0001134	92.08	gold quality
right lobe of thyroid gland	UBERON:0001119	92.03	gold quality
heart	UBERON:0000948	91.96	gold quality
right uterine tube	UBERON:0001302	91.95	gold quality
calcaneal tendon	UBERON:0003701	91.74	gold quality
tibial artery	UBERON:0007610	91.67	gold quality
popliteal artery	UBERON:0002250	91.66	gold quality
right atrium auricular region	UBERON:0006631	91.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting ZNG1B, 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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 68.4% of screened cell lines.

Cross-species orthologs

0 orthologs

Paralogs (4): ZNG1E (ENSG00000147996), ZNG1A (ENSG00000172785), ZNG1C (ENSG00000196873), ZNG1F (ENSG00000215126)

Protein

Protein identifiers

Zinc-regulated GTPase metalloprotein activator 1B — Q8IUF1 (reviewed: Q8IUF1)

Alternative names: Cobalamin synthase W domain-containing protein 2

All UniProt accessions (4): C9J3G2, Q8IUF1, F8WEU0, F8WFD0

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 ZNG1B 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.

RefSeq proteins (6): NP_001317265, NP_001317266, NP_001317268, NP_001317269, NP_001317271, NP_742000* (*=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 (13 total): binding site 6, 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-Q8IUF1-F1	75.45	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: 71 (showing top): GOBP_PROTEIN_MATURATION, chr2q14, GRADE_COLON_AND_RECTAL_CANCER_UP, 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 (4): GTP binding (GO:0005525), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), nucleotide binding (GO:0000166)

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
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNG1B	CCDC74B	Q96LY2	542
ZNG1B	SETD2	Q9BYW2	497
ZNG1B	TMEM14B	Q9NUH8	401
ZNG1B	ZNF90	Q03938	400
ZNG1B	CHCHD5	Q9BSY4	397
ZNG1B	RABL2A	Q9UBK7	370
ZNG1B	DHRS4	Q9BTZ2	356
ZNG1B	ARHGAP11B	Q3KRB8	347
ZNG1B	FEM1C	Q96JP0	324
ZNG1B	RCSD1	Q6JBY9	323
ZNG1B	ARHGAP42	A6NI28	322
ZNG1B	SLC35A1	P78382	290
ZNG1B	NOTCH2NLB	P0DPK3	288
ZNG1B	STRN3	Q13033	277
ZNG1B	ZNF292	O60281	274

IntAct

45 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
ZNG1B		psi-mi:“MI:0915”(physical association)	0.560
NSUN3	HSPD1	psi-mi:“MI:0914”(association)	0.560
ERF	TBL1X	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
ADAMTS4	MANBA	psi-mi:“MI:0914”(association)	0.530
ZNG1B	METAP1	psi-mi:“MI:0914”(association)	0.530
OPALIN	BTAF1	psi-mi:“MI:0914”(association)	0.530
ECE1	ZNG1B	psi-mi:“MI:0915”(physical association)	0.370
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
ZNG1B	TCERG1	psi-mi:“MI:0914”(association)	0.350
ZNG1A	AGAP1	psi-mi:“MI:0914”(association)	0.350
SFTA2	SEPTIN2	psi-mi:“MI:0914”(association)	0.350
PAN2	ARCN1	psi-mi:“MI:0914”(association)	0.350
ELK1	TPP1	psi-mi:“MI:0914”(association)	0.350
ELK1	PPP6C	psi-mi:“MI:0914”(association)	0.350
SMYD2	HSPA4L	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZNG1B	NME4	psi-mi:“MI:0914”(association)	0.350
ZNG1A	TCERG1	psi-mi:“MI:0914”(association)	0.350
HSPA12A	ARHGEF10	psi-mi:“MI:0914”(association)	0.350
CBR4	DUSP14	psi-mi:“MI:0914”(association)	0.350
VEGFD	RPSA2	psi-mi:“MI:0914”(association)	0.350
UCN3	VWA8	psi-mi:“MI:0914”(association)	0.350
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
GZMH	DENND11	psi-mi:“MI:0914”(association)	0.350
ADAM7	RIOK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): CBWD2 (Affinity Capture-MS), CBWD7 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), HSPA12A (Affinity Capture-MS), EGLN1 (Affinity Capture-MS), NEK4 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), CBWD2 (Affinity Capture-MS), CBWD7 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), TCERG1 (Affinity Capture-MS), HSPA12A (Affinity Capture-MS), CBWD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A193KX02, A0A397HK53, A1Y9I9, A4IG53, A5WWC6, B6CZ46, B6CZ56, B6CZ62, B8NR70, L0TAD5, O42898, P37059, P55205, P58781, P86243, Q0IIS3, Q0P464, Q28C60, Q28DI5, Q2KHV5, Q2VQV9, Q32LS6, Q3V1F8, Q4V339, Q5JTY5, Q5RIA9, Q5XI69, Q5XI79, Q66KL0, Q68EZ3, Q6DCK1, Q6GQ37, Q6PE54, Q6Q2C2, Q6TL19, Q7L592, Q7L5L3, Q8IUF1, Q8IX18, Q8NKC1

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2552 predictions. Top by Δscore:

Variant	Effect	Δscore
2:113441345:TTATA:T	acceptor_loss	1.0000
2:113441346:TATA:T	acceptor_loss	1.0000
2:113441348:TA:T	acceptor_loss	1.0000
2:113441350:G:GC	acceptor_loss	1.0000
2:113441433:GGAAG:G	donor_gain	1.0000
2:113441434:GAAG:G	donor_gain	1.0000
2:113441434:GAAGG:G	donor_gain	1.0000
2:113441435:AAGGT:A	donor_loss	1.0000
2:113441436:AGG:A	donor_loss	1.0000
2:113441438:G:C	donor_loss	1.0000
2:113441438:G:GG	donor_gain	1.0000
2:113441439:T:A	donor_loss	1.0000
2:113443859:G:GG	donor_gain	1.0000
2:113443861:G:GT	donor_gain	1.0000
2:113443861:GAA:G	donor_gain	1.0000
2:113443864:G:GG	donor_gain	1.0000
2:113443869:G:GT	donor_gain	1.0000
2:113443870:A:T	donor_gain	1.0000
2:113444962:A:AG	acceptor_gain	1.0000
2:113444963:G:GG	acceptor_gain	1.0000
2:113445051:CCCAG:C	donor_loss	1.0000
2:113445052:CCAG:C	donor_loss	1.0000
2:113445053:CAG:C	donor_loss	1.0000
2:113445054:AG:A	donor_loss	1.0000
2:113445055:GG:G	donor_loss	1.0000
2:113445057:T:A	donor_loss	1.0000
2:113454735:TTGTA:T	acceptor_loss	1.0000
2:113454736:TGTAG:T	acceptor_loss	1.0000
2:113454737:GTAG:G	acceptor_loss	1.0000
2:113454738:TAGG:T	acceptor_loss	1.0000

AlphaMissense

2598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:113462443:A:T	K204I	0.998
2:113445023:T:A	I133K	0.995
2:113437999:T:A	V44D	0.992
2:113441356:G:T	G54W	0.992
2:113441411:C:A	A72E	0.992
2:113438013:G:T	G49W	0.991
2:113441353:G:C	A53P	0.991
2:113438014:G:A	G49E	0.990
2:113441360:A:T	K55M	0.990
2:113441363:C:T	T56I	0.990
2:113462444:A:C	K204N	0.990
2:113462444:A:T	K204N	0.990
2:113441359:A:C	K55Q	0.989
2:113441360:A:C	K55T	0.989
2:113441361:G:C	K55N	0.989
2:113441361:G:T	K55N	0.989
2:113441417:T:C	I74T	0.989
2:113441428:T:C	F78L	0.989
2:113441430:T:A	F78L	0.989
2:113441430:T:G	F78L	0.989
2:113445023:T:G	I133R	0.989
2:113445026:T:C	L134P	0.989
2:113495160:T:A	V331D	0.989
2:113445032:A:T	E136V	0.988
2:113462443:A:C	K204T	0.988
2:113441357:G:T	G54V	0.987
2:113441357:G:A	G54E	0.986
2:113443844:T:C	C107R	0.986
2:113445013:T:C	F130L	0.986
2:113445015:T:A	F130L	0.986

dbSNP variants (sampled 300 via entrez): RS1000045085 (2:113476621 C>T), RS1000184934 (2:113440587 T>C), RS1000251478 (2:113487235 A>C), RS1000468439 (2:113441096 A>G), RS1000522571 (2:113439132 C>A,G), RS1000629982 (2:113447632 T>A,G), RS1000698428 (2:113449929 A>C,G,T), RS1000804990 (2:113439401 C>A), RS1000878191 (2:113469847 A>G), RS1001119675 (2:113455562 T>C), RS1001288340 (2:113466553 G>A,C), RS1001349992 (2:113456270 C>T), RS1001350255 (2:113469338 G>A,C), RS1001415890 (2:113447100 T>A,G), RS1001530990 (2:113484510 A>C,G)

Disease associations

OMIM: gene MIM:611079 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002711_1	Sleep duration	1.000000e-10
GCST008841_1	Depressive symptom (sleep problems) (binary trait)	1.000000e-10
GCST009391_645	Metabolite levels	9.000000e-06
GCST012180_3	Cigarettes smoked per day in Schizophrenia	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007006	depressive symptom measurement
EFO:0010504	inositol measurement
EFO:0006525	cigarettes per day measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	decreases expression	1
Thiram	decreases expression	1
Aflatoxin B1	decreases methylation	1
Levonorgestrel	affects cotreatment, decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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