ZNG1F

Summary

ZNG1F (Zn regulated GTPase metalloprotein activator 1F, HGNC:31978) is a protein-coding gene on chromosome 9p11.2, encoding Zinc-regulated GTPase metalloprotein activator 1F (Q4V339). 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 644019 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_001085457

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31978
Approved symbol	ZNG1F
Name	Zn regulated GTPase metalloprotein activator 1F
Location	9p11.2
Locus type	gene with protein product
Status	Approved
Aliases	OTTHUMG00000066820, OTTHUMG00000067194
Ensembl gene	ENSG00000215126
Ensembl biotype	protein_coding
Entrez	644019

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 12 protein_coding, 6 nonsense_mediated_decay, 6 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000377391, ENST00000382436, ENST00000456520, ENST00000457288, ENST00000467791, ENST00000486387, ENST00000490294, ENST00000494538, ENST00000610358, ENST00000610377, ENST00000611553, ENST00000613125, ENST00000613716, ENST00000617722, ENST00000617917, ENST00000620776, ENST00000622791, ENST00000894097, ENST00000894098, ENST00000894099, ENST00000894100, ENST00000894101, ENST00000894102, ENST00000894103, ENST00000894104, ENST00000894105, ENST00000958079

RefSeq mRNA: 3 — MANE Select: NM_001085457 NM_001085457, NM_001386876, NM_001386877

CCDS: CCDS43827

Canonical transcript exons

ENST00000377391 — 15 exons

Exon	Start	End
ENSE00001604394	41131309	41131840
ENSE00001885224	41189105	41189317
ENSE00004012905	41183564	41183660
ENSE00004012906	41162333	41162377
ENSE00004012907	41185993	41186079
ENSE00004012908	41145281	41145332
ENSE00004012909	41182375	41182466
ENSE00004012910	41174293	41174352
ENSE00004012911	41133674	41133742
ENSE00004012912	41132228	41132357
ENSE00004012913	41166784	41166830
ENSE00004012914	41172712	41172749
ENSE00004012915	41133505	41133570
ENSE00004012916	41156383	41156439
ENSE00004012917	41165001	41165087

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 91.60.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	91.60	gold quality
cerebellar hemisphere	UBERON:0002245	91.60	gold quality
cerebellum	UBERON:0002037	91.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.92	gold quality
superior frontal gyrus	UBERON:0002661	88.91	gold quality
primary visual cortex	UBERON:0002436	88.79	gold quality
lower esophagus mucosa	UBERON:0035834	88.03	gold quality
granulocyte	CL:0000094	87.72	gold quality
right uterine tube	UBERON:0001302	87.49	gold quality
right frontal lobe	UBERON:0002810	87.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.13	gold quality
nucleus accumbens	UBERON:0001882	87.01	gold quality
adenohypophysis	UBERON:0002196	86.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.56	gold quality
pituitary gland	UBERON:0000007	86.55	gold quality
skin of abdomen	UBERON:0001416	86.40	gold quality
skin of leg	UBERON:0001511	86.32	gold quality
body of pancreas	UBERON:0001150	86.29	gold quality
zone of skin	UBERON:0000014	86.28	gold quality
Ammon’s horn	UBERON:0001954	86.26	gold quality
caudate nucleus	UBERON:0001873	86.12	gold quality
mucosa of transverse colon	UBERON:0004991	85.95	gold quality
putamen	UBERON:0001874	85.90	gold quality
anterior cingulate cortex	UBERON:0009835	85.86	gold quality
brain	UBERON:0000955	85.68	gold quality
cortex of kidney	UBERON:0001225	85.14	gold quality
spleen	UBERON:0002106	85.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.95	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.19
E-MTAB-6524	no	17.84
E-HCAD-31	no	2.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting ZNG1F, 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-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-568	99.98	69.86	2084
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), ZNG1C (ENSG00000196873)

Protein

Protein identifiers

Zinc-regulated GTPase metalloprotein activator 1F — Q4V339 (reviewed: Q4V339)

Alternative names: Cobalamin synthase W domain-containing protein 6

All UniProt accessions (8): A0A087WU66, A0A087WX94, A0A087X1C0, A0A0B4J2E3, Q4V339, F2Z3P0, H0Y5V3, Q5JTY2

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 ZNG1F 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 (3): NP_001078926, NP_001373805, NP_001373806 (=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 (12 total): binding site 6, short sequence motif 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4V339-F1	75.86	0.35

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: 34 (showing top): chr9p11, GOBP_PROTEIN_MATURATION, GOMF_METALLOCHAPERONE_ACTIVITY, GOMF_MOLECULAR_CARRIER_ACTIVITY, NFE2L2.V2, 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
ZNG1F	SETD2	Q9BYW2	549
ZNG1F	ANKRD20A3P	Q5VUR7	544
ZNG1F	FAM72C	H0Y354	491
ZNG1F	FAM72B	Q86X60	484
ZNG1F	ANKRD20A2P	Q5SQ80	479
ZNG1F	ANKRD20A4P	Q4UJ75	477
ZNG1F	HSPB3	Q12988	469
ZNG1F	FAM72D	Q6L9T8	449
ZNG1F	ANKRD20A1	Q5TYW2	435
ZNG1F	ZNF836	Q6ZNA1	430
ZNG1F	FAM72A	Q5TYM5	427
ZNG1F	ABRA	Q8N0Z2	413
ZNG1F	DHRS4L2	Q6PKH6	400
ZNG1F	B8ZZ87	B8ZZ87	379
ZNG1F	TBC1D19	Q8N5T2	370

IntAct

18 interactions, top by confidence:

A	B	Type	Score
RNASEH2C	RNASEH2A	psi-mi:“MI:0914”(association)	0.640
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
ECE1	ZNG1F	psi-mi:“MI:0915”(physical association)	0.370
ZNG1B	TCERG1	psi-mi:“MI:0914”(association)	0.350
ZNG1A	AGAP1	psi-mi:“MI:0914”(association)	0.350
HDAC7	ZMYM6	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
M		psi-mi:“MI:0914”(association)	0.350
MRPL27		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
FAM170A	RPSA2	psi-mi:“MI:0914”(association)	0.350
DTWD2	ATP1A3	psi-mi:“MI:0914”(association)	0.350
P/V	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): CBWD6 (Affinity Capture-MS), CBWD6 (Affinity Capture-MS), CBWD6 (Affinity Capture-MS), CBWD6 (Affinity Capture-MS), CBWD6 (Reconstituted Complex), CBWD6 (Affinity Capture-MS), CBWD6 (Affinity Capture-MS), CBWD6 (Affinity Capture-MS), CBWD6 (Affinity Capture-MS), CBWD6 (Affinity Capture-MS), CBWD6 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1398 predictions. Top by Δscore:

Variant	Effect	Δscore
9:41131837:CTGC:C	acceptor_gain	1.0000
9:41131841:C:CC	acceptor_gain	1.0000
9:41132221:GACTT:G	donor_loss	1.0000
9:41132222:ACTT:A	donor_loss	1.0000
9:41132223:CTT:C	donor_loss	1.0000
9:41132224:TTA:T	donor_loss	1.0000
9:41132225:TA:T	donor_loss	1.0000
9:41132226:A:AC	donor_gain	1.0000
9:41132226:A:C	donor_loss	1.0000
9:41132226:AC:A	donor_gain	1.0000
9:41132227:C:CT	donor_gain	1.0000
9:41132227:CC:C	donor_gain	1.0000
9:41132227:CCA:C	donor_gain	1.0000
9:41132227:CCAA:C	donor_gain	1.0000
9:41132227:CCAAT:C	donor_gain	1.0000
9:41133699:T:TA	donor_gain	1.0000
9:41133739:TACT:T	acceptor_gain	1.0000
9:41133740:ACTCT:A	acceptor_loss	1.0000
9:41133741:CT:C	acceptor_gain	1.0000
9:41133743:C:A	acceptor_loss	1.0000
9:41133743:C:CC	acceptor_gain	1.0000
9:41133744:T:G	acceptor_loss	1.0000
9:41133751:C:CT	acceptor_gain	1.0000
9:41133752:A:T	acceptor_gain	1.0000
9:41164983:A:C	donor_gain	1.0000
9:41182369:TCTTA:T	donor_loss	1.0000
9:41182370:CTTA:C	donor_loss	1.0000
9:41182371:TTACC:T	donor_loss	1.0000
9:41182372:TACCA:T	donor_loss	1.0000
9:41182373:A:AG	donor_loss	1.0000

AlphaMissense

2598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:41165052:T:A	K204I	0.982
9:41133566:A:G	L297P	0.978
9:41131831:A:G	L364S	0.973
9:41132233:A:G	L359P	0.972
9:41132317:A:T	V331D	0.969
9:41131840:C:T	G361D	0.968
9:41132236:A:T	V358D	0.967
9:41133505:C:A	K317N	0.965
9:41133505:C:G	K317N	0.965
9:41156403:A:C	F248L	0.964
9:41156403:A:T	F248L	0.964
9:41156405:A:G	F248L	0.964
9:41131816:A:G	L369P	0.957
9:41133509:A:G	L316P	0.957
9:41132357:C:G	G318R	0.956
9:41132357:C:T	G318R	0.956
9:41131840:C:A	G361V	0.954
9:41132242:C:G	R356P	0.954
9:41133732:G:A	T276I	0.950
9:41165070:T:A	D198V	0.946
9:41133680:A:C	F293L	0.945
9:41133680:A:T	F293L	0.945
9:41133682:A:G	F293L	0.945
9:41132228:C:G	G361R	0.943
9:41165051:T:A	K204N	0.943
9:41165051:T:G	K204N	0.943
9:41132356:C:T	G318E	0.941
9:41133512:C:G	R315T	0.937
9:41132244:A:C	N355K	0.936
9:41132244:A:T	N355K	0.936

dbSNP variants (sampled 300 via entrez): RS1000201935 (9:41145888 G>A), RS1000453851 (9:41184651 C>T), RS1000506989 (9:41150829 C>T), RS1000535819 (9:41150449 C>A,T), RS1000659552 (9:41169468 G>A), RS1000725796 (9:41161095 C>A), RS1000787162 (9:41190097 T>C), RS1001046831 (9:41134212 A>G,T), RS1001094430 (9:41166787 G>A), RS1001188971 (9:41162318 G>T), RS1001295075 (9:41185205 G>A), RS1001465984 (9:41132028 A>G), RS1001497142 (9:41130941 G>T), RS1001520252 (9:41133863 A>C,G), RS1001730774 (9:41147548 CTA>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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
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
jinfukang	decreases expression	1
Antimycin A	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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