ZNG1A

Summary

ZNG1A (Zn regulated GTPase metalloprotein activator 1A, HGNC:17134) is a protein-coding gene on chromosome 9p24.3, encoding Zinc-regulated GTPase metalloprotein activator 1A (Q9BRT8). Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them.

Predicted to enable GTPase activity and zinc chaperone activity. Involved in kidney development. Predicted to be located in nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 55871 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_018491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17134
Approved symbol	ZNG1A
Name	Zn regulated GTPase metalloprotein activator 1A
Location	9p24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172785
Ensembl biotype	protein_coding
OMIM	611078
Entrez	55871

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 20 protein_coding, 9 nonsense_mediated_decay, 6 retained_intron, 5 protein_coding_CDS_not_defined

ENST00000314367, ENST00000356521, ENST00000377400, ENST00000377447, ENST00000382389, ENST00000382393, ENST00000382447, ENST00000431099, ENST00000462513, ENST00000464198, ENST00000465014, ENST00000475411, ENST00000475990, ENST00000483817, ENST00000487575, ENST00000489272, ENST00000495302, ENST00000498044, ENST00000611457, ENST00000612045, ENST00000613355, ENST00000613508, ENST00000613988, ENST00000616803, ENST00000616944, ENST00000618061, ENST00000618361, ENST00000619157, ENST00000620292, ENST00000905979, ENST00000905980, ENST00000905981, ENST00000905982, ENST00000905983, ENST00000905984, ENST00000937294, ENST00000937295, ENST00000966633, ENST00000966634, ENST00000966635

RefSeq mRNA: 16 — MANE Select: NM_018491 NM_001145355, NM_001145356, NM_001399796, NM_001399797, NM_001399798, NM_001399799, NM_001399800, NM_001399801, NM_001399802, NM_001399803, NM_001399804, NM_001399805, NM_001399807, NM_001399808, NM_001399809, NM_018491

CCDS: CCDS47947, CCDS47948, CCDS6438, CCDS94369, CCDS94370

Canonical transcript exons

ENST00000356521 — 15 exons

Exon	Start	End
ENSE00001492045	178816	179056
ENSE00003467830	162432	162469
ENSE00003498549	156481	156527
ENSE00003509987	154709	154795
ENSE00003525354	134979	135030
ENSE00003537099	123386	123454
ENSE00003575658	146102	146158
ENSE00003587421	121961	122090
ENSE00003634857	123217	123282
ENSE00003637879	172081	172172
ENSE00003644588	175698	175784
ENSE00003649382	173270	173366
ENSE00003650051	163978	164037
ENSE00003654203	152034	152078
ENSE00003732326	120837	121573

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.54.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	95.54	gold quality
monocyte	CL:0000576	95.20	gold quality
body of pancreas	UBERON:0001150	95.14	gold quality
leukocyte	CL:0000738	94.80	gold quality
pancreas	UBERON:0001264	94.08	gold quality
adult mammalian kidney	UBERON:0000082	93.30	gold quality
left adrenal gland cortex	UBERON:0035825	93.20	gold quality
adrenal gland	UBERON:0002369	93.16	gold quality
islet of Langerhans	UBERON:0000006	93.11	gold quality
right adrenal gland cortex	UBERON:0035827	92.99	gold quality
right adrenal gland	UBERON:0001233	92.90	gold quality
left adrenal gland	UBERON:0001234	92.87	gold quality
calcaneal tendon	UBERON:0003701	92.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.83	gold quality
kidney	UBERON:0002113	92.83	gold quality
lower esophagus	UBERON:0013473	92.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.81	gold quality
mucosa of stomach	UBERON:0001199	92.72	gold quality
endometrium	UBERON:0001295	92.69	gold quality
left lobe of thyroid gland	UBERON:0001120	92.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.59	gold quality
zone of skin	UBERON:0000014	92.48	gold quality
skin of abdomen	UBERON:0001416	92.46	gold quality
skin of leg	UBERON:0001511	92.45	gold quality
tonsil	UBERON:0002372	92.45	gold quality
esophagus	UBERON:0001043	92.43	gold quality
thyroid gland	UBERON:0002046	92.39	gold quality
cortex of kidney	UBERON:0001225	92.29	gold quality
colonic epithelium	UBERON:0000397	92.24	gold quality
right lobe of thyroid gland	UBERON:0001119	92.24	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)

52 targeting ZNG1A, 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

Literature-anchored findings (GeneRIF, showing 1)

• The identification of a deletion in CBWD1 gene in two siblings with CAKUT implies a role for CBWD1 in the etiology of some cases of CAKUT (PMID:31862704)

Cross-species orthologs

0 orthologs

Paralogs (4): ZNG1B (ENSG00000136682), ZNG1E (ENSG00000147996), ZNG1C (ENSG00000196873), ZNG1F (ENSG00000215126)

Protein

Protein identifiers

Zinc-regulated GTPase metalloprotein activator 1A — Q9BRT8 (reviewed: Q9BRT8)

Alternative names: Cobalamin synthase W domain-containing protein 1, NPC-A-6 COBW domain-containing protein 1

All UniProt accessions (12): A0A087WTC0, A0A087WU37, A0A087WVU7, A0A087WWK6, A0A087WY70, A0A087WZQ3, A0A087X0Y9, A0A087X140, A0A087X1Y1, A0A0B4J1T6, Q9BRT8, F2Z2T4

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 ZNG1A 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.

Tissue specificity. Ubiquitously expressed. Up-regulated in cultured astrocytes treated with dopamine.

Disease relevance. Congenital anomalies of the kidney and urinary tract (CAKUT). A disorder encompassing a broad spectrum of renal and urinary tract malformations that include renal agenesis, kidney hypodysplasia, multicystic kidney dysplasia, duplex collecting system, posterior urethral valves and ureter abnormalities. Congenital anomalies of kidney and urinary tract are the commonest cause of chronic kidney disease in children. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Induction. Down-regulated in response to zinc: repressed by ZNF658 in response to zinc by binding to the zinc transcriptional regulatory element (ZTRE) (5’-C[AC]C[TAG]CC[TC]-N(0-50)-[GA]G[ATC]G[TG]G-3’) found in the promoter region of CBWD1. Increased expression in response to dopamine treatment.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BRT8-1	1	yes
Q9BRT8-2	2
Q9BRT8-3	3
Q9BRT8-4	4

RefSeq proteins (16): NP_001138827, NP_001138828, NP_001386725, NP_001386726, NP_001386727, NP_001386728, NP_001386729, NP_001386730, NP_001386731, NP_001386732, NP_001386733, NP_001386734, NP_001386736, NP_001386737, NP_001386738, NP_060961* (*=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 (20 total): binding site 6, splice variant 4, sequence conflict 3, short sequence motif 2, chain 1, domain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRT8-F1	75.97	0.37

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: 70 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_PROTEIN_MATURATION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BASAKI_YBX1_TARGETS_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, DANG_BOUND_BY_MYC, GRYDER_PAX3FOXO1_TOP_ENHANCERS, BENPORATH_MYC_MAX_TARGETS, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, JOHNSTONE_PARVB_TARGETS_2_DN, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3, GOMF_METALLOCHAPERONE_ACTIVITY, GOMF_MOLECULAR_CARRIER_ACTIVITY, ESC_V6.5_UP_EARLY.V1_UP

GO Biological Process (1): kidney development (GO:0001822)

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
animal organ development	1
renal system development	1
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

532 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNG1A	FOXD4	Q12950	600
ZNG1A	KIF22	Q14807	583
ZNG1A	ANKRD20A3P	Q5VUR7	506
ZNG1A	SETD2	Q9BYW2	497
ZNG1A	DOCK8	Q8NF50	479
ZNG1A	UQCRQ	O14949	475
ZNG1A	UQCR10	Q9UDW1	465
ZNG1A	UQCRB	P14927	454
ZNG1A	FAM72C	H0Y354	448
ZNG1A	FAM72B	Q86X60	444
ZNG1A	ANKRD20A2P	Q5SQ80	419
ZNG1A	SPMIP4	Q8N865	418
ZNG1A	ANKRD20A4P	Q4UJ75	418
ZNG1A	FAM72D	Q6L9T8	406
ZNG1A	KANK1	Q14678	402

IntAct

149 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
VEGFD	ADAM9	psi-mi:“MI:0914”(association)	0.640
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
NTF3	BDNF	psi-mi:“MI:0914”(association)	0.590
SSX3	ZNG1A	psi-mi:“MI:0915”(physical association)	0.560
ZMYND19	ZNG1A	psi-mi:“MI:0915”(physical association)	0.560
ZNG1A	ERN1	psi-mi:“MI:0915”(physical association)	0.560
ZNG1A	FKBP1A	psi-mi:“MI:0915”(physical association)	0.560
FOS	ZNG1A	psi-mi:“MI:0915”(physical association)	0.560
ZNG1A	GRB2	psi-mi:“MI:0915”(physical association)	0.560
ZNG1A	UQCRC1	psi-mi:“MI:0915”(physical association)	0.560
BRK1	ZNG1A	psi-mi:“MI:0915”(physical association)	0.560
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
BRINP3	BUB1	psi-mi:“MI:0914”(association)	0.530

BioGRID (249): CBWD1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), CBWD6 (Affinity Capture-MS), CBWD7 (Affinity Capture-MS), CBWD2 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), ZNF146 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2557 predictions. Top by Δscore:

Variant	Effect	Δscore
9:121570:CTGC:C	acceptor_gain	1.0000
9:121574:C:CA	acceptor_loss	1.0000
9:121574:C:CC	acceptor_gain	1.0000
9:121575:T:A	acceptor_loss	1.0000
9:121954:GACTT:G	donor_loss	1.0000
9:121955:ACTTA:A	donor_loss	1.0000
9:121956:CTTAC:C	donor_loss	1.0000
9:121957:TTA:T	donor_loss	1.0000
9:121958:T:TG	donor_loss	1.0000
9:121959:A:AC	donor_gain	1.0000
9:121959:A:AT	donor_loss	1.0000
9:121959:AC:A	donor_gain	1.0000
9:121960:C:CT	donor_gain	1.0000
9:121960:CC:C	donor_gain	1.0000
9:121960:CCA:C	donor_gain	1.0000
9:121960:CCAA:C	donor_gain	1.0000
9:121960:CCAAG:C	donor_gain	1.0000
9:123411:T:TA	donor_gain	1.0000
9:123451:TACT:T	acceptor_gain	1.0000
9:123453:CT:C	acceptor_gain	1.0000
9:123453:CTCTG:C	acceptor_loss	1.0000
9:123454:TC:T	acceptor_loss	1.0000
9:123455:C:CC	acceptor_gain	1.0000
9:123455:CTGTA:C	acceptor_loss	1.0000
9:123456:T:G	acceptor_loss	1.0000
9:123463:C:CT	acceptor_gain	1.0000
9:154698:T:C	donor_gain	1.0000
9:154703:TCGTA:T	donor_loss	1.0000
9:154704:CGTA:C	donor_loss	1.0000
9:154705:GTA:G	donor_loss	1.0000

AlphaMissense

2591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:154760:T:A	K204I	0.996
9:172113:A:T	I133K	0.992
9:178839:A:T	V44D	0.990
9:175779:C:A	G54W	0.988
9:122050:A:T	V331D	0.987
9:175705:A:C	F78L	0.987
9:175705:A:T	F78L	0.987
9:175707:A:G	F78L	0.987
9:175724:G:T	A72E	0.987
9:175774:C:A	K55N	0.987
9:175774:C:G	K55N	0.987
9:175775:T:A	K55M	0.987
9:146122:A:C	F248L	0.986
9:146122:A:T	F248L	0.986
9:146124:A:G	F248L	0.986
9:154759:T:A	K204N	0.986
9:154759:T:G	K204N	0.986
9:178824:C:T	G49E	0.986
9:178825:C:A	G49W	0.986
9:172121:A:C	F130L	0.985
9:172121:A:T	F130L	0.985
9:172123:A:G	F130L	0.985
9:173310:A:G	W100R	0.985
9:173310:A:T	W100R	0.985
9:175772:G:A	T56I	0.985
9:175775:T:G	K55T	0.985
9:175782:C:G	A53P	0.985
9:175718:A:G	I74T	0.984
9:123221:A:G	L316P	0.983
9:172113:A:C	I133R	0.983

dbSNP variants (sampled 300 via entrez): RS1000017970 (9:128734 G>A,T), RS1000043326 (9:167113 G>T), RS1000093532 (9:137275 G>A,T), RS1000168832 (9:136893 A>C,G), RS1000206587 (9:176476 G>C), RS1000221841 (9:172413 A>C), RS1000237783 (9:176670 T>C), RS1000271019 (9:140761 C>G,T), RS1000273059 (9:160457 G>A,C), RS1000441599 (9:128929 G>A), RS1000448893 (9:146554 CCCTT>C), RS1000457169 (9:146848 G>C), RS1000552752 (9:172570 A>C,G), RS1000635650 (9:156696 T>C), RS1000639865 (9:151971 T>A,C,G)

Disease associations

OMIM: gene MIM:611078 | 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
GCST006628_56	Systolic blood pressure	3.000000e-11
GCST010304_49	Cutaneous malignant melanoma	9.000000e-07
GCST90002395_19	Mean platelet volume	5.000000e-17
GCST90002401_472	Platelet distribution width	2.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
trichostatin A	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Caffeine	decreases phosphorylation	1
Plant Extracts	affects cotreatment, increases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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