CZIB

Summary

CZIB (CXXC motif containing zinc binding protein, HGNC:26059) is a protein-coding gene on chromosome 1p32.3, encoding CXXC motif containing zinc binding protein (Q9NWV4).

Enables zinc ion binding activity.

Source: NCBI Gene 54987 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_017887

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26059
Approved symbol	CZIB
Name	CXXC motif containing zinc binding protein
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20580
Ensembl gene	ENSG00000162384
Ensembl biotype	protein_coding
Entrez	54987

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000294360, ENST00000470385, ENST00000474227, ENST00000478839, ENST00000483739, ENST00000489755, ENST00000602807, ENST00000912019, ENST00000912020, ENST00000912021, ENST00000912022, ENST00000912023, ENST00000912024

RefSeq mRNA: 3 — MANE Select: NM_017887 NM_001304759, NM_001304760, NM_017887

CCDS: CCDS576

Canonical transcript exons

ENST00000294360 — 8 exons

Exon	Start	End
ENSE00001064635	53214099	53214736
ENSE00001064637	53220570	53220634
ENSE00001064640	53220261	53220344
ENSE00003552193	53218414	53218495
ENSE00003565938	53218867	53218923
ENSE00003570366	53215991	53216056
ENSE00003601941	53218172	53218203
ENSE00003658182	53216782	53216859

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 97.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.3463 / max 243.9932, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12398	24.4415	1818
12397	0.9048	590

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.71	gold quality
body of uterus	UBERON:0009853	97.62	gold quality
right coronary artery	UBERON:0001625	97.49	gold quality
popliteal artery	UBERON:0002250	97.30	gold quality
tibial artery	UBERON:0007610	97.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.30	gold quality
right ovary	UBERON:0002118	97.25	gold quality
endocervix	UBERON:0000458	97.23	gold quality
artery	UBERON:0001637	97.20	gold quality
left uterine tube	UBERON:0001303	97.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.15	gold quality
lower esophagus	UBERON:0013473	97.14	gold quality
left ovary	UBERON:0002119	97.13	gold quality
aorta	UBERON:0000947	96.95	gold quality
left coronary artery	UBERON:0001626	96.93	gold quality
right uterine tube	UBERON:0001302	96.89	gold quality
coronary artery	UBERON:0001621	96.79	gold quality
descending thoracic aorta	UBERON:0002345	96.60	gold quality
peripheral nervous system	UBERON:0000010	96.58	gold quality
tibial nerve	UBERON:0001323	96.58	gold quality
thoracic aorta	UBERON:0001515	96.56	gold quality
mucosa of stomach	UBERON:0001199	96.55	gold quality
ascending aorta	UBERON:0001496	96.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.02	gold quality
ectocervix	UBERON:0012249	96.01	gold quality
smooth muscle tissue	UBERON:0001135	95.99	gold quality
peritoneum	UBERON:0002358	95.96	gold quality
omental fat pad	UBERON:0010414	95.96	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)

35 targeting CZIB, 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-1250-3P	99.96	70.04	4038
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-4637	97.69	68.14	632
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-6892-5P	97.27	68.60	847
HSA-MIR-8069	97.05	66.79	718

Literature-anchored findings (GeneRIF, showing 1)

• Study performed yeast two-hybrid screening of the human proteome and found an uncharacterized protein encoded as open reading frame 123 in chromosome 1 (C1orf123) that can interact specifically with the heavy metal-associated domain of a copper chaperone for superoxide dismutase. (PMID:30260988)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	czib	ENSDARG00000063341
mus_musculus	Czib	ENSMUSG00000028608
rattus_norvegicus	Czib	ENSRNOG00000012724
drosophila_melanogaster	CG4646	FBGN0033810
caenorhabditis_elegans		WBGENE00009776

Protein

Protein identifiers

CXXC motif containing zinc binding protein — Q9NWV4 (reviewed: Q9NWV4)

Alternative names: UPF0587 protein C1orf123

All UniProt accessions (1): Q9NWV4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Monomer.

Domain organisation. The N-terminal and the C-terminal half of the protein have a very similar 3D-structure, suggesting they arose from duplication. Requires a bound zinc ion for normal folding and solubility.

Similarity. Belongs to the UPF0587 family.

RefSeq proteins (3): NP_001291688, NP_001291689, NP_060357* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008584	CXXC_Zn-binding_euk	Family

Pfam: PF05907

UniProt features (27 total): strand 10, binding site 4, turn 4, mutagenesis site 4, helix 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5ZRT	X-RAY DIFFRACTION	1.9
5ZLQ	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWV4-F1	97.11	0.97

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 (4): 33; 36; 67; 70

Post-translational modifications (1): 75

Mutagenesis-validated functional residues (4):

Position	Phenotype
33	disrupts protein folding and solubility; when associated with a-36; a-67 and a-70.
36	disrupts protein folding and solubility; when associated with a-33; a-67 and a-70.
67	disrupts protein folding and solubility; when associated with a-33; a-36 and a-70.
70	disrupts protein folding and solubility; when associated with a-33; a-36 and a-67.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, BROWNE_HCMV_INFECTION_14HR_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, KIM_BIPOLAR_DISORDER_OLIGODENDROCYTE_DENSITY_CORR_UP, BRUINS_UVC_RESPONSE_LATE, CAMP_UP.V1_UP, ATF6_TARGET_GENES, FEV_TARGET_GENES, GUCY1B1_TARGET_GENES, HOXB4_TARGET_GENES, HOXB6_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CZIB	CCS	O14618	574
CZIB	RPS13	P19116	452
CZIB	RPS15	P11174	450
CZIB	RCCD1	A6NED2	447
CZIB	GARRE1	O15063	447
CZIB	RSAD1	Q9HA92	435
CZIB	UBLCP1	Q8WVY7	431
CZIB	LRATD1	Q96KN4	425
CZIB	RESF1	Q9HCM1	423
CZIB	DOP1A	Q5JWR5	410
CZIB	DPM3	Q9P2X0	396
CZIB	PHC2	Q8IXK0	392
CZIB	LRATD2	Q96KN1	392
CZIB	DPM2	O94777	388
CZIB	TMEM131	Q92545	385
CZIB	RFTN1	Q14699	385

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CZIB	CLTCL1	psi-mi:“MI:0915”(physical association)	0.400
CZIB	CCS	psi-mi:“MI:0915”(physical association)	0.370
ANXA1	CZIB	psi-mi:“MI:0915”(physical association)	0.370
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
VAMP4	NBAS	psi-mi:“MI:0914”(association)	0.350
CZIB	SFPQ	psi-mi:“MI:0914”(association)	0.350
CZIB	ERI3	psi-mi:“MI:0914”(association)	0.350
CACFD1	ORC4	psi-mi:“MI:0914”(association)	0.350
CD247	COL1A1	psi-mi:“MI:0914”(association)	0.350
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
CDKN1A	CZIB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (72): C1orf123 (Co-fractionation), C1orf123 (Co-fractionation), C1orf123 (Co-fractionation), C1orf123 (Co-fractionation), C1orf123 (Co-fractionation), HYOU1 (Co-fractionation), PRPF19 (Co-fractionation), C1orf123 (Affinity Capture-MS), C1orf123 (Affinity Capture-MS), C1orf123 (Proximity Label-MS), C1orf123 (Affinity Capture-MS), C1orf123 (Affinity Capture-RNA), BICD2 (Affinity Capture-MS), ERI3 (Affinity Capture-MS), RPS4Y1 (Affinity Capture-MS)

ESM2 similar proteins: A0A7U2QYM2, A0FKG7, A0JN39, D2SW95, O55236, O60508, O60942, P23514, P36954, P36958, P53618, P60898, P60899, P97789, Q32P66, Q32P73, Q5BJZ6, Q5R4A0, Q5R4J9, Q5R8R4, Q5R922, Q5RB77, Q5VQ78, Q5XK67, Q5ZIA5, Q66HV4, Q6H8D5, Q6H8D6, Q6NLH0, Q7ZVX6, Q80UM3, Q80UY1, Q8C878, Q8IZH2, Q8L5V0, Q8L828, Q8TBC4, Q99MI7, Q9BXJ9, Q9C827

Diamond homologs: A1Z9A2, A7SJ66, O74797, Q290L7, Q32P66, Q3B8G0, Q498R7, Q55C72, Q8BHG2, Q9BI88, Q9NWV4, P25654

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1271 predictions. Top by Δscore:

Variant	Effect	Δscore
1:53215986:CATA:C	donor_loss	1.0000
1:53215989:ACCT:A	donor_loss	1.0000
1:53215990:C:A	donor_loss	1.0000
1:53215990:CCTT:C	donor_gain	1.0000
1:53216052:CCAGC:C	acceptor_gain	1.0000
1:53216053:CAGC:C	acceptor_gain	1.0000
1:53216053:CAGCC:C	acceptor_gain	1.0000
1:53216054:AGC:A	acceptor_gain	1.0000
1:53216055:GC:G	acceptor_gain	1.0000
1:53216056:CC:C	acceptor_gain	1.0000
1:53216056:CCT:C	acceptor_loss	1.0000
1:53216057:C:CA	acceptor_loss	1.0000
1:53216057:C:CC	acceptor_gain	1.0000
1:53216065:C:CT	acceptor_gain	1.0000
1:53216778:ACAC:A	donor_loss	1.0000
1:53216779:CACCT:C	donor_loss	1.0000
1:53218170:A:AC	donor_gain	1.0000
1:53218171:C:CC	donor_gain	1.0000
1:53218412:A:AC	donor_gain	1.0000
1:53218413:C:CC	donor_gain	1.0000
1:53218491:CTGTC:C	acceptor_gain	1.0000
1:53220184:A:AC	donor_gain	1.0000
1:53220185:C:CC	donor_gain	1.0000
1:53214732:CAGTC:C	acceptor_gain	0.9900
1:53214736:CCTGG:C	acceptor_loss	0.9900
1:53214737:C:CC	acceptor_gain	0.9900
1:53214737:CTGG:C	acceptor_loss	0.9900
1:53214738:T:C	acceptor_loss	0.9900
1:53215989:A:AC	donor_gain	0.9900
1:53215990:C:CC	donor_gain	0.9900

AlphaMissense

1063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:53220272:A:G	W27R	0.998
1:53220272:A:T	W27R	0.998
1:53218444:A:G	C67R	0.997
1:53214733:A:G	W137R	0.995
1:53214733:A:T	W137R	0.995
1:53216822:A:G	F100S	0.994
1:53218435:A:G	C70R	0.994
1:53218443:C:G	C67S	0.994
1:53218444:A:T	C67S	0.994
1:53218917:A:G	C33R	0.994
1:53216043:G:T	A118D	0.993
1:53220265:A:G	L29P	0.993
1:53216049:A:G	F116S	0.992
1:53216791:G:C	F110L	0.992
1:53216791:G:T	F110L	0.992
1:53216793:A:G	F110L	0.992
1:53216801:G:T	P107Q	0.992
1:53216813:C:G	R103P	0.992
1:53218420:A:G	S75P	0.992
1:53218434:C:G	C70S	0.992
1:53218435:A:T	C70S	0.992
1:53218916:C:G	C33S	0.992
1:53218917:A:T	C33S	0.992
1:53220323:C:G	A10P	0.992
1:53218461:G:T	A61D	0.991
1:53220322:G:T	A10D	0.991
1:53220334:A:G	L6P	0.991
1:53216817:A:G	C102R	0.990
1:53220276:G:C	F25L	0.990
1:53220276:G:T	F25L	0.990

dbSNP variants (sampled 300 via entrez): RS1000367395 (1:53221844 G>C), RS1000543563 (1:53216472 C>G), RS1001054868 (1:53219880 G>C), RS1001380444 (1:53218699 G>A), RS1001548360 (1:53219521 T>C), RS1002548202 (1:53213671 G>A), RS1002664370 (1:53213955 CTGTGTAG>C), RS1002891683 (1:53219838 C>T), RS1003054243 (1:53216752 C>G,T), RS1003450416 (1:53215687 T>C,G), RS1003488750 (1:53218595 AC>A), RS1003658753 (1:53220827 G>T), RS1003846575 (1:53216796 C>A), RS1003972104 (1:53221274 G>C), RS1004855113 (1:53213964 C>T)

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

8 associations (top):

Study	Trait	p-value
GCST010696_8	Cortical thickness (min-P)	3.000000e-08
GCST010697_47	Cortical surface area (min-P)	7.000000e-14
GCST010698_52	Subcortical volume (min-P)	2.000000e-10
GCST010699_95	Brain morphology (min-P)	3.000000e-12
GCST010700_60	Cortical thickness (MOSTest)	1.000000e-09
GCST010701_101	Cortical surface area (MOSTest)	2.000000e-12
GCST010702_171	Subcortical volume (MOSTest)	3.000000e-16
GCST010703_172	Brain morphology (MOSTest)	4.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol A	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Diethylstilbestrol	decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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