ZXDB

Summary

ZXDB (zinc finger X-linked duplicated B, HGNC:13199) is a protein-coding gene on chromosome Xp11.21, encoding Zinc finger X-linked protein ZXDB (P98169). Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.

The ZXDB gene is one of a pair of duplicated zinc finger genes on chromosome Xp11.21 (Greig et al., 1993 [PubMed 8268913]); see also ZXDA (MIM 300235).

Source: NCBI Gene 158586 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 68 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_007157

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13199
Approved symbol	ZXDB
Name	zinc finger X-linked duplicated B
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	ZNF905
Ensembl gene	ENSG00000198455
Ensembl biotype	protein_coding
OMIM	300236
Entrez	158586

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000374888

RefSeq mRNA: 1 — MANE Select: NM_007157 NM_007157

CCDS: CCDS35313

Canonical transcript exons

ENST00000374888 — 1 exons

Exon	Start	End
ENSE00001465020	57592011	57597477

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 81.86.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0645 / max 36.0566, expressed in 211 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196514	0.7540	171
196515	0.1603	66
196516	0.1502	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	81.86	gold quality
cortical plate	UBERON:0005343	80.20	gold quality
palpebral conjunctiva	UBERON:0001812	79.92	gold quality
ventricular zone	UBERON:0003053	79.66	gold quality
ganglionic eminence	UBERON:0004023	79.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	77.64	gold quality
right lobe of liver	UBERON:0001114	77.52	gold quality
islet of Langerhans	UBERON:0000006	77.49	gold quality
superficial temporal artery	UBERON:0001614	75.21	silver quality
parietal pleura	UBERON:0002400	75.05	gold quality
gastrocnemius	UBERON:0001388	74.69	gold quality
liver	UBERON:0002107	74.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.49	gold quality
muscle of leg	UBERON:0001383	74.21	gold quality
Brodmann (1909) area 23	UBERON:0013554	73.99	gold quality
stromal cell of endometrium	CL:0002255	73.93	gold quality
descending thoracic aorta	UBERON:0002345	73.86	gold quality
popliteal artery	UBERON:0002250	73.55	gold quality
tibial artery	UBERON:0007610	73.54	gold quality
right coronary artery	UBERON:0001625	73.30	gold quality
pancreas	UBERON:0001264	73.26	gold quality
left uterine tube	UBERON:0001303	73.20	gold quality
prefrontal cortex	UBERON:0000451	73.09	gold quality
aorta	UBERON:0000947	73.04	gold quality
pleura	UBERON:0000977	73.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.98	gold quality
gall bladder	UBERON:0002110	72.79	gold quality
endometrium	UBERON:0001295	72.77	gold quality
lower lobe of lung	UBERON:0008949	72.69	gold quality
skin of abdomen	UBERON:0001416	72.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-11	no	181.22
E-ANND-3	no	3.30

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2576.1	ZXDB	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605320

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

172 targeting ZXDB, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-651-3P	99.94	73.48	5177
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

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-156n14.3	ENSDARG00000052351
danio_rerio	zic6	ENSDARG00000071496
drosophila_melanogaster	opa	FBGN0003002
drosophila_melanogaster	ci	FBGN0004859
drosophila_melanogaster	lmd	FBGN0039039
caenorhabditis_elegans		WBGENE00004335
caenorhabditis_elegans		WBGENE00006604
caenorhabditis_elegans		WBGENE00010936

Paralogs (14): ZIC2 (ENSG00000043355), ZXDC (ENSG00000070476), GLI2 (ENSG00000074047), GLI3 (ENSG00000106571), GLIS3 (ENSG00000107249), GLI1 (ENSG00000111087), GLIS2 (ENSG00000126603), AEBP2 (ENSG00000139154), ZIC5 (ENSG00000139800), ZIC1 (ENSG00000152977), ZIC3 (ENSG00000156925), GLIS1 (ENSG00000174332), ZIC4 (ENSG00000174963), ZXDA (ENSG00000198205)

Protein

Protein identifiers

Zinc finger X-linked protein ZXDB — P98169 (reviewed: P98169)

All UniProt accessions (1): P98169

UniProt curated annotations — full annotation on UniProt →

Function. Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.

Subunit / interactions. Self-associates. Interacts with ZXDC and CIITA.

Subcellular location. Nucleus.

Tissue specificity. May be expressed in brain, heart, kidney, liver, lung, muscle and placenta.

Similarity. Belongs to the ZXD family.

RefSeq proteins (1): NP_009088* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051061

Pfam: PF00096

UniProt features (21 total): zinc finger region 10, region of interest 5, sequence variant 4, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98169-F1	54.46	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GCM_NF2, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_LIVER_CANCER_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, CTGAGCC_MIR24, GOMF_C2H2_ZINC_FINGER_DOMAIN_BINDING, GOMF_TRANSCRIPTION_COACTIVATOR_ACTIVITY, chrXp11, GRYDER_PAX3FOXO1_ENHANCERS_KO_DOWN, DANG_REGULATED_BY_MYC_DN, GOMF_TRANSCRIPTION_COREGULATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, SFMBT1_TARGET_GENES, MIR651_3P, MIR3658

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (6): transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), C2H2 zinc finger domain binding (GO:0070742), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription regulator activity	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
transition metal ion binding	1
protein domain specific binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZXDB	NSUN3	Q9H649	593
ZXDB	AP3B1	O00203	571
ZXDB	CCDC144NL	Q6NUI1	413
ZXDB	TCF15	Q12870	412
ZXDB	DPY19L3	Q6ZPD9	407
ZXDB	TMEM164	Q5U3C3	387
ZXDB	MANEAL	Q5VSG8	387
ZXDB	PRPSAP1	Q14558	377
ZXDB	PPP1R3G	B7ZBB8	375
ZXDB	CNTNAP3B	Q96NU0	368
ZXDB	ZC3H8	Q8N5P1	355
ZXDB	ATP12A	P54707	353
ZXDB	FAM8A1	Q9UBU6	352
ZXDB	NLRP13	Q86W25	351
ZXDB	KRTAP5-11	Q6L8G4	349

IntAct

12 interactions, top by confidence:

A	B	Type	Score
EIF4A3	ZXDB	psi-mi:“MI:0915”(physical association)	0.560
USP20	ZXDB	psi-mi:“MI:0915”(physical association)	0.560
ZXDB	ZGPAT	psi-mi:“MI:0915”(physical association)	0.560
ZXDB	SETD1A	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
EIF4A3	ZXDB	psi-mi:“MI:0915”(physical association)	0.000
USP20	ZXDB	psi-mi:“MI:0915”(physical association)	0.000
ZGPAT	ZXDB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): ZXDB (Two-hybrid), ZXDB (Two-hybrid), ZXDB (Two-hybrid), ZXDB (Affinity Capture-RNA), CENPB (Affinity Capture-MS), NTSR1 (Affinity Capture-MS), FAM172A (Affinity Capture-MS), TAF9B (Affinity Capture-MS), FBLN5 (Affinity Capture-MS), VPS72 (Affinity Capture-MS), TSEN2 (Affinity Capture-MS), TRRAP (Affinity Capture-MS), C18orf25 (Affinity Capture-MS), FBXO38 (Affinity Capture-MS), CXXC1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ4, A2APT9, A6NEL2, A6NP61, B1ASB6, B1WBS3, B2RXF5, F6WEQ6, O15015, O43918, O88282, O88286, O95785, P98168, P98169, Q2M3G4, Q2MHN3, Q2QGD7, Q3U1J1, Q3U381, Q497V6, Q5SW24, Q5SXM2, Q6YND2, Q6ZMQ8, Q6ZMY3, Q7TN08, Q7TSX9, Q80SU3, Q80YE4, Q811H0, Q8BG26, Q8BZW2, Q8C8V1, Q8IX07, Q8IY92, Q8N143, Q8N1G0, Q8NC74, Q8TBE0

Diamond homologs: A2CE44, P98168, P98169, Q2QGD7, Q8C8V1

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — BRCA.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

15 predictions. Top by Δscore:

Variant	Effect	Δscore
X:57592349:G:A	donor_gain	0.3900
X:57592379:C:A	donor_gain	0.3900
X:57593267:G:GG	donor_gain	0.3400
X:57592348:G:A	donor_gain	0.3200
X:57592344:C:A	donor_gain	0.3100
X:57594564:CAAAA:C	acceptor_gain	0.3000
X:57594565:AAAAA:A	acceptor_gain	0.3000
X:57596245:AAAGT:A	acceptor_gain	0.2900
X:57592164:TCCCC:T	donor_gain	0.2700
X:57593761:GCA:G	donor_gain	0.2700
X:57592402:G:GT	donor_gain	0.2500
X:57593266:A:AG	donor_gain	0.2500
X:57592403:G:T	donor_gain	0.2300
X:57592389:GGCC:G	donor_gain	0.2100
X:57592341:ACCC:A	donor_gain	0.2000

AlphaMissense

5252 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:57592991:T:C	F315L	1.000
X:57592993:C:A	F315L	1.000
X:57592993:C:G	F315L	1.000
X:57593018:C:A	H324N	1.000
X:57593018:C:G	H324D	1.000
X:57593020:C:A	H324Q	1.000
X:57593020:C:G	H324Q	1.000
X:57593081:T:C	F345L	1.000
X:57593082:T:C	F345S	1.000
X:57593083:C:A	F345L	1.000
X:57593083:C:G	F345L	1.000
X:57593096:A:G	N350D	1.000
X:57593100:T:C	L351P	1.000
X:57593108:C:G	H354D	1.000
X:57593258:T:C	F404L	1.000
X:57593260:T:A	F404L	1.000
X:57593260:T:G	F404L	1.000
X:57593285:C:A	H413N	1.000
X:57593285:C:G	H413D	1.000
X:57593287:T:A	H413Q	1.000
X:57593287:T:G	H413Q	1.000
X:57593324:T:C	C426R	1.000
X:57593325:G:A	C426Y	1.000
X:57593326:C:G	C426W	1.000
X:57593357:A:G	K437E	1.000
X:57593359:G:C	K437N	1.000
X:57593359:G:T	K437N	1.000
X:57593363:T:C	C439R	1.000
X:57593367:G:C	R440T	1.000
X:57593367:G:T	R440M	1.000

dbSNP variants (sampled 300 via entrez): RS1000283649 (X:57596855 T>TGAG), RS1000336991 (X:57596535 C>G,T), RS1001885710 (X:57594816 TG>T), RS1001962032 (X:57596927 G>C), RS1002399855 (X:57594824 C>G,T), RS1003843224 (X:57590483 T>C), RS1003893634 (X:57590052 C>T), RS1006150947 (X:57597572 T>A), RS1006488414 (X:57597047 G>A), RS1007661852 (X:57596600 A>G), RS1008056213 (X:57594139 G>A,T), RS1008628085 (X:57596467 G>A), RS1009446529 (X:57595938 CTG>C), RS1011456928 (X:57591128 C>A,G,T), RS1012711422 (X:57597604 A>G)

Disease associations

OMIM: gene MIM:300236 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002040_3	Blood trace element (Zn levels)	1.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	4
sodium arsenite	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
hydroxyhydroquinone	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Coumestrol	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dinitrofluorobenzene	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Oxazolone	increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	affects expression	1
Zinc	decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	affects expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_HD51	HEK293 eGFP-ZXDB	Transformed cell line	Female

Clinical trials (associated diseases)

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