ZXDA

Summary

ZXDA (zinc finger X-linked duplicated A, HGNC:13198) is a protein-coding gene on chromosome Xp11.21, encoding Zinc finger X-linked protein ZXDA (P98168). Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.

This gene encodes one of two duplicated zinc finger genes on chromosome Xp11. This gene is the telomeric copy; GeneID 158586 ZXDB is the more centromeric copy. The two genes have 98% nucleotide sequence similarity, and the predicted proteins contain 10 tandem zinc finger motifs.

Source: NCBI Gene 7789 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_007156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13198
Approved symbol	ZXDA
Name	zinc finger X-linked duplicated A
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	ZNF896
Ensembl gene	ENSG00000198205
Ensembl biotype	protein_coding
OMIM	300235
Entrez	7789

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000358697

RefSeq mRNA: 1 — MANE Select: NM_007156 NM_007156

CCDS: CCDS14376

Canonical transcript exons

ENST00000358697 — 1 exons

Exon	Start	End
ENSE00001414587	57905430	57910458

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 85.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5574 / max 24.9916, expressed in 84 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199434	0.3904	74
199432	0.1045	61
199433	0.0625	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	85.15	gold quality
buccal mucosa cell	CL:0002336	84.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.76	gold quality
calcaneal tendon	UBERON:0003701	76.56	gold quality
germinal epithelium of ovary	UBERON:0001304	74.82	gold quality
cortical plate	UBERON:0005343	74.27	gold quality
tendon	UBERON:0000043	73.10	gold quality
ganglionic eminence	UBERON:0004023	72.80	gold quality
ventricular zone	UBERON:0003053	72.28	gold quality
tibia	UBERON:0000979	72.09	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.27	silver quality
islet of Langerhans	UBERON:0000006	71.15	gold quality
medial globus pallidus	UBERON:0002477	71.08	silver quality
stromal cell of endometrium	CL:0002255	71.05	gold quality
parietal pleura	UBERON:0002400	71.01	gold quality
cauda epididymis	UBERON:0004360	70.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.79	silver quality
pleura	UBERON:0000977	69.74	gold quality
caput epididymis	UBERON:0004358	69.13	gold quality
corpus epididymis	UBERON:0004359	69.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	68.65	gold quality
visceral pleura	UBERON:0002401	68.60	gold quality
biceps brachii	UBERON:0001507	68.47	silver quality
deltoid	UBERON:0001476	68.46	silver quality
skin of hip	UBERON:0001554	68.10	gold quality
muscle of leg	UBERON:0001383	67.71	gold quality
pigmented layer of retina	UBERON:0001782	67.20	gold quality
globus pallidus	UBERON:0001875	66.89	silver quality
muscle organ	UBERON:0001630	66.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.58

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CD74
CDKN2A
HLA-E

JASPAR motifs

Motif	Name	Family
MA2596.1	ZXDA	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605320

miRNA regulators (miRDB)

126 targeting ZXDA, 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-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778

Literature-anchored findings (GeneRIF, showing 2)

• ZXDA and ZXDC form an important regulatory complex for MHC II gene transcription. (PMID:17493635)
• Role of ZXD proteins in regulating MHC II transcription. (PMID:19777325)

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), ZXDB (ENSG00000198455)

Protein

Protein identifiers

Zinc finger X-linked protein ZXDA — P98168 (reviewed: P98168)

All UniProt accessions (1): P98168

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_009087* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051061

Pfam: PF00096, PF13912

UniProt features (17 total): zinc finger region 10, region of interest 3, sequence variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98168-F1	55.14	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): CTGAGCC_MIR24, GOMF_C2H2_ZINC_FINGER_DOMAIN_BINDING, HAMAI_APOPTOSIS_VIA_TRAIL_UP, GOMF_TRANSCRIPTION_COACTIVATOR_ACTIVITY, chrXp11, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, GOMF_TRANSCRIPTION_COREGULATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR8485, MIR651_3P, MIR5696, MIR340_5P, MIR30B_5P_MIR30C_5P, MIR30D_5P, MIR30E_5P

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

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZXDA	ZXDC	Q2QGD7	799
ZXDA	DPY19L3	Q6ZPD9	376
ZXDA	MANEAL	Q5VSG8	362
ZXDA	ACVR1C	Q8NER5	349
ZXDA	PRPSAP1	Q14558	349
ZXDA	RTL9	Q8NET4	348
ZXDA	PPP1R3G	B7ZBB8	336
ZXDA	OCRL	Q01968	332
ZXDA	TCF15	Q12870	328
ZXDA	PLEKHH2	Q8IVE3	323
ZXDA	NALF2	O75949	321
ZXDA	NLRP13	Q86W25	317
ZXDA	ZC3H8	Q8N5P1	315
ZXDA	MARCHF10	Q8NA82	315
ZXDA	CHST10	O43529	307

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ZXDC	CIITA	psi-mi:“MI:0914”(association)	0.670
ZXDA	ZXDC	psi-mi:“MI:0915”(physical association)	0.560
ZXDA	CIITA	psi-mi:“MI:0915”(physical association)	0.480
CIITA	ZXDA	psi-mi:“MI:0915”(physical association)	0.480
ZXDA	CIITA	psi-mi:“MI:0914”(association)	0.480
ZXDA	ZXDA	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (19): ZXDA (Affinity Capture-RNA), ZXDA (Affinity Capture-MS), FBXO38 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), CSNK2A1 (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), FBXO38 (Affinity Capture-MS), CENPB (Affinity Capture-MS), PPP6C (Affinity Capture-MS), PPP2R2A (Affinity Capture-MS), RBX1 (Affinity Capture-MS), SUGT1 (Affinity Capture-MS), CUL1 (Affinity Capture-MS), SKP1 (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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5 predictions. Top by Δscore:

Variant	Effect	Δscore
X:57910300:TGGGG:T	donor_gain	0.4200
X:57910102:G:T	donor_gain	0.3100
X:57910132:C:T	donor_gain	0.3000
X:57910133:C:T	donor_gain	0.2400
X:57910137:G:T	donor_gain	0.2400

AlphaMissense

5233 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:57908858:G:C	F521L	1.000
X:57908858:G:T	F521L	1.000
X:57908859:A:G	F521S	1.000
X:57908860:A:G	F521L	1.000
X:57908891:G:C	F510L	1.000
X:57908891:G:T	F510L	1.000
X:57908893:A:G	F510L	1.000
X:57908921:G:C	H500Q	1.000
X:57908921:G:T	H500Q	1.000
X:57908923:G:C	H500D	1.000
X:57908931:A:G	L497P	1.000
X:57908943:C:A	R493M	1.000
X:57908948:G:C	F491L	1.000
X:57908948:G:T	F491L	1.000
X:57908949:A:G	F491S	1.000
X:57908950:A:G	F491L	1.000
X:57908977:A:G	C482R	1.000
X:57909011:G:C	H470Q	1.000
X:57909011:G:T	H470Q	1.000
X:57909013:G:C	H470D	1.000
X:57909013:G:T	H470N	1.000
X:57909015:C:A	R469M	1.000
X:57909021:A:G	L467P	1.000
X:57909032:G:C	S463R	1.000
X:57909032:G:T	S463R	1.000
X:57909034:T:G	S463R	1.000
X:57909038:G:C	F461L	1.000
X:57909038:G:T	F461L	1.000
X:57909039:A:G	F461S	1.000
X:57909040:A:G	F461L	1.000

dbSNP variants (sampled 300 via entrez): RS1000033789 (X:57907602 A>T), RS1000187148 (X:57906608 C>T), RS1003409086 (X:57907424 T>C), RS1003582238 (X:57906064 G>A), RS1004485075 (X:57910449 C>T), RS1004854589 (X:57905300 C>T), RS1005227330 (X:57908467 C>A,T), RS1005242750 (X:57911771 TTTCTTTC>T), RS1005526373 (X:57905666 T>C), RS1005896195 (X:57912129 T>C), RS1009258590 (X:57907700 G>A), RS1010072115 (X:57906126 G>A), RS1010338422 (X:57906729 A>G), RS1010453779 (X:57906699 T>A,G), RS1010619098 (X:57907324 T>C)

Disease associations

OMIM: gene MIM:300235 | disease phenotypes: MIM:617667

GenCC curated gene-disease

Mondo (1): Fraser syndrome 3 (MONDO:0054739)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002040_3	Blood trace element (Zn levels)	1.000000e-12
GCST003983_8	Male-pattern baldness	6.000000e-20
GCST006661_307	Male-pattern baldness	1.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
hydroxyhydroquinone	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
Sunitinib	increases expression	1
Amiodarone	increases expression	1
Cadmium	increases expression	1
Methotrexate	increases expression	1
Urethane	affects expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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