ZXDC

Summary

ZXDC (ZXD family zinc finger C, HGNC:28160) is a protein-coding gene on chromosome 3q21.3, encoding Zinc finger protein ZXDC (Q2QGD7). Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.

Enables C2H2 zinc finger domain binding activity; LRR domain binding activity; and transcription coactivator activity. Involved in positive regulation of DNA-templated transcription. Predicted to be active in nucleus.

Source: NCBI Gene 79364 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 135 total
• MANE Select transcript: NM_025112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28160
Approved symbol	ZXDC
Name	ZXD family zinc finger C
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC11349, FLJ13861
Ensembl gene	ENSG00000070476
Ensembl biotype	protein_coding
OMIM	615746
Entrez	79364

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000336332, ENST00000389709, ENST00000514463, ENST00000515545, ENST00000894120, ENST00000894121, ENST00000894122, ENST00000916142, ENST00000916143, ENST00000959114

RefSeq mRNA: 2 — MANE Select: NM_025112 NM_001040653, NM_025112

CCDS: CCDS43145, CCDS43146

Canonical transcript exons

ENST00000389709 — 10 exons

Exon	Start	End
ENSE00000560196	126461535	126462220
ENSE00000777289	126459653	126459737
ENSE00001178817	126466155	126466325
ENSE00001236179	126470895	126471025
ENSE00001506697	126471973	126472051
ENSE00001506698	126472153	126472305
ENSE00001506699	126474959	126475891
ENSE00003460430	126437601	126438461
ENSE00003557038	126439632	126439727
ENSE00003586703	126441765	126441946

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 89.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1039 / max 401.6199, expressed in 1784 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44344	14.9709	1784
44342	0.1065	37
44343	0.0265	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	89.44	gold quality
right lobe of liver	UBERON:0001114	88.98	gold quality
muscle of leg	UBERON:0001383	88.89	gold quality
sural nerve	UBERON:0015488	88.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.48	gold quality
ganglionic eminence	UBERON:0004023	88.32	gold quality
right uterine tube	UBERON:0001302	88.19	gold quality
granulocyte	CL:0000094	87.87	gold quality
body of pancreas	UBERON:0001150	87.86	gold quality
left ovary	UBERON:0002119	87.10	gold quality
right ovary	UBERON:0002118	86.84	gold quality
muscle organ	UBERON:0001630	86.79	gold quality
mucosa of stomach	UBERON:0001199	86.59	gold quality
skin of leg	UBERON:0001511	86.40	gold quality
monocyte	CL:0000576	86.26	gold quality
mononuclear cell	CL:0000842	86.22	gold quality
leukocyte	CL:0000738	86.15	gold quality
ventricular zone	UBERON:0003053	86.13	gold quality
blood	UBERON:0000178	85.96	gold quality
tibial nerve	UBERON:0001323	85.90	gold quality
skin of abdomen	UBERON:0001416	85.72	gold quality
endocervix	UBERON:0000458	85.63	gold quality
endothelial cell	CL:0000115	85.53	silver quality
minor salivary gland	UBERON:0001830	85.32	gold quality
metanephros cortex	UBERON:0010533	85.28	gold quality
left uterine tube	UBERON:0001303	85.25	gold quality
right lobe of thyroid gland	UBERON:0001119	84.87	gold quality
spleen	UBERON:0002106	84.79	gold quality
ectocervix	UBERON:0012249	84.73	gold quality
tibia	UBERON:0000979	84.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CCL2
CD74
CDKN1C	Activation
CDKN2A
CIITA	Activation
HLA-E
IL5

JASPAR motifs

Motif	Name	Family
MA2577.1	ZXDC	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605320

Upstream regulators (CollecTRI, top): GATA1, GATA3

miRNA regulators (miRDB)

20 targeting ZXDC, 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-4789-3P	99.99	70.75	2484
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-3184-3P	96.96	66.91	845
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-4638-5P	92.31	65.23	86

Literature-anchored findings (GeneRIF, showing 7)

• ZXDC is an important regulator of both MHC class I and class II transcription (PMID:16600381)
• ZXDA and ZXDC form an important regulatory complex for MHC II gene transcription. (PMID:17493635)
• study found sumoylation does not appear to disrupt or modulate interaction of ZXDC with binding partners; sumoylation of ZXDC is required for full activity of transcriptional activation domain; study suggests sumoylation is an important regulator of ZXDC (PMID:17696781)
• Role of ZXD proteins in regulating MHC II transcription. (PMID:19777325)
• Data show that ZXDC1 is a regulator in the process of myeloid function and that ZXDC1 is responsible for Ccl2 gene de-repression by BCL6. (PMID:23954399)
• an expression quantitative trait loci of the ZXDC gene is associated with IFN-gamma production following Mycobacterium tuberculosis antigen-specific stimulation. (PMID:28993696)
• CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease. (PMID:36497052)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-156n14.3	ENSDARG00000052351
danio_rerio	zic6	ENSDARG00000071496
mus_musculus	Zxdc	ENSMUSG00000034430
rattus_norvegicus	Zxdc	ENSRNOG00000025818
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), GLI2 (ENSG00000074047), GLI3 (ENSG00000106571), GLIS3 (ENSG00000107249), GLI1 (ENSG00000111087), GLIS2 (ENSG00000126603), AEBP2 (ENSG00000139154), ZIC5 (ENSG00000139800), ZIC1 (ENSG00000152977), ZIC3 (ENSG00000156925), GLIS1 (ENSG00000174332), ZIC4 (ENSG00000174963), ZXDA (ENSG00000198205), ZXDB (ENSG00000198455)

Protein

Protein identifiers

Zinc finger protein ZXDC — Q2QGD7 (reviewed: Q2QGD7)

Alternative names: ZXD-like zinc finger protein

All UniProt accessions (2): Q2QGD7, H0YAA9

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 ZXDA and CIITA.

Subcellular location. Nucleus.

Tissue specificity. Expressed at high levels in heart, kidney, liver and testis, at moderate levels in brain and stomach, and at low levels in lung, muscle, placenta, small intestine and spleen.

Post-translational modifications. Sumoylated at Lys-660 with SUMO1, SUMO2 and SUMO3; sumoylation enhances the activity of the transcriptional activation domain.

Miscellaneous. Doesn’t interact with CIITA. Represses MHC class II transcription possibly via dominant-negative association with isoform 1.

Similarity. Belongs to the ZXD family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q2QGD7-1	1	yes
Q2QGD7-2	2
Q2QGD7-3	3, ZXDC2

RefSeq proteins (2): NP_001035743, NP_079388* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051061

Pfam: PF00096

UniProt features (33 total): zinc finger region 10, region of interest 7, compositionally biased region 5, modified residue 3, splice variant 3, sequence conflict 2, chain 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2QGD7-F1	52.68	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 34, 172, 665, 660

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, MODULE_493, chr3q21, GNF2_DDX5, ACEVEDO_LIVER_CANCER_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GOMF_C2H2_ZINC_FINGER_DOMAIN_BINDING, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_LRR_DOMAIN_BINDING, GOMF_TRANSCRIPTION_COACTIVATOR_ACTIVITY, CHYLA_CBFA2T3_TARGETS_UP, BRUINS_UVC_RESPONSE_MIDDLE, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_7

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

GO Molecular Function (7): transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), LRR domain binding (GO:0030275), 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
protein domain specific binding	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
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZXDC	ZXDA	P98168	799
ZXDC	CIITA	P33076	616
ZXDC	ARMC10	Q8N2F6	345
ZXDC	ZFYVE21	Q9BQ24	341
ZXDC	SHISA4	Q96DD7	340
ZXDC	SLC35E3	Q7Z769	324
ZXDC	KIAA1549L	Q6ZVL6	308
ZXDC	RNF213	Q63HN8	305
ZXDC	SNX11	Q9Y5W9	299
ZXDC	PPP2R2C	Q9Y2T4	292
ZXDC	CPN2	P22792	290
ZXDC	LRRC41	Q15345	288
ZXDC	NXN	Q6DKJ4	277
ZXDC	GLT1D1	Q96MS3	275
ZXDC	ANKRD46	Q86W74	272

IntAct

95 interactions, top by confidence:

A	B	Type	Score
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
WDR5	ZXDC	psi-mi:“MI:0915”(physical association)	0.800
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
CIITA	ZXDC	psi-mi:“MI:0915”(physical association)	0.670
ZXDC	CIITA	psi-mi:“MI:0914”(association)	0.670
POGZ	ZXDC	psi-mi:“MI:0915”(physical association)	0.670
ATXN1	ZXDC	psi-mi:“MI:0915”(physical association)	0.670
ZXDC	ATXN1	psi-mi:“MI:0915”(physical association)	0.670
ZXDA	ZXDC	psi-mi:“MI:0915”(physical association)	0.560
ZXDC	ZMYND19	psi-mi:“MI:0915”(physical association)	0.560
ZXDC	MEPE	psi-mi:“MI:0915”(physical association)	0.560
ZXDC	CBR4	psi-mi:“MI:0915”(physical association)	0.560
SUOX	ZXDC	psi-mi:“MI:0915”(physical association)	0.560
ZXDC		psi-mi:“MI:0915”(physical association)	0.560
ZXDC	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
ZXDC	PMP22	psi-mi:“MI:0915”(physical association)	0.560
ZXDC	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
ZXDC	PSEN2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (46): ZXDC (Two-hybrid), ZXDC (Two-hybrid), ZXDC (Affinity Capture-RNA), ZXDC (Affinity Capture-MS), ZXDC (Affinity Capture-MS), ZXDC (Affinity Capture-MS), ZXDC (Affinity Capture-RNA), ZXDC (Protein-RNA), ZXDC (Proximity Label-MS), WDR5 (Two-hybrid), POGZ (Two-hybrid), SUOX (Two-hybrid), POGZ (Two-hybrid), CBR4 (Two-hybrid), MEPE (Two-hybrid)

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

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	ZXDC	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	105
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2340 predictions. Top by Δscore:

Variant	Effect	Δscore
3:126470897:T:A	donor_gain	1.0000
3:126471021:GTTTC:G	acceptor_gain	1.0000
3:126471023:TTC:T	acceptor_gain	1.0000
3:126471024:TC:T	acceptor_gain	1.0000
3:126471024:TCCT:T	acceptor_loss	1.0000
3:126471025:CC:C	acceptor_gain	1.0000
3:126471025:CCT:C	acceptor_loss	1.0000
3:126471026:C:CA	acceptor_loss	1.0000
3:126471026:C:CC	acceptor_gain	1.0000
3:126471027:T:C	acceptor_loss	1.0000
3:126472053:T:C	acceptor_gain	1.0000
3:126472302:CAGC:C	acceptor_gain	1.0000
3:126461631:T:TA	donor_gain	0.9900
3:126461635:T:TA	donor_gain	0.9900
3:126462216:GAGAT:G	acceptor_gain	0.9900
3:126462218:GAT:G	acceptor_gain	0.9900
3:126462221:C:CC	acceptor_gain	0.9900
3:126462221:CTGA:C	acceptor_loss	0.9900
3:126462222:T:C	acceptor_loss	0.9900
3:126466063:T:TA	donor_gain	0.9900
3:126470890:TCTAC:T	donor_loss	0.9900
3:126470891:CTAC:C	donor_loss	0.9900
3:126470892:TA:T	donor_loss	0.9900
3:126470893:A:AT	donor_loss	0.9900
3:126470894:C:G	donor_loss	0.9900
3:126471022:TTTC:T	acceptor_gain	0.9900
3:126471030:C:CT	acceptor_gain	0.9900
3:126471030:C:T	acceptor_gain	0.9900
3:126472053:T:TC	acceptor_gain	0.9900
3:126472055:A:C	acceptor_gain	0.9900

AlphaMissense

5564 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:126466284:G:C	H438D	1.000
3:126466309:G:C	F429L	1.000
3:126466309:G:T	F429L	1.000
3:126466310:A:G	F429S	1.000
3:126466311:A:G	F429L	1.000
3:126470907:A:G	C420R	1.000
3:126470943:G:C	H408D	1.000
3:126470951:A:G	L405P	1.000
3:126470968:G:C	F399L	1.000
3:126470968:G:T	F399L	1.000
3:126470969:A:G	F399S	1.000
3:126470970:A:G	F399L	1.000
3:126470997:A:G	C390R	1.000
3:126471980:G:C	H378D	1.000
3:126471999:G:C	S371R	1.000
3:126471999:G:T	S371R	1.000
3:126472001:T:G	S371R	1.000
3:126472005:G:C	F369L	1.000
3:126472005:G:T	F369L	1.000
3:126472006:A:G	F369S	1.000
3:126472007:A:G	F369L	1.000
3:126472034:A:G	C360R	1.000
3:126472038:A:C	F358L	1.000
3:126472038:A:T	F358L	1.000
3:126472040:A:G	F358L	1.000
3:126472157:A:C	H352Q	1.000
3:126472157:A:T	H352Q	1.000
3:126472159:G:C	H352D	1.000
3:126472167:A:G	L349P	1.000
3:126472169:G:C	H348Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000057859 (3:126451245 A>G), RS1000128586 (3:126457134 C>A,G), RS1000222175 (3:126468034 G>A,T), RS1000264833 (3:126473093 C>T), RS1000319989 (3:126461308 T>C,G), RS1000361189 (3:126441474 C>T), RS1000395670 (3:126456936 G>A), RS1000476445 (3:126455597 G>A), RS1000506226 (3:126461368 G>A), RS1000519525 (3:126444607 A>G), RS1000666947 (3:126472612 T>C,G), RS1000738549 (3:126444963 C>A), RS1000822443 (3:126467088 C>A,T), RS1000861558 (3:126450122 A>G), RS1001034946 (3:126450276 C>G)

Disease associations

OMIM: gene MIM:615746 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005024_19	Pursuit maintenance gain	6.000000e-06
GCST009391_1006	Metabolite levels	4.000000e-06
GCST009391_2023	Metabolite levels	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement
EFO:0010359	lysophosphatidylcholine 18:0 measurement
EFO:0010371	lysophosphatidylethanolamine 22:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression, increases expression	7
Air Pollutants	affects expression, affects cotreatment, decreases expression, increases abundance	2
Ozone	affects expression, affects cotreatment, decreases expression, increases abundance	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
geldanamycin	increases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	decreases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Atrazine	decreases expression	1

Clinical trials (associated diseases)

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