ZFX

Summary

ZFX (zinc finger protein X-linked, HGNC:12869) is a protein-coding gene on chromosome Xp22.11, encoding Zinc finger X-chromosomal protein (P17010). Probable transcriptional activator. It is a selective cancer dependency (DepMap: 23.7% of cell lines).

This gene on the X chromosome is structurally similar to a related gene on the Y chromosome. It encodes a member of the krueppel C2H2-type zinc-finger protein family. The full-length protein contains an acidic transcriptional activation domain (AD), a nuclear localization sequence (NLS) and a DNA binding domain (DBD) consisting of 13 C2H2-type zinc fingers. Studies in mouse embryonic and adult hematopoietic stem cells showed that this gene was required as a transcriptional regulator for self-renewal of both stem cell types, but it was dispensable for growth and differentiation of their progeny. Multiple alternatively spliced transcript variants encoding different isoforms have been identified, but the full-length nature of some variants has not been determined.

Source: NCBI Gene 7543 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked syndromic complex neurodevelopmental disorder (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 249 total — 7 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 201
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 23.7% of screened cell lines
• MANE Select transcript: NM_003410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12869
Approved symbol	ZFX
Name	zinc finger protein X-linked
Location	Xp22.11
Locus type	gene with protein product
Status	Approved
Aliases	ZNF926
Ensembl gene	ENSG00000005889
Ensembl biotype	protein_coding
OMIM	314980
Entrez	7543

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 30 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000304543, ENST00000338565, ENST00000379177, ENST00000379188, ENST00000419690, ENST00000428571, ENST00000459724, ENST00000474385, ENST00000480195, ENST00000497813, ENST00000539115, ENST00000867190, ENST00000867191, ENST00000867192, ENST00000867193, ENST00000867194, ENST00000867195, ENST00000867196, ENST00000923535, ENST00000923536, ENST00000923537, ENST00000923538, ENST00000923539, ENST00000949205, ENST00000949206, ENST00000949207, ENST00000949208, ENST00000949209, ENST00000949210, ENST00000949211, ENST00000949212, ENST00000949213, ENST00000949214, ENST00000949215

RefSeq mRNA: 6 — MANE Select: NM_003410 NM_001178084, NM_001178085, NM_001178086, NM_001178095, NM_001330327, NM_003410

CCDS: CCDS14211, CCDS55390, CCDS83461

Canonical transcript exons

ENST00000304543 — 10 exons

Exon	Start	End
ENSE00001176296	24179183	24179770
ENSE00001231744	24152720	24152830
ENSE00001231749	24151691	24151800
ENSE00001598623	24208218	24208370
ENSE00001708883	24210193	24216255
ENSE00001722640	24149729	24149794
ENSE00002688681	24172715	24172800
ENSE00002732075	24208900	24209040
ENSE00003471331	24207712	24207855
ENSE00003592125	24207326	24207475

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 92.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3541 / max 169.8142, expressed in 1783 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195794	10.2338	1756
195791	2.7226	1232
195792	0.6577	385
195790	0.3967	173
195793	0.1819	90
195795	0.1189	29
209633	0.0425	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.96	gold quality
sural nerve	UBERON:0015488	92.24	gold quality
germinal epithelium of ovary	UBERON:0001304	91.22	gold quality
tendon	UBERON:0000043	90.14	gold quality
colonic epithelium	UBERON:0000397	89.51	gold quality
adrenal tissue	UBERON:0018303	88.96	gold quality
monocyte	CL:0000576	88.61	gold quality
mononuclear cell	CL:0000842	88.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.76	gold quality
leukocyte	CL:0000738	87.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.46	gold quality
stromal cell of endometrium	CL:0002255	87.19	gold quality
tibia	UBERON:0000979	87.10	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.90	gold quality
biceps brachii	UBERON:0001507	86.78	gold quality
epithelium of nasopharynx	UBERON:0001951	86.06	gold quality
nasopharynx	UBERON:0001728	86.04	gold quality
ventricular zone	UBERON:0003053	85.68	gold quality
ovary	UBERON:0000992	85.59	gold quality
left ovary	UBERON:0002119	85.39	gold quality
body of uterus	UBERON:0009853	85.30	gold quality
endometrium	UBERON:0001295	85.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.15	gold quality
muscle of leg	UBERON:0001383	84.90	gold quality
gastrocnemius	UBERON:0001388	84.86	gold quality
tonsil	UBERON:0002372	84.79	gold quality
bone marrow cell	CL:0002092	84.72	gold quality
right ovary	UBERON:0002118	84.61	gold quality
granulocyte	CL:0000094	84.37	gold quality
left uterine tube	UBERON:0001303	84.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.75
E-GEOD-98556	no	764.34

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
FBP1	Repression
HLA-A
HLA-E
NOTCH1
OCRL

miRNA regulators (miRDB)

312 targeting ZFX, 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-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• high expression of ZFX is associated with laryngeal squamous cell carcinoma progression and knockdown of ZFX may block tumor cell growth mainly by promoting cell apoptosis (PMID:22009483)
• Zfx may play a critical role in cell proliferation, cell cycle distribution, and apoptosis of human malignant glioma cells. (PMID:22185393)
• ZFX was differentially expressed in different tumour types and grades of gastric cancer. (PMID:22357206)
• ZFX acts as a molecular rheostat regulating the balance between self-renewal and differentiation in human Embryonic stem cells. (PMID:22879936)
• disseminated gastric cancer cells could survive in bone marrow when low expression of miR-144 permits upregulation of ZFX. This may play a key role in the progression of gastric cancer. (PMID:22955854)
• This study demonistrated that ZFX regulates glioma cell proliferation and survival. (PMID:23322077)
• ZFX may play an important role in cell growth control and cell cycle progression of 95D cells. (PMID:23461064)
• ZFX plays a prominent role in gastric cancer tumorigenicity and may have potential applications in the diagnosis or treatment of GC. (PMID:23587796)
• Zinc finger X-chromosomal protein promoted the growth and migration of gallbladder cancer cells. (PMID:23860324)
• ZFX is over-expressed in children with B-acute lymphoblastic leukemia and its levels are higher in those with a poor prognosis than those with a good prognosis (PMID:23866268)
• ZFX knockdown prevented tumor cell growth and migration in vitro and decreased proportion of tumor bearing mice and reduced mean tumor volume in a subcutaneous tumor model. (PMID:24228108)
• Expression of ZFX promotes tumor growth in hepatocellular carcinoma. (PMID:24585547)
• These data demonstrate that ZFX functions as a critical upstream regulator of c-Myc and plays essential roles in the maintenance of the glioma stem cells phenotype (PMID:24831540)
• our findings for the first time demonstrated that ZFX expression may be associated with the progress of colorectal cancer (PMID:25031734)
• ZFX is essential for the development and progression of squamous cell carcinoma of the tongue. (PMID:25355536)
• Study detected the expression of ZFX in 42 patients with renal cancer and found the expression of ZFX was specifically upregulated in cancer tissues at the mRNA and protein levels. (PMID:25441684)
• Our results provide evidence suggesting that ZFX overexpression is associated with the development of tongue SCC and ZFX knockdown is a potential treatment for tumor suppression (PMID:25916205)
• Nasopharyngeal carcinoma patients with high ZFX expression had lower 5-year overall survival rates, progression-free survival rates, loco-regional relapse-free survival rates and distant metastasis-free survival rates than those with low ZFX expression (PMID:26097576)
• ZFX expression may have a role in poor prognosis of renal cell carcinoma patients (PMID:26540164)
• Zinc finger protein x-linked contributes to patient prognosis, and regulates cell proliferation and apoptosis in human laryngeal squamous cell carcinoma. (PMID:26823701)
• EZH2 and ZFX genes do not seem to have an impact on the onset of most parathyroid tumours, both benign and malignant, though further studies on larger cohorts of different ethnicity are needed. (PMID:26876532)
• ZFX is a novel oncogene promoting cell proliferation and inducing imatinib resistance via PI3K/Akt signaling pathway (PMID:26912059)
• Findings indicate that zinc-finger protein X-linked (ZFX) promotes colorectal cancer (CRC) progression by suppressing dual specificity phosphatase 5 (DUSP5) expression and suggest that ZFX is a prognostic biomarker and potentially useful therapeutic target in stage II/III CRC patients. (PMID:26967242)
• Zinc finger and X-linked factor ZFX transactivates the SET transcript 2 promoter through binding to a site closely located to the transcription start site. (PMID:27775603)
• demonstrated that ZFX is aberrantly expressed in multiple human leukemic cells and it modulates the growth and drug response of leukemic cells partially via B4GALT1, which suggests that ZFX is a new regulator of leukemic cells and warrants intensive investigations on this ‘stemness’ regulator in these deadly diseases (PMID:27797721)
• The research findings indicate that Zinc finger protein X-linked (ZFX) activates and maintains EpCAM(+) liver cancer stem cells by promoting nuclear translocation and transactivation of beta-catenin. Furthermore, combination of ZFX and epithelial cell adhesion molecule (EpCAM) may serve as a significant indicator for prognosis of patients with hepatocellular carcinoma. (PMID:28156061)
• miR-144 has been demonstrated to act as a tumour suppressor in hepatocellular carcinoma (HCC) cell growth and motility by directly targeting ZFX, which implicates its potential applications in the development of HCC treatment (PMID:28229969)
• colon cancer-associated transcript-1 knockdown inhibits proliferation and invasion of laryngeal squamous cell cancer cells through enhancing zinc finger protein, X-linked by sponging microRNA-218, elucidating a novel colon cancer-associated transcript-1-microRNA-218-zinc finger protein, X-linked regulatory axis in laryngeal squamous cell cancer and providing a promising therapeutic target for laryngeal cancer (PMID:28631575)
• ZFX acts as a transcriptional activator in multiple types of human tumors by binding downstream from transcription start sites at the majority of CpG island promoters. (PMID:29429977)
• ZFX-spliced transcripts could be considered as novel tumor markers with a probable value in diagnosis, prognosis, and therapy of breast cancer. (PMID:29753316)
• MiR-493 functioned as tumor suppressor in HCC cells by regulating ZFX expression. Thus, miR-493 may provide potential value for HCC treatment. (PMID:29758928)
• The depletion of ZFX using lentiviral shRNAs significantly inhibited cell proliferation by inducing cell cycle arrest in G0/G1 phase and resulted in increased cell apoptosis and invasive repression. (PMID:30007968)
• AR-V7 has both ARE/FOXA1 canonical and ZFX-directed non-canonical regulatory functions in the evolution of anti-androgen therapeutic resistance. (PMID:30270106)
• LncRNA SNHG20 contributes to cell proliferation and invasion by upregulating ZFX expression sponging miR-495-3p in gastric cancer (PMID:30520073)
• Our data indicate that CCAT1 promotes triple-negative breast cancer progression by targeting the miR-218/ZFX axis (PMID:31310241)
• Homoharringtonine may enhance the effect of imatinib on chronic myelogenous leukemia cells by downregulating ZFX. (PMID:31432109)
• Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters. (PMID:32406922)
• Zfx-induced upregulation of UBE2J1 facilitates endometrial cancer progression via PI3K/AKT pathway. (PMID:33632059)
• Circ_0000520 contributes to triple-negative breast cancer progression through mediating the miR-1296/ZFX axis. (PMID:34324278)
• Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt. (PMID:38325380)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfx	ENSMUSG00000079509
rattus_norvegicus	Zfx	ENSRNOG00000005624

Paralogs (38): ZBTB11 (ENSG00000066422), ZFAT (ENSG00000066827), ZFY (ENSG00000067646), ZNF586 (ENSG00000083828), IKZF5 (ENSG00000095574), ZNF419 (ENSG00000105136), ZNF549 (ENSG00000121406), ZSCAN20 (ENSG00000121903), ZNF304 (ENSG00000131845), PRDM15 (ENSG00000141956), ZNF660 (ENSG00000144792), ZNF711 (ENSG00000147180), ZNF773 (ENSG00000152439), ZNF256 (ENSG00000152454), ZNF837 (ENSG00000152475), ZNF691 (ENSG00000164011), ZNF610 (ENSG00000167554), E4F1 (ENSG00000167967), ZNF562 (ENSG00000171466), ZNF561 (ENSG00000171469), ZNF584 (ENSG00000171574), ZIK1 (ENSG00000171649), ZNF570 (ENSG00000171827), ZSCAN2 (ENSG00000176371), ZNF552 (ENSG00000178935), ZNF154 (ENSG00000179909), ZNF792 (ENSG00000180884), ZNF793 (ENSG00000188227), ZNF548 (ENSG00000188785), ZNF79 (ENSG00000196152), ZNF418 (ENSG00000196724), ZNF772 (ENSG00000197128), ZNF583 (ENSG00000198440), ZNF480 (ENSG00000198464), ZNF551 (ENSG00000204519), ZNF134 (ENSG00000213762), ZNF587B (ENSG00000269343), ZNF8 (ENSG00000278129)

Protein

Protein identifiers

Zinc finger X-chromosomal protein — P17010 (reviewed: P17010)

All UniProt accessions (4): P17010, C9J682, C9JGU9, E9PEP7

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcriptional activator.

Subcellular location. Nucleus.

Disease relevance. Intellectual developmental disorder, X-linked, syndromic 37 (MRXS37) [MIM:301118] A syndromic neurodevelopmental disorder characterized by developmental delay, intellectual disability, behavioral abnormalities, hypotonia, congenital anomalies, and facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family. ZFX/ZFY subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P17010-1	1	yes
P17010-2	2
P17010-3	3

RefSeq proteins (6): NP_001171555, NP_001171556, NP_001171557, NP_001171566, NP_001317256, NP_003401* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006794	Transcrp_activ_Zfx/Zfy-dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050752	C2H2-ZF_domain	Family

Pfam: PF00096, PF04704, PF13909

UniProt features (27 total): zinc finger region 13, sequence conflict 6, sequence variant 4, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17010-F1	54.07	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 (1): 274

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 702 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GGGNRMNNYCAT_UNKNOWN, TTTGTAG_MIR520D, SP3_Q3, YY1_Q6, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, YY1_02, TGTGTGA_MIR377, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, MODULE_123, SCHLOSSER_SERUM_RESPONSE_DN, ZHANG_RESPONSE_TO_CANTHARIDIN_UP, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, WANG_CISPLATIN_RESPONSE_AND_XPC_DN

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), chromatin insulator sequence binding (GO:0043035), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
nuclear lumen	2
intracellular membraneless organelle	2
regulation of DNA-templated transcription	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
chromatin DNA binding	1
nucleic acid binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFX	RPS4X	P12631	911
ZFX	MYCN	P04198	876
ZFX	SRY	Q05066	861
ZFX	MYC	P01106	783
ZFX	USP9X	Q93008	747
ZFX	NR1I2	O75469	735
ZFX	UBA1	P22314	729
ZFX	E2F1	Q01094	722
ZFX	KDM5D	Q9BY66	714
ZFX	USP9Y	O00507	712
ZFX	UTY	O14607	675
ZFX	KDM5C	P41229	670
ZFX	ZPR1	O75312	660
ZFX	EIF2S3	P41091	654
ZFX	MEA1	Q16626	649

IntAct

10 interactions, top by confidence:

A	B	Type	Score
HSCB	ZFX	psi-mi:“MI:0915”(physical association)	0.370
CDC23	VWA8	psi-mi:“MI:0914”(association)	0.350
CENPQ	CENPX	psi-mi:“MI:0914”(association)	0.350
RPL31	RPSA2	psi-mi:“MI:0914”(association)	0.350
KRR1	PES1	psi-mi:“MI:0914”(association)	0.350
ZNF346	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
LARP7	U2SURP	psi-mi:“MI:0914”(association)	0.350
ZFY	ZFX	psi-mi:“MI:0914”(association)	0.350
ZFX		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): ZFX (Affinity Capture-MS), ZFX (Affinity Capture-MS), ZFX (Affinity Capture-MS), ZFX (Proximity Label-MS), ZFX (Affinity Capture-RNA), ZFX (Affinity Capture-RNA), ZFX (Affinity Capture-MS), ZFX (Negative Genetic), ZFX (Negative Genetic), ZFX (Affinity Capture-RNA), ZFX (Affinity Capture-MS), ZFX (Affinity Capture-MS), ZFX (Affinity Capture-MS), ZFX (Affinity Capture-MS), ZFX (Affinity Capture-MS)

ESM2 similar proteins: A1L1J6, A2ANX9, A7Y7X5, E9Q8T2, G5E8B9, O15060, O43167, O43829, O62836, O95625, P08048, P0C6P6, P10925, P17010, P17012, P20662, P52739, Q01611, Q08376, Q0VCB0, Q2FAY8, Q3TTC2, Q4V8R6, Q52V16, Q5DU09, Q5PPG4, Q5R5M1, Q5R5N5, Q5RAU9, Q5SVQ8, Q6B4Z5, Q6GNP2, Q6INV8, Q7TS63, Q7ZVR6, Q80V63, Q80X44, Q811F1, Q8K3J5, Q92010

Diamond homologs: A0A9P4XV22, A2ANX9, B1H2Q6, O62836, P08048, P0CJ78, P10925, P17010, P17012, P20662, P27705, P28698, P52288, P80944, Q01611, Q03081, Q03125, Q0VDT2, Q29419, Q3U3I9, Q52V16, Q567C6, Q5U2Z0, Q6B4Z5, Q7RTV3, Q95LI3, Q966L8, Q96EG3, Q9UDV6, Q9UL36, Q9Y462, A1L2U9, A2A884, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, O35615, O77459

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZFX	“down-regulates quantity by repression”	FBP1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	3
Uncertain significance	76
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
3066049	NM_003410.4(ZFX):c.2312C>T (p.Thr771Met)	Pathogenic
3066050	NM_003410.4(ZFX):c.2321A>G (p.Tyr774Cys)	Pathogenic
3066051	NM_003410.4(ZFX):c.2357G>A (p.Arg786Gln)	Pathogenic
3066052	NM_003410.4(ZFX):c.1319dup (p.Leu440fs)	Pathogenic
3066053	NM_003410.4(ZFX):c.115_116del (p.Val39fs)	Pathogenic
3367188	NM_003410.4(ZFX):c.1996_1997del (p.Met666fs)	Pathogenic
4813719	NM_003410.4(ZFX):c.1763_1764del (p.Ser588fs)	Pathogenic
4070904	NM_003410.4(ZFX):c.2363C>G (p.Pro788Arg)	Likely pathogenic
4083411	NM_003410.4(ZFX):c.529dup (p.Ser177fs)	Likely pathogenic
4819279	NM_003410.4(ZFX):c.458T>G (p.Val153Gly)	Likely pathogenic

SpliceAI

1755 predictions. Top by Δscore:

Variant	Effect	Δscore
X:24172707:T:A	acceptor_gain	1.0000
X:24172796:AACAG:A	donor_loss	1.0000
X:24172797:ACAGG:A	donor_loss	1.0000
X:24172798:CAG:C	donor_loss	1.0000
X:24172799:AGG:A	donor_loss	1.0000
X:24172800:GG:G	donor_loss	1.0000
X:24172801:GTATA:G	donor_loss	1.0000
X:24172802:T:A	donor_loss	1.0000
X:24179742:C:T	donor_gain	1.0000
X:24179752:G:GT	donor_gain	1.0000
X:24179766:TTCCT:T	donor_gain	1.0000
X:24179769:CT:C	donor_gain	1.0000
X:24179771:G:GG	donor_gain	1.0000
X:24207321:TTTA:T	acceptor_loss	1.0000
X:24207323:TAGT:T	acceptor_loss	1.0000
X:24207324:A:AG	acceptor_gain	1.0000
X:24207324:A:AT	acceptor_loss	1.0000
X:24207324:AGT:A	acceptor_gain	1.0000
X:24207324:AGTG:A	acceptor_gain	1.0000
X:24207325:G:GT	acceptor_gain	1.0000
X:24207325:GT:G	acceptor_gain	1.0000
X:24207325:GTG:G	acceptor_gain	1.0000
X:24207325:GTGG:G	acceptor_gain	1.0000
X:24207325:GTGGA:G	acceptor_gain	1.0000
X:24207473:TAGG:T	donor_loss	1.0000
X:24207476:G:GG	donor_gain	1.0000
X:24207476:GT:G	donor_loss	1.0000
X:24207702:T:TA	acceptor_gain	1.0000
X:24207706:T:A	acceptor_gain	1.0000
X:24207709:TAGGT:T	acceptor_loss	1.0000

AlphaMissense

5445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:24210237:T:C	C427R	1.000
X:24210239:C:G	C427W	1.000
X:24210246:T:C	C430R	1.000
X:24210247:G:A	C430Y	1.000
X:24210248:T:G	C430W	1.000
X:24210258:T:C	F434L	1.000
X:24210259:T:C	F434S	1.000
X:24210260:T:A	F434L	1.000
X:24210260:T:G	F434L	1.000
X:24210330:T:C	C458R	1.000
X:24210519:T:C	C521R	1.000
X:24210528:T:C	C524R	1.000
X:24210529:G:A	C524Y	1.000
X:24210567:C:A	H537N	1.000
X:24210567:C:G	H537D	1.000
X:24210569:C:A	H537Q	1.000
X:24210569:C:G	H537Q	1.000
X:24210606:T:C	C550R	1.000
X:24210607:G:A	C550Y	1.000
X:24210608:T:G	C550W	1.000
X:24210615:T:C	C553R	1.000
X:24210627:T:C	F557L	1.000
X:24210628:T:C	F557S	1.000
X:24210629:T:A	F557L	1.000
X:24210629:T:G	F557L	1.000
X:24210646:T:C	L563P	1.000
X:24210656:C:A	H566Q	1.000
X:24210656:C:G	H566Q	1.000
X:24210690:T:C	C578R	1.000
X:24210861:T:C	C635R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000450 (X:24192935 G>T), RS1000117552 (X:24195005 C>G), RS1000124900 (X:24185047 G>A,C), RS1000154106 (X:24201371 A>G), RS1000294109 (X:24185015 C>T), RS1000309557 (X:24160784 A>G), RS1000315168 (X:24151371 G>A), RS1000337604 (X:24152726 A>G), RS1000354905 (X:24173738 G>A), RS1000419437 (X:24212067 G>A,C), RS1000445208 (X:24161502 T>C), RS1000453603 (X:24152419 C>T), RS1000471669 (X:24211522 T>A), RS1000472986 (X:24197545 G>A), RS1000624525 (X:24150930 A>G)

Disease associations

OMIM: gene MIM:314980 | disease phenotypes: MIM:301118

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, X-linked, syndromic 37	Strong	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked syndromic complex neurodevelopmental disorder	Strong	XL

Mondo (1): intellectual developmental disorder, X-linked, syndromic 37 (MONDO:0958322)

Orphanet (0):

HPO phenotypes

201 total (30 of 201 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000121	Nephrocalcinosis
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000201	Pierre-Robin sequence
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000262	Turricephaly
HP:0000272	Malar flattening
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000337	Broad forehead
HP:0000341	Narrow forehead

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004953_3	Disturbances of the gamma-frequency band of electroencephalography measures in schizophrenia	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008388	gamma wave measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725039 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	IC50	40	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178567: Inhibition of ZFX (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	6
trichostatin A	affects expression, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
geldanamycin	increases expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
S-1,2-dichlorovinyl-N-acetylcysteine	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
GW 7604	increases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697297	Binding	Inhibition of ZFX (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2PM	HAP1 ZFX (-) 2	Cancer cell line	Male
CVCL_E2PN	HAP1 ZFX (-) 3	Cancer cell line	Male
CVCL_GZ97	K562 eGFP-ZFX	Cancer cell line	Female
CVCL_XV30	HAP1 ZFX (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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