ZNF143

Summary

ZNF143 (zinc finger protein 143, HGNC:12928) is a protein-coding gene on chromosome 11p15.4, encoding Zinc finger protein 143 (P52747). Transcription factor that activates expression of genes transcribed by both RNA polymerases II and III, and which is required to safeguard mitochondrial activity. It is a selective cancer dependency (DepMap: 14.5% of cell lines).

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of snRNA transcription by RNA polymerase II. Predicted to be located in nucleoplasm.

Source: NCBI Gene 7702 — RefSeq curated summary.

At a glance

• Gene–disease (curated): methylmalonic acidemia (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 219 total
• Cancer dependency (DepMap): dependent in 14.5% of screened cell lines
• Transcription factor: yes — 35 downstream targets (CollecTRI)
• MANE Select transcript: NM_003442

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12928
Approved symbol	ZNF143
Name	zinc finger protein 143
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	SBF, pHZ-1, STAF
Ensembl gene	ENSG00000166478
Ensembl biotype	protein_coding
OMIM	603433
Entrez	7702

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 47 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000299606, ENST00000396597, ENST00000396602, ENST00000396604, ENST00000412390, ENST00000414370, ENST00000417726, ENST00000438144, ENST00000447186, ENST00000496276, ENST00000526657, ENST00000527597, ENST00000530463, ENST00000531943, ENST00000532305, ENST00000532577, ENST00000533542, ENST00000534265, ENST00000871182, ENST00000871183, ENST00000871184, ENST00000871185, ENST00000871186, ENST00000871187, ENST00000871188, ENST00000871189, ENST00000934537, ENST00000934538, ENST00000934539, ENST00000934540, ENST00000934541, ENST00000934542, ENST00000934543, ENST00000965737, ENST00000965738, ENST00000965739, ENST00000965740, ENST00000965741, ENST00000965742, ENST00000965743, ENST00000965744, ENST00000965745, ENST00000965746, ENST00000965747, ENST00000965748, ENST00000965749, ENST00000965750, ENST00000965751, ENST00000965752, ENST00000965753

RefSeq mRNA: 3 — MANE Select: NM_003442 NM_001282656, NM_001282657, NM_003442

CCDS: CCDS60720, CCDS60721, CCDS7799

Canonical transcript exons

ENST00000396602 — 16 exons

Exon	Start	End
ENSE00001103319	9472677	9472769
ENSE00001103326	9496303	9496378
ENSE00001103330	9494646	9494765
ENSE00001103337	9525240	9525386
ENSE00001103350	9512448	9512596
ENSE00001103357	9508619	9508846
ENSE00001103361	9479472	9479546
ENSE00001103385	9501091	9501270
ENSE00001223230	9516201	9516362
ENSE00001223265	9497675	9497800
ENSE00001525604	9527530	9528524
ENSE00001930643	9461012	9461076
ENSE00002140238	9471302	9471420
ENSE00003598985	9473941	9474024
ENSE00003673927	9474550	9474633
ENSE00003789248	9478390	9478586

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 92.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8409 / max 628.1184, expressed in 1800 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112978	13.5902	1770
112979	4.0926	1258
112977	1.1580	675

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.21	gold quality
ventricular zone	UBERON:0003053	92.04	gold quality
ganglionic eminence	UBERON:0004023	91.68	gold quality
monocyte	CL:0000576	91.35	gold quality
mononuclear cell	CL:0000842	91.07	gold quality
leukocyte	CL:0000738	91.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.45	gold quality
islet of Langerhans	UBERON:0000006	89.88	gold quality
left testis	UBERON:0004533	89.82	gold quality
right testis	UBERON:0004534	89.50	gold quality
colonic epithelium	UBERON:0000397	89.46	gold quality
endothelial cell	CL:0000115	89.38	gold quality
secondary oocyte	CL:0000655	89.13	gold quality
gastrocnemius	UBERON:0001388	89.04	gold quality
cortical plate	UBERON:0005343	88.88	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.63	gold quality
testis	UBERON:0000473	88.51	gold quality
muscle of leg	UBERON:0001383	88.47	gold quality
ectocervix	UBERON:0012249	88.29	gold quality
lower esophagus mucosa	UBERON:0035834	88.15	gold quality
popliteal artery	UBERON:0002250	88.13	gold quality
tibial artery	UBERON:0007610	88.13	gold quality
granulocyte	CL:0000094	87.99	gold quality
embryo	UBERON:0000922	87.87	gold quality
endocervix	UBERON:0000458	87.22	gold quality
blood	UBERON:0000178	87.15	gold quality
aorta	UBERON:0000947	87.00	gold quality
stromal cell of endometrium	CL:0002255	86.91	gold quality
right lung	UBERON:0002167	86.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.51
E-MTAB-4850	no	1276.74

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

35 targets.

Target	Regulation
BUB1B	Activation
CD74
CDC6
CHMP4A
CLN3
EEFSEC
ERVK-11
ESCO2	Unknown
FBXW7	Activation
FEN1
FGF4
HMOX1	Unknown
IFNA1
IRF3
MT-TL1
NANOG
NOS2	Repression
PCYT1A	Activation
PLK1
POLR2A
POLR2F
PTGS2	Repression
PTPN5
RNU6-1
SCARNA2	Unknown
SKP2
STUB1
TALDO1	Unknown
TCP1	Activation
TERT

JASPAR motifs

Motif	Name	Family
MA0088.2	ZNF143	More than 3 adjacent zinc fingers
MA0088.3	ZNF143	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:9009278, PMID:39676670

Upstream regulators (CollecTRI, top): NANOG, SP3, ZNF76, ZNF91

miRNA regulators (miRDB)

69 targeting ZNF143, 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-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8087	99.90	69.55	1351
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-137-3P	99.87	74.74	2401
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 36)

• human interferon regulatory factor-3 (IRF-3) gene promoter contains a functional SPH element that is bound by SBF/Staf in vitro and in transfected cells (PMID:11724783)
• ZNF143 plays a key role in basal and tissue-specific expression of transaldolase and regulation of the metabolic network controlling cell survival and differentiation (PMID:14702349)
• interplay of ZNF143, p73 and ZNF143 target genes is involved in DNA repair gene expression and cisplatin resistance (PMID:17297437)
• A pivotal role for transcription factor hStaf/ZNF143 in the expression of the BUB1B gene was demonstrated. (PMID:17478512)
• Transcription factor ZNF143 is required for expression of TFAM gene. (PMID:17707600)
• Staf activates U6 transcription from a preassembled chromatin template in vitro and associates with several proteins linked to chromatin modification, among them chromodomain-helicase-DNA binding protein 8 (CHD8). (PMID:17938208)
• These results demonstrated that the Staf binding site functioned as the basal transcriptional activator of the S phase-specific gene ESCO2, but other mechanisms are required for cell cycle-dependent expression. (PMID:20116366)
• data suggest that IGF-1 induces ZNF143 expression in cancer cells via PI3-kinase and reactive oxygen species generation during receptor internalization. (PMID:20733350)
• ZNF143 might be a master regulator of the cell cycle. (PMID:20860770)
• The data provides the demonstration that hStaf/ZNF143 is indeed a transcription factor controlling the expression of divergent protein-protein and protein-non-coding RNA gene pairs. (PMID:21177654)
• GIPC is involved in IGF-1 signaling leading to ZNF143 expression through the regulation of ROS production, which may play a role for colon cancer tumorigenesis. (PMID:21909943)
• ZNF143 upregulated GPX1 activity and protecting cells from oxidative damage. (PMID:23152058)
• HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy. (PMID:23539139)
• High zinc-finger protein 143 is associated with cancer cell migration and invasion through ZEB1 and E-cadherin in colon cancer. (PMID:24009065)
• ZNF143 expresses different 3’-untranslated regions (3’-UTR) as a result of alternative polyadenylation (PMID:24952353)
• THAP11, ZNF143, and HCF-1 form a mutually dependent complex on chromatin, which is independent of E2F occupancy. (PMID:25437553)
• ZNF143 is directly recruited to the promoter of genes engage in chromatin interactions, where it binds to its DNA recognition sequence. (PMID:25645053)
• The results show that as an important partner of CTCF, ZNF143 helps establishing the conserved chromatin structure by cooperating with cohesin. (PMID:27414788)
• Data show that zinc finger protein 143 (ZNF143) promotes epithelial-mesenchymal transition (EMT) through regulating PI3K/AKT pathway in gastric cancer (GC) cells. (PMID:27449034)
• The inhibition of ZNF143 activity by small molecules induced tumor regression. (PMID:28192620)
• The zinc finger, ZNF143, binds to the CCCAGCAG site in the CEBPA promoter. (PMID:28900037)
• Secretion of interleukin (IL)-8 was increased when ZNF143 expression was reduced. (PMID:30933430)
• a subset of breast cancer cells with low expression of ZNF143 might exhibit better survival via an autophagic process by regulating the p53Beclin1 axis. (PMID:30935019)
• this study revealed that A1CF can upregulate the expression of FAM224A via strengthening its stability, which in turn, influenced the negative modulation of miR-590-3p on transcription factor ZNF143. (PMID:31186064)
• ZNF143 is dynamically bound to a subset of its interphase sites during mitosis. (PMID:31864705)
• ZNF143 Suppresses Cell Apoptosis and Promotes Proliferation in Gastric Cancer via ROS/p53 Axis. (PMID:32076462)
• ZNF143-Mediated H3K9 Trimethylation Upregulates CDC6 by Activating MDIG in Hepatocellular Carcinoma. (PMID:32312832)
• LIN28B regulates transcription and potentiates MYCN-induced neuroblastoma through binding to ZNF143 at target gene promotors. (PMID:32601179)
• DNA methylome analysis identifies BMI-related epigenetic changes associated with non-small cell lung cancer susceptibility. (PMID:33939316)
• BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) promotes lung adenocarcinoma by interacting with Zinc Finger Protein ZNF143 and regulating glycolysis. (PMID:35068350)
• ZNF143 Expression is Associated with COPD and Tumor Microenvironment in Non-Small Cell Lung Cancer. (PMID:35400998)
• ZNF143 regulates autophagic flux to alleviate myocardial ischemia/reperfusion injury through Raptor. (PMID:35988805)
• ATF1 promotes the malignancy of lung adenocarcinoma cells by transcriptionally regulating ZNF143 expression. (PMID:37158648)
• ZNF143 facilitates the growth and migration of glioma cells by regulating KPNA2-mediated Hippo signalling. (PMID:37423952)
• LOC644656 promotes cisplatin resistance in cervical cancer by recruiting ZNF143 and activating the transcription of E6-AP. (PMID:38395183)
• CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1. (PMID:38642782)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf143a	ENSDARG00000012887
danio_rerio	znf143b	ENSDARG00000041581
mus_musculus	Zfp143	ENSMUSG00000061079
rattus_norvegicus	Zfp143	ENSRNOG00000010087

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

Zinc finger protein 143 — P52747 (reviewed: P52747)

Alternative names: SPH-binding factor, Selenocysteine tRNA gene transcription-activating factor

All UniProt accessions (13): C9J2G7, C9JCG1, C9JRS3, C9JTC5, E7EN86, P52747, E9PJF2, E9PLN4, E9PLS7, E9PMY8, E9PPB0, E9PS81, H7C1P6

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that activates expression of genes transcribed by both RNA polymerases II and III, and which is required to safeguard mitochondrial activity. Specifically recognizes and binds the Staf-binding site (SBS), a consensus DNA-binding motif present in thousands of promoters. Activates the gene for selenocysteine tRNA (tRNAsec). Activates expression of small nuclear RNA (snRNA) transcribed by RNA polymerases II and III. Also activates expression of mRNAs and acts as a key regulator of cell proliferation and differentiation by specifically activating expression of a subset of nuclear-encoded mitochondrial genes, thereby controlling mitochondrial function. Involved in the maintenance of embryonic stem cells by promoting association of POU5F1/OCT4 to promoters, leading to NANOG expresion.

Subunit / interactions. Interacts with CHD8. Forms a complex with HCFC1 and THAP11. Interacts with POU5F1/OCT4; promoting POU5F1/OCT4-binding to promoters.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the GLI C2H2-type zinc-finger protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
P52747-1	1	yes
P52747-2	2
P52747-3	3

RefSeq proteins (3): NP_001269585, NP_001269586, NP_003433* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (21 total): zinc finger region 7, sequence variant 4, sequence conflict 3, cross-link 2, splice variant 2, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52747-F1	50.91	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): 213, 406, 1, 352

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-76071	RNA Polymerase III Transcription Initiation From Type 3 Promoter

MSigDB gene sets: 188 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_255, AAGCCAT_MIR135A_MIR135B, MAZ_Q6, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, MODULE_317, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, MODULE_379, GROSS_HYPOXIA_VIA_HIF1A_DN, MODULE_123, MODULE_157, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, AFP1_Q6

GO Biological Process (6): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), regulation of transcription by RNA polymerase III (GO:0006359), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of transcription by RNA polymerase III (GO:0045945), positive regulation of snRNA transcription by RNA polymerase II (GO:1905382)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), core promoter sequence-specific DNA binding (GO:0001046), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
RNA Polymerase III Transcription	1
RNA Polymerase III Transcription Initiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
transcription by RNA polymerase III	2
regulation of transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
positive regulation of transcription by RNA polymerase II	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase III	1
snRNA transcription by RNA polymerase II	1
regulation of snRNA transcription by RNA polymerase II	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription cis-regulatory region binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF143	SIX5	Q8N196	908
ZNF143	TCP11	Q8WWU5	891
ZNF143	THAP11	Q96EK4	823
ZNF143	RAD21	O60216	796
ZNF143	CTCF	P49711	762
ZNF143	SMC3	Q9UQE7	750
ZNF143	CHD8	Q9HCK8	745
ZNF143	CEBPB	P17676	608
ZNF143	GATA1	P15976	582
ZNF143	MXI1	P50539	560
ZNF143	JUND	P17535	552
ZNF143	LIN28B	Q6ZN17	539
ZNF143	REST	Q13127	530
ZNF143	GABPA	Q06546	522
ZNF143	YY1	P25490	499

IntAct

86 interactions, top by confidence:

A	B	Type	Score
ZNF143	FHL2	psi-mi:“MI:0915”(physical association)	0.670
ZNF143	GFAP	psi-mi:“MI:0915”(physical association)	0.590
SNRPB	ZNF143	psi-mi:“MI:0915”(physical association)	0.560
POGZ	ZNF143	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	EAF1	psi-mi:“MI:0915”(physical association)	0.560
LMO1	ZNF143	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	NUDT22	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	EXOSC1	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	LMO3	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	IL16	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	FAM90A1	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	TCAF1	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	ZNF512B	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	SPANXN3	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	TAB2	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	LIN54	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	ZNF438	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	IQUB	psi-mi:“MI:0915”(physical association)	0.560
SUOX	ZNF143	psi-mi:“MI:0915”(physical association)	0.560
ZNF143	YJU2	psi-mi:“MI:0915”(physical association)	0.560
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
RNF26	NME2P1	psi-mi:“MI:0914”(association)	0.530
APBA3	ZNF143	psi-mi:“MI:0915”(physical association)	0.370
	ZNF143	psi-mi:“MI:0915”(physical association)	0.370
FOXQ1	DDX39A	psi-mi:“MI:0914”(association)	0.350
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
BAG1	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Two-hybrid), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Affinity Capture-MS), ZNF143 (Two-hybrid), ZNF143 (Two-hybrid)

ESM2 similar proteins: A6QQW0, B4F7E9, O15391, O43167, O62836, O70230, O70494, P08048, P15337, P17010, P17012, P18846, P20385, P25490, P27699, P36508, P52747, P79145, P81069, P81269, Q00420, Q00899, Q01147, Q01611, Q02447, Q03060, Q03061, Q06547, Q08DA8, Q0V8G2, Q1LYE3, Q1LZH5, Q1RMI3, Q4V8R6, Q52KB5, Q52V16, Q58DZ6, Q5XIU2, Q66K89, Q6B4Z5

Diamond homologs: A6QQW0, B4F7E9, O70230, P36508, P52747, P79288, Q13886, Q1LYE3, Q58DZ6, Q5XIU2, Q8BMU0, Q91853, O35739, O95600, P57682, Q01713, Q60980, O08584, O35738, O35819, O43474, O62259, O75840, O89090, P08047, P0CG40, P46099, P58334, Q01714, Q02446, Q0VA40, Q13887, Q14V87, Q19A40, Q5XGT8, Q60793, Q60843, Q62445, Q64HY3, Q64HY5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZNF143	“up-regulates quantity by expression”	TCP1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	64
Benign	43

Top pathogenic / likely-pathogenic (0)

SpliceAI

2440 predictions. Top by Δscore:

Variant	Effect	Δscore
11:9471418:CAG:C	donor_loss	1.0000
11:9471419:AG:A	donor_loss	1.0000
11:9471420:GG:G	donor_loss	1.0000
11:9471421:G:GC	donor_loss	1.0000
11:9471422:T:G	donor_loss	1.0000
11:9472672:A:AG	acceptor_gain	1.0000
11:9472673:ATAG:A	acceptor_loss	1.0000
11:9472675:A:AG	acceptor_gain	1.0000
11:9472675:AGAT:A	acceptor_gain	1.0000
11:9472676:G:GC	acceptor_loss	1.0000
11:9472676:G:GG	acceptor_gain	1.0000
11:9472676:GATG:G	acceptor_gain	1.0000
11:9472765:TAAAG:T	donor_loss	1.0000
11:9472766:AAAGG:A	donor_loss	1.0000
11:9472767:AAGGT:A	donor_loss	1.0000
11:9472768:AGGTA:A	donor_loss	1.0000
11:9472770:G:T	donor_loss	1.0000
11:9473837:GAGCT:G	donor_gain	1.0000
11:9473845:GTTGT:G	donor_gain	1.0000
11:9473846:T:G	donor_gain	1.0000
11:9473936:TATA:T	acceptor_loss	1.0000
11:9473938:TAGA:T	acceptor_loss	1.0000
11:9473939:A:AG	acceptor_gain	1.0000
11:9473939:A:T	acceptor_loss	1.0000
11:9473940:G:GA	acceptor_gain	1.0000
11:9473940:GAT:G	acceptor_gain	1.0000
11:9473940:GATGC:G	acceptor_gain	1.0000
11:9474020:AAGTA:A	donor_gain	1.0000
11:9474022:GTA:G	donor_gain	1.0000
11:9474023:TA:T	donor_gain	1.0000

AlphaMissense

4188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:9494761:T:C	L254P	1.000
11:9496306:C:G	H257D	1.000
11:9496320:C:A	H261Q	1.000
11:9496320:C:G	H261Q	1.000
11:9496342:T:A	C269S	1.000
11:9496342:T:C	C269R	1.000
11:9496343:G:C	C269S	1.000
11:9496357:T:C	C274R	1.000
11:9496369:T:C	F278L	1.000
11:9496370:T:C	F278S	1.000
11:9496371:T:A	F278L	1.000
11:9496371:T:G	F278L	1.000
11:9497692:C:A	H287N	1.000
11:9497692:C:G	H287D	1.000
11:9497694:C:A	H287Q	1.000
11:9497694:C:G	H287Q	1.000
11:9497700:A:C	R289S	1.000
11:9497700:A:T	R289S	1.000
11:9497704:C:G	H291D	1.000
11:9497706:T:A	H291Q	1.000
11:9497706:T:G	H291Q	1.000
11:9497722:T:G	Y297D	1.000
11:9497728:T:A	C299S	1.000
11:9497728:T:C	C299R	1.000
11:9497729:G:C	C299S	1.000
11:9497730:T:G	C299W	1.000
11:9497743:T:A	C304S	1.000
11:9497743:T:C	C304R	1.000
11:9497744:G:C	C304S	1.000
11:9497745:T:G	C304W	1.000

dbSNP variants (sampled 300 via entrez): RS1000140102 (11:9526009 C>T), RS1000157718 (11:9461468 C>T), RS1000180202 (11:9464466 T>C), RS1000204026 (11:9500459 A>C), RS1000245420 (11:9506865 A>T), RS1000259423 (11:9470118 T>C), RS1000260129 (11:9510164 G>T), RS1000305705 (11:9491792 G>A), RS1000311093 (11:9510412 C>G), RS1000326542 (11:9499282 A>G), RS1000362466 (11:9460382 T>A,C), RS1000376204 (11:9487742 A>C,G), RS1000418304 (11:9503034 T>C), RS1000422784 (11:9464676 C>T), RS1000490918 (11:9526341 G>A)

Disease associations

OMIM: gene MIM:603433 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
methylmalonic acidemia	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
methylmalonic aciduria and homocystinuria	Limited	AR

Mondo (1): methylmalonic acidemia (MONDO:0002012)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008162_39	Hip circumference	4.000000e-06
GCST008839_59	Height	5.000000e-22
GCST010148_16	Cutaneous squamous cell carcinoma	9.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001927	cutaneous squamous cell carcinoma

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537358	Methylmalonic acidemia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
Silicon Dioxide	increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
diphenyleneiodonium	decreases reaction, increases expression	1
monodansylcadaverine	increases expression, decreases reaction, increases abundance	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
cupric oxide	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Wortmannin	decreases reaction, increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2PP	HAP1 ZNF143 (-) 2	Cancer cell line	Male
CVCL_XV31	HAP1 ZNF143 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02426775	PHASE3	COMPLETED	Carglumic Acid in Methylmalonic Acidemia and Propionic Acidemia
NCT07163364	PHASE3	NOT_YET_RECRUITING	A Study to Evaluate the Effects and Safety of Hydroxocobalamin in Participants With Combined Methylmalonic Academia (cblC Type)
NCT01341379	PHASE2	WITHDRAWN	Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate
NCT01597440	PHASE2	TERMINATED	Long-term Outcome of N-Carbamylglutamate Treatment in Propionic Acidemia and Methylmalonic Acidemia
NCT01599286	PHASE2	COMPLETED	Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia
NCT04732429	PHASE2	TERMINATED	Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia
NCT04836494	PHASE1	TERMINATED	A First in Human, Dose Escalation Study to Evaluate the Safety and Tolerability of BBP-671 in Healthy Volunteers and Patients With Propionic Acidemia or Methylmalonic Acidemia
NCT03810690	PHASE1/PHASE2	WITHDRAWN	Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia
NCT04581785	PHASE1/PHASE2	TERMINATED	Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia
NCT04899310	PHASE1/PHASE2	TERMINATED	A Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia
NCT05295433	PHASE1/PHASE2	RECRUITING	An Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705
NCT05778877	PHASE1/PHASE2	WITHDRAWN	A Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of SEL-302 in Pediatric Subjects With MMA
NCT00078078	Not specified	RECRUITING	Clinical and Laboratory Study of Methylmalonic Acidemia
NCT01289158	Not specified	UNKNOWN	Combined Malonic and Methylmalonic Aciduria (CMAMMA): Gene Identification and Outcome Study
NCT03484767	Not specified	COMPLETED	The MaP Study: Mapping the Patient Journey in MMA and PA
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04176523	Not specified	RECRUITING	Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach
NCT05040178	Not specified	RECRUITING	An Observational Study of Carbaglu® for the Treatment of MMA and PA in Adults and Pediatrics
NCT05330039	Not specified	COMPLETED	Characterization of Intestinal Microbiota in Children With Inborn Errors of Metabolism (IEM)
NCT05438485	Not specified	TERMINATED	Natural History Study of Patients With Methylmalonic Acidemia and Propionic Acidemia
NCT05506254	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up Study of Patients Who Received hLB-001 Gene Therapy
NCT06664840	Not specified	NOT_YET_RECRUITING	MyRareDiet A Novel Diet Tracking Tool
NCT07432880	Not specified	NOT_YET_RECRUITING	A Prospective Study of Pediatric Participants up to 16 Years of Age With Methylmalonic Acidemia (MMA) Due to Mutations in the MMUT Gene