ZNF148

Summary

ZNF148 (zinc finger protein 148, HGNC:12933) is a protein-coding gene on chromosome 3q21.2, encoding Zinc finger protein 148 (Q9UQR1). Involved in transcriptional regulation.

The protein encoded by this gene is a member of the Kruppel family of zinc finger DNA binding proteins. The encoded protein activates transcription of the T-cell receptor and intestinal alkaline phosphatase genes but represses transcription of the ornithine decarboxylase, vimentin, gastrin, stomelysin, and enolase genes. Increased expression of this gene results in decreased patient survival rates from colorectal cancer, while mutations in this gene have been associated with global developmental delay, hypoplastic corpus callosum, and dysmorphic facies.

Source: NCBI Gene 7707 — RefSeq curated summary.

At a glance

• Gene–disease (curated): global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 118 total — 5 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 43
• Transcription factor: yes — 35 downstream targets (CollecTRI)
• MANE Select transcript: NM_021964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12933
Approved symbol	ZNF148
Name	zinc finger protein 148
Location	3q21.2
Locus type	gene with protein product
Status	Approved
Aliases	BERF-1, ZBP-89, BFCOL1, HT-BETA, ZFP148, pHZ-52
Ensembl gene	ENSG00000163848
Ensembl biotype	protein_coding
OMIM	601897
Entrez	7707

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 48 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000360647, ENST00000465763, ENST00000468369, ENST00000471196, ENST00000484491, ENST00000485866, ENST00000492394, ENST00000495019, ENST00000496732, ENST00000497929, ENST00000700044, ENST00000700212, ENST00000859977, ENST00000859978, ENST00000859979, ENST00000859980, ENST00000859981, ENST00000859982, ENST00000859983, ENST00000859984, ENST00000859985, ENST00000859986, ENST00000859987, ENST00000859988, ENST00000859989, ENST00000859990, ENST00000859991, ENST00000859992, ENST00000859993, ENST00000859994, ENST00000859995, ENST00000859996, ENST00000859997, ENST00000859998, ENST00000859999, ENST00000860000, ENST00000860001, ENST00000860002, ENST00000917691, ENST00000960068, ENST00000960069, ENST00000960070, ENST00000960071, ENST00000960072, ENST00000960073, ENST00000960074, ENST00000960075, ENST00000960076, ENST00000960077, ENST00000960078, ENST00000960079

RefSeq mRNA: 13 — MANE Select: NM_021964 NM_001348424, NM_001348425, NM_001348426, NM_001348427, NM_001348428, NM_001348429, NM_001348430, NM_001348431, NM_001348432, NM_001348433, NM_001348434, NM_001348436, NM_021964

CCDS: CCDS3031

Canonical transcript exons

ENST00000360647 — 9 exons

Exon	Start	End
ENSE00001270515	125313308	125313656
ENSE00001353980	125323309	125323444
ENSE00001353998	125375102	125375325
ENSE00001391551	125331158	125331238
ENSE00001432906	125225669	125233939
ENSE00003464115	125288103	125288228
ENSE00003654682	125279124	125279247
ENSE00003668759	125234211	125234329
ENSE00003733073	125277726	125277809

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.3102 / max 66.4794, expressed in 1131 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44298	1.1529	611
44297	0.8309	496
44296	0.3265	187

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caput epididymis	UBERON:0004358	97.89	gold quality
corpus epididymis	UBERON:0004359	97.63	gold quality
saphenous vein	UBERON:0007318	97.61	gold quality
superior surface of tongue	UBERON:0007371	97.44	gold quality
pylorus	UBERON:0001166	97.35	gold quality
pericardium	UBERON:0002407	97.20	gold quality
nipple	UBERON:0002030	97.17	gold quality
mammary duct	UBERON:0001765	97.12	gold quality
cardia of stomach	UBERON:0001162	96.97	gold quality
cranial nerve II	UBERON:0000941	96.93	gold quality
calcaneal tendon	UBERON:0003701	96.82	gold quality
renal medulla	UBERON:0000362	96.79	gold quality
cauda epididymis	UBERON:0004360	96.70	gold quality
secondary oocyte	CL:0000655	96.34	gold quality
epithelium of mammary gland	UBERON:0003244	96.14	gold quality
vena cava	UBERON:0004087	96.02	gold quality
trigeminal ganglion	UBERON:0001675	95.92	gold quality
gluteal muscle	UBERON:0002000	95.92	gold quality
endothelial cell	CL:0000115	95.72	gold quality
superior vestibular nucleus	UBERON:0007227	95.66	gold quality
pancreatic ductal cell	CL:0002079	95.54	gold quality
tongue	UBERON:0001723	95.45	gold quality
ventral tegmental area	UBERON:0002691	95.09	gold quality
inferior vagus X ganglion	UBERON:0005363	95.01	gold quality
medulla oblongata	UBERON:0001896	94.85	gold quality
pharyngeal mucosa	UBERON:0000355	94.83	gold quality
body of tongue	UBERON:0011876	94.79	gold quality
corpus callosum	UBERON:0002336	94.76	gold quality
urethra	UBERON:0000057	94.26	gold quality
triceps brachii	UBERON:0001509	94.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

35 targets.

Target	Regulation
ADORA2A	Unknown
ATM
BAK1
CDKN1A	Unknown
CDKN2A	Unknown
CISH
COL1A2
CXCL5	Unknown
ENO3	Repression
EPB41
GAST	Activation
GATA1	Unknown
GHR
IAPP
IFNG
IRS2	Unknown
ITGAM	Repression
MMP3	Activation
NFYA
NOTCH1
OAS1
ODC1	Unknown
PDGFRA
PKD1
RNLS	Unknown
SOX18	Repression
SPI1
SPTA1
STAT1	Unknown
TBXT

JASPAR motifs

Motif	Name	Family
MA1653.1	ZNF148	More than 3 adjacent zinc fingers
MA1653.2	ZNF148	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:15635072

Upstream regulators (CollecTRI, top): ID1, SP1, ZNF148

miRNA regulators (miRDB)

406 targeting ZNF148, 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-3646	100.00	73.56	5283
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3120-5P	100.00	65.56	965
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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707

Literature-anchored findings (GeneRIF, showing 40)

• ZBP-89 is a repressor of the human beta 2-integrin CD11b gene during differentiation of monocytes into macrophages (PMID:12393719)
• ZBP-89 co-localized with p53 in the nucleus in about 67% (12 of 18) of all cases positive for the nuclear p53 protein, suggesting that ZBP-89 may play a role in the nuclear accumulation of the p53 protein in a subset recurrent hepatocellular carcinoma. (PMID:12759240)
• interaction of Stat3 and ZBP-89 may be crucial for overcoming the effects of the repressor ZBP-89, which suggests a novel mode for Stat3 gene activation. (PMID:14712222)
• ZBP-89-mediated apoptosis occurs via a p53-independent mechanism that requires JNK activation. (PMID:14963412)
• No association with psoriasis susceptibility (PMID:15175029)
• We conclude that ZBP-89 is a direct transcriptional activator of the enterocyte differentiation marker IAP. (PMID:16384873)
• Ectopic expression of ZBP-89 amplified the inhibitory effect of Fatty Acids on L2 -GH promoter activity. (PMID:16825291)
• ZBP-89 is an important co-activator of wild-type p53 and both proteins are negatively affected by functionally inactive p53 mutants. (PMID:16827139)
• Enhanced ZNF148 expression activates intestinal apoptosis, therefore ZNF148 is a therapeutic target to inhibit colon cancer development. (PMID:17019648)
• ataxia telangiectasia mutated protein phosphorylation of ZBP-89 contributes to Histone deacetylase inhibitors induction of p21(waf1) gene expression (PMID:17560543)
• ZBP-89 functions as a repressor by recruiting HDAC1 to the vimentin promoter. (PMID:17663720)
• sumoylation provides a reversible post-translational mechanism to control the activity of ZBP-89. (PMID:17940278)
• ZBP-89 plays a role in erythroid and megakaryocytic development by cooperating with GATA-1 and/or FOG-1 in a developmental stage-specific manner. (PMID:18250154)
• Transcription factors Sp3, ZBP-89 and NF-Y are capable of binding to the SOX18 promoter region. (PMID:18496767)
• both NF-kappaB and ZBP-89 bind to the site in vivo and provide evidence of competitive binding to MMP-3 promoter. (PMID:19275880)
• ZBP-89 greatly enhanced the killing effectiveness of 5-fluorouracil or staurosporine in hepatocellular carcinoma cells. (PMID:19362768)
• ZBP-89 iss able to restrain senescence in NCI-H460 human lung cancer cells, through epigenetically regulating p(16INK4a) expression. (PMID:19583777)
• Alternative binding of ZBP89 or SP1 to the described region in the IRS2 promoter regulates neuronal IRS2 expression in a PI3K-dependent manner. (PMID:19875459)
• An activating role for ZBP-89 in human globin gene regulation and erythroid differentiation. (PMID:21828133)
• ZBP-89 is a regulator of Pdcd4 gene, binding to the basal promoter either alone or by interacting with Sp family members. (PMID:22111549)
• We found that the TP53-G245D variant but not TP53-R249S abrogated HDAC inhibitor p21 induction by binding to ZBP-89 and retaining it in the cytoplasm. (PMID:22214764)
• Colony formation was reduced dramatically in those hepatocellular carcinoma cell lines in which ZBP-89 overexpression was demonstrated; this appeared to correlate with increased apoptosis. (PMID:22372401)
• this study provides vigorous evidence that ZBP-89 was significantly downregulated in clear cell renal cell carcinoma(CCRCC) and could be served as a promising biomarker for prediction of distal metastasis and prognosis of patient with CCRCC. (PMID:22982674)
• lower expression of ZNF148 in colorectal cancer was significantly associated with worse clinicopathologic variables, including lymph node metastases, poor differentiation, and a higher rate of disease recurrence (PMID:23576061)
• zinc-binding protein-89 upregulates the expression of Bak by targeting multiple components of the epigenetic pathway in hepatocellular carcinoma. (PMID:23954442)
• ZBP-89 attenuates HDAC3 by increasing IkappaB degradation, dependent on Pin1 but independent of NF-Kappab (PMID:25623232)
• A larger role ZBP-89 plays in gene regulation during inflammation.ZBP-89 regulates of MMP-1 expression.ZBP-89 and NF-kappaB appear to bind cooperatively on both promoters. (PMID:26891870)
• ZNF148 as a gene involved in a newly described intellectual disability syndrome with a recurrent phenotype and postulate that the ZNF148 is a hitherto unrecognized but crucial transcription factor in the development of the corpus callosum. (PMID:27964749)
• The results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele. (PMID:28447668)
• Downregulation of ZNF148 drives the formation of a muscle phenotype with rapid expression of myosin heavy chain, even in proliferative conditions. This phenotype was most likely mediated by the robust and swift upregulation of MYOD and MEF2C. (PMID:28811660)
• Our findings suggested that ZBP-89 and Sp1 overexpression induced Bak expression in a genetic manner. Increased Bak level was associated with poor patient survival, whereas high level of Sp1 is a beneficial factor for patient survival. (PMID:29653560)
• ZBP-89 is a potential tumor suppressor in hepatocellular carcinoma (HCC) and it can inhibit the growth of HCC via multiple channels; higher expression of ZBP-89 may predict better survivals and lower recurrence of HCC patients (PMID:30142986)
• ZNF148(FL) could increase proliferation, invasion, and migration of colorectal cancer cells, while ZNF148(DeltaN) showed opposite effect; the two splicing isoforms of ZNF148 may exert a mutual antagonistic effect to each other on the malignant biological activities. (PMID:30463804)
• ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway. (PMID:31874246)
• Here, we show that succinate accumulation induced by SDHB loss of function increased the expression of zinc finger protein 148 (ZNF148, also named ZBP-89) in astrointestinal stromal tumor (GIST) cells. Meanwhile, ZNF148 is found to be phosphorylated by ERK at Ser306, and this phosphorylation results in ZNF148 binding to Forkhead box M1 (FOXM1) (PMID:32060966)
• Loss of microRNA-147 function alleviates synovial inflammation through ZNF148 in rheumatoid and experimental arthritis. (PMID:33864383)
• Identification of the MALAT1/miR-106a-5p/ZNF148 feedback loop in regulating HaCaT cell proliferation, migration and apoptosis. (PMID:36710662)
• Upregulation of the ZNF148/PTX3 axis promotes malignant transformation of dendritic cells in glioma stem-like cells microenvironment. (PMID:37063077)
• Loss of ZNF148 enhances insulin secretion in human pancreatic beta cells. (PMID:37288664)
• Further delineation of the rare GDACCF (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies syndrome): genotype and phenotype of 22 patients with ZNF148 mutations. (PMID:37580113)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf148	ENSDARG00000055106
mus_musculus	Zfp148	ENSMUSG00000022811
rattus_norvegicus	Zfp148	ENSRNOG00000001789

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), ZNF143 (ENSG00000166478), 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 148 — Q9UQR1 (reviewed: Q9UQR1)

Alternative names: Transcription factor ZBP-89, Zinc finger DNA-binding protein 89

All UniProt accessions (5): C9J6Y6, C9JRX0, C9K0U4, Q9UQR1, G5E9X2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transcriptional regulation. Represses the transcription of a number of genes including gastrin, stromelysin and enolase. Binds to the G-rich box in the enhancer region of these genes.

Subunit / interactions. Interacts with HNRNPDL. Interacts with the 5FMC complex; the interaction requires association with CHTOP. Interacts with CAVIN1.

Subcellular location. Nucleus.

Post-translational modifications. Sumoylated with SUMO2. Desumoylated by SENP3, resulting in the stimulation of transcription of its target genes.

Disease relevance. Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies (GDACCF) [MIM:617260] An autosomal dominant syndrome characterized by underdevelopment of the corpus callosum, mild to moderate developmental delay and intellectual disability, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UQR1-1	1	yes
Q9UQR1-2	2

RefSeq proteins (13): NP_001335353, NP_001335354, NP_001335355, NP_001335356, NP_001335357, NP_001335358, NP_001335359, NP_001335360, NP_001335361, NP_001335362, NP_001335363, NP_001335365, NP_068799* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050752	C2H2-ZF_domain	Family

Pfam: PF00096

UniProt features (36 total): cross-link 11, modified residue 9, sequence conflict 5, zinc finger region 4, splice variant 2, region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQR1-F1	47.05	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 (20): 194, 250, 301, 306, 412, 607, 665, 784, 6, 88, 115, 132, 291, 308, 356, 356, 402, 421, 424, 51

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 367 (showing top): FXR_IR1_Q6, WANG_CLIM2_TARGETS_UP, JI_RESPONSE_TO_FSH_UP, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AATGGAG_MIR136, MARTINEZ_RB1_TARGETS_UP, GOBP_NEURAL_NUCLEUS_DEVELOPMENT, NF1_Q6_01, BLALOCK_ALZHEIMERS_DISEASE_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_SUBSTANTIA_NIGRA_DEVELOPMENT, GOBP_MIDBRAIN_DEVELOPMENT, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, OCT1_07

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), cellular defense response (GO:0006968), gamete generation (GO:0007276), negative regulation of gene expression (GO:0010629), substantia nigra development (GO:0021762), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
defense response	1
sexual reproduction	1
multicellular organismal reproductive process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
midbrain development	1
neural nucleus development	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
DNA binding	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

1570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF148	TP53	P04637	796
ZNF148	ODC1	P11926	788
ZNF148	TAF4	O00268	636
ZNF148	GATA1	P15976	616
ZNF148	HDAC1	Q13547	615
ZNF148	ZFPM1	Q8IX07	574
ZNF148	CDKN1A	P38936	555
ZNF148	GAST	P01350	549
ZNF148	EP300	Q09472	539
ZNF148	SPI1	P17947	532
ZNF148	MMP3	P08254	507
ZNF148	E2F1	Q01094	506
ZNF148	HLX	Q14774	499
ZNF148	STAT3	P40763	491
ZNF148	NFE2	Q16621	488

IntAct

94 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
FAM22F	ZNF148	psi-mi:“MI:0915”(physical association)	0.560
ZNF148	DEUP1	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	ZNF148	psi-mi:“MI:0915”(physical association)	0.560
KRT31	ZNF148	psi-mi:“MI:0915”(physical association)	0.560
ZNF148	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
CEP70	ZNF148	psi-mi:“MI:0915”(physical association)	0.560
ZNF148	GORASP2	psi-mi:“MI:0915”(physical association)	0.560
TRIM10	ZNF148	psi-mi:“MI:0915”(physical association)	0.560
DEUP1	ZNF148	psi-mi:“MI:0915”(physical association)	0.560
ZNF148	GLRX3	psi-mi:“MI:0915”(physical association)	0.560
SIAH1	ZNF148	psi-mi:“MI:0915”(physical association)	0.560
ZNF148	CEP70	psi-mi:“MI:0915”(physical association)	0.560
GORASP2	ZNF148	psi-mi:“MI:0915”(physical association)	0.560
ZNF148	TRIM10	psi-mi:“MI:0915”(physical association)	0.560
ZNF148	KRT31	psi-mi:“MI:0915”(physical association)	0.560
BCOR	CBX4	psi-mi:“MI:0914”(association)	0.530
PCGF1	CBX4	psi-mi:“MI:0914”(association)	0.530

BioGRID (155): ZNF148 (Two-hybrid), ZNF148 (Two-hybrid), TRIM10 (Two-hybrid), GLRX3 (Two-hybrid), GORASP2 (Two-hybrid), NUTM2F (Two-hybrid), CEP70 (Two-hybrid), CCDC67 (Two-hybrid), ZNF148 (Biochemical Activity), ZNF148 (Affinity Capture-MS), ZNF148 (Affinity Capture-MS), ZNF148 (Affinity Capture-MS), ZNF148 (Affinity Capture-MS), ZNF148 (Affinity Capture-RNA), ZNF148 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GSA2, A0A1L8H0H2, A0JP82, A0MS83, A2AWL7, A2RRX6, A2X0Q0, A6NCI8, A9ZPC9, F8VPJ6, K9JHZ4, O13186, O46567, O60284, O75362, P15822, P35547, P37275, P48552, P52551, P79269, Q03172, Q14207, Q28DZ0, Q2KHR2, Q3V0A6, Q3Y4E1, Q4JK59, Q4V7J0, Q5DTW7, Q5R782, Q5W1J6, Q5ZJK5, Q61624, Q62806, Q6N021, Q6YXZ4, Q7SZL5, Q80TY4, Q8BMA5

Diamond homologs: A0MS83, Q3Y4E1, Q5R782, Q61624, Q62806, Q6NZQ6, Q8NDX6, Q99LI5, Q9UQR1, Q9Y2X9, A0JC51, A2ANX9, O15391, O57311, O57415, O60481, O62836, O73689, O95409, P08048, P0C6P6, P10925, P17010, P17012, P18747, P20662, P22227, P25490, P34694, P46684, P80944, Q00899, Q10RP4, Q12145, Q15915, Q29419, Q2FAY8, Q3TTC2, Q3UH06, Q3US17

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATM	up-regulates	ZNF148	phosphorylation
ZNF148	“down-regulates quantity by repression”	SOX18	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional regulation by RUNX1	5	10.8×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	16.0×	1e-03
DNA replication	5	9.1×	1e-02
chromatin remodeling	10	8.0×	7e-05
transcription by RNA polymerase II	9	7.0×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	10
Uncertain significance	67
Likely benign	11
Benign	5

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1701964	NM_021964.3(ZNF148):c.1195_1199del (p.Arg399fs)	Pathogenic
2577929	NM_021964.3(ZNF148):c.1456G>T (p.Glu486Ter)	Pathogenic
374843	NM_021964.3(ZNF148):c.1583dup (p.Ser529fs)	Pathogenic
374844	NM_021964.3(ZNF148):c.970dup (p.Ser324fs)	Pathogenic
4813599	NM_021964.3(ZNF148):c.702G>T (p.Met234Ile)	Pathogenic
1685478	NM_021964.3(ZNF148):c.734A>G (p.His245Arg)	Likely pathogenic
1698700	NM_021964.3(ZNF148):c.1268C>A (p.Ser423Ter)	Likely pathogenic
3893248	NM_021964.3(ZNF148):c.668-1G>A	Likely pathogenic
4294457	NM_021964.3(ZNF148):c.1548del (p.Ile517fs)	Likely pathogenic
4526485	NM_021964.3(ZNF148):c.917C>G (p.Ser306Ter)	Likely pathogenic
4635147	NM_021964.3(ZNF148):c.1251T>G (p.Tyr417Ter)	Likely pathogenic
624226	NM_021964.3(ZNF148):c.1191_1194del (p.Ser397fs)	Likely pathogenic
666563	NM_021964.3(ZNF148):c.1504C>T (p.Gln502Ter)	Likely pathogenic
807528	NM_021964.3(ZNF148):c.845A>G (p.Asp282Gly)	Likely pathogenic
987124	NM_021964.3(ZNF148):c.1170_1173del (p.Leu390fs)	Likely pathogenic

SpliceAI

2311 predictions. Top by Δscore:

Variant	Effect	Δscore
3:125233988:C:CT	acceptor_gain	1.0000
3:125233989:A:T	acceptor_gain	1.0000
3:125279119:AATAC:A	donor_loss	1.0000
3:125279120:ATAC:A	donor_loss	1.0000
3:125279121:TACC:T	donor_loss	1.0000
3:125279122:A:C	donor_loss	1.0000
3:125279123:C:CG	donor_loss	1.0000
3:125279248:C:CC	acceptor_gain	1.0000
3:125288100:TACT:T	donor_loss	1.0000
3:125288101:A:AC	donor_gain	1.0000
3:125288101:ACTTT:A	donor_loss	1.0000
3:125288102:C:CC	donor_gain	1.0000
3:125288224:CTTAT:C	acceptor_gain	1.0000
3:125288226:TATCT:T	acceptor_loss	1.0000
3:125288228:TCTG:T	acceptor_loss	1.0000
3:125288229:C:CC	acceptor_gain	1.0000
3:125288230:T:A	acceptor_loss	1.0000
3:125313302:ACTT:A	donor_loss	1.0000
3:125313304:TTA:T	donor_loss	1.0000
3:125313305:T:TG	donor_loss	1.0000
3:125313306:A:AC	donor_gain	1.0000
3:125313306:A:C	donor_loss	1.0000
3:125313307:C:CT	donor_gain	1.0000
3:125313307:CA:C	donor_gain	1.0000
3:125313307:CAG:C	donor_gain	1.0000
3:125313307:CAGG:C	donor_gain	1.0000
3:125313307:CAGGG:C	donor_gain	1.0000
3:125313325:A:AC	donor_gain	1.0000
3:125313326:C:CC	donor_gain	1.0000
3:125313330:AGT:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004499 (3:125256557 T>C), RS1000098168 (3:125336173 C>T), RS1000115229 (3:125248569 C>T), RS1000125819 (3:125250699 GTTTT>G), RS1000133704 (3:125343770 G>A), RS1000152003 (3:125284346 TAACAGTCACCAAA>T), RS1000167888 (3:125362840 C>A), RS1000202149 (3:125229454 T>C), RS1000216272 (3:125274086 T>C), RS1000223146 (3:125356348 A>G,T), RS1000232206 (3:125255269 C>A,T), RS1000251020 (3:125361752 G>C), RS1000296526 (3:125356671 C>T), RS1000311043 (3:125268360 A>C,G), RS1000330293 (3:125341765 C>T)

Disease associations

OMIM: gene MIM:601897 | disease phenotypes: MIM:617260, MIM:613780

GenCC curated gene-disease

Disease	Classification	Inheritance
global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies	Strong	Autosomal dominant

Mondo (2): global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies (MONDO:0014994), aortic aneurysm, familial thoracic 7 (MONDO:0013418)

Orphanet (0):

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000107	Renal cyst
HP:0000110	Renal dysplasia
HP:0000154	Wide mouth
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000341	Narrow forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000540	Hypermetropia
HP:0000582	Upslanted palpebral fissure
HP:0000824	Decreased response to growth hormone stimulation test
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001319	Neonatal hypotonia
HP:0001643	Patent ductus arteriosus
HP:0001680	Coarctation of aorta
HP:0001718	Mitral stenosis
HP:0001762	Talipes equinovarus
HP:0001763	Pes planus
HP:0002002	Deep philtrum
HP:0002007	Frontal bossing
HP:0002079	Hypoplasia of the corpus callosum

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008971_35	Urate levels	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	8
entinostat	decreases expression, affects cotreatment	2
Indomethacin	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
trichostatin A	decreases expression	1
afimoxifene	increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	increases expression	1
coumarin	affects phosphorylation	1
tamibarotene	affects expression, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Resveratrol	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_GZ99	K562 eGFP-ZNF148	Cancer cell line	Female
CVCL_HA19	MCF-7 eGFP-ZNF148	Cancer cell line	Female
CVCL_XW08	HEK293 eGFP-ZNF148	Transformed cell line	Female

Clinical trials (associated diseases)

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