ZNF648

Summary

ZNF648 (zinc finger protein 648, HGNC:18190) is a protein-coding gene on chromosome 1q25.3, encoding Zinc finger protein 648 (Q5T619). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 127665 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_001009992

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18190
Approved symbol	ZNF648
Name	zinc finger protein 648
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46813
Ensembl gene	ENSG00000179930
Ensembl biotype	protein_coding
Entrez	127665

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000339948, ENST00000673963

RefSeq mRNA: 1 — MANE Select: NM_001009992 NM_001009992

CCDS: CCDS30952

Canonical transcript exons

ENST00000339948 — 2 exons

Exon	Start	End
ENSE00001411040	182054570	182058073
ENSE00001445044	182061568	182061712

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 78.73.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.04	gold quality
liver	UBERON:0002107	49.53	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	47.81	gold quality
right lobe of liver	UBERON:0001114	45.31	silver quality
sural nerve	UBERON:0015488	41.95	gold quality
skeletal muscle tissue	UBERON:0001134	41.10	gold quality
ovary	UBERON:0000992	40.58	gold quality
bone marrow cell	CL:0002092	40.19	gold quality
left ovary	UBERON:0002119	39.87	silver quality
ganglionic eminence	UBERON:0004023	39.16	gold quality
muscle tissue	UBERON:0002385	38.85	gold quality
adenohypophysis	UBERON:0002196	38.07	silver quality
pituitary gland	UBERON:0000007	37.29	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
right ovary	UBERON:0002118	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
endometrium	UBERON:0001295	35.59	gold quality
superior frontal gyrus	UBERON:0002661	35.52	gold quality
rectum	UBERON:0001052	35.43	silver quality
body of pancreas	UBERON:0001150	34.97	gold quality
pancreas	UBERON:0001264	34.93	gold quality
bone marrow	UBERON:0002371	34.87	gold quality
tonsil	UBERON:0002372	34.71	gold quality
apex of heart	UBERON:0002098	34.70	gold quality
fundus of stomach	UBERON:0001160	34.61	silver quality
urinary bladder	UBERON:0001255	34.31	gold quality
granulocyte	CL:0000094	34.12	gold quality
testis	UBERON:0000473	33.95	gold quality
mucosa of transverse colon	UBERON:0004991	33.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.63

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2512.1	ZNF648	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605320

miRNA regulators (miRDB)

59 targeting ZNF648, 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-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-203A-3P	99.49	70.56	2806

Literature-anchored findings (GeneRIF, showing 1)

• Characterization and evolutionary origin of novel C₂H₂ zinc finger protein (ZNF648) required for both erythroid and megakaryocyte differentiation in humans. (PMID:33054117)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf648	ENSDARG00000104823
mus_musculus	Zfp648	ENSMUSG00000066797
rattus_norvegicus	Zfp648	ENSRNOG00000031569
drosophila_melanogaster	CG18476	FBGN0037931
drosophila_melanogaster	CG10669	FBGN0039329

Paralogs (5): ZNF664 (ENSG00000179195), ZNF721 (ENSG00000182903), ZFP62 (ENSG00000196670), ZNF485 (ENSG00000198298), ZNF808 (ENSG00000198482)

Protein

Protein identifiers

Zinc finger protein 648 — Q5T619 (reviewed: Q5T619)

All UniProt accessions (2): Q5T619, A0A669KBK7

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_001009992* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (16 total): zinc finger region 10, region of interest 2, sequence variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T619-F1	61.00	0.01

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chr1q25, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR3671, MIR548D_3P, MIR548H_3P_MIR548Z, MIR548BB_3P, MIR548AC, MIR580_5P, MIR17_3P, MIR4709_5P, MIR3164, MIR6820_3P, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), DNA binding (GO:0003677), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF648	OR52N4	Q8NGI2	510
ZNF648	TIGD7	Q6NT04	447
ZNF648	TIGD6	Q17RP2	432
ZNF648	PSKH1	P11801	393
ZNF648	KRAS	P01116	366
ZNF648	MRE11	P49959	364
ZNF648	POLE	Q07864	353
ZNF648	MSH3	P20585	349
ZNF648	MSH6	P52701	348
ZNF648	PPP1R3A	Q16821	338
ZNF648	CHRAC1	Q9NRG0	324
ZNF648	KLK9	Q9UKQ9	324
ZNF648	CACNA1E	Q15878	284
ZNF648	PINK1	Q9BXM7	282
ZNF648	ABCA13	Q86UQ4	279

IntAct

188 interactions, top by confidence:

A	B	Type	Score
ZNF648	ZNF71	psi-mi:“MI:0915”(physical association)	0.560
LDOC1	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	DVL3	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	ZNF275	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	NUDT22	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	AXIN2	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	MDFI	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	TNS2	psi-mi:“MI:0915”(physical association)	0.560
ZNF250	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
FSD2	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	OSBPL3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
MCC	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	RINT1	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	ZNF837	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	BICD2	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	KANK2	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	CEP70	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	TRIM41	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	HOOK2	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	RBAK	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	CDR2L	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (64): ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid), ZNF648 (Two-hybrid)

ESM2 similar proteins: A0A1D5NS60, A0JN76, A1YFX5, A2T7G6, A6NJL1, D2HQI1, F1MJR8, O14901, P0CG00, P10754, P22227, P98182, Q0IJ29, Q1L8W0, Q3SWU4, Q5DW34, Q5EAC5, Q5EXX3, Q5RHB5, Q5SXI5, Q5T619, Q66H04, Q6NRM8, Q6NV66, Q6ZSB9, Q7M6U3, Q7TS63, Q7TSH3, Q7ZWZ4, Q801P1, Q86VK4, Q8BKX7, Q8BXX2, Q8NAM6, Q8NAP3, Q8NCP5, Q8R0A2, Q91VW9, Q96IT1, Q96N77

Diamond homologs: A8MQ14, P17097, P21506, Q03936, Q15937, Q29RZ4, Q3KNS6, Q3V080, Q5RBX0, Q5RBY9, Q5T619, Q6DD87, Q6J6I6, Q6PG37, Q6ZMV8, Q7TNU6, Q7TSH9, Q8BIF9, Q8NEM1, Q8NHY6, Q8TBZ5, Q969W8, Q96EG3, Q96N77, Q96NG8, Q9BSG1, Q9UJL9, Q9Y2G7, Q9Y2P0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

170 predictions. Top by Δscore:

Variant	Effect	Δscore
1:182058071:TAC:T	acceptor_gain	0.9900
1:182058073:CCTG:C	acceptor_loss	0.9900
1:182058075:T:C	acceptor_loss	0.9900
1:182061562:GCTTA:G	donor_loss	0.9900
1:182061564:TTA:T	donor_loss	0.9900
1:182061565:TA:T	donor_loss	0.9900
1:182058069:GATAC:G	acceptor_gain	0.9800
1:182058072:AC:A	acceptor_gain	0.9800
1:182058073:CC:C	acceptor_gain	0.9800
1:182058074:C:CC	acceptor_gain	0.9800
1:182061047:T:A	donor_gain	0.9700
1:182061446:T:A	donor_gain	0.9700
1:182057946:T:TA	donor_gain	0.9600
1:182058070:ATAC:A	acceptor_gain	0.9600
1:182058077:C:CT	acceptor_gain	0.9600
1:182061012:A:T	donor_gain	0.9400
1:182061566:A:AC	donor_gain	0.9400
1:182061567:C:CC	donor_gain	0.9400
1:182058078:A:T	acceptor_gain	0.9200
1:182061458:T:A	donor_gain	0.8500
1:182058088:G:C	acceptor_gain	0.8100
1:182057778:T:TA	donor_gain	0.7900
1:182058088:G:GC	acceptor_gain	0.7600
1:182061565:TAC:T	donor_gain	0.7200
1:182061567:CCT:C	donor_gain	0.7000
1:182061564:TTAC:T	donor_gain	0.6900
1:182061683:CG:C	donor_gain	0.6900
1:182061068:T:TA	donor_gain	0.6800
1:182061435:CCCCT:C	donor_gain	0.6700
1:182061102:T:TA	donor_gain	0.6600

AlphaMissense

3737 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:182056388:G:C	F541L	1.000
1:182056388:G:T	F541L	1.000
1:182056390:A:G	F541L	1.000
1:182056556:A:C	F485L	1.000
1:182056556:A:T	F485L	1.000
1:182056558:A:G	F485L	1.000
1:182056724:G:C	F429L	1.000
1:182056724:G:T	F429L	1.000
1:182056726:A:G	F429L	1.000
1:182056979:G:C	F344L	1.000
1:182056979:G:T	F344L	1.000
1:182056981:A:G	F344L	1.000
1:182056363:G:C	H550D	0.999
1:182056371:A:G	L547P	0.999
1:182056389:A:G	F541S	0.999
1:182056390:A:T	F541I	0.999
1:182056445:G:C	H522Q	0.999
1:182056445:G:T	H522Q	0.999
1:182056472:G:C	F513L	0.999
1:182056472:G:T	F513L	0.999
1:182056474:A:G	F513L	0.999
1:182056529:G:C	H494Q	0.999
1:182056529:G:T	H494Q	0.999
1:182056531:G:C	H494D	0.999
1:182056531:G:T	H494N	0.999
1:182056539:A:G	L491P	0.999
1:182056557:A:G	F485S	0.999
1:182056558:A:T	F485I	0.999
1:182056601:G:C	H470Q	0.999
1:182056601:G:T	H470Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000207103 (1:182066464 C>T), RS1000230368 (1:182070834 C>T), RS1000391367 (1:182060395 T>C), RS1000489484 (1:182056951 G>A,C), RS1000600020 (1:182066869 C>T), RS1000726443 (1:182058904 A>C,G), RS1000832250 (1:182069227 C>T), RS1000974325 (1:182064926 G>A), RS1001191010 (1:182068888 G>T), RS1001488739 (1:182061035 G>A), RS1001518169 (1:182060809 A>G), RS1001699430 (1:182054759 T>C), RS1001853685 (1:182059387 G>A,C), RS1001898055 (1:182060499 T>C,G), RS1001917492 (1:182059996 G>A,C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000755_7	HDL cholesterol	3.000000e-10
GCST002153_1	Cardiovascular heart disease in diabetics	2.000000e-08
GCST002223_65	HDL cholesterol	5.000000e-20
GCST002363_9	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 3 peripheral neuropathy)	6.000000e-08
GCST002899_14	HDL cholesterol	4.000000e-09
GCST004232_17	HDL cholesterol levels	8.000000e-22
GCST007565_115	Morning person	2.000000e-25
GCST007565_144	Morning person	3.000000e-16
GCST008070_22	HDL cholesterol levels	5.000000e-11
GCST008070_95	HDL cholesterol levels	3.000000e-07
GCST008075_105	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-18
GCST008075_53	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-13
GCST008078_44	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-07
GCST008079_74	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-06
GCST008084_126	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-07
GCST008084_13	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-14
GCST008084_224	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-22
GCST008085_165	HDL cholesterol levels in current drinkers	9.000000e-09
GCST008085_26	HDL cholesterol levels in current drinkers	4.000000e-12
GCST008086_39	LDL cholesterol levels in current drinkers	7.000000e-06
GCST010241_80	Apolipoprotein A1 levels	2.000000e-13
GCST010242_473	HDL cholesterol levels	7.000000e-37
GCST010243_80	Apolipoprotein B levels	7.000000e-11
GCST011348_68	High density lipoprotein cholesterol levels	5.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0000180	HIV-1 infection
EFO:0008328	chronotype measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methyleugenol	decreases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
Allergens	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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