ZNF649

Summary

ZNF649 (zinc finger protein 649, HGNC:25741) is a protein-coding gene on chromosome 19q13.41, encoding Zinc finger protein 649 (Q9BS31). Transcriptional repressor.

Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of osteoblast differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of DNA-templated transcription. Located in nucleus.

Source: NCBI Gene 65251 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_023074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25741
Approved symbol	ZNF649
Name	zinc finger protein 649
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12644
Ensembl gene	ENSG00000198093
Ensembl biotype	protein_coding
OMIM	611903
Entrez	65251

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 retained_intron

ENST00000354957, ENST00000595418, ENST00000596690, ENST00000597882, ENST00000599530, ENST00000599671, ENST00000600738, ENST00000862520, ENST00000930182, ENST00000966435, ENST00000966436, ENST00000966437, ENST00000966438

RefSeq mRNA: 1 — MANE Select: NM_023074 NM_023074

CCDS: CCDS12843

Canonical transcript exons

ENST00000354957 — 5 exons

Exon	Start	End
ENSE00000842697	51889235	51891897
ENSE00002521632	51896472	51896567
ENSE00002977947	51904914	51905017
ENSE00003588383	51900093	51900294
ENSE00003787335	51896852	51896978

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 87.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7044 / max 315.5645, expressed in 1603 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182508	7.9264	1521
182507	1.8181	812
182509	1.7642	856
182506	0.1957	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	87.63	gold quality
ganglionic eminence	UBERON:0004023	84.98	gold quality
cortical plate	UBERON:0005343	84.88	gold quality
ventricular zone	UBERON:0003053	84.47	gold quality
sural nerve	UBERON:0015488	84.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.11	gold quality
calcaneal tendon	UBERON:0003701	82.04	gold quality
islet of Langerhans	UBERON:0000006	80.58	gold quality
endometrium	UBERON:0001295	79.90	gold quality
smooth muscle tissue	UBERON:0001135	79.69	gold quality
tonsil	UBERON:0002372	79.57	gold quality
prostate gland	UBERON:0002367	79.44	gold quality
urinary bladder	UBERON:0001255	79.27	gold quality
placenta	UBERON:0001987	79.03	gold quality
popliteal artery	UBERON:0002250	78.54	gold quality
tibial artery	UBERON:0007610	78.52	gold quality
colonic epithelium	UBERON:0000397	78.16	gold quality
quadriceps femoris	UBERON:0001377	77.78	gold quality
monocyte	CL:0000576	77.62	gold quality
leukocyte	CL:0000738	77.41	gold quality
skeletal muscle tissue	UBERON:0001134	77.27	gold quality
adrenal tissue	UBERON:0018303	76.91	gold quality
mucosa of stomach	UBERON:0001199	76.77	gold quality
stromal cell of endometrium	CL:0002255	76.64	gold quality
thymus	UBERON:0002370	76.64	gold quality
muscle tissue	UBERON:0002385	76.61	gold quality
rectum	UBERON:0001052	76.57	gold quality
ovary	UBERON:0000992	76.49	gold quality
lymph node	UBERON:0000029	76.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	517.54
E-ANND-3	no	3.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting ZNF649, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 2)

• These results suggest that ZNF649 protein may act as a transcriptional repressor in mitogen-activated protein kinase signaling pathway to mediate cellular functions. (PMID:15950191)
• We detected African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for ulcerative colitis. (PMID:27693347)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG14442	FBGN0029893
drosophila_melanogaster	CG14440	FBGN0029894

Paralogs (11): IKZF2 (ENSG00000030419), ZNF821 (ENSG00000102984), ZNF639 (ENSG00000121864), IKZF4 (ENSG00000123411), ZNF382 (ENSG00000161298), IKZF3 (ENSG00000161405), ZNF613 (ENSG00000176024), IKZF1 (ENSG00000185811), ZNF567 (ENSG00000189042), ZNF564 (ENSG00000249709), ZNF350 (ENSG00000256683)

Protein

Protein identifiers

Zinc finger protein 649 — Q9BS31 (reviewed: Q9BS31)

All UniProt accessions (5): Q9BS31, M0QX90, M0QYA0, M0R098, M0R1B1

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. Regulator of transcriptional factor complexes and may suppress SRE and AP-1 transcription activities mediated by growth factor signaling pathways.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in heart, skeletal muscle, and brain. Lower expression in liver, lung, kidney, pancreas and placenta.

Domain organisation. The KRAB domain is required for transcriptional repression.

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

RefSeq proteins (1): NP_075562* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF01352

UniProt features (19 total): zinc finger region 10, sequence variant 2, sequence conflict 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BS31-F1	68.54	0.23

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): 112

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins

MSigDB gene sets: 51 (showing top): MODULE_95, FALVELLA_SMOKERS_WITH_LUNG_CANCER, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MODULE_163, REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, NFE2L2.V2, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, CIITA_TARGET_GENES, E2F5_TARGET_GENES, FOXE1_TARGET_GENES, H1_6_TARGET_GENES, SUPT16H_TARGET_GENES, ZNF175_TARGET_GENES, ZNF197_TARGET_GENES, ZNF407_TARGET_GENES

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), 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 factor activity (GO:0003700), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	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

386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF649	KNCN	A6PVL3	392
ZNF649	LSAMP	Q13449	392
ZNF649	SNX20	Q7Z614	391
ZNF649	FAM222A	Q5U5X8	350
ZNF649	ETV3L	Q6ZN32	323
ZNF649	FAM120A2P	Q5T035	317
ZNF649	C9JR48	C9JR48	295
ZNF649	TRIM28	Q13263	283
ZNF649	AVL9	Q8NBF6	276
ZNF649	DNTTIP1	Q9H147	271
ZNF649	HHLA1	C9JL84	254
ZNF649	DHX35	Q9H5Z1	231
ZNF649	GORAB	Q5T7V8	230
ZNF649	MIPOL1	Q8TD10	228
ZNF649	SETDB1	Q15047	224

IntAct

16 interactions, top by confidence:

A	B	Type	Score
ZNF649	TRIM28	psi-mi:“MI:0915”(physical association)	0.670
LMNA	ZNF649	psi-mi:“MI:0915”(physical association)	0.560
ZNF649	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
SUV39H1	ZNF649	psi-mi:“MI:0915”(physical association)	0.510
ZNF649	SUV39H1	psi-mi:“MI:0915”(physical association)	0.510
CBX5	ZNF568	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
TRIM63	ZNF649	psi-mi:“MI:0915”(physical association)	0.000
TRIM55	ZNF649	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): ZNF649 (Affinity Capture-MS), ZNF649 (Two-hybrid), ZNF649 (Two-hybrid), ZNF649 (Affinity Capture-MS), ZNF649 (Affinity Capture-MS), ZNF649 (Affinity Capture-MS), ZNF649 (Affinity Capture-MS), ZNF649 (Proximity Label-MS), ZNF649 (Affinity Capture-MS), ZNF649 (Affinity Capture-MS), ZNF649 (Cross-Linking-MS (XL-MS)), ZNF649 (Affinity Capture-MS), ZNF649 (Affinity Capture-RNA), ZNF649 (Affinity Capture-MS), ZNF649 (Affinity Capture-MS)

ESM2 similar proteins: A0JPL0, A3KN36, A7MBI1, A8MT65, B2RXC5, D3ZVT0, P08042, P21506, P51508, P52738, Q02525, Q06730, Q12901, Q2KI58, Q2M218, Q2M3W8, Q2M3X9, Q2VY69, Q49AA0, Q4R6J4, Q4V8A8, Q5FWF6, Q5HY98, Q5RB33, Q5RC79, Q5REF1, Q5T5D7, Q5VIY5, Q61967, Q6P2D0, Q6ZN11, Q86XU0, Q86Y25, Q8N782, Q8N859, Q8NB42, Q8TF39, Q8TF47, Q8WXB4, Q95K49

Diamond homologs: A0A1W2PQL4, A0JNB1, A0JPL0, A6NK53, A6QLU5, A6QPT6, A7MBI1, A8MT65, A8MUV8, A8MWA4, B2RXC5, B4DU55, B4DX44, E9PYI1, O14628, O75346, P0CH99, P0CI00, P17014, P17030, P17032, P17098, P51786, P85977, Q02386, Q06730, Q06732, Q0VAW7, Q12901, Q13360, Q14586, Q14588, Q14590, Q16587, Q2M3X9, Q2VY69, Q32M78, Q3ZCX4, Q49AA0, Q4R6J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1353 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51896468:TTA:T	donor_loss	1.0000
19:51896469:TA:T	donor_loss	1.0000
19:51896470:A:AC	donor_gain	1.0000
19:51896470:ACCTG:A	donor_loss	1.0000
19:51896471:C:CC	donor_gain	1.0000
19:51896471:C:CT	donor_loss	1.0000
19:51896564:TACC:T	acceptor_gain	1.0000
19:51896566:CC:C	acceptor_gain	1.0000
19:51896567:CC:C	acceptor_gain	1.0000
19:51896568:C:CG	acceptor_loss	1.0000
19:51896569:T:G	acceptor_loss	1.0000
19:51896851:CCCA:C	donor_gain	1.0000
19:51896854:A:AC	donor_gain	1.0000
19:51896855:C:CC	donor_gain	1.0000
19:51896890:T:TA	donor_gain	1.0000
19:51896976:TTC:T	acceptor_gain	1.0000
19:51896979:C:CC	acceptor_gain	1.0000
19:51896980:T:C	acceptor_loss	1.0000
19:51896470:AC:A	donor_gain	0.9900
19:51896471:CC:C	donor_gain	0.9900
19:51896471:CCTG:C	donor_gain	0.9900
19:51896471:CCTGG:C	donor_gain	0.9900
19:51896568:C:CC	acceptor_gain	0.9900
19:51896572:T:C	acceptor_gain	0.9900
19:51896572:T:TC	acceptor_gain	0.9900
19:51896814:TGGG:T	donor_gain	0.9900
19:51896850:A:AG	donor_loss	0.9900
19:51896851:C:A	donor_loss	0.9900
19:51896891:C:A	donor_gain	0.9900
19:51896974:GATTC:G	acceptor_gain	0.9900

AlphaMissense

3356 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51891123:C:G	R338P	0.999
19:51891071:G:C	F355L	0.998
19:51891071:G:T	F355L	0.998
19:51891073:A:G	F355L	0.998
19:51891155:G:C	F327L	0.998
19:51891155:G:T	F327L	0.998
19:51891157:A:G	F327L	0.998
19:51890903:G:C	F411L	0.997
19:51890903:G:T	F411L	0.997
19:51890905:A:G	F411L	0.997
19:51891239:G:C	F299L	0.997
19:51891239:G:T	F299L	0.997
19:51891241:A:G	F299L	0.997
19:51891323:G:C	F271L	0.997
19:51891323:G:T	F271L	0.997
19:51891325:A:G	F271L	0.997
19:51891407:G:C	F243L	0.997
19:51891407:G:T	F243L	0.997
19:51891409:A:G	F243L	0.997
19:51891491:G:C	F215L	0.997
19:51891491:G:T	F215L	0.997
19:51891493:A:G	F215L	0.997
19:51890886:A:G	L417P	0.996
19:51891138:A:G	L333P	0.996
19:51891156:A:G	F327S	0.996
19:51891296:A:C	H280Q	0.996
19:51891296:A:T	H280Q	0.996
19:51891044:A:C	H364Q	0.995
19:51891044:A:T	H364Q	0.995
19:51891054:A:G	L361P	0.995

dbSNP variants (sampled 300 via entrez): RS1000097541 (19:51901626 C>G), RS1000178939 (19:51898973 G>A), RS1000204402 (19:51904138 T>C), RS1000646421 (19:51890642 C>T), RS1000806392 (19:51905144 G>C,T), RS1001096457 (19:51890943 C>A), RS1001479151 (19:51893995 C>A,T), RS1001527964 (19:51893612 C>T), RS1002421931 (19:51903830 G>A), RS1002475797 (19:51899498 A>T), RS1002482016 (19:51895501 G>A), RS1002497190 (19:51900114 C>G), RS1002534194 (19:51895158 G>C), RS1002608637 (19:51899459 G>A), RS1002616184 (19:51893281 CAT>C)

Disease associations

OMIM: gene MIM:611903 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007277_24	Tourette syndrome	9.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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