ZNF646

Summary

ZNF646 (zinc finger protein 646, HGNC:29004) is a protein-coding gene on chromosome 16p11.2, encoding Zinc finger protein 646 (O15015). 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 9726 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 337 total
• MANE Select transcript: NM_014699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29004
Approved symbol	ZNF646
Name	zinc finger protein 646
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0296
Ensembl gene	ENSG00000167395
Ensembl biotype	protein_coding
OMIM	619299
Entrez	9726

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000300850, ENST00000394979, ENST00000428260, ENST00000564189, ENST00000914100

RefSeq mRNA: 1 — MANE Select: NM_014699 NM_014699

CCDS: CCDS10702

Canonical transcript exons

ENST00000300850 — 3 exons

Exon	Start	End
ENSE00001112638	31076246	31081701
ENSE00001363993	31074422	31074631
ENSE00001373077	31082971	31084196

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 90.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3565 / max 177.1443, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153763	18.6151	1810
153764	0.6678	358
153765	0.0736	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	90.48	gold quality
type B pancreatic cell	CL:0000169	88.43	gold quality
vena cava	UBERON:0004087	86.68	gold quality
inferior olivary complex	UBERON:0002127	86.37	gold quality
right testis	UBERON:0004534	86.09	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	85.98	silver quality
left testis	UBERON:0004533	85.90	gold quality
olfactory bulb	UBERON:0002264	85.46	gold quality
heart right ventricle	UBERON:0002080	84.76	gold quality
granulocyte	CL:0000094	83.89	gold quality
testis	UBERON:0000473	83.70	gold quality
body of tongue	UBERON:0011876	83.47	gold quality
buccal mucosa cell	CL:0002336	82.40	gold quality
pons	UBERON:0000988	82.05	gold quality
pericardium	UBERON:0002407	81.71	silver quality
sural nerve	UBERON:0015488	81.30	gold quality
subthalamic nucleus	UBERON:0001906	81.04	silver quality
triceps brachii	UBERON:0001509	80.94	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.88	gold quality
ganglionic eminence	UBERON:0004023	80.81	gold quality
pharyngeal mucosa	UBERON:0000355	80.55	silver quality
blood	UBERON:0000178	80.35	gold quality
tongue squamous epithelium	UBERON:0006919	80.33	gold quality
inferior vagus X ganglion	UBERON:0005363	80.17	silver quality
biceps brachii	UBERON:0001507	79.97	gold quality
pylorus	UBERON:0001166	79.86	silver quality
nasal cavity epithelium	UBERON:0005384	79.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.68	gold quality
stromal cell of endometrium	CL:0002255	79.61	gold quality
cardia of stomach	UBERON:0001162	79.40	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting ZNF646, 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-9-5P	100.00	72.28	2361
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-3192-3P	98.62	65.80	970
HSA-MIR-4457	98.09	67.12	1274

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp646	ENSMUSG00000049739
rattus_norvegicus	Zfp646	ENSRNOG00000026115

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

Zinc finger protein 646 — O15015 (reviewed: O15015)

All UniProt accessions (3): C9J3L0, O15015, H3BSD0

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.

Isoforms (2)

UniProt ID	Names	Canonical?
O15015-2	2	yes
O15015-1	1

RefSeq proteins (1): NP_055514* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13912

UniProt features (71 total): zinc finger region 31, region of interest 11, compositionally biased region 10, sequence variant 9, cross-link 7, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15015-F1	50.66	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 (8): 612, 451, 534, 557, 688, 1157, 1168, 1178

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, AP4_Q6, CAGCTG_AP4_Q5, SOX9_B1, chr16p11, MODULE_123, RYTTCCTG_ETS2_B, MODULE_98, YY1_01, SOX5_01, YYCATTCAWW_UNKNOWN, RAMASWAMY_METASTASIS_DN, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GCCATNTTG_YY1_Q6

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

1054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF646	ZNF843	Q8N446	540
ZNF646	KAT8	Q9H7Z6	527
ZNF646	SHISA2	Q6UWI4	505
ZNF646	PALD1	Q9ULE6	481
ZNF646	SLITRK6	Q9H5Y7	470
ZNF646	MEX3C	Q5U5Q3	458
ZNF646	ADAMTS14	Q8WXS8	457
ZNF646	ZDHHC24	Q6UX98	453
ZNF646	SDR39U1	Q9NRG7	439
ZNF646	STX4	Q12846	425
ZNF646	CCDC93	Q567U6	412
ZNF646	ASB8	Q9H765	411
ZNF646	DCAF12	Q5T6F0	407
ZNF646	PARP2	Q9UGN5	402
ZNF646	NKAPL	Q5M9Q1	399

IntAct

49 interactions, top by confidence:

A	B	Type	Score
ZNF646	PRKG1	psi-mi:“MI:0915”(physical association)	0.670
PRKG1	ZNF646	psi-mi:“MI:0915”(physical association)	0.670
ZNF646	MDFI	psi-mi:“MI:0915”(physical association)	0.620
MDFI	ZNF646	psi-mi:“MI:0915”(physical association)	0.620
EMSY	ZNF646	psi-mi:“MI:0915”(physical association)	0.560
ZNF646	EMSY	psi-mi:“MI:0915”(physical association)	0.560
LEUTX	ZNF646	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
ZNF646	GAPDH	psi-mi:“MI:0915”(physical association)	0.400
	ZNF646	psi-mi:“MI:0915”(physical association)	0.370
ZNF646	NINL	psi-mi:“MI:0915”(physical association)	0.370
TRAF2	ZNF646	psi-mi:“MI:0915”(physical association)	0.370
UBE2I	ZNF646	psi-mi:“MI:0915”(physical association)	0.370
Set	ZKSCAN1	psi-mi:“MI:0914”(association)	0.350
C9orf72	CHD2	psi-mi:“MI:0914”(association)	0.350
RPS19	ZNF320	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
RPL36	GTPBP10	psi-mi:“MI:0914”(association)	0.350
EFEMP1	ZNF316	psi-mi:“MI:0914”(association)	0.350
OASL	ZNF316	psi-mi:“MI:0914”(association)	0.350
RPL19		psi-mi:“MI:0914”(association)	0.350
RPL13		psi-mi:“MI:0914”(association)	0.350
SRSF4		psi-mi:“MI:0914”(association)	0.350
H1-7		psi-mi:“MI:0914”(association)	0.350

BioGRID (54): ZNF646 (Two-hybrid), C11orf30 (Two-hybrid), ZNF646 (Affinity Capture-MS), NINL (Two-hybrid), ZNF646 (Two-hybrid), ZNF646 (Two-hybrid), ZNF646 (Two-hybrid), ZNF646 (Affinity Capture-MS), ZNF646 (Affinity Capture-MS), ZNF646 (Affinity Capture-MS), ZNF646 (Affinity Capture-MS), ZNF646 (Affinity Capture-MS), ZNF646 (Affinity Capture-MS), ZNF646 (Affinity Capture-MS), ZNF646 (Affinity Capture-RNA)

ESM2 similar proteins: A0JNJ4, A2APT9, A6NEL2, A6NP61, B1ASB6, B1WBS3, B2RXF5, F6WEQ6, O15015, O43918, O88282, O88286, O95785, P98168, P98169, Q2M3G4, Q2MHN3, Q2QGD7, Q3U1J1, Q3U381, Q497V6, Q5SW24, Q5SXM2, Q6YND2, Q6ZMQ8, Q6ZMY3, Q7TN08, Q7TSX9, Q80SU3, Q80YE4, Q811H0, Q8BG26, Q8BZW2, Q8C8V1, Q8IX07, Q8IY92, Q8N143, Q8N1G0, Q8NC74, Q8TBE0

Diamond homologs: O15015, Q07231, Q6NV66, A1L2U9, B1WAZ8, P31509, P39770, P39806, Q01798, Q01800, Q02026, Q02027, Q0IH98, Q12145, Q12531, Q17R98, Q3B7M4, Q505G8, Q6P882, Q8BI69, Q8CJ78, Q8IX07, Q8NCA9, Q91X45, Q99PV8, Q9BE73, Q9C0K0, Q9H165, Q9QYE3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
Peptide chain elongation	5	18.7×	2e-04
Viral mRNA Translation	5	18.7×	2e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	5	18.5×	2e-04
Selenocysteine synthesis	5	17.7×	2e-04
Eukaryotic Translation Termination	5	17.7×	2e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	5	17.3×	2e-04
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	5	17.3×	2e-04
Formation of a pool of free 40S subunits	5	16.5×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	5	21.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	304
Likely benign	24
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

790 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31084117:A:AC	donor_gain	1.0000
16:31084118:C:CC	donor_gain	1.0000
16:31081677:G:GT	donor_gain	0.9900
16:31084121:A:AC	donor_gain	0.9900
16:31084122:T:C	donor_gain	0.9900
16:31084138:T:TA	donor_gain	0.9900
16:31082580:G:GT	donor_gain	0.9700
16:31076240:TCCTA:T	acceptor_loss	0.9600
16:31076242:CTA:C	acceptor_loss	0.9600
16:31076243:TA:T	acceptor_loss	0.9600
16:31076244:A:AC	acceptor_loss	0.9600
16:31076245:G:GC	acceptor_loss	0.9600
16:31081690:T:TA	donor_gain	0.9600
16:31082965:CCCCA:C	acceptor_loss	0.9600
16:31082966:CCCAG:C	acceptor_loss	0.9600
16:31082967:CCAG:C	acceptor_loss	0.9600
16:31082968:CA:C	acceptor_loss	0.9600
16:31082969:AGG:A	acceptor_loss	0.9600
16:31082970:GGA:G	acceptor_gain	0.9600
16:31084147:AG:A	donor_gain	0.9600
16:31074476:C:G	donor_gain	0.9500
16:31074753:A:G	donor_gain	0.9500
16:31076244:A:AG	acceptor_gain	0.9500
16:31076245:G:GG	acceptor_gain	0.9500
16:31081680:G:GT	donor_gain	0.9500
16:31081685:G:GT	donor_gain	0.9500
16:31081691:G:GA	donor_gain	0.9500
16:31082969:A:AG	acceptor_gain	0.9500
16:31082970:G:GG	acceptor_gain	0.9500
16:31084059:A:AC	donor_gain	0.9500

AlphaMissense

12049 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31077147:T:C	F275L	0.999
16:31077148:T:C	F275S	0.999
16:31077149:C:A	F275L	0.999
16:31077149:C:G	F275L	0.999
16:31077471:T:G	Y383D	0.999
16:31077498:C:G	H392D	0.999
16:31079565:T:C	C1081R	0.999
16:31079574:T:C	C1084R	0.999
16:31079604:T:G	Y1094D	0.999
16:31079613:C:G	H1097D	0.999
16:31079615:T:A	H1097Q	0.999
16:31079615:T:G	H1097Q	0.999
16:31080039:T:C	F1239L	0.999
16:31080041:C:A	F1239L	0.999
16:31080041:C:G	F1239L	0.999
16:31080123:T:C	F1267L	0.999
16:31080125:C:A	F1267L	0.999
16:31080125:C:G	F1267L	0.999
16:31077126:T:C	C268R	0.998
16:31077128:T:G	C268W	0.998
16:31077135:T:C	C271R	0.998
16:31077137:T:G	C271W	0.998
16:31077174:C:G	H284D	0.998
16:31077176:C:A	H284Q	0.998
16:31077176:C:G	H284Q	0.998
16:31077444:T:C	F374L	0.998
16:31077446:C:A	F374L	0.998
16:31077446:C:G	F374L	0.998
16:31077486:A:C	S388R	0.998
16:31077488:C:A	S388R	0.998

dbSNP variants (sampled 300 via entrez): RS1000169971 (16:31074952 G>A), RS1000402423 (16:31072655 G>C), RS1000718213 (16:31083157 A>C), RS1000822655 (16:31077929 A>G), RS1001180413 (16:31075559 A>G,T), RS1001190608 (16:31077334 CAGATG>C), RS1001264271 (16:31076927 C>G), RS1001324583 (16:31075068 C>T), RS1001385254 (16:31080771 C>T), RS1001763317 (16:31071430 G>A), RS1002076385 (16:31070865 T>C), RS1002149601 (16:31072736 C>T), RS1002233753 (16:31071105 C>T), RS1002386082 (16:31081972 T>C), RS1002731217 (16:31076270 G>C)

Disease associations

OMIM: gene MIM:619299 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004902_10	Parkinson’s disease	5.000000e-12
GCST007293_141	Body fat distribution (arm fat ratio)	4.000000e-15
GCST007293_82	Body fat distribution (arm fat ratio)	3.000000e-15
GCST007293_99	Body fat distribution (arm fat ratio)	1.000000e-14
GCST008129_86	Body mass index	7.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs749671	VKORC1, ZNF646		0.00	0

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Atrazine	decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8J1	SEES3-1V human ZNF646, clone1	Embryonic stem cell	Male
CVCL_A8J2	SEES3-1V human ZNF646, clone2	Embryonic stem cell	Male
CVCL_A8J3	SEES3-1V human ZNF646, clone3	Embryonic stem cell	Male
CVCL_TZ42	HAP1 ZNF646 (-) 1	Cancer cell line	Male
CVCL_XV34	HAP1 ZNF646 (-) 2	Cancer cell line	Male
CVCL_XV35	HAP1 ZNF646 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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