ZNF181

Summary

ZNF181 (zinc finger protein 181, HGNC:12971) is a protein-coding gene on chromosome 19q13.11, encoding Zinc finger protein 181 (Q2M3W8). May be involved in transcriptional regulation.

Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See MIM 604749 for additional information on zinc finger proteins.

Source: NCBI Gene 339318 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_001029997

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12971
Approved symbol	ZNF181
Name	zinc finger protein 181
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	HHZ181, MGC44316
Ensembl gene	ENSG00000197841
Ensembl biotype	protein_coding
OMIM	606741
Entrez	339318

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000392232, ENST00000448715, ENST00000459757, ENST00000492450, ENST00000593781, ENST00000595708, ENST00000599244, ENST00000903975, ENST00000903976, ENST00000951028

RefSeq mRNA: 2 — MANE Select: NM_001029997 NM_001029997, NM_001145665

CCDS: CCDS32990, CCDS46043

Canonical transcript exons

ENST00000492450 — 4 exons

Exon	Start	End
ENSE00001856310	34734243	34735046
ENSE00002449786	34739523	34739621
ENSE00002509772	34739148	34739268
ENSE00003724961	34740611	34745378

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 93.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6235 / max 114.8289, expressed in 1691 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175153	5.8957	1640
175152	1.7278	894

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.37	gold quality
muscle of leg	UBERON:0001383	87.71	gold quality
gastrocnemius	UBERON:0001388	87.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.46	gold quality
cortical plate	UBERON:0005343	86.34	gold quality
body of pancreas	UBERON:0001150	85.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.91	gold quality
ventricular zone	UBERON:0003053	84.86	gold quality
ganglionic eminence	UBERON:0004023	84.42	gold quality
left ovary	UBERON:0002119	84.06	gold quality
islet of Langerhans	UBERON:0000006	83.05	gold quality
pancreas	UBERON:0001264	83.00	gold quality
right ovary	UBERON:0002118	82.98	gold quality
adrenal tissue	UBERON:0018303	82.93	gold quality
cerebellar hemisphere	UBERON:0002245	82.50	gold quality
right atrium auricular region	UBERON:0006631	82.42	gold quality
cerebellar cortex	UBERON:0002129	82.37	gold quality
apex of heart	UBERON:0002098	82.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.19	gold quality
lower esophagus	UBERON:0013473	82.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.11	gold quality
left uterine tube	UBERON:0001303	82.01	gold quality
heart left ventricle	UBERON:0002084	81.95	gold quality
right adrenal gland	UBERON:0001233	81.91	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.74	gold quality
smooth muscle tissue	UBERON:0001135	81.66	gold quality
right adrenal gland cortex	UBERON:0035827	81.62	gold quality
body of uterus	UBERON:0009853	81.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

68 targeting ZNF181, 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-188-3P	100.00	68.76	1240
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-3156-3P	99.76	66.72	939

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf646	ENSDARG00000061424
danio_rerio	si:dkey-154p10.3	ENSDARG00000068366
danio_rerio	si:dkey-89b17.4	ENSDARG00000075545
danio_rerio	zgc:66472	ENSDARG00000075916
danio_rerio	si:ch211-148l7.4	ENSDARG00000094469
danio_rerio	znf576.1	ENSDARG00000097819
drosophila_melanogaster	az2	FBGN0025185
drosophila_melanogaster	CG2129	FBGN0030008
drosophila_melanogaster	CG1602	FBGN0033186
drosophila_melanogaster	CG18011	FBGN0033491
drosophila_melanogaster	CG12942	FBGN0033569
drosophila_melanogaster	indra	FBGN0035213
drosophila_melanogaster	CG30020	FBGN0050020
drosophila_melanogaster	mld	FBGN0263490
caenorhabditis_elegans	ztf-15	WBGENE00011066
caenorhabditis_elegans		WBGENE00015649

Paralogs (36): ZNF302 (ENSG00000089335), ZNF184 (ENSG00000096654), CTCF (ENSG00000102974), ZNF574 (ENSG00000105732), ZBTB24 (ENSG00000112365), ZNF142 (ENSG00000115568), CTCFL (ENSG00000124092), ZNF473 (ENSG00000142528), ZNF827 (ENSG00000151612), ZNF689 (ENSG00000156853), ZNF208 (ENSG00000160321), ZNF91 (ENSG00000167232), ZNF526 (ENSG00000167625), ZNF764 (ENSG00000169951), ZNF747 (ENSG00000169955), ZNF282 (ENSG00000170265), ZNF160 (ENSG00000170949), ZNF497 (ENSG00000174586), ZBTB34 (ENSG00000177125), ZNF771 (ENSG00000179965), ZNF48 (ENSG00000180035), ZNF594 (ENSG00000180626), ZBTB37 (ENSG00000185278), ZFP92 (ENSG00000189420), ZNF107 (ENSG00000196247), ZNF729 (ENSG00000196350), ZNF569 (ENSG00000196437), ZNF420 (ENSG00000197050), ZNF785 (ENSG00000197162), ZNF665 (ENSG00000197497), ZNF347 (ENSG00000197937), ZNF84 (ENSG00000198040), ZBTB48 (ENSG00000204859), ZNF845 (ENSG00000213799), ZNF99 (ENSG00000213973), ZNF688 (ENSG00000229809)

Protein

Protein identifiers

Zinc finger protein 181 — Q2M3W8 (reviewed: Q2M3W8)

Alternative names: HHZ181

All UniProt accessions (5): Q2M3W8, F8W889, M0R074, M0R1Q2, M0R361

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 (3)

UniProt ID	Names	Canonical?
Q2M3W8-1	1	yes
Q2M3W8-2	2
Q2M3W8-3	3

RefSeq proteins (2): NP_001025168, NP_001139137 (=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
IPR050636	C2H2-ZF_domain-containing	Family

Pfam: PF00096, PF01352, PF13912

UniProt features (17 total): zinc finger region 11, cross-link 2, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2M3W8-F1	63.90	0.07

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 (2): 109, 126

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, ZWANG_DOWN_BY_2ND_EGF_PULSE, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, BARX1_TARGET_GENES, CREB3L4_TARGET_GENES, DLX4_TARGET_GENES, H1_6_TARGET_GENES, KLF7_TARGET_GENES, NKX2_2_TARGET_GENES, RBM34_TARGET_GENES, ZNF146_TARGET_GENES, ZNF30_TARGET_GENES, ZNF391_TARGET_GENES, ZNF561_TARGET_GENES, ZNF766_TARGET_GENES

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (5): 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), 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
regulation of metabolic process	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
macromolecule metabolic process	1
primary metabolic process	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
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF181	SCGB2B2	Q4G0G5	505
ZNF181	ZMAT5	Q9UDW3	429
ZNF181	ZNF608	Q9ULD9	387
ZNF181	ZBTB21	Q9ULJ3	372
ZNF181	ZZZ3	Q8IYH5	365
ZNF181	UBA2	Q9UBT2	349
ZNF181	KMT2B	Q9UMN6	339
ZNF181	LSM14A	Q8ND56	336
ZNF181	WTIP	A6NIX2	325
ZNF181	MORF4L2	Q15014	305
ZNF181	GRXCR1	A8MXD5	300
ZNF181	NBPF1	Q3BBV0	299
ZNF181	ZDHHC11	Q9H8X9	290
ZNF181	BLTP1	Q2LD37	245
ZNF181	PGM5	Q15124	244

IntAct

10 interactions, top by confidence:

A	B	Type	Score
ZNF181	PDIA3	psi-mi:“MI:0915”(physical association)	0.400
ZNF181	DDX46	psi-mi:“MI:0915”(physical association)	0.400
ZNF181	NPM1	psi-mi:“MI:0915”(physical association)	0.400
EPHA1	ZNF181	psi-mi:“MI:0915”(physical association)	0.000
APP	ZNF181	psi-mi:“MI:0915”(physical association)	0.000
ZNF181	dnaJ2	psi-mi:“MI:0915”(physical association)	0.000
CBS	ZNF181	psi-mi:“MI:0915”(physical association)	0.000
OPTN	ZNF181	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): ZNF181 (Synthetic Growth Defect), ZNF181 (Proximity Label-MS), ZNF181 (Proximity Label-MS), DDX46 (Proximity Label-MS), ZNF181 (Two-hybrid), ZNF181 (Affinity Capture-MS), ZNF181 (Two-hybrid), ZNF181 (Two-hybrid), ZNF181 (Affinity Capture-MS), ZNF181 (Affinity Capture-RNA), ZNF181 (Proximity Label-MS), ZNF181 (Proximity Label-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: A2A761, A2VDP4, A3KN32, A6QLU5, A6QPT6, A7MBI1, A8MT65, B4DU55, E9PYI1, O60765, O95780, P15622, P17014, P17032, P17098, P21506, P51508, P51814, P52736, P52738, P52742, Q02975, Q06730, Q06732, Q0VCB0, Q14587, Q16587, Q2KI58, Q2M3W8, Q3V080, Q49AA0, Q4R6C2, Q4V8A8, Q571J5, Q5HYK9, Q5JUW0, Q5JVG2, Q5MCW4, Q5MYW4, Q5R4K8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

487 predictions. Top by Δscore:

Variant	Effect	Δscore
19:34737733:G:GT	donor_gain	1.0000
19:34735043:TCAG:T	donor_loss	0.9900
19:34735044:CAG:C	donor_loss	0.9900
19:34735045:AGG:A	donor_loss	0.9900
19:34735046:GG:G	donor_loss	0.9900
19:34735047:G:A	donor_loss	0.9900
19:34735048:T:G	donor_loss	0.9900
19:34739143:TTCA:T	acceptor_loss	0.9800
19:34739144:TCAGG:T	acceptor_loss	0.9800
19:34739145:CA:C	acceptor_loss	0.9800
19:34739264:TGTAG:T	donor_loss	0.9800
19:34739266:TAGG:T	donor_loss	0.9800
19:34739267:AG:A	donor_loss	0.9800
19:34739268:GG:G	donor_loss	0.9800
19:34739269:G:GC	donor_loss	0.9800
19:34739270:T:C	donor_loss	0.9800
19:34740605:TTTCA:T	acceptor_loss	0.9800
19:34740606:TTCAG:T	acceptor_loss	0.9800
19:34740607:TCAGA:T	acceptor_loss	0.9800
19:34740608:CAGA:C	acceptor_loss	0.9800
19:34740609:A:AC	acceptor_loss	0.9800
19:34740609:A:AG	acceptor_gain	0.9800
19:34740610:G:GG	acceptor_gain	0.9800
19:34737753:AAACT:A	donor_gain	0.9700
19:34739265:GTAG:G	donor_gain	0.9700
19:34739521:A:G	acceptor_gain	0.9700
19:34739617:TCCAG:T	donor_loss	0.9700
19:34739618:CCAG:C	donor_loss	0.9700
19:34739619:CAGGT:C	donor_loss	0.9700
19:34739620:AG:A	donor_loss	0.9700

AlphaMissense

3821 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:34741957:T:C	F526L	0.998
19:34741959:T:A	F526L	0.998
19:34741959:T:G	F526L	0.998
19:34741873:T:C	F498L	0.997
19:34741875:C:A	F498L	0.997
19:34741875:C:G	F498L	0.997
19:34741892:T:C	L504P	0.997
19:34741201:T:C	F274L	0.996
19:34741203:T:A	F274L	0.996
19:34741203:T:G	F274L	0.996
19:34741285:T:C	F302L	0.996
19:34741287:T:A	F302L	0.996
19:34741287:T:G	F302L	0.996
19:34741537:T:C	F386L	0.996
19:34741539:C:A	F386L	0.996
19:34741539:C:G	F386L	0.996
19:34741369:T:C	F330L	0.995
19:34741371:T:A	F330L	0.995
19:34741371:T:G	F330L	0.995
19:34741705:T:C	F442L	0.995
19:34741707:C:A	F442L	0.995
19:34741707:C:G	F442L	0.995
19:34741789:T:C	F470L	0.995
19:34741791:T:A	F470L	0.995
19:34741791:T:G	F470L	0.995
19:34741976:T:C	L532P	0.995
19:34739223:T:G	Y29D	0.993
19:34741142:G:C	R254P	0.993
19:34741388:T:C	L336P	0.993
19:34741453:T:C	F358L	0.993

dbSNP variants (sampled 300 via entrez): RS1001169493 (19:34743707 G>A), RS1001219030 (19:34732930 G>GCCCT), RS1001326344 (19:34743471 A>G), RS1001806463 (19:34732899 G>T), RS1001986163 (19:34738550 G>A,T), RS1002100816 (19:34738465 C>G), RS1002101095 (19:34737023 AT>A), RS1002335147 (19:34732724 A>G), RS1002708900 (19:34735540 G>A), RS1003232916 (19:34735231 C>T), RS1003968089 (19:34737880 C>G), RS1004020490 (19:34738431 C>T), RS1004519115 (19:34744921 C>A), RS10048591 (19:34745639 G>A), RS1006361341 (19:34736533 G>A)

Disease associations

OMIM: gene MIM:606741 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

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
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Cisplatin	increases expression	1
Folic Acid	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Potassium Chloride	decreases expression, decreases response to substance	1
Dronabinol	decreases expression, decreases response to substance	1
Tunicamycin	increases expression	1
Urethane	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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