ZNF440

Summary

ZNF440 (zinc finger protein 440, HGNC:20874) is a protein-coding gene on chromosome 19p13.2, encoding Zinc finger protein 440 (Q8IYI8). May be involved in transcriptional regulation.

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

Source: NCBI Gene 126070 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 107 total
• MANE Select transcript: NM_152357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20874
Approved symbol	ZNF440
Name	zinc finger protein 440
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ37933
Ensembl gene	ENSG00000171295
Ensembl biotype	protein_coding
Entrez	126070

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000304060, ENST00000414255, ENST00000427505, ENST00000457526, ENST00000587795, ENST00000588954

RefSeq mRNA: 1 — MANE Select: NM_152357 NM_152357

CCDS: CCDS42503

Canonical transcript exons

ENST00000304060 — 4 exons

Exon	Start	End
ENSE00001244043	11831368	11835216
ENSE00001484873	11814273	11814450
ENSE00003679566	11830283	11830409
ENSE00003693605	11830617	11830677

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 91.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5955 / max 124.4996, expressed in 1622 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173968	7.5955	1622

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	91.68	gold quality
bronchial epithelial cell	CL:0002328	91.63	gold quality
right uterine tube	UBERON:0001302	91.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.12	gold quality
colonic epithelium	UBERON:0000397	85.98	gold quality
epithelium of bronchus	UBERON:0002031	85.77	gold quality
bronchus	UBERON:0002185	85.00	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.71	gold quality
skin of abdomen	UBERON:0001416	83.38	gold quality
rectum	UBERON:0001052	82.66	gold quality
skin of leg	UBERON:0001511	81.90	gold quality
transverse colon	UBERON:0001157	80.79	gold quality
calcaneal tendon	UBERON:0003701	80.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.37	gold quality
zone of skin	UBERON:0000014	79.74	gold quality
cortical plate	UBERON:0005343	79.68	gold quality
esophagus mucosa	UBERON:0002469	79.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.54	gold quality
body of pancreas	UBERON:0001150	78.03	gold quality
minor salivary gland	UBERON:0001830	77.98	gold quality
mucosa of transverse colon	UBERON:0004991	77.94	gold quality
body of stomach	UBERON:0001161	77.81	gold quality
right lung	UBERON:0002167	77.42	gold quality
monocyte	CL:0000576	77.31	gold quality
adrenal tissue	UBERON:0018303	77.21	gold quality
skin of hip	UBERON:0001554	77.20	gold quality
stomach	UBERON:0000945	77.17	gold quality
ganglionic eminence	UBERON:0004023	77.13	gold quality
leukocyte	CL:0000738	77.10	gold quality
sural nerve	UBERON:0015488	77.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting ZNF440, 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-6873-3P	100.00	71.42	2626
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4776-3P	100.00	68.73	1340
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-150-5P	99.99	66.69	1976
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-5010-3P	99.83	70.60	2357

Literature-anchored findings (GeneRIF, showing 1)

• Zinc finger protein-440 promotes cartilage degenerative mechanisms in human facet and knee osteoarthritis chondrocytes. (PMID:33347923)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp78	ENSMUSG00000055150
rattus_norvegicus		ENSRNOG00000083797
drosophila_melanogaster	CG2712	FBGN0024975
drosophila_melanogaster	Phs	FBGN0036522
drosophila_melanogaster	CG3281	FBGN0260741

Paralogs (62): ZNF582 (ENSG00000018869), ZNF264 (ENSG00000083844), ZNF343 (ENSG00000088876), ZNF684 (ENSG00000117010), ZNF133 (ENSG00000125846), ZNF557 (ENSG00000130544), ZNF337 (ENSG00000130684), ZNF20 (ENSG00000132010), ZFP37 (ENSG00000136866), ZNF614 (ENSG00000142556), KRBOX4 (ENSG00000147121), ZNF599 (ENSG00000153896), ZNF19 (ENSG00000157429), ZNF589 (ENSG00000164048), PRDM9 (ENSG00000164256), ZNF180 (ENSG00000167384), ZNF558 (ENSG00000167785), ZNF35 (ENSG00000169981), ZNF778 (ENSG00000170100), ZNF439 (ENSG00000171291), ZNF556 (ENSG00000172000), ZNF554 (ENSG00000172006), ZNF596 (ENSG00000172748), ZNF80 (ENSG00000174255), ZNF266 (ENSG00000174652), ZNF25 (ENSG00000175395), ZNF77 (ENSG00000175691), ZNF169 (ENSG00000175787), ZNF404 (ENSG00000176222), ZNF491 (ENSG00000177599), ZNF620 (ENSG00000177842), ZNF619 (ENSG00000177873), ZNF875 (ENSG00000181666), ZNF329 (ENSG00000181894), ZFP90 (ENSG00000184939), ZNF566 (ENSG00000186017), ZNF529 (ENSG00000186020), ZNF749 (ENSG00000186230), ZNF555 (ENSG00000186300), ZNF70 (ENSG00000187792)

Protein

Protein identifiers

Zinc finger protein 440 — Q8IYI8 (reviewed: Q8IYI8)

All UniProt accessions (5): C9J3D9, C9JG89, C9JV94, Q8IYI8, K7EJ55

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_689570* (*=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, PF13894

UniProt features (19 total): zinc finger region 12, sequence variant 4, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYI8-F1	62.11	0.09

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 62 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, chr19p13, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, KYNG_WERNER_SYNDROM_AND_NORMAL_AGING_DN, ZWANG_DOWN_BY_2ND_EGF_PULSE, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, FOXJ2_TARGET_GENES, ZFHX3_TARGET_GENES, ZNF257_TARGET_GENES, ZNF410_TARGET_GENES, MIR4262, MIR6809_3P, MIR181A_5P_MIR181B_5P, MIR181D_5P, MIR181C_5P

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 transcription regulatory region sequence-specific DNA binding (GO:0000977), 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)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
transcription cis-regulatory region binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	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

412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF440	MAFIP	Q8WZ33	621
ZNF440	OR6C4	Q8NGE1	574
ZNF440	C19orf44	Q9H6X5	475
ZNF440	CWF19L2	Q2TBE0	432
ZNF440	CLCC1	Q96S66	370
ZNF440	TMEM120B	A0PK00	365
ZNF440	DUS3L	Q96G46	358
ZNF440	EVC	P57679	290
ZNF440	HTR3E	A5X5Y0	290
ZNF440	SPATA22	Q8NHS9	287
ZNF440	USP53	Q70EK8	274
ZNF440	MTFMT	Q96DP5	270
ZNF440	TMPRSS11A	Q6ZMR5	269
ZNF440	LONP2	Q86WA8	250
ZNF440	J3KSM2	J3KSM2	248

IntAct

116 interactions, top by confidence:

A	B	Type	Score
MDFI	ZNF440	psi-mi:“MI:0915”(physical association)	0.880
ZNF440	MDFI	psi-mi:“MI:0915”(physical association)	0.880
ZNF440	TRAF1	psi-mi:“MI:0915”(physical association)	0.780
TRAF1	ZNF440	psi-mi:“MI:0915”(physical association)	0.780
ZNF440	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
MID2	ZNF440	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	ZNF440	psi-mi:“MI:0915”(physical association)	0.720
ZNF440	MID2	psi-mi:“MI:0915”(physical association)	0.720
ZNF440	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
ZNF440	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
ZNF440		psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	ZNF440	psi-mi:“MI:0915”(physical association)	0.560
	ZNF440	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (52): ZNF440 (Two-hybrid), ZNF440 (Two-hybrid), ZNF440 (Two-hybrid), ZNF440 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), NOTCH2NL (Two-hybrid), ZNF440 (Two-hybrid), ZNF440 (Two-hybrid), CCNDBP1 (Two-hybrid), MDFI (Two-hybrid), TRAF1 (Two-hybrid), ZNF440 (Two-hybrid), ZNF440 (Affinity Capture-RNA), MDFI (Two-hybrid)

ESM2 similar proteins: A0A1W2PQL4, A2RRD8, A6NHJ4, B4DX44, O75346, O95780, P0CB33, P15621, P21506, P51508, P51814, Q0VGE8, Q15928, Q15973, Q2M218, Q2M3X9, Q3KNS6, Q3MIS6, Q3SXZ3, Q494X3, Q5HY98, Q5RBQ3, Q5RCJ2, Q5RER9, Q5VIY5, Q6J6I6, Q6ZMW2, Q7L2R6, Q86XU0, Q86Y25, Q8IYI8, Q8IYN0, Q8IYX0, Q8N184, Q8N782, Q8N823, Q8N9Z0, Q8NB42, Q8NDP4, Q8NEP9

Diamond homologs: A0JPK3, A8MT65, C9JN71, E9QAG8, G3X9G7, O75820, P16373, P16374, P16415, P17017, P17024, P17025, P51815, P52737, Q08AG5, Q08ER8, Q0D2J5, Q15973, Q2M218, Q3KP31, Q3V080, Q494X3, Q4R4C7, Q5MYW4, Q5R9F0, Q5R9S5, Q5REI6, Q5REK1, Q68EA5, Q6P560, Q6P5C7, Q6ZQV5, Q7L945, Q86T29, Q8BGV5, Q8C6P8, Q8IYI8, Q8IZC7, Q8N7K0, Q8N972

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
Keratinization	13	29.0×	4e-15

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	14
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

817 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11814437:G:GT	donor_gain	1.0000
19:11830267:ATGT:A	acceptor_gain	1.0000
19:11830268:T:G	acceptor_gain	1.0000
19:11831357:A:AG	acceptor_gain	1.0000
19:11831358:T:G	acceptor_gain	1.0000
19:11831363:GACA:G	acceptor_loss	1.0000
19:11831365:CA:C	acceptor_loss	1.0000
19:11831366:A:AG	acceptor_gain	1.0000
19:11831366:A:AT	acceptor_loss	1.0000
19:11831366:AG:A	acceptor_gain	1.0000
19:11831367:G:GA	acceptor_gain	1.0000
19:11831367:GG:G	acceptor_gain	1.0000
19:11831367:GGA:G	acceptor_gain	1.0000
19:11831367:GGAGT:G	acceptor_gain	1.0000
19:11814437:G:T	donor_gain	0.9900
19:11814451:G:GG	donor_gain	0.9900
19:11814452:T:A	donor_loss	0.9900
19:11830265:A:AG	acceptor_gain	0.9900
19:11830265:ACAT:A	acceptor_gain	0.9900
19:11830266:C:G	acceptor_gain	0.9900
19:11830267:AT:A	acceptor_gain	0.9900
19:11830268:T:TA	acceptor_gain	0.9900
19:11830270:T:TA	acceptor_gain	0.9900
19:11830409:GGT:G	donor_loss	0.9900
19:11830410:G:GC	donor_loss	0.9900
19:11830410:G:GG	donor_gain	0.9900
19:11830411:T:A	donor_loss	0.9900
19:11830673:TTCAG:T	donor_loss	0.9900
19:11830674:TCAGG:T	donor_loss	0.9900
19:11830675:CAG:C	donor_loss	0.9900

AlphaMissense

3968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11832389:T:C	F405L	0.992
19:11832391:C:A	F405L	0.992
19:11832391:C:G	F405L	0.992
19:11832473:T:C	F433L	0.992
19:11832475:C:A	F433L	0.992
19:11832475:C:G	F433L	0.992
19:11832575:T:C	F467L	0.991
19:11832577:T:A	F467L	0.991
19:11832577:T:G	F467L	0.991
19:11832305:T:C	F377L	0.984
19:11832307:C:A	F377L	0.984
19:11832307:C:G	F377L	0.984
19:11832395:T:C	S407P	0.980
19:11832418:T:A	H414Q	0.979
19:11832418:T:G	H414Q	0.979
19:11832390:T:C	F405S	0.978
19:11832408:T:C	L411P	0.977
19:11832430:C:A	H418Q	0.976
19:11832430:C:G	H418Q	0.976
19:11830317:T:C	F13S	0.975
19:11830316:T:C	F13L	0.974
19:11830318:C:A	F13L	0.974
19:11830318:C:G	F13L	0.974
19:11832416:C:G	H414D	0.974
19:11831885:T:C	F237L	0.969
19:11831887:T:A	F237L	0.969
19:11831887:T:G	F237L	0.969
19:11831801:T:C	F209L	0.966
19:11831803:C:A	F209L	0.966
19:11831803:C:G	F209L	0.966

dbSNP variants (sampled 300 via entrez): RS1000153301 (19:11821230 G>A), RS1000821042 (19:11831708 G>A), RS1000863354 (19:11820607 AG>A), RS1000926537 (19:11816483 G>A), RS1000983691 (19:11815434 A>G), RS1001310542 (19:11820419 C>T), RS1001488313 (19:11834285 C>T), RS1001510221 (19:11818479 C>T), RS1001545305 (19:11816238 G>A), RS1001719240 (19:11813273 C>A), RS1001875210 (19:11831345 A>G), RS1001879011 (19:11814825 C>G), RS1002084839 (19:11813685 A>C), RS1002197218 (19:11825386 A>G,T), RS1002293125 (19:11828845 C>G,T)

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

2 associations (top):

Study	Trait	p-value
GCST004521_294	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST90002407_363	White blood cell count	8.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	3
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
resorcinol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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