ZNF808

Summary

ZNF808 (zinc finger protein 808, HGNC:33230) is a protein-coding gene on chromosome 19q13.41, encoding Zinc finger protein 808 (Q8N4W9). Transcriptional repressor that targets mainly transposable elements.

Enables transcription cis-regulatory region binding activity. Involved in cell differentiation; negative regulation of gene expression; and pancreas development. Predicted to be active in nucleus.

Source: NCBI Gene 388558 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pancreatic agenesis 3 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 184 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_001039886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33230
Approved symbol	ZNF808
Name	zinc finger protein 808
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198482
Ensembl biotype	protein_coding
OMIM	620970
Entrez	388558

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000359798, ENST00000461321, ENST00000461779, ENST00000465448, ENST00000486474, ENST00000487863, ENST00000875424

RefSeq mRNA: 4 — MANE Select: NM_001039886 NM_001039886, NM_001321424, NM_001321425, NM_001363550

CCDS: CCDS46167, CCDS86799

Canonical transcript exons

ENST00000359798 — 5 exons

Exon	Start	End
ENSE00001912526	52527668	52527711
ENSE00001948517	52553107	52556336
ENSE00002525018	52532908	52533009
ENSE00002536249	52547512	52547638
ENSE00003509527	52543266	52543347

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 89.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7806 / max 60.2069, expressed in 1538 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177309	3.5762	1462
177310	1.2044	516

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	89.88	gold quality
corpus callosum	UBERON:0002336	85.59	gold quality
calcaneal tendon	UBERON:0003701	85.12	gold quality
bone marrow cell	CL:0002092	85.08	gold quality
tonsil	UBERON:0002372	83.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.51	gold quality
bone marrow	UBERON:0002371	82.38	gold quality
skeletal muscle tissue	UBERON:0001134	81.81	gold quality
monocyte	CL:0000576	81.31	gold quality
leukocyte	CL:0000738	81.04	gold quality
adrenal tissue	UBERON:0018303	80.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.37	gold quality
endometrium	UBERON:0001295	79.36	gold quality
muscle tissue	UBERON:0002385	79.23	gold quality
right uterine tube	UBERON:0001302	77.97	gold quality
kidney	UBERON:0002113	77.90	gold quality
islet of Langerhans	UBERON:0000006	77.78	gold quality
granulocyte	CL:0000094	77.34	gold quality
rectum	UBERON:0001052	77.16	gold quality
cortex of kidney	UBERON:0001225	76.67	gold quality
right lobe of thyroid gland	UBERON:0001119	76.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.37	gold quality
urinary bladder	UBERON:0001255	76.31	gold quality
adult mammalian kidney	UBERON:0000082	75.91	gold quality
blood	UBERON:0000178	75.81	gold quality
thyroid gland	UBERON:0002046	75.78	gold quality
uterine cervix	UBERON:0000002	75.67	gold quality
lymph node	UBERON:0000029	75.39	gold quality
left lobe of thyroid gland	UBERON:0001120	75.24	gold quality
smooth muscle tissue	UBERON:0001135	75.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting ZNF808, 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-4768-5P	100.00	69.49	2861
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-1257	98.97	68.02	1133

Literature-anchored findings (GeneRIF, showing 2)

• Biallelic loss of function variant in ZNF808 is associated with non-syndromic neonatal diabetes. (PMID:37308312)
• Primate-specific ZNF808 is essential for pancreatic development in humans. (PMID:37973953)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG18476	FBGN0037931
drosophila_melanogaster	CG10669	FBGN0039329

Paralogs (5): ZNF664 (ENSG00000179195), ZNF648 (ENSG00000179930), ZNF721 (ENSG00000182903), ZFP62 (ENSG00000196670), ZNF485 (ENSG00000198298)

Protein

Protein identifiers

Zinc finger protein 808 — Q8N4W9 (reviewed: Q8N4W9)

All UniProt accessions (5): C9IZE3, C9J0J5, C9J871, C9JVX0, Q8N4W9

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor that targets mainly transposable elements. Primarily targets the long terminal repeat of endogenous retroviruses classified as MER11 elements which comprise subfamilies A, B and C. May silence transposable elements through the establishment of heterochromatin-associated trimethylation of ‘Lys-9’ of histone H3 (H3K9me3). Can also bind to certain gene promoters and other genomic regions. Represses transcription of specific MER11 elements during differentiation toward pancreatic lineages in early pancreas development. By repressing transcription, prevents a liver gene expression program from being aberrantly activated during pancreas differentiation.

Subcellular location. Nucleus.

Tissue specificity. Broadly expressed.

Disease relevance. Genetic variation in ZNF808 is associated with non-syndromic neonatal diabetes. Homozygous truncation variants were identified in patients with pancreatic agenesis, a rare congenital condition resulting from inappropriate pancreas development. Pancreatic agenesis is defined by neonatal diabetes, which is diagnosed before 6 months of age, and exocrine pancreatic insufficiency.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N4W9-1	1	yes
Q8N4W9-2	2

RefSeq proteins (4): NP_001034975, NP_001308353, NP_001308354, NP_001350479 (=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
IPR050589	Ikaros_C2H2-ZF	Family

Pfam: PF00096, PF01352

UniProt features (40 total): zinc finger region 24, sequence variant 11, chain 1, domain 1, region of interest 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4W9-F1	68.90	0.01

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): 173

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): GOBP_PANCREAS_DEVELOPMENT, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, CBX5_TARGET_GENES, SALL4_TARGET_GENES, ZNF274_TARGET_GENES, ZNF30_TARGET_GENES, ZNF350_TARGET_GENES, ZNF561_TARGET_GENES, ZNF768_TARGET_GENES, MIR616_5P, MIR371B_5P, MIR373_5P, MIR6809_3P

GO Biological Process (7): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of gene expression (GO:0010629), cell differentiation (GO:0030154), pancreas development (GO:0031016), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), negative regulation of macromolecule biosynthetic process (GO:0010558)

GO Molecular Function (5): transcription cis-regulatory region binding (GO:0000976), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	2
regulation of gene expression	2
regulation of macromolecule biosynthetic process	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
negative regulation of macromolecule biosynthetic process	1
cellular developmental process	1
animal organ development	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
negative regulation of macromolecule metabolic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF808	KRTAP1-5	Q9BYS1	400
ZNF808	KRT222	Q8N1A0	371
ZNF808	MIDEAS	Q6PJG2	352
ZNF808	LUZP4	Q9P127	348
ZNF808	TMEM65	Q6PI78	323
ZNF808	NBPF1	Q3BBV0	311
ZNF808	IGSF9B	Q9UPX0	311
ZNF808	MIPOL1	Q8TD10	308
ZNF808	RIMS4	Q9H426	305
ZNF808	GALNT9	Q9HCQ5	301
ZNF808	KAZN	Q674X7	299
ZNF808	DIP2C	Q9Y2E4	297
ZNF808	TMEM128	Q5BJH2	291
ZNF808	LRFN5	Q96NI6	290
ZNF808	ECHDC3	Q96DC8	287

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
ZNF22	NPM1	psi-mi:“MI:0914”(association)	0.350
ZNF808	MTREX	psi-mi:“MI:0914”(association)	0.350
ZNF22	SURF6	psi-mi:“MI:0914”(association)	0.350
ZNF554	TRIM37	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): ZNF808 (Affinity Capture-MS), ZNF808 (Affinity Capture-MS), ZNF808 (Affinity Capture-MS), ZNF808 (Affinity Capture-RNA), ZNF808 (Affinity Capture-MS), ZNF808 (Affinity Capture-MS), ZNF808 (Affinity Capture-MS), ZNF808 (Affinity Capture-MS), ZNF808 (Co-fractionation), ZNF808 (Co-fractionation), C20orf27 (Co-fractionation), ZNF808 (Affinity Capture-MS), ZNF808 (Affinity Capture-MS), ZNF808 (Affinity Capture-RNA)

ESM2 similar proteins: A2VDQ7, A6NNF4, A8MQ14, A8MTY0, E9QAG8, O75290, O75373, P08043, P0CJ79, P10751, P17017, P17027, P17039, P35789, P51522, P51523, Q08AN1, Q14585, Q14587, Q3SYV7, Q3ZCX4, Q4R4C7, Q52M93, Q5MCW4, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6ECI4, Q6JLC9, Q6P3V2, Q6P5C7, Q6ZN57, Q86UE3, Q86XN6, Q86YE8, Q8C827, Q8IYB9, Q8N4W9, Q8N7M2

Diamond homologs: A0A1W2PQL4, A2RRD8, A2VDQ7, A6NHJ4, A6NK75, A6NN14, A6NNF4, A6NP11, B4DX44, B4DXR9, E9PW05, O14628, O43345, O75290, O75346, O75373, O75820, P0CB33, P0CJ79, P0DKX0, P10755, P17032, P17035, P52738, Q02386, Q03923, Q03936, Q05481, Q08AN1, Q09FC8, Q0VGE8, Q14586, Q14593, Q147U1, Q15928, Q3MIS6, Q3SXZ3, Q494X3, Q4R6C2, Q5HY98

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	148
Likely benign	18
Benign	4

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
3366910	NM_001039886.4(ZNF808):c.637del (p.Pro212_Leu213insTer)	Pathogenic
3366911	ZNF808, EX4-5DEL	Pathogenic
3366912	NM_001039886.4(ZNF808):c.696_697del (p.Pro232_Cys233insTer)	Pathogenic
3366913	NM_001039886.4(ZNF808):c.1136del (p.Ala379fs)	Pathogenic
3366914	NM_001039886.4(ZNF808):c.1584C>A (p.Tyr528Ter)	Pathogenic
3366915	NM_001039886.4(ZNF808):c.2309del (p.Asn770fs)	Pathogenic
2505171	NM_001039886.4(ZNF808):c.1448dup (p.Tyr483Ter)	Likely pathogenic
3901191	NM_001039886.4(ZNF808):c.1948del (p.Thr650fs)	Likely pathogenic
4278975	NM_001039886.4(ZNF808):c.1447dup (p.Tyr483fs)	Likely pathogenic

SpliceAI

908 predictions. Top by Δscore:

Variant	Effect	Δscore
19:52527711:GGTG:G	donor_loss	1.0000
19:52527712:G:C	donor_loss	1.0000
19:52527712:G:GG	donor_gain	1.0000
19:52527713:T:A	donor_loss	1.0000
19:52531647:G:GT	donor_gain	1.0000
19:52527710:TG:T	donor_gain	0.9900
19:52527711:GG:G	donor_gain	0.9900
19:52543259:C:G	acceptor_gain	0.9900
19:52543265:GGATT:G	acceptor_gain	0.9900
19:52543320:A:T	donor_gain	0.9900
19:52547599:G:T	donor_gain	0.9900
19:52527707:CCATG:C	donor_gain	0.9800
19:52527708:CATG:C	donor_gain	0.9800
19:52527709:ATG:A	donor_gain	0.9800
19:52543263:CA:C	acceptor_loss	0.9800
19:52543265:G:GT	acceptor_loss	0.9800
19:52543332:C:T	donor_gain	0.9800
19:52543350:G:GT	donor_gain	0.9800
19:52543356:A:AG	donor_gain	0.9800
19:52553106:GAT:G	acceptor_gain	0.9800
19:52527699:TC:T	donor_gain	0.9700
19:52543258:A:AG	acceptor_gain	0.9700
19:52543261:T:G	acceptor_gain	0.9700
19:52543264:AG:A	acceptor_gain	0.9700
19:52543265:GG:G	acceptor_gain	0.9700
19:52543315:A:T	donor_gain	0.9700
19:52543343:CTCAG:C	donor_loss	0.9700
19:52543344:TCAG:T	donor_loss	0.9700
19:52543345:CAGG:C	donor_loss	0.9700
19:52543346:AGGTG:A	donor_loss	0.9700

AlphaMissense

6014 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:52555482:T:C	F856L	0.996
19:52555484:C:A	F856L	0.996
19:52555484:C:G	F856L	0.996
19:52553970:T:C	F352L	0.995
19:52553972:T:A	F352L	0.995
19:52553972:T:G	F352L	0.995
19:52554222:T:C	F436L	0.995
19:52554224:C:A	F436L	0.995
19:52554224:C:G	F436L	0.995
19:52554810:T:C	F632L	0.995
19:52554812:C:A	F632L	0.995
19:52554812:C:G	F632L	0.995
19:52555146:T:C	F744L	0.995
19:52555148:C:A	F744L	0.995
19:52555148:C:G	F744L	0.995
19:52555398:T:C	F828L	0.995
19:52555400:T:A	F828L	0.995
19:52555400:T:G	F828L	0.995
19:52555062:T:C	F716L	0.994
19:52555064:C:A	F716L	0.994
19:52555064:C:G	F716L	0.994
19:52554054:T:C	F380L	0.993
19:52554056:T:A	F380L	0.993
19:52554056:T:G	F380L	0.993
19:52553802:T:C	F296L	0.992
19:52553804:C:A	F296L	0.992
19:52553804:C:G	F296L	0.992
19:52553886:T:C	F324L	0.992
19:52553888:T:A	F324L	0.992
19:52553888:T:G	F324L	0.992

dbSNP variants (sampled 300 via entrez): RS1000141530 (19:52565652 C>G,T), RS1000220837 (19:52558229 G>C), RS1000244577 (19:52552967 C>A,T), RS1000334833 (19:52563487 C>G), RS1000342035 (19:52531272 G>A), RS1000342485 (19:52526567 G>A), RS1000419499 (19:52557987 T>C), RS1000431474 (19:52565844 A>C,G), RS1000500921 (19:52535598 A>G), RS1000680096 (19:52532374 C>G,T), RS1000813049 (19:52559077 A>G), RS1000862382 (19:52526315 A>G), RS1000987802 (19:52544462 C>T), RS1001071699 (19:52564433 A>T), RS1001106661 (19:52549757 C>G)

Disease associations

OMIM: gene MIM:620970 | disease phenotypes: MIM:620991, MIM:617862

GenCC curated gene-disease

Disease	Classification	Inheritance
pancreatic agenesis 3	Strong	Autosomal recessive

Mondo (2): pancreatic agenesis 3 (MONDO:0975839), neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (MONDO:0060640)

Orphanet (0):

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001518	Small for gestational age
HP:0001622	Premature birth
HP:0001738	Exocrine pancreatic insufficiency
HP:0001903	Anemia
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0011463	Childhood onset
HP:0100651	Type I diabetes mellitus
HP:0100801	Pancreatic aplasia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006035_13	Breast cancer and/or colorectal cancer	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, affects expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
Cadmium	increases palmitoylation, decreases reaction, increases abundance	1
Doxorubicin	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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