ZFAND5

Summary

ZFAND5 (zinc finger AN1-type containing 5, HGNC:13008) is a protein-coding gene on chromosome 9q21.13, encoding AN1-type zinc finger protein 5 (O76080). Involved in protein degradation via the ubiquitin-proteasome system. It is a selective cancer dependency (DepMap: 18.7% of cell lines).

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to act upstream of or within several processes, including face development; fibroblast migration; and platelet-derived growth factor receptor signaling pathway. Predicted to be located in cytoplasm.

Source: NCBI Gene 7763 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total
• Cancer dependency (DepMap): dependent in 18.7% of screened cell lines
• MANE Select transcript: NM_001102420

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13008
Approved symbol	ZFAND5
Name	zinc finger AN1-type containing 5
Location	9q21.13
Locus type	gene with protein product
Status	Approved
Aliases	ZFAND5A
Ensembl gene	ENSG00000107372
Ensembl biotype	protein_coding
OMIM	604761
Entrez	7763

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000237937, ENST00000343431, ENST00000376956, ENST00000376960, ENST00000376962, ENST00000471197, ENST00000487330, ENST00000488164, ENST00000896944, ENST00000896945, ENST00000896946, ENST00000896947, ENST00000896948, ENST00000896949, ENST00000916941, ENST00000962950, ENST00000962951, ENST00000962952

RefSeq mRNA: 6 — MANE Select: NM_001102420 NM_001102420, NM_001102421, NM_001278243, NM_001278244, NM_001278245, NM_006007

CCDS: CCDS6642

Canonical transcript exons

ENST00000376962 — 7 exons

Exon	Start	End
ENSE00001472252	72363470	72363606
ENSE00001892220	72364696	72365208
ENSE00003504766	72359418	72359521
ENSE00003562959	72356931	72357056
ENSE00003599001	72360110	72360221
ENSE00003691614	72360628	72360787
ENSE00003848541	72351413	72356101

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 151.0287 / max 2587.3566, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100946	148.3586	1826
100945	2.6094	1302
100944	0.0606	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	99.70	gold quality
mucosa of stomach	UBERON:0001199	99.65	gold quality
seminal vesicle	UBERON:0000998	99.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.47	gold quality
right lung	UBERON:0002167	99.44	gold quality
oocyte	CL:0000023	99.39	gold quality
nerve	UBERON:0001021	99.39	gold quality
tibial nerve	UBERON:0001323	99.39	gold quality
tibia	UBERON:0000979	99.36	gold quality
biceps brachii	UBERON:0001507	99.36	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.35	gold quality
adult organism	UBERON:0007023	99.34	gold quality
popliteal artery	UBERON:0002250	99.33	gold quality
epithelium of nasopharynx	UBERON:0001951	99.32	gold quality
left ovary	UBERON:0002119	99.32	gold quality
tibial artery	UBERON:0007610	99.32	gold quality
adrenal tissue	UBERON:0018303	99.31	gold quality
secondary oocyte	CL:0000655	99.29	gold quality
gluteal muscle	UBERON:0002000	99.25	gold quality
postcentral gyrus	UBERON:0002581	99.21	gold quality
right ovary	UBERON:0002118	99.20	gold quality
amniotic fluid	UBERON:0000173	99.19	gold quality
artery	UBERON:0001637	99.19	gold quality
lower lobe of lung	UBERON:0008949	99.18	gold quality
mucosa of urinary bladder	UBERON:0001259	99.16	gold quality
visceral pleura	UBERON:0002401	99.16	gold quality
corpus epididymis	UBERON:0004359	99.16	gold quality
type B pancreatic cell	CL:0000169	99.15	gold quality
buccal mucosa cell	CL:0002336	99.14	gold quality
cauda epididymis	UBERON:0004360	99.12	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	810.86
E-GEOD-134144	yes	37.31
E-CURD-46	yes	37.14
E-HCAD-4	yes	34.87
E-HCAD-13	yes	21.94
E-CURD-88	yes	19.52
E-MTAB-9467	yes	19.27
E-CURD-119	yes	9.69
E-MTAB-6819	no	999.39
E-MTAB-9543	no	2.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

322 targeting ZFAND5, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• redundant and distinct roles in regulating NFkappaB activation and apoptosis (PMID:14754897)
• ZNF216 is a potent inhibitory factor for osteoclast differentiation and the mechanism is unlikely due to direct attenuation of the NF-kappa B pathway (PMID:16194934)
• Zfand5 can enhance ARE-containing mRNA stability by competing with tristetraprolin for mRNA binding. (PMID:22665488)
• Our results indicate that ZNF216 overexpression sensitizes to apoptosis the NIH3T3/EGFR/ZNF216 cells thus antagonizing the effect of activated EGFR-mediated survival in control cells that do not overexpress the ZNF216. (PMID:27732953)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfand5	ENSMUSG00000024750
rattus_norvegicus	Zfand5	ENSRNOG00000018107
drosophila_melanogaster	CG15368	FBGN0030104
drosophila_melanogaster	CG43675	FBGN0263750
drosophila_melanogaster	drn	FBGN0266410
caenorhabditis_elegans	mstr-1	WBGENE00009050

Paralogs (2): ZFAND6 (ENSG00000086666), ZFAND3 (ENSG00000156639)

Protein

Protein identifiers

AN1-type zinc finger protein 5 — O76080 (reviewed: O76080)

Alternative names: Zinc finger A20 domain-containing protein 2, Zinc finger protein 216

All UniProt accessions (2): O76080, Q5QPB1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in protein degradation via the ubiquitin-proteasome system. May act by anchoring ubiquitinated proteins to the proteasome. Plays a role in ubiquitin-mediated protein degradation during muscle atrophy. Plays a role in the regulation of NF-kappa-B activation and apoptosis. Inhibits NF-kappa-B activation triggered by overexpression of RIPK1 and TRAF6 but not of RELA. Also inhibits tumor necrosis factor (TNF), IL-1 and TLR4-induced NF-kappa-B activation in a dose-dependent manner. Overexpression sensitizes cells to TNF-induced apoptosis. Is a potent inhibitory factor for osteoclast differentiation.

Subunit / interactions. Interacts with ubiquitin and polyubiquitinated proteins. Identified in a heterotrimeric complex with ubiquitin and SQSTM1, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule. Homooligomer and/or heterooligomer. Interacts (via A20-type domain) with IKBKG and RIPK1 and with TRAF6 (via AN1-type domain).

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in skeletal muscle. Expressed in fetal cochlea. Also expressed in infant brain, fetal heart, pancreatic islet, melanocyte, pineal gland, placenta, corneal stroma, and parathyroid tumor. Weakly expressed or undetectable in adult brain, heart, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung and peripheral blood leukocytes. Expressed in rhabdomyosarcoma RD cells (at protein level).

Domain organisation. The A20-type zinc finger directly binds polyubiquitin chains and associates with the 26S proteasome. The zinc-finger A20-type domain is essential for inhibition of NF-kappa-B activation.

RefSeq proteins (6): NP_001095890, NP_001095891, NP_001265172, NP_001265173, NP_001265174, NP_005998 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000058	Znf_AN1	Domain
IPR002653	Znf_A20	Domain
IPR035896	AN1-like_Znf	Homologous_superfamily
IPR050652	AN1_A20_ZnFinger	Family

Pfam: PF01428, PF01754

UniProt features (22 total): binding site 12, modified residue 3, compositionally biased region 3, zinc finger region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9BUI	ELECTRON MICROSCOPY	3.9
7QXW	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76080-F1	72.39	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (12): 33; 154; 157; 168; 170; 175; 178; 184; 186; 14; 18; 30

Post-translational modifications (3): 48, 58, 209

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 411 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, AP1_01, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GCM_GSPT1, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, RORA1_01, GCM_ZNF198, GOBP_RESPIRATORY_SYSTEM_PROCESS, GENTILE_RESPONSE_CLUSTER_D3, MEF2_02, RIZKI_TUMOR_INVASIVENESS_3D_DN, NAGASHIMA_NRG1_SIGNALING_UP, GGGTGGRR_PAX4_03

GO Biological Process (8): in utero embryonic development (GO:0001701), vasculature development (GO:0001944), respiratory system process (GO:0003016), fibroblast migration (GO:0010761), platelet-derived growth factor receptor signaling pathway (GO:0048008), skeletal system morphogenesis (GO:0048705), smooth muscle tissue development (GO:0048745), face development (GO:0060324)

GO Molecular Function (4): DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chordate embryonic development	1
system development	1
circulatory system development	1
system process	1
respiratory gaseous exchange by respiratory system	1
ameboidal-type cell migration	1
cell surface receptor protein tyrosine kinase signaling pathway	1
skeletal system development	1
animal organ morphogenesis	1
muscle tissue development	1
anatomical structure development	1
head development	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFAND5	PAX6	P26367	760
ZFAND5	IKBKG	Q9Y6K9	669
ZFAND5	C9orf85	Q96MD7	610
ZFAND5	CDC34	P49427	574
ZFAND5	TRIM75	A6NK02	569
ZFAND5	ZNF629	Q9UEG4	558
ZFAND5	ZNF44	P15621	558
ZFAND5	ZNF501	Q96CX3	558
ZFAND5	K7ESF6	K7ESF6	557
ZFAND5	ZNF436	Q9C0F3	554
ZFAND5	ZNF569	Q5MCW4	552
ZFAND5	PKN1	Q16512	548
ZFAND5	ZNF235	Q14590	547
ZFAND5	C9orf57	Q5W0N0	507
ZFAND5	ZFAND2A	Q8N6M9	476

IntAct

16 interactions, top by confidence:

A	B	Type	Score
ZFAND5	CETN1	psi-mi:“MI:0915”(physical association)	0.590
ZFAND5	UBC	psi-mi:“MI:0915”(physical association)	0.540
UBC	ZFAND5	psi-mi:“MI:0915”(physical association)	0.540
ZFAND5	UBC	psi-mi:“MI:0407”(direct interaction)	0.540
ZFAND5	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
LRRK2	ZFAND5	psi-mi:“MI:0407”(direct interaction)	0.440
PKM	ZFAND5	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
ZFAND5	COA7	psi-mi:“MI:0915”(physical association)	0.400
ZFAND5	MYH11	psi-mi:“MI:0915”(physical association)	0.400
ZFAND5	PSMD6	psi-mi:“MI:0915”(physical association)	0.400
ZFAND5	RAD23B	psi-mi:“MI:0915”(physical association)	0.400
UBE3A	TXNL1	psi-mi:“MI:0914”(association)	0.350
PSMC4	PSMD1	psi-mi:“MI:0914”(association)	0.350
Map3k1	ZFAND5	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (50): ZFAND5 (Biochemical Activity), ZFAND5 (Biochemical Activity), CETN1 (Affinity Capture-MS), ZFAND5 (Reconstituted Complex), ZFAND5 (Affinity Capture-MS), ZFAND5 (Reconstituted Complex), IKBKG (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), ZFAND5 (Affinity Capture-Western), UBC (Reconstituted Complex), ZFAND5 (Reconstituted Complex), COA7 (Proximity Label-MS), ZFAND5 (Proximity Label-MS), ZFAND5 (Proximity Label-MS), CETN1 (Affinity Capture-MS)

ESM2 similar proteins: A2YEZ6, A2Z2J6, A3BDI8, A3C039, A9YUB1, D4A4T9, O49663, O76080, O94880, Q09818, Q0VBD2, Q15649, Q28E45, Q29RL2, Q2KI09, Q3EA33, Q4R7U2, Q5EAW4, Q5RD91, Q5RHY1, Q5ZML4, Q67YE6, Q69LE0, Q6H754, Q6H7P8, Q6NNI8, Q6NUA0, Q6Z541, Q7L590, Q7Y1W9, Q84PD8, Q852K5, Q852K6, Q8H0X0, Q8VEE1, Q942F8, Q94B40, Q9D1P4, Q9D4H9, Q9ERV1

Diamond homologs: A2YEZ6, A2Z2J6, A3BDI8, A3C039, B5DF11, D3Z3C6, O49663, O76080, O88878, P0C282, Q0DJC7, Q3EA33, Q3SZY7, Q5JLA7, Q5JN07, Q5R7S6, Q69LE0, Q6DGF4, Q6FIF0, Q6H754, Q6H7P8, Q6NNI8, Q6Z541, Q7Y1W9, Q84PD8, Q852K5, Q852K6, Q852K8, Q86XD8, Q8H0X0, Q942F8, Q94B40, Q9DCH6, Q9H8U3, Q9LHJ8, Q9SJM6, Q9STJ9, Q9SZ69, Q9ZNU9, O18973

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	ZFAND5	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 14 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
Antigen processing: Ubiquitination & Proteasome degradation	5	16.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	5	21.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

856 predictions. Top by Δscore:

Variant	Effect	Δscore
9:72356100:CC:C	acceptor_gain	1.0000
9:72356101:CC:C	acceptor_gain	1.0000
9:72356946:T:A	donor_gain	1.0000
9:72357052:GACAA:G	acceptor_gain	1.0000
9:72357054:CAA:C	acceptor_gain	1.0000
9:72357055:AA:A	acceptor_gain	1.0000
9:72357057:C:CC	acceptor_gain	1.0000
9:72359517:CATTT:C	acceptor_gain	1.0000
9:72359519:TTT:T	acceptor_gain	1.0000
9:72359520:TT:T	acceptor_gain	1.0000
9:72359520:TTC:T	acceptor_loss	1.0000
9:72359522:C:CA	acceptor_loss	1.0000
9:72359522:C:CC	acceptor_gain	1.0000
9:72359526:T:C	acceptor_gain	1.0000
9:72359533:C:CT	acceptor_gain	1.0000
9:72360104:TCTTA:T	donor_loss	1.0000
9:72360105:CTTAC:C	donor_loss	1.0000
9:72360106:TTAC:T	donor_loss	1.0000
9:72360107:TACC:T	donor_loss	1.0000
9:72360108:A:C	donor_loss	1.0000
9:72360109:C:CA	donor_loss	1.0000
9:72360222:C:CC	acceptor_gain	1.0000
9:72360222:C:CG	acceptor_loss	1.0000
9:72360223:T:C	acceptor_loss	1.0000
9:72360785:CTG:C	acceptor_gain	1.0000
9:72360794:A:C	acceptor_gain	1.0000
9:72356928:TACCT:T	donor_loss	0.9900
9:72356929:AC:A	donor_loss	0.9900
9:72356930:CC:C	donor_loss	0.9900
9:72356931:C:T	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000067963 (9:72364189 C>G,T), RS1000090968 (9:72358082 T>C), RS1000253469 (9:72358345 A>C), RS1000447990 (9:72364935 AG>A,AGG), RS1000686946 (9:72354384 T>C,G), RS1000855363 (9:72357169 T>A,C), RS1001001361 (9:72362698 C>T), RS1001071365 (9:72362894 G>A,C,T), RS1001104218 (9:72358401 GAC>G), RS1001144109 (9:72365173 G>A,C), RS1001308973 (9:72357463 A>G), RS1001496040 (9:72356860 C>T), RS1001516169 (9:72359581 A>G,T), RS1001591841 (9:72354075 C>T), RS1001777246 (9:72360571 T>C)

Disease associations

OMIM: gene MIM:604761 | 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
GCST009310_12	Sensorimotor dexterity	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008354	cognitive function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases stability, decreases expression, affects cotreatment, increases abundance	4
Valproic Acid	affects expression, decreases expression, decreases methylation	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	decreases expression, affects cotreatment, increases expression, affects expression	3
Arsenic Trioxide	increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
cylindrospermopsin	increases expression	1
chloropicrin	affects expression	1
acyline	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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