ZFAND3

Summary

ZFAND3 (zinc finger AN1-type containing 3, HGNC:18019) is a protein-coding gene on chromosome 6p21.2, encoding AN1-type zinc finger protein 3 (Q9H8U3).

Predicted to enable DNA binding activity and zinc ion binding activity.

Source: NCBI Gene 60685 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_021943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18019
Approved symbol	ZFAND3
Name	zinc finger AN1-type containing 3
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13222
Ensembl gene	ENSG00000156639
Ensembl biotype	protein_coding
OMIM	607455
Entrez	60685

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000287218, ENST00000373389, ENST00000373391, ENST00000440482, ENST00000463847, ENST00000469208, ENST00000474522, ENST00000894323, ENST00000894324, ENST00000894325

RefSeq mRNA: 2 — MANE Select: NM_021943 NM_001410904, NM_021943

CCDS: CCDS4836, CCDS93913

Canonical transcript exons

ENST00000287218 — 6 exons

Exon	Start	End
ENSE00001085877	38061593	38061775
ENSE00001192289	38152235	38154624
ENSE00001460453	37819727	37820016
ENSE00001671630	37929959	37929999
ENSE00001945392	38082392	38082457
ENSE00003475830	38116572	38116739

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.6846 / max 1085.8611, expressed in 1826 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67658	52.9303	1823
67660	4.6485	1479
67656	4.3663	1661
67657	3.2049	1456
67659	3.0236	1324
67655	2.9995	1534
67661	0.7712	402
67662	0.6779	394
67654	0.4495	194
67673	0.3086	117

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.69	gold quality
right testis	UBERON:0004534	98.59	gold quality
sperm	CL:0000019	97.92	gold quality
stromal cell of endometrium	CL:0002255	97.64	gold quality
ventricular zone	UBERON:0003053	97.23	gold quality
ganglionic eminence	UBERON:0004023	96.96	gold quality
male germ cell	CL:0000015	96.80	gold quality
gastrocnemius	UBERON:0001388	96.72	gold quality
muscle of leg	UBERON:0001383	96.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.16	gold quality
popliteal artery	UBERON:0002250	95.98	gold quality
tibial artery	UBERON:0007610	95.97	gold quality
testis	UBERON:0000473	95.96	gold quality
gall bladder	UBERON:0002110	95.56	gold quality
monocyte	CL:0000576	95.46	gold quality
islet of Langerhans	UBERON:0000006	95.44	gold quality
cortical plate	UBERON:0005343	95.38	gold quality
mononuclear cell	CL:0000842	95.29	gold quality
leukocyte	CL:0000738	95.26	gold quality
aorta	UBERON:0000947	95.15	gold quality
right coronary artery	UBERON:0001625	95.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.88	gold quality
smooth muscle tissue	UBERON:0001135	94.55	gold quality
descending thoracic aorta	UBERON:0002345	94.45	gold quality
thoracic aorta	UBERON:0001515	94.31	gold quality
lower esophagus	UBERON:0013473	94.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.29	gold quality
ascending aorta	UBERON:0001496	94.23	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.04	gold quality
left coronary artery	UBERON:0001626	93.97	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.71
E-ANND-2	no	1416.88
E-MTAB-6058	no	25.95
E-CURD-119	no	4.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

153 targeting ZFAND3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-185-3P	99.95	67.01	1743

Literature-anchored findings (GeneRIF, showing 3)

• Replication of lead type 2 diabetes mellitus SNPs in GLIS3, KCNK16, and ZFAND3 was observed in American Indians. Sex-specific T2DM signals in GLIS3 and ZFAND3, which are distinct from the East Asian GWAS signals, were also identified. (PMID:27862917)
• ZFAND3 was identified as a type 2 diabetes susceptibility gene. ZFAND3 plays a role in insulin secretion in vitro. (PMID:28580277)
• AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion. (PMID:33311477)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfand3	ENSDARG00000052833
mus_musculus	Zfand3	ENSMUSG00000044477
rattus_norvegicus	Zfand3	ENSRNOG00000059659

Paralogs (2): ZFAND6 (ENSG00000086666), ZFAND5 (ENSG00000107372)

Protein

Protein identifiers

AN1-type zinc finger protein 3 — Q9H8U3 (reviewed: Q9H8U3)

Alternative names: Testis-expressed protein 27

All UniProt accessions (4): Q9H8U3, C9JQ48, E2QRF5, H0Y398

RefSeq proteins (2): NP_001397833, NP_068762* (*=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 (27 total): binding site 12, compositionally biased region 5, zinc finger region 2, strand 2, helix 2, region of interest 2, chain 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1X4W	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H8U3-F1	69.71	0.30

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): 18; 20; 32; 35; 157; 160; 174; 176; 181; 184; 190; 192

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 211 (showing top): CREL_01, GCM_MAP4K4, GGGNRMNNYCAT_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, CAGCTG_AP4_Q5, GTGCCTT_MIR506, ACCAATC_MIR509, FOSTER_TOLERANT_MACROPHAGE_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GGGNNTTTCC_NFKB_Q6_01, ATTCTTT_MIR186, GGCKCATGS_UNKNOWN, AACTTT_UNKNOWN, ACTTTAT_MIR1425P

GO Biological Process (0):

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 (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

1014 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFAND3	PAX6	P26367	667
ZFAND3	R3HDML	Q9H3Y0	621
ZFAND3	KCNK16	Q96T55	600
ZFAND3	HSPB3	Q12988	590
ZFAND3	FITM2	Q8N6M3	576
ZFAND3	PSMD6	Q15008	570
ZFAND3	GCC1	Q96CN9	570
ZFAND3	C2CD4A	Q8NCU7	545
ZFAND3	MAEA	Q7L5Y9	543
ZFAND3	ZFAND6	Q6FIF0	498
ZFAND3	N4BP1	O75113	467
ZFAND3	CDC123	O75794	467
ZFAND3	USP33	Q8TEY7	460
ZFAND3	KLHL42	Q9P2K6	454
ZFAND3	GLIS3	Q8NEA6	449

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ZFAND3	FAM25C	psi-mi:“MI:0915”(physical association)	0.560
PEX5	ZFAND3	psi-mi:“MI:0915”(physical association)	0.560
INCA1	ZFAND3	psi-mi:“MI:0915”(physical association)	0.560
FAM25C	ZFAND3	psi-mi:“MI:0915”(physical association)	0.560
ZFAND3	PEX5	psi-mi:“MI:0915”(physical association)	0.000
ZFAND3	INCA1	psi-mi:“MI:0915”(physical association)	0.000
ZFAND3	GOLM1	psi-mi:“MI:0915”(physical association)	0.000
Map3k1	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (18): ZFAND3 (Biochemical Activity), ZFAND3 (Affinity Capture-RNA), ZFAND3 (Affinity Capture-RNA), ZFAND3 (Affinity Capture-RNA), ZFAND3 (Two-hybrid), FAM25A (Two-hybrid), FAM25G (Two-hybrid), INCA1 (Two-hybrid), FAM25C (Two-hybrid), ZFAND3 (Affinity Capture-RNA), ZFAND3 (Co-fractionation), ZFAND3 (Co-fractionation), ZFAND3 (Co-fractionation), ZFAND3 (Proximity Label-MS), ZFAND3 (Affinity Capture-RNA)

ESM2 similar proteins: A2VE56, A6QPH9, I3LHS8, O08781, O14545, O54836, P0C6S7, Q14CM0, Q3SZY7, Q3U2E2, Q497H0, Q4R3D6, Q4R970, Q58D05, Q5F3F2, Q5FWF5, Q5R7S6, Q5RDJ2, Q5U2M7, Q5VT97, Q66J85, Q68FE8, Q69Z69, Q6DGF4, Q6FIF0, Q6N043, Q6P2K3, Q70EL2, Q7Z6G8, Q8BIZ1, Q8IWR0, Q8K214, Q8K387, Q8N7W2, Q8N9Z9, Q8NA31, Q8ND82, Q8QFX1, Q91YD3, Q96B23

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2986 predictions. Top by Δscore:

Variant	Effect	Δscore
6:37820013:GGGG:G	donor_gain	1.0000
6:37820014:GGG:G	donor_gain	1.0000
6:37820014:GGGG:G	donor_gain	1.0000
6:37820015:GGG:G	donor_gain	1.0000
6:37820016:GGTA:G	donor_loss	1.0000
6:37820017:GTA:G	donor_loss	1.0000
6:38061588:TTCA:T	acceptor_loss	1.0000
6:38061590:CA:C	acceptor_loss	1.0000
6:38061591:A:AG	acceptor_gain	1.0000
6:38061592:G:GA	acceptor_gain	1.0000
6:38061592:GA:G	acceptor_gain	1.0000
6:38061592:GAT:G	acceptor_gain	1.0000
6:38061592:GATT:G	acceptor_gain	1.0000
6:38061592:GATTT:G	acceptor_gain	1.0000
6:38061771:GGAGT:G	donor_gain	1.0000
6:38061772:GAGT:G	donor_gain	1.0000
6:38061772:GAGTG:G	donor_gain	1.0000
6:38061773:AGTG:A	donor_loss	1.0000
6:38061774:GT:G	donor_gain	1.0000
6:38061775:TGTA:T	donor_loss	1.0000
6:38061776:G:GG	donor_gain	1.0000
6:38061777:T:A	donor_loss	1.0000
6:38111608:G:GT	donor_gain	1.0000
6:38116565:T:TA	acceptor_gain	1.0000
6:38116569:CAGAT:C	acceptor_loss	1.0000
6:38116570:A:AG	acceptor_gain	1.0000
6:38116570:AGATT:A	acceptor_loss	1.0000
6:38116571:G:GG	acceptor_gain	1.0000
6:38152345:A:T	donor_gain	1.0000
6:37820012:TGGGG:T	donor_gain	0.9900

AlphaMissense

1491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:37819997:T:C	C18R	1.000
6:37819999:T:G	C18W	1.000
6:37820003:T:C	C20R	1.000
6:37820009:T:C	F22L	1.000
6:37820010:T:C	F22S	1.000
6:37820011:C:A	F22L	1.000
6:37820011:C:G	F22L	1.000
6:37820014:G:C	W23C	1.000
6:37820014:G:T	W23C	1.000
6:37820015:G:A	G24R	1.000
6:37820015:G:C	G24R	1.000
6:37820015:G:T	G24W	1.000
6:37929979:T:C	L31P	1.000
6:37929981:T:A	C32S	1.000
6:37929981:T:C	C32R	1.000
6:37929982:G:A	C32Y	1.000
6:37929982:G:C	C32S	1.000
6:37929982:G:T	C32F	1.000
6:37929983:T:G	C32W	1.000
6:37929990:T:A	C35S	1.000
6:37929990:T:C	C35R	1.000
6:37929991:G:C	C35S	1.000
6:38116679:T:A	C157S	1.000
6:38116679:T:C	C157R	1.000
6:38116680:G:C	C157S	1.000
6:38116681:C:G	C157W	1.000
6:38116688:T:A	C160S	1.000
6:38116688:T:C	C160R	1.000
6:38116689:G:C	C160S	1.000
6:38116724:G:A	G172R	1.000

dbSNP variants (sampled 300 via entrez): RS1000003471 (6:37992409 C>T), RS1000011192 (6:38085347 C>T), RS1000013551 (6:37952172 G>A), RS1000060577 (6:37828219 G>C), RS1000062919 (6:37999954 C>T), RS1000077332 (6:37916883 C>G), RS1000097078 (6:38079325 T>C), RS1000097557 (6:38118773 A>C,T), RS1000098062 (6:37966168 T>G), RS1000110631 (6:37885786 G>T), RS1000115853 (6:37922453 A>C,G,T), RS1000118316 (6:37834480 T>C), RS1000120572 (6:38088559 G>A), RS1000125524 (6:38049804 A>G), RS1000128668 (6:37874727 C>T)

Disease associations

OMIM: gene MIM:607455 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001208_2	Insulin resistance/response	4.000000e-06
GCST001351_3	Type 2 diabetes	2.000000e-10
GCST002481_11	Acne (severe)	2.000000e-06
GCST003264_1071	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST011353_44	Serum alkaline phosphatase levels	5.000000e-09
GCST011494_28	Daytime nap	1.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0004533	alkaline phosphatase measurement
EFO:0007828	daytime rest measurement

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
rs200858088	ZFAND3		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
cupric chloride	increases expression	1
triphenyltin	decreases expression	1
tributyltinisothiocyanate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Hydrogen Peroxide	increases expression, affects cotreatment	1
Lead	affects splicing	1
Testosterone	decreases expression	1
Theophylline	affects cotreatment, increases expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A8B7	SEES3-1V human ZFAND3, clone1	Embryonic stem cell	Male
CVCL_A8B8	SEES3-1V human ZFAND3, clone2	Embryonic stem cell	Male
CVCL_A8B9	SEES3-1V human ZFAND3, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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