ZFAND2A

Summary

ZFAND2A (zinc finger AN1-type containing 2A, HGNC:28073) is a protein-coding gene on chromosome 7p22.3, encoding AN1-type zinc finger protein 2A (Q8N6M9).

Predicted to enable zinc ion binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein targeting to ER. Predicted to act upstream of or within cellular response to arsenic-containing substance and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Predicted to be located in nucleus. Predicted to be part of proteasome complex. Predicted to be active in endoplasmic reticulum.

Source: NCBI Gene 90637 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_182491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28073
Approved symbol	ZFAND2A
Name	zinc finger AN1-type containing 2A
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	AIRAP
Ensembl gene	ENSG00000178381
Ensembl biotype	protein_coding
OMIM	610699
Entrez	90637

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000316495, ENST00000397083, ENST00000401903, ENST00000471448, ENST00000478137, ENST00000484977, ENST00000574135, ENST00000898905, ENST00000898906, ENST00000898907, ENST00000898908, ENST00000898909, ENST00000898910, ENST00000898911, ENST00000898912, ENST00000898913, ENST00000898914, ENST00000898915, ENST00000898916, ENST00000928430, ENST00000928431

RefSeq mRNA: 3 — MANE Select: NM_182491 NM_001365381, NM_001365383, NM_182491

CCDS: CCDS5323, CCDS94044

Canonical transcript exons

ENST00000316495 — 5 exons

Exon	Start	End
ENSE00001216739	1155453	1155584
ENSE00001216747	1157656	1157750
ENSE00001923349	1152907	1153224
ENSE00003681365	1158158	1158257
ENSE00003897581	1159964	1160196

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7634 / max 309.9327, expressed in 1804 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82405	12.6873	1793
82406	2.2945	1183
82404	1.7240	579
82407	0.0575	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.19	gold quality
secondary oocyte	CL:0000655	98.15	gold quality
right lobe of liver	UBERON:0001114	95.91	gold quality
anterior cingulate cortex	UBERON:0009835	95.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.98	gold quality
hypothalamus	UBERON:0001898	94.73	gold quality
right frontal lobe	UBERON:0002810	94.73	gold quality
monocyte	CL:0000576	94.71	gold quality
amygdala	UBERON:0001876	94.27	gold quality
leukocyte	CL:0000738	94.16	gold quality
spinal cord	UBERON:0002240	94.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.05	gold quality
nucleus accumbens	UBERON:0001882	93.99	gold quality
caudate nucleus	UBERON:0001873	93.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.74	gold quality
putamen	UBERON:0001874	93.72	gold quality
liver	UBERON:0002107	93.51	gold quality
mucosa of transverse colon	UBERON:0004991	93.34	gold quality
substantia nigra	UBERON:0002038	92.82	gold quality
granulocyte	CL:0000094	92.39	gold quality
epithelial cell of pancreas	CL:0000083	92.38	gold quality
cerebellar hemisphere	UBERON:0002245	92.34	gold quality
cerebellar cortex	UBERON:0002129	92.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.20	gold quality
cartilage tissue	UBERON:0002418	92.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.92	gold quality
midbrain	UBERON:0001891	91.88	gold quality
Ammon’s horn	UBERON:0001954	91.88	gold quality
lower esophagus mucosa	UBERON:0035834	91.79	gold quality
body of pancreas	UBERON:0001150	91.78	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	2863.16
E-ANND-3	yes	8.52
E-MTAB-10137	no	671.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF1, HSF2, SSRP1

miRNA regulators (miRDB)

11 targeting ZFAND2A, 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-10401-5P	99.99	65.79	948
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-4301	95.00	65.22	554
HSA-MIR-615-3P	90.62	68.07	69

Literature-anchored findings (GeneRIF, showing 4)

• The HSF1 binding HSE sequence in the AIRAP promoter critical for heat-induced transcription was identified. (PMID:20185824)
• Data indicate that both heat shock factors HSF1 and HSF2 are recruited to the arsenite-inducible RNA-associated protein (AIRAP) promoter and regulate bortezomib-induced AIRAP expression. (PMID:24619424)
• arsenite- inducible regulatory particle-associated protein (AIRAP) transcript to be translationally induced during arsenite stress conditions. (PMID:24898249)
• The findings identify ZFAND2A/AIRAP as a novel stress-regulated survival factor implicated in the stabilization of the antiapoptotic protein cIAP2 and as a new potential therapeutic target in melanoma (PMID:31540997)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfand2a	ENSMUSG00000053581
rattus_norvegicus	Zfand2a	ENSRNOG00000032917
drosophila_melanogaster	CG12795	FBGN0031535
caenorhabditis_elegans		WBGENE00000097

Paralogs (2): ZFAND1 (ENSG00000104231), ZFAND2B (ENSG00000158552)

Protein

Protein identifiers

AN1-type zinc finger protein 2A — Q8N6M9 (reviewed: Q8N6M9)

All UniProt accessions (4): Q8N6M9, A8MYA3, I3L1X3, J3KQ25

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Nucleus.

RefSeq proteins (3): NP_001352310, NP_001352312, NP_872297* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000058	Znf_AN1	Domain
IPR035896	AN1-like_Znf	Homologous_superfamily
IPR057357	Znf-C2H2_ZFAND2A/B	Domain

Pfam: PF01428, PF25403

UniProt features (20 total): binding site 16, zinc finger region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6M9-F1	85.06	0.54

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 (16): 44; 100; 105; 115; 118; 123; 126; 132; 134; 10; 15; 25 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, chr7p22, GERY_CEBP_TARGETS, WANG_LMO4_TARGETS_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (4): positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein targeting to ER (GO:0045047), cellular response to arsenic-containing substance (GO:0071243)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): proteasome complex (GO:0000502), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein targeting	1
establishment of protein localization to endoplasmic reticulum	1
response to arsenic-containing substance	1
cellular response to chemical stimulus	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFAND2A	PAX6	P26367	562
ZFAND2A	ZFAND5	O76080	476
ZFAND2A	SPCS2	Q15005	453
ZFAND2A	LSMEM1	Q8N8F7	447
ZFAND2A	INHBA	P08476	428
ZFAND2A	ZFAND4	Q86XD8	428
ZFAND2A	SOAT1	P35610	427
ZFAND2A	NGB	Q9NPG2	426
ZFAND2A	TMEM247	A6NEH6	425
ZFAND2A	COL25A1	Q9BXS0	424
ZFAND2A	QPCT	Q16769	423
ZFAND2A	AKAP12	Q02952	422
ZFAND2A	AKR1B10	O60218	409
ZFAND2A	AKR1C1	P52896	406
ZFAND2A	APP	P05067	400

IntAct

20 interactions, top by confidence:

A	B	Type	Score
DAZAP2	ZFAND2A	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	ZFAND2A	psi-mi:“MI:0915”(physical association)	0.560
ZFAND2A	RNF216	psi-mi:“MI:0915”(physical association)	0.560
ZFAND2A	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
ZFAND2A	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
PSMD6	ZFAND2A	psi-mi:“MI:0915”(physical association)	0.560
ZFAND2A	RPL30	psi-mi:“MI:0915”(physical association)	0.370
ZFAND2A	H2AX	psi-mi:“MI:0914”(association)	0.350
ZFAND2A	PSMD11	psi-mi:“MI:0914”(association)	0.350
ZFAND2A	DAZAP2	psi-mi:“MI:0915”(physical association)	0.000
ZFAND2A	TRIM23	psi-mi:“MI:0915”(physical association)	0.000
ZFAND2A	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
ZFAND2A	RNF216	psi-mi:“MI:0915”(physical association)	0.000
ZFAND2A	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): ZFAND2A (Affinity Capture-RNA), ZFAND2A (Affinity Capture-RNA), ZFAND2A (Two-hybrid), ZFAND2A (Two-hybrid), ZFAND2A (Two-hybrid), DAZAP2 (Two-hybrid), UBQLN2 (Two-hybrid), BIRC3 (Co-localization), BIRC3 (Affinity Capture-Western), ZFAND2A (Affinity Capture-Western), RAD50 (Affinity Capture-MS), H2AFX (Affinity Capture-MS), SEMA4C (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS)

ESM2 similar proteins: A0JMY5, A2YEZ6, A3BDI8, A6QLA0, A9YUB1, B1AY10, D4A4T9, E0X9N4, O74853, P40798, P47226, P53971, Q09YN8, Q0D5B9, Q108U9, Q12986, Q15326, Q17QE2, Q18034, Q29RL2, Q2IBC3, Q2LAP6, Q2QLA1, Q2QLG8, Q4R7U2, Q54BK0, Q5PXT2, Q5R966, Q5RD91, Q5U2P3, Q5ZA07, Q5ZML4, Q67YE6, Q6DIR5, Q6IDS6, Q6NUA0, Q6ZNB6, Q7ZXE9, Q8N6M9, Q8R5C8

Diamond homologs: P53899, Q0D5B9, Q55BU1, Q55GW8, Q5R966, Q5U2P3, Q8N6M9, Q8VZ42, Q9JII7, Q9SCM4, Q4KLG9, Q67YE6, Q6H595, Q8BFR6, Q8TCF1, Q8WV99, Q91X58

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

922 predictions. Top by Δscore:

Variant	Effect	Δscore
7:1155447:CCTTA:C	donor_loss	1.0000
7:1155448:CTTAC:C	donor_loss	1.0000
7:1155449:TTACC:T	donor_loss	1.0000
7:1155450:TAC:T	donor_loss	1.0000
7:1155451:A:C	donor_loss	1.0000
7:1155452:C:A	donor_loss	1.0000
7:1157749:ATCT:A	acceptor_loss	1.0000
7:1157750:TC:T	acceptor_loss	1.0000
7:1157751:C:CC	acceptor_gain	1.0000
7:1158155:CA:C	donor_loss	1.0000
7:1158156:A:AC	donor_gain	1.0000
7:1158157:C:A	donor_loss	1.0000
7:1158157:C:CC	donor_gain	1.0000
7:1158157:CCT:C	donor_gain	1.0000
7:1158157:CCTAG:C	donor_gain	1.0000
7:1158161:G:C	donor_gain	1.0000
7:1158253:GTCAC:G	acceptor_gain	1.0000
7:1158254:TCAC:T	acceptor_gain	1.0000
7:1158255:CAC:C	acceptor_gain	1.0000
7:1158255:CACC:C	acceptor_gain	1.0000
7:1158256:AC:A	acceptor_gain	1.0000
7:1158256:ACCT:A	acceptor_loss	1.0000
7:1158257:CC:C	acceptor_gain	1.0000
7:1158258:C:CC	acceptor_gain	1.0000
7:1158258:CTACA:C	acceptor_loss	1.0000
7:1158259:T:C	acceptor_loss	1.0000
7:1159960:GTACC:G	donor_loss	1.0000
7:1159961:TACCT:T	donor_loss	1.0000
7:1159963:CCTGG:C	donor_gain	1.0000
7:1155452:CCTT:C	donor_gain	0.9900

AlphaMissense

986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:1157746:A:C	F20L	0.981
7:1157746:A:T	F20L	0.981
7:1157748:A:G	F20L	0.981
7:1155566:A:G	C57R	0.979
7:1157710:G:C	F32L	0.974
7:1157710:G:T	F32L	0.974
7:1157712:A:G	F32L	0.974
7:1153126:T:A	R127S	0.970
7:1153126:T:G	R127S	0.970
7:1153141:G:C	F122L	0.969
7:1153141:G:T	F122L	0.969
7:1153143:A:G	F122L	0.969
7:1153127:C:G	R127T	0.960
7:1153208:C:G	C100S	0.958
7:1153209:A:T	C100S	0.958
7:1155508:A:T	V76D	0.958
7:1155565:C:G	C57S	0.958
7:1155566:A:T	C57S	0.958
7:1158184:C:G	C10S	0.958
7:1158185:A:T	C10S	0.958
7:1153129:G:C	H126Q	0.954
7:1153129:G:T	H126Q	0.954
7:1157676:A:G	C44R	0.953
7:1155556:C:G	C60S	0.951
7:1155557:A:T	C60S	0.951
7:1158185:A:G	C10R	0.951
7:1153111:G:C	H132Q	0.949
7:1153111:G:T	H132Q	0.949
7:1155498:G:C	H79Q	0.949
7:1155498:G:T	H79Q	0.949

dbSNP variants (sampled 300 via entrez): RS1000015486 (7:1161609 TCCTC>T), RS1000070686 (7:1156745 C>G,T), RS1000156965 (7:1148808 G>A), RS1000753917 (7:1149748 G>A), RS1000901204 (7:1161022 G>A,C,T), RS1001116824 (7:1150281 G>A), RS1001172819 (7:1157072 A>G), RS1001284388 (7:1157724 A>G), RS1001466414 (7:1157529 G>A,C), RS1001584259 (7:1157117 A>G), RS1001684180 (7:1160721 G>A,C), RS1001822725 (7:1150291 C>A,G,T), RS1001849337 (7:1149472 G>A), RS1001876466 (7:1150144 G>A), RS1002175274 (7:1157868 G>A,C)

Disease associations

OMIM: gene MIM:610699 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005164_3	GLP-1 levels in response to oral glucose tolerance test (fasting)	5.000000e-06
GCST006630_8	Diastolic blood pressure	4.000000e-24
GCST007930_159	Medication use (agents acting on the renin-angiotensin system)	3.000000e-08
GCST90002386_122	High light scatter reticulocyte percentage of red cells	3.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004307	glucose tolerance test
EFO:0008465	glucagon-like peptide-1 measurement
EFO:0006336	diastolic blood pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases expression, decreases expression, increases abundance	5
Cyclosporine	increases expression	5
Valproic Acid	decreases expression, decreases methylation, increases expression, affects expression	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
Bortezomib	decreases response to substance, affects cleavage, increases reaction, increases expression, decreases reaction (+2 more)	3
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	3
Copper	affects reaction, increases expression, affects binding, decreases expression, decreases reaction	3
Tobacco Smoke Pollution	increases expression	3
diethyl maleate	increases expression	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	2
bardoxolone methyl	affects expression, decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Formaldehyde	increases expression	2
Silver	increases expression	2
Tunicamycin	increases expression	2
Thapsigargin	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
2-butenal	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1

Clinical trials (associated diseases)

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