ANKRD22

Summary

ANKRD22 (ankyrin repeat domain 22, HGNC:28321) is a protein-coding gene on chromosome 10q23.31, encoding Ankyrin repeat domain-containing protein 22 (Q5VYY1).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 49 total — 2 pathogenic
• MANE Select transcript: NM_144590

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28321
Approved symbol	ANKRD22
Name	ankyrin repeat domain 22
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC22805
Ensembl gene	ENSG00000152766
Ensembl biotype	protein_coding
Entrez	118932

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371930, ENST00000476963, ENST00000892167

RefSeq mRNA: 1 — MANE Select: NM_144590 NM_144590

CCDS: CCDS7390

Canonical transcript exons

ENST00000371930 — 6 exons

Exon	Start	End
ENSE00001006986	88823280	88823378
ENSE00001006987	88826038	88826115
ENSE00001097618	88828559	88828666
ENSE00001097619	88831835	88832026
ENSE00001456465	88819896	88823018
ENSE00001456468	88851587	88851844

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 97.28.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5277 / max 357.7841, expressed in 305 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110474	1.3063	189
110473	0.4760	136
110478	0.2556	82
110476	0.2230	57
110477	0.0941	32
110472	0.0550	23
110475	0.0495	19
110471	0.0482	17
110470	0.0200	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	97.28	gold quality
upper leg skin	UBERON:0004262	96.39	gold quality
gingival epithelium	UBERON:0001949	95.73	gold quality
esophagus squamous epithelium	UBERON:0006920	95.73	gold quality
gingiva	UBERON:0001828	95.43	gold quality
mammalian vulva	UBERON:0000997	95.36	gold quality
oral cavity	UBERON:0000167	94.52	gold quality
penis	UBERON:0000989	93.94	gold quality
lower esophagus mucosa	UBERON:0035834	93.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.48	gold quality
buccal mucosa cell	CL:0002336	90.03	gold quality
skin of abdomen	UBERON:0001416	89.60	gold quality
colonic mucosa	UBERON:0000317	89.55	gold quality
zone of skin	UBERON:0000014	89.40	gold quality
skin of leg	UBERON:0001511	88.88	gold quality
skin of hip	UBERON:0001554	88.51	gold quality
esophagus mucosa	UBERON:0002469	88.43	gold quality
ileal mucosa	UBERON:0000331	87.63	gold quality
nasal cavity epithelium	UBERON:0005384	87.14	gold quality
pylorus	UBERON:0001166	86.79	gold quality
epithelium of nasopharynx	UBERON:0001951	86.21	gold quality
trabecular bone tissue	UBERON:0002483	85.51	gold quality
pharyngeal mucosa	UBERON:0000355	84.36	gold quality
nipple	UBERON:0002030	84.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.02	gold quality
bone marrow	UBERON:0002371	83.37	gold quality
mucosa of transverse colon	UBERON:0004991	83.30	gold quality
body of stomach	UBERON:0001161	82.88	gold quality
vermiform appendix	UBERON:0001154	82.12	gold quality
cardia of stomach	UBERON:0001162	81.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

148 targeting ANKRD22, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
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-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 5)

• ANKRD22 exhibits oncogene activity that promotes tumor progression in NSCLC through the transcriptional regulation of E2F1. (PMID:28667340)
• ANKRD22, a novel tumor microenvironment-induced mitochondrial protein promotes metabolic reprogramming of colorectal cancer cells. (PMID:31903135)
• ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets. (PMID:34584137)
• ANKRD22 promotes glioma proliferation, migration, invasion, and epithelial-mesenchymal transition by upregulating E2F1-mediated MELK expression. (PMID:37164633)
• ANKRD22 knockdown suppresses papillary thyroid cell carcinoma growth and migration and modulates the Wnt/beta-catenin signaling pathway. (PMID:37586180)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankrd22	ENSDARG00000002298
mus_musculus	Ankrd22	ENSMUSG00000024774
rattus_norvegicus	Ankrd22	ENSRNOG00000019190
drosophila_melanogaster	iPLA2-VIA	FBGN0036053
drosophila_melanogaster	mask	FBGN0043884
caenorhabditis_elegans		WBGENE00011240
caenorhabditis_elegans		WBGENE00011423

Paralogs (4): NFKBIA (ENSG00000100906), NFKBIB (ENSG00000104825), TONSL (ENSG00000160949), PLA2G6 (ENSG00000184381)

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 22 — Q5VYY1 (reviewed: Q5VYY1)

All UniProt accessions (1): Q5VYY1

RefSeq proteins (1): NP_653191* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR042802	ANR22	Family

Pfam: PF12796

UniProt features (9 total): repeat 4, sequence variant 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VYY1-F1	93.75	0.82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_LEUKOCYTE_MIGRATION, GOBP_CALCIUM_ION_IMPORT, TGANTCA_AP1_C, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_UP, NFE2_01, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, chr10q23

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

1730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD22	STAMBPL1	Q96FJ0	578
ANKRD22	BATF2	Q8N1L9	575
ANKRD22	SLC25A45	Q8N413	571
ANKRD22	FCGR1BP	Q92637	506
ANKRD22	BMAL2	Q8WYA1	457
ANKRD22	LIPF	P07098	439
ANKRD22	ZNF831	Q5JPB2	436
ANKRD22	MCOLN3	Q8TDD5	425
ANKRD22	MMP25	Q9NPA2	424
ANKRD22	MMP24	Q9Y5R2	422
ANKRD22	MMP28	Q9H239	422
ANKRD22	SCARF1	Q14162	411
ANKRD22	ARHGAP9	Q9BRR9	407
ANKRD22	SMAGP	Q0VAQ4	405
ANKRD22	BLK	P51451	403

IntAct

18 interactions, top by confidence:

A	B	Type	Score
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
SS18L1	ANKRD22	psi-mi:“MI:0915”(physical association)	0.370
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
C18orf21	A2ML1	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
MYCBP	A2ML1	psi-mi:“MI:0914”(association)	0.350
PKP2	A2ML1	psi-mi:“MI:0914”(association)	0.350
PLD6	ANKRD22	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): ANKRD22 (Affinity Capture-MS), CCDC102A (Affinity Capture-MS), DNM1 (Affinity Capture-MS), SLC7A2 (Affinity Capture-MS), HEATR5B (Affinity Capture-MS), SYNGR2 (Affinity Capture-MS), ANKRD22 (Affinity Capture-MS), NUDT2 (Affinity Capture-MS), ANKRD22 (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS), USO1 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ANKRD22 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), HOOK3 (Affinity Capture-MS)

ESM2 similar proteins: A0PJZ0, A6NHY2, A7E2S9, C7B178, D3J162, G5E8K5, P42570, P42773, P53355, Q08E43, Q10311, Q14DN9, Q18297, Q2T9W8, Q3EC11, Q4R3S3, Q4R544, Q4UJC4, Q4UJJ2, Q5EFR1, Q5I126, Q5I148, Q5I155, Q5I159, Q5I160, Q5R6D7, Q5RCK5, Q5TYM7, Q5VYY1, Q60772, Q60773, Q6XJU9, Q80YE7, Q86WC6, Q91ZT9, Q91ZU0, Q92527, Q9BGT9, Q9CQM6, Q9D119

Diamond homologs: A2ARS0, A4II29, C7B178, C9JTQ0, D3J162, Q18297, Q337A0, Q38898, Q4JHE0, Q5U5A6, Q5VYY1, Q641X1, Q6KAE5, Q7T3Y0, Q7Z6K4, Q91ZA8, Q96KQ7, Q9CQM6, Q9D3J5, Q9Z148, A8VU90, G5EGA3, Q05823, Q8NAG6, Q9FPH0, Q9J512, A1L520, A1Z7A6, O42287, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P10569, P19706, P35197, P38682

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2684602	GRCh37/hg19 10q11.21-24.2(chr10:42709645-100834951)x3	Pathogenic
4755382	GRCh38/hg38 10q23.31(chr10:87732891-88930708)x1	Pathogenic

SpliceAI

923 predictions. Top by Δscore:

Variant	Effect	Δscore
10:88823374:CCATA:C	acceptor_gain	1.0000
10:88823375:CATA:C	acceptor_gain	1.0000
10:88823375:CATAC:C	acceptor_gain	1.0000
10:88823377:TA:T	acceptor_gain	1.0000
10:88823379:C:CC	acceptor_gain	1.0000
10:88826036:A:AC	donor_gain	1.0000
10:88826037:C:CC	donor_gain	1.0000
10:88826037:CA:C	donor_gain	1.0000
10:88831900:G:A	donor_gain	1.0000
10:88832022:ATGGG:A	acceptor_gain	1.0000
10:88832023:TGGG:T	acceptor_gain	1.0000
10:88832024:GGG:G	acceptor_gain	1.0000
10:88832025:GG:G	acceptor_gain	1.0000
10:88832026:GCTGG:G	acceptor_loss	1.0000
10:88832027:C:CA	acceptor_loss	1.0000
10:88832027:C:CC	acceptor_gain	1.0000
10:88832033:C:CT	acceptor_gain	1.0000
10:88832034:G:T	acceptor_gain	1.0000
10:88820230:A:AG	acceptor_gain	0.9900
10:88820231:G:GG	acceptor_gain	0.9900
10:88823376:ATA:A	acceptor_gain	0.9900
10:88826030:AAAC:A	donor_loss	0.9900
10:88826031:AACT:A	donor_loss	0.9900
10:88826032:AC:A	donor_loss	0.9900
10:88826033:CTT:C	donor_loss	0.9900
10:88826034:TTACA:T	donor_loss	0.9900
10:88826035:T:G	donor_loss	0.9900
10:88826036:ACACA:A	donor_loss	0.9900
10:88826037:C:T	donor_loss	0.9900
10:88826037:CACA:C	donor_gain	0.9900

AlphaMissense

1249 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:88831838:G:C	N70K	0.991
10:88831838:G:T	N70K	0.991
10:88831906:A:G	C48R	0.989
10:88828654:A:G	C76R	0.987
10:88831920:G:T	P43H	0.987
10:88831904:G:C	C48W	0.986
10:88831908:G:T	A47D	0.986
10:88832010:G:T	A13D	0.985
10:88831920:G:C	P43R	0.984
10:88831839:T:A	N70I	0.983
10:88831872:A:G	L59P	0.980
10:88823317:A:G	L154P	0.979
10:88823351:A:G	C143R	0.979
10:88826041:A:C	D132E	0.979
10:88826041:A:T	D132E	0.979
10:88828652:G:C	C76W	0.979
10:88826043:C:G	D132H	0.978
10:88831909:C:G	A47P	0.977
10:88831905:C:T	C48Y	0.976
10:88828641:G:T	A80D	0.975
10:88823349:A:C	C143W	0.974
10:88826042:T:A	D132V	0.974
10:88823362:A:G	L139S	0.972
10:88828642:C:G	A80P	0.972
10:88831840:T:A	N70Y	0.972
10:88831917:A:G	L44P	0.972
10:88823317:A:T	L154H	0.971
10:88831926:T:C	D41G	0.971
10:88832014:C:G	A12P	0.967
10:88831926:T:G	D41A	0.966

dbSNP variants (sampled 300 via entrez): RS1000057088 (10:88834174 A>C,G,T), RS1000127764 (10:88823897 A>G), RS1000145390 (10:88841002 C>A,T), RS1000184125 (10:88850031 C>A,G,T), RS1000233901 (10:88848172 G>A), RS1000244003 (10:88844551 G>T), RS1000274364 (10:88836142 C>T), RS1000403643 (10:88829783 T>G), RS1000508354 (10:88829060 G>T), RS1000528665 (10:88850944 G>A,T), RS1000573694 (10:88844999 G>A,C,T), RS1000661155 (10:88835217 T>C), RS1000688644 (10:88836573 A>G,T), RS1000750819 (10:88839761 G>A), RS1000768042 (10:88829356 T>C,G)

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
GCST003815_78	Late-onset Alzheimer’s disease	4.000000e-06
GCST006099_1	Accelerometer-based physical activity measurement (average acceleration)	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0008002	physical activity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Valproic Acid	increases expression, affects cotreatment	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
afuresertib	decreases expression	1
bisphenol F	decreases methylation	1
fluorene-9-bisphenol	increases expression	1
TL8-506	affects cotreatment, increases expression	1
bisphenol A	increases methylation	1
sodium arsenate	increases abundance, decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	increases abundance, decreases expression	1
sulforaphane	increases expression	1
perfluorooctanoic acid	increases expression	1
gadodiamide	increases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	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
dorsomorphin	affects cotreatment, increases expression	1
gardiquimod	increases expression, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Oxaliplatin	increases expression	1
Zoledronic Acid	increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	increases expression, affects cotreatment	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0B5	SEES3-1V human ANKRD22, clone1	Embryonic stem cell	Male
CVCL_A0B6	SEES3-1V human ANKRD22, clone2	Embryonic stem cell	Male
CVCL_A0B7	SEES3-1V human ANKRD22, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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