ANKRD16

Summary

ANKRD16 (ankyrin repeat domain 16, HGNC:23471) is a protein-coding gene on chromosome 10p15.1, encoding Ankyrin repeat domain-containing protein 16 (Q6P6B7). Required to prevent the misactivation of serine (Ser) with tRNA(Ala) by promoting the hydrolysis of Ser-mischarged tRNA(Ala), thereby playing a role in translational fidelity.

Predicted to be involved in tRNA modification. Predicted to be located in cytoplasm and nucleus.

Source: NCBI Gene 54522 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_019046

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23471
Approved symbol	ANKRD16
Name	ankyrin repeat domain 16
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434N1511
Ensembl gene	ENSG00000134461
Ensembl biotype	protein_coding
OMIM	618017
Entrez	54522

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000191063, ENST00000380092, ENST00000380094, ENST00000492368, ENST00000881552, ENST00000881553, ENST00000958071, ENST00000958072, ENST00000958073

RefSeq mRNA: 3 — MANE Select: NM_019046 NM_001009941, NM_001009943, NM_019046

CCDS: CCDS31136, CCDS31137

Canonical transcript exons

ENST00000380094 — 8 exons

Exon	Start	End
ENSE00001000814	5878097	5878287
ENSE00001194671	5887847	5888067
ENSE00001231162	5861616	5862691
ENSE00001852182	5889041	5889893
ENSE00003292335	5880298	5880376
ENSE00003331744	5883006	5883167
ENSE00003489313	5883969	5884077
ENSE00003540760	5885723	5885765

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 81.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.2225 / max 83.3943, expressed in 1666 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108119	5.0576	1655
108120	0.1649	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.22	gold quality
ileal mucosa	UBERON:0000331	78.32	silver quality
ectocervix	UBERON:0012249	78.21	gold quality
endocervix	UBERON:0000458	78.04	gold quality
left ovary	UBERON:0002119	78.02	gold quality
cortical plate	UBERON:0005343	77.86	gold quality
prefrontal cortex	UBERON:0000451	77.71	gold quality
body of stomach	UBERON:0001161	77.67	gold quality
stromal cell of endometrium	CL:0002255	77.60	gold quality
right ovary	UBERON:0002118	77.35	gold quality
right uterine tube	UBERON:0001302	77.29	gold quality
ganglionic eminence	UBERON:0004023	77.03	gold quality
body of uterus	UBERON:0009853	76.98	gold quality
skin of leg	UBERON:0001511	76.37	gold quality
ventricular zone	UBERON:0003053	76.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.14	gold quality
skin of abdomen	UBERON:0001416	76.13	gold quality
right frontal lobe	UBERON:0002810	76.10	gold quality
stomach	UBERON:0000945	76.01	gold quality
left testis	UBERON:0004533	75.85	gold quality
right testis	UBERON:0004534	75.69	gold quality
left uterine tube	UBERON:0001303	75.66	gold quality
tibial nerve	UBERON:0001323	75.20	gold quality
zone of skin	UBERON:0000014	75.06	gold quality
right adrenal gland	UBERON:0001233	75.01	gold quality
right coronary artery	UBERON:0001625	75.00	gold quality
left adrenal gland cortex	UBERON:0035825	74.93	gold quality
testis	UBERON:0000473	74.92	gold quality
anterior cingulate cortex	UBERON:0009835	74.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

41 targeting ANKRD16, 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-5193	100.00	67.26	1744
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-3121-5P	97.30	66.62	1146

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankrd16	ENSDARG00000003822
mus_musculus	Ankrd16	ENSMUSG00000047909
rattus_norvegicus	Ankrd16	ENSRNOG00000028168
caenorhabditis_elegans		WBGENE00014077

Paralogs (1): ASB1 (ENSG00000065802)

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 16 — Q6P6B7 (reviewed: Q6P6B7)

All UniProt accessions (1): Q6P6B7

UniProt curated annotations — full annotation on UniProt →

Function. Required to prevent the misactivation of serine (Ser) with tRNA(Ala) by promoting the hydrolysis of Ser-mischarged tRNA(Ala), thereby playing a role in translational fidelity. Binds directly to the catalytic domain of AARS/AlaRS and captures Ser that is misactivated by AARS/AlaRS, preventing the charging of Ser adenylates to tRNA(Ala) and precluding Ser misincorporation in nascent peptides.

Subunit / interactions. Interacts with AARS; the interaction is direct.

Subcellular location. Cytoplasm. Nucleus.

Domain organisation. Side chains of Lys-102, Lys-135 and Lys-165 capture Ser that is misactivated by AARS/AlaRS.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P6B7-1	1	yes
Q6P6B7-2	2

RefSeq proteins (3): NP_001009941, NP_001009943, NP_061919* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF12796, PF13606, PF13637

UniProt features (17 total): repeat 9, site 3, splice variant 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P6B7-F1	94.32	0.91

Functional residue map

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

Catalytic / active sites (3): 102 (required to capture ser that is misactivated by aars/alars); 135 (required to capture ser that is misactivated by aars/alars); 165 (required to capture ser that is misactivated by aars/alars)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_MODIFICATION, TGAGATT_MIR216, GOBP_TRNA_PROCESSING, chr10p15, GOBP_TRNA_MODIFICATION, LINDGREN_BLADDER_CANCER_CLUSTER_1_UP, EIF4E_UP, ASH1L_TARGET_GENES, CEBPZ_TARGET_GENES, HDAC4_TARGET_GENES, KLF7_TARGET_GENES, PRKDC_TARGET_GENES, RBM34_TARGET_GENES, SALL4_TARGET_GENES

GO Biological Process (1): tRNA modification (GO:0006400)

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

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA processing	1
RNA modification	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD16	FBH1	Q8NFZ0	636
ANKRD16	RPP14	O95059	507
ANKRD16	OR51V1	Q9H2C8	473
ANKRD16	PCMTD2	Q9NV79	471
ANKRD16	NSMCE4A	Q9NXX6	459
ANKRD16	ZMIZ1	Q9ULJ6	431
ANKRD16	TMEM14C	Q9P0S9	409
ANKRD16	AARS1	P49588	404
ANKRD16	PRXL2C	Q7RTV5	392
ANKRD16	CCDC12	Q8WUD4	390
ANKRD16	RBM17	Q96I25	390
ANKRD16	YARS2	Q9Y2Z4	363
ANKRD16	TOX3	O15405	360
ANKRD16	MPV17L	Q2QL34	354
ANKRD16	SOWAHA	Q2M3V2	349

IntAct

6 interactions, top by confidence:

A	B	Type	Score
Oxnad1	KPNA6	psi-mi:“MI:0914”(association)	0.350
Spred2	TARS3	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
CD19	MYZAP	psi-mi:“MI:0914”(association)	0.350
ANKRD16	RHOA	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): ANKRD16 (Affinity Capture-MS), ANKRD16 (Affinity Capture-MS), ANKRD16 (Reconstituted Complex), ANKRD16 (Affinity Capture-MS), GAMT (Affinity Capture-MS), RHOA (Affinity Capture-MS), ANKRD16 (Affinity Capture-RNA)

ESM2 similar proteins: A2AS55, B2RXR6, O15084, O75832, P0C927, Q08DV6, Q0P5B9, Q29RM5, Q2TB02, Q3SX45, Q495B1, Q499M5, Q4V890, Q502K3, Q505D1, Q53RE8, Q5F478, Q5RFS1, Q5U2S6, Q5ZLC8, Q6GPE5, Q6P6B7, Q6P9Z4, Q70X92, Q7T3P8, Q810B6, Q8BTI7, Q8C0T1, Q8C6Y6, Q8K0L0, Q8N8A2, Q8NB46, Q8NI38, Q8WXH4, Q91ZT8, Q96AX9, Q96DX5, Q96NS5, Q96Q27, Q9BSK4

Diamond homologs: A2AQH4, A2AS55, A6NGH8, A6QR20, O14974, Q2T9W8, Q499M5, Q5H9F3, Q641X1, Q6P6B7, Q6W2J9, Q86WC6, Q8CGN4, Q9BQI6, Q9D119, Q9UU77, Q9XZC0, A4II29, A5WVX9, B4E2M5, D3Z7P3, E9PTT0, G5EGA3, O83515, O94925, P13264, Q01317, Q15653, Q21920, Q3SX45, Q3U0L2, Q4FE45, Q4JHE0, Q502K3, Q54HW1, Q5U5A6, Q6NSI1, Q6NY19, Q7T3Y0, Q7Z6K4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1576 predictions. Top by Δscore:

Variant	Effect	Δscore
10:5880617:T:TC	acceptor_gain	1.0000
10:5883001:CAAA:C	donor_loss	1.0000
10:5883003:AACC:A	donor_loss	1.0000
10:5883010:G:C	donor_gain	1.0000
10:5883163:CAAGC:C	acceptor_gain	1.0000
10:5883164:AAGC:A	acceptor_gain	1.0000
10:5883165:AGCC:A	acceptor_loss	1.0000
10:5883166:GCCT:G	acceptor_loss	1.0000
10:5883168:C:CC	acceptor_gain	1.0000
10:5883176:C:CT	acceptor_gain	1.0000
10:5883177:A:T	acceptor_gain	1.0000
10:5883965:ATAC:A	donor_gain	1.0000
10:5883965:ATACC:A	donor_gain	1.0000
10:5883967:ACC:A	donor_gain	1.0000
10:5883968:CCC:C	donor_gain	1.0000
10:5883970:C:CA	donor_gain	1.0000
10:5889037:CTACC:C	donor_loss	1.0000
10:5889038:TACC:T	donor_loss	1.0000
10:5889039:ACC:A	donor_loss	1.0000
10:5862687:CAACT:C	acceptor_gain	0.9900
10:5862690:CT:C	acceptor_gain	0.9900
10:5862692:C:CC	acceptor_gain	0.9900
10:5863862:C:CT	acceptor_gain	0.9900
10:5863863:A:T	acceptor_gain	0.9900
10:5863873:C:CT	acceptor_gain	0.9900
10:5878127:T:TA	donor_gain	0.9900
10:5878174:T:A	donor_gain	0.9900
10:5880554:T:C	acceptor_gain	0.9900
10:5880554:T:TC	acceptor_gain	0.9900
10:5880613:CACAT:C	acceptor_gain	0.9900

AlphaMissense

2334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:5887947:A:C	S145R	0.992
10:5887947:A:T	S145R	0.992
10:5887949:T:G	S145R	0.992
10:5887980:G:C	N134K	0.992
10:5887980:G:T	N134K	0.992
10:5887878:G:C	S168R	0.991
10:5887878:G:T	S168R	0.991
10:5887880:T:G	S168R	0.991
10:5887970:A:G	W138R	0.991
10:5887970:A:T	W138R	0.991
10:5889139:C:A	K72N	0.991
10:5889139:C:G	K72N	0.991
10:5889042:A:G	W105R	0.990
10:5889042:A:T	W105R	0.990
10:5887945:C:G	R146P	0.989
10:5887866:C:A	R172S	0.988
10:5887866:C:G	R172S	0.988
10:5887981:T:A	N134I	0.988
10:5887962:A:C	S140R	0.986
10:5887962:A:T	S140R	0.986
10:5887964:T:G	S140R	0.986
10:5888046:G:C	C112W	0.986
10:5887951:G:T	A144D	0.985
10:5888067:C:A	W105C	0.984
10:5888067:C:G	W105C	0.984
10:5884022:C:G	A212P	0.983
10:5888048:A:G	C112R	0.983
10:5883011:C:G	A282P	0.982
10:5888047:C:T	C112Y	0.982
10:5887965:G:C	N139K	0.981

dbSNP variants (sampled 300 via entrez): RS1000007378 (10:5881978 C>T), RS1000020695 (10:5862257 A>G,T), RS1000030463 (10:5862546 T>C,G), RS1000152350 (10:5871959 C>T), RS1000169381 (10:5876093 A>G), RS1000226493 (10:5872209 T>C), RS1000241947 (10:5887430 T>C), RS1000247355 (10:5883322 C>CT), RS1000291722 (10:5872692 G>A,C,T), RS1000411469 (10:5867038 C>T), RS1000517457 (10:5861944 C>T), RS1000632540 (10:5871929 C>A,T), RS1000633147 (10:5882432 G>C), RS1000635675 (10:5890912 C>T), RS1000795036 (10:5876433 C>A)

Disease associations

OMIM: gene MIM:618017 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000678_12	Breast cancer	5.000000e-07
GCST001762_685	Obesity-related traits	6.000000e-06
GCST008916_1	Asthma	6.000000e-17
GCST011956_39	Systemic lupus erythematosus	7.000000e-10
GCST90002393_323	Monocyte count	1.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	increases methylation	2
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Carbamazepine	affects expression	1
Ethyl Methanesulfonate	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methotrexate	decreases expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Copper Sulfate	decreases expression	1
Genistein	decreases expression	1

Clinical trials (associated diseases)

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