ANKRD46

Summary

ANKRD46 (ankyrin repeat domain 46, HGNC:27229) is a protein-coding gene on chromosome 8q22.3, encoding Ankyrin repeat domain-containing protein 46 (Q86W74).

This gene encodes a protein containing multiple ankyrin repeats. Ankyrin domains function in protein-protein interactions in a variety of cellular processes. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 157567 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 48 total — 3 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001270377

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27229
Approved symbol	ANKRD46
Name	ankyrin repeat domain 46
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186106
Ensembl biotype	protein_coding
Entrez	157567

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 33 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000335659, ENST00000358990, ENST00000519316, ENST00000519597, ENST00000520311, ENST00000520552, ENST00000520713, ENST00000521345, ENST00000523000, ENST00000524072, ENST00000524319, ENST00000862175, ENST00000862176, ENST00000862177, ENST00000862178, ENST00000862179, ENST00000862180, ENST00000862181, ENST00000862182, ENST00000862183, ENST00000862184, ENST00000862185, ENST00000862186, ENST00000862187, ENST00000862188, ENST00000862189, ENST00000862190, ENST00000862191, ENST00000940151, ENST00000946478, ENST00000946479, ENST00000946480, ENST00000946481, ENST00000946482, ENST00000946483

RefSeq mRNA: 4 — MANE Select: NM_001270377 NM_001270377, NM_001270378, NM_001270379, NM_198401

CCDS: CCDS59109, CCDS6287

Canonical transcript exons

ENST00000335659 — 5 exons

Exon	Start	End
ENSE00001339679	100527845	100528003
ENSE00001339680	100533209	100533311
ENSE00001339682	100529523	100529860
ENSE00001339685	100559711	100559759
ENSE00002126866	100520772	100522771

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.8929 / max 239.5490, expressed in 1762 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94150	20.1804	1759
94149	0.5578	358
94148	0.1548	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.37	gold quality
cortical plate	UBERON:0005343	97.51	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.11	gold quality
postcentral gyrus	UBERON:0002581	96.37	gold quality
superior frontal gyrus	UBERON:0002661	96.08	gold quality
pons	UBERON:0000988	96.07	gold quality
choroid plexus epithelium	UBERON:0003911	96.01	gold quality
biceps brachii	UBERON:0001507	95.93	gold quality
parietal lobe	UBERON:0001872	95.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.81	gold quality
orbitofrontal cortex	UBERON:0004167	95.80	gold quality
frontal pole	UBERON:0002795	95.78	gold quality
secondary oocyte	CL:0000655	95.73	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.63	gold quality
middle temporal gyrus	UBERON:0002771	95.30	gold quality
vastus lateralis	UBERON:0001379	95.26	gold quality
oocyte	CL:0000023	94.87	gold quality
prefrontal cortex	UBERON:0000451	94.78	gold quality
entorhinal cortex	UBERON:0002728	94.76	gold quality
superior vestibular nucleus	UBERON:0007227	94.75	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.53	gold quality
nephron tubule	UBERON:0001231	94.50	gold quality
primary visual cortex	UBERON:0002436	94.50	gold quality
quadriceps femoris	UBERON:0001377	94.43	gold quality
skeletal muscle tissue	UBERON:0001134	94.21	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.08	gold quality
diaphragm	UBERON:0001103	94.06	gold quality
occipital lobe	UBERON:0002021	93.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

120 targeting ANKRD46, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
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-548AS-5P	99.94	71.22	3482

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankrd46b	ENSDARG00000015780
danio_rerio	ankrd46a	ENSDARG00000044328
mus_musculus	Ankrd46	ENSMUSG00000048307
rattus_norvegicus	Ankrd46	ENSRNOG00000025504

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 46 — Q86W74 (reviewed: Q86W74)

Alternative names: Ankyrin repeat small protein

All UniProt accessions (6): Q86W74, E5RFM7, E5RHV2, E5RI04, E5RI20, J3KP26

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86W74-2	1	yes
Q86W74-1	2

RefSeq proteins (4): NP_001257306, NP_001257307, NP_001257308, NP_940683 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR039323	ANKRD_45/46/60	Family

Pfam: PF12796

UniProt features (7 total): repeat 4, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W74-F1	76.94	0.39

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 180 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, HORIUCHI_WTAP_TARGETS_DN, XU_GH1_AUTOCRINE_TARGETS_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, ONKEN_UVEAL_MELANOMA_UP, LIAO_METASTASIS, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, chr8q22, DODD_NASOPHARYNGEAL_CARCINOMA_UP, DING_LUNG_CANCER_EXPRESSION_BY_COPY_NUMBER, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, PIT1_Q6, EVI1_04, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD46	VRTN	Q9H8Y1	484
ANKRD46	ANKS1A	Q92625	481
ANKRD46	ACAP1	Q15027	456
ANKRD46	AGFG2	O95081	456
ANKRD46	CUL1	Q13616	450
ANKRD46	SPRYD4	Q8WW59	428
ANKRD46	G2E3	Q7L622	422
ANKRD46	RBX1	P62877	418
ANKRD46	SNX13	Q9Y5W8	405
ANKRD46	CARS2	Q9HA77	404
ANKRD46	LRCH4	O75427	403
ANKRD46	GNB2	P11016	399
ANKRD46	DIP2C	Q9Y2E4	396
ANKRD46	DNMT3A	Q9Y6K1	381
ANKRD46	SMCO3	A2RU48	378

IntAct

42 interactions, top by confidence:

A	B	Type	Score
ANKRD46	ATRN	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
GPHA2	PLXNA2	psi-mi:“MI:0914”(association)	0.530
MGRN1	ATRN	psi-mi:“MI:0914”(association)	0.530
PON2	NPC1	psi-mi:“MI:0914”(association)	0.530
PSG3	MGRN1	psi-mi:“MI:0914”(association)	0.530
ANKRD46	NBAS	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
RNF149	CCDC85C	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
PSG1	IKBKB	psi-mi:“MI:0914”(association)	0.350
PVRIG	CLSTN1	psi-mi:“MI:0914”(association)	0.350
PSG3	PSG1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-C	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
EDN3	POTEF	psi-mi:“MI:0914”(association)	0.350
ITM2C		psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (154): ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS)

ESM2 similar proteins: A0PJZ0, A2VDR2, A7E2S9, O89019, P42570, Q05823, Q05921, Q15327, Q20500, Q21209, Q3SX00, Q3ZBX7, Q4KL97, Q4R3S3, Q4V869, Q52T38, Q5BKI6, Q5I126, Q5I144, Q5I159, Q5R8C8, Q5TYM7, Q5U243, Q641X1, Q65XV2, Q66HD5, Q6JAN1, Q6NSI1, Q6TNT2, Q71S21, Q71S22, Q76K24, Q7ZT11, Q865U8, Q86W74, Q8BTZ5, Q8R560, Q8UVC1, Q8UVC3, Q92527

Diamond homologs: A2ARS0, B2RXR6, C7B178, C9JTQ0, P0C927, P19838, Q00PJ3, Q07E43, Q08353, Q21920, Q29RM5, Q2QL84, Q337A0, Q3KP44, Q3SX00, Q3UES3, Q3UUF8, Q4FE45, Q4JHE0, Q4V890, Q502K3, Q5R8C8, Q5ZLC8, Q60J38, Q6KAE5, Q6TNT2, Q76K24, Q7EZ44, Q86W74, Q86WC6, Q8BTI7, Q8BTZ5, Q8C0T1, Q8NB46, Q8VHS5, Q9BSK4, Q9D119, Q9H2K2, Q9N3Q8, Q9Z2G1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
153234	GRCh38/hg38 8q22.2-23.1(chr8:100179408-106524667)x1	Pathogenic
563534	GRCh37/hg19 8q22.2-22.3(chr8:100551211-103676738)x1	Pathogenic
57124	GRCh38/hg38 8q22.2-22.3(chr8:100023254-101190270)x3	Pathogenic
148247	GRCh38/hg38 8q22.2-22.3(chr8:99580206-101547228)x1	Likely pathogenic

SpliceAI

1007 predictions. Top by Δscore:

Variant	Effect	Δscore
8:100522767:TGGCA:T	acceptor_gain	1.0000
8:100522768:GGCA:G	acceptor_gain	1.0000
8:100522769:GCA:G	acceptor_gain	1.0000
8:100522770:CA:C	acceptor_gain	1.0000
8:100522770:CAC:C	acceptor_gain	1.0000
8:100522771:AC:A	acceptor_loss	1.0000
8:100522772:C:CC	acceptor_gain	1.0000
8:100522773:T:G	acceptor_loss	1.0000
8:100522774:G:C	acceptor_gain	1.0000
8:100522774:G:GC	acceptor_gain	1.0000
8:100527840:AGTAC:A	donor_loss	1.0000
8:100527841:GTACC:G	donor_loss	1.0000
8:100527842:TACC:T	donor_loss	1.0000
8:100527843:ACCTT:A	donor_loss	1.0000
8:100527844:C:T	donor_loss	1.0000
8:100527844:CCTT:C	donor_gain	1.0000
8:100527846:TTTC:T	donor_gain	1.0000
8:100527857:G:C	donor_gain	1.0000
8:100527999:GATTG:G	acceptor_gain	1.0000
8:100528000:ATTG:A	acceptor_gain	1.0000
8:100528001:TTG:T	acceptor_gain	1.0000
8:100528002:TG:T	acceptor_gain	1.0000
8:100528004:C:CC	acceptor_gain	1.0000
8:100529516:AACTT:A	donor_loss	1.0000
8:100529517:ACTT:A	donor_loss	1.0000
8:100529518:CTTA:C	donor_loss	1.0000
8:100529519:TTA:T	donor_loss	1.0000
8:100529520:TACC:T	donor_loss	1.0000
8:100529521:A:AC	donor_gain	1.0000
8:100529522:C:CA	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000060293 (8:100550583 C>T), RS1000075664 (8:100514538 C>T), RS1000106208 (8:100531172 G>A), RS1000157863 (8:100536217 C>G,T), RS1000242277 (8:100530026 T>G), RS1000280380 (8:100541932 A>G,T), RS1000296581 (8:100515855 A>T), RS1000445884 (8:100523115 C>A,T), RS1000492392 (8:100536493 T>C,G), RS1000499919 (8:100509379 A>T), RS1000527416 (8:100555482 A>G,T), RS1000537063 (8:100555022 A>T), RS1000586546 (8:100539789 C>G), RS1000616017 (8:100540134 T>C), RS1000665860 (8:100548789 T>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

3 associations (top):

Study	Trait	p-value
GCST000852_4	Atrioventricular conduction	9.000000e-06
GCST002942_4	Percentage gas trapping	1.000000e-06
GCST005951_63	Body mass index	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007628	gas trapping measurement
EFO:0004340	body mass index

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
Valproic Acid	affects expression, increases expression	3
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Formaldehyde	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Urethane	decreases expression	1
Zinc	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Sodium Selenite	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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