ANKRD66

Summary

ANKRD66 (ankyrin repeat domain 66, HGNC:44669) is a protein-coding gene on chromosome 6p12.3, encoding Ankyrin repeat domain-containing protein 66 (B4E2M5).

At a glance

• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_001162435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44669
Approved symbol	ANKRD66
Name	ankyrin repeat domain 66
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000230062
Ensembl biotype	protein_coding
Entrez	100287718

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000445060, ENST00000565422, ENST00000958136, ENST00000958137

RefSeq mRNA: 1 — MANE Select: NM_001162435 NM_001162435

CCDS: CCDS59024

Canonical transcript exons

ENST00000565422 — 5 exons

Exon	Start	End
ENSE00002228124	46751937	46752111
ENSE00002314874	46753722	46753950
ENSE00002581281	46746933	46746990
ENSE00002587047	46758723	46759506
ENSE00003565305	46749896	46749979

Expression profiles

Bgee: expression breadth broad, 37 present calls, max score 91.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2293 / max 78.7724, expressed in 53 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68142	0.1896	48
68143	0.0271	10
204016	0.0126	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	91.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.59	gold quality
fallopian tube	UBERON:0003889	74.52	gold quality
right lung	UBERON:0002167	64.90	gold quality
endometrium	UBERON:0001295	60.55	gold quality
left uterine tube	UBERON:0001303	52.21	gold quality
lung	UBERON:0002048	50.73	gold quality
prefrontal cortex	UBERON:0000451	48.12	gold quality
caudate nucleus	UBERON:0001873	47.44	gold quality
hypothalamus	UBERON:0001898	44.54	gold quality
upper lobe of left lung	UBERON:0008952	44.19	gold quality
Ammon’s horn	UBERON:0001954	44.00	gold quality
corpus callosum	UBERON:0002336	43.46	gold quality
temporal lobe	UBERON:0001871	43.42	gold quality
amygdala	UBERON:0001876	43.27	gold quality
colonic epithelium	UBERON:0000397	41.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	41.05	gold quality
anterior cingulate cortex	UBERON:0009835	41.03	gold quality
bone marrow cell	CL:0002092	40.77	gold quality
frontal cortex	UBERON:0001870	40.17	gold quality
endocervix	UBERON:0000458	40.15	gold quality
cerebral cortex	UBERON:0000956	38.88	gold quality
nucleus accumbens	UBERON:0001882	38.22	gold quality
superior frontal gyrus	UBERON:0002661	37.68	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
brain	UBERON:0000955	36.27	gold quality
bone marrow	UBERON:0002371	35.22	gold quality
monocyte	CL:0000576	35.19	gold quality
apex of heart	UBERON:0002098	34.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting ANKRD66, 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-4482-3P	99.98	72.50	3147
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-1182	96.41	64.89	336
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-1915-5P	95.25	65.78	571

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ANKRD66	ENSDARG00000090489
mus_musculus	Ankrd66	ENSMUSG00000096140
rattus_norvegicus	Ankrd66	ENSRNOG00000068669

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 66 — B4E2M5 (reviewed: B4E2M5)

All UniProt accessions (2): B4E2M5, H3BTF0

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (1): NP_001155907* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR050776	Ank_Repeat/CDKN_Inhibitor	Family

Pfam: PF12796

UniProt features (6 total): repeat 3, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B4E2M5-F1	85.04	0.64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 14 (showing top): chr6p12, FOSTER_TOLERANT_MACROPHAGE_DN, METTL14_TARGET_GENES, SRSF9_TARGET_GENES, MIR1915_5P, MIR1182, GAO_ESOPHAGUS_25W_C1_CILIATED_EPITHELIAL_CELLS, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_CEREBRUM_ASTROCYTES, DESCARTES_FETAL_LUNG_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_STOMACH_CILIATED_EPITHELIAL_CELLS, NOTCH3_TARGET_GENES, TRAVAGLINI_LUNG_CILIATED_CELL, TRAVAGLINI_LUNG_PROXIMAL_CILIATED_CELL

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

786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD66	ANKUB1	A6NFN9	545
ANKRD66	HOATZ	Q6PI97	540
ANKRD66	LRRC71	Q8N4P6	490
ANKRD66	FAM216B	Q8N7L0	469
ANKRD66	MAP3K19	Q56UN5	446
ANKRD66	TMEM273	Q5T292	423
ANKRD66	WDR31	Q8NA23	418
ANKRD66	DYNLT5	Q8N7M0	409
ANKRD66	ODAPH	Q17RF5	398
ANKRD66	CALHM2	Q9HA72	384
ANKRD66	SERTAD4	Q9NUC0	375
ANKRD66	TRAPPC8	Q9Y2L5	368
ANKRD66	DAW1	Q8N136	365
ANKRD66	TMC5	Q6UXY8	362
ANKRD66	TMEM255A	Q5JRV8	361

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ANKRD66		psi-mi:“MI:0915”(physical association)	0.370

ESM2 similar proteins: A6NK59, A7MB89, B4E2M5, P0C6P7, P0C927, Q08DV6, Q29RM5, Q3SX45, Q3SZE4, Q3UMR0, Q495B1, Q4V890, Q5R5S1, Q5REW9, Q5RFS1, Q5U2S6, Q5ZM55, Q6GPE5, Q7T3P8, Q810B6, Q8C0T1, Q8C6Y6, Q8CEF1, Q8CEL2, Q8HXA6, Q8K0L0, Q8N9B4, Q8VHS6, Q8WXH4, Q8WXK1, Q91ZT8, Q96DX5, Q96JP0, Q96NW4, Q96Q27, Q9BSK4, Q9CQ31, Q9GKW8, Q9H0C1, Q9P2R3

Diamond homologs: A0A084B9Z8, B4E2M5, P42773, Q03017, Q4FE45, Q4JHE0, Q502M6, Q60772, Q61982, Q6RI86, Q8BLA8, Q9R172, Q9UM47, A0A0R4IQZ2, A5WVX9, B3DN87, B8A4F0, C8VCL4, E1BLT8, E7F587, E7FH11, E9PTT0, E9QCD3, F1Q7H8, F1QAM1, F1QHM7, F1QX91, O60069, O74384, O80685, P14585, P42836, P59267, P59268, Q04629, Q0WQK2, Q10L01, Q21920, Q2T9W8, Q2TGI5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

417 predictions. Top by Δscore:

Variant	Effect	Δscore
6:46746986:AGACA:A	donor_gain	1.0000
6:46746987:GACA:G	donor_gain	1.0000
6:46746987:GACAG:G	donor_gain	1.0000
6:46746989:CA:C	donor_gain	1.0000
6:46746991:G:GG	donor_gain	1.0000
6:46749895:GGGCT:G	acceptor_gain	1.0000
6:46749980:G:GG	donor_gain	1.0000
6:46751932:CACA:C	acceptor_loss	1.0000
6:46751934:CAGTT:C	acceptor_loss	1.0000
6:46751935:A:AG	acceptor_gain	1.0000
6:46751935:A:G	acceptor_loss	1.0000
6:46751935:AGTT:A	acceptor_gain	1.0000
6:46751936:G:GC	acceptor_gain	1.0000
6:46751936:GT:G	acceptor_gain	1.0000
6:46751936:GTT:G	acceptor_gain	1.0000
6:46751936:GTTG:G	acceptor_gain	1.0000
6:46751936:GTTGT:G	acceptor_gain	1.0000
6:46752109:AAGG:A	donor_loss	1.0000
6:46752112:GTGA:G	donor_loss	1.0000
6:46753709:T:TA	acceptor_gain	1.0000
6:46753951:G:GG	donor_gain	1.0000
6:46746988:ACA:A	donor_gain	0.9900
6:46746988:ACAGT:A	donor_loss	0.9900
6:46746989:CAGT:C	donor_loss	0.9900
6:46746990:AGTA:A	donor_loss	0.9900
6:46746991:GTA:G	donor_loss	0.9900
6:46749894:A:AG	acceptor_gain	0.9900
6:46749894:AG:A	acceptor_gain	0.9900
6:46749895:G:GG	acceptor_gain	0.9900
6:46749895:GG:G	acceptor_gain	0.9900

AlphaMissense

1650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:46752082:G:C	R100P	0.991
6:46753811:G:C	A140P	0.989
6:46753908:C:A	A172E	0.985
6:46752099:G:C	A106P	0.984
6:46753805:T:C	F138L	0.984
6:46753807:T:A	F138L	0.984
6:46753807:T:G	F138L	0.984
6:46753790:T:A	W133R	0.983
6:46753790:T:C	W133R	0.983
6:46753809:C:A	A139E	0.983
6:46753907:G:C	A172P	0.983
6:46752102:G:C	A107P	0.981
6:46753812:C:A	A140E	0.980
6:46752088:C:G	P102R	0.979
6:46753877:G:C	D162H	0.979
6:46753896:C:A	P168Q	0.978
6:46753896:C:G	P168R	0.977
6:46752100:C:A	A106D	0.976
6:46751991:G:C	A70P	0.975
6:46752088:C:A	P102Q	0.975
6:46753792:G:C	W133C	0.975
6:46753792:G:T	W133C	0.975
6:46753879:C:A	D162E	0.975
6:46753879:C:G	D162E	0.975
6:46752096:T:A	W105R	0.974
6:46752096:T:C	W105R	0.974
6:46753779:C:T	T129I	0.973
6:46753800:C:A	A136D	0.972
6:46752103:C:A	A107E	0.971
6:46752063:G:C	D94H	0.970

dbSNP variants (sampled 300 via entrez): RS1000069057 (6:46759281 G>A), RS1000202916 (6:46746882 G>A,T), RS1000457613 (6:46754141 G>A), RS1001067536 (6:46748752 T>G), RS1001216448 (6:46751324 G>A), RS1001278496 (6:46751471 C>A,T), RS1001288036 (6:46746056 T>C), RS1001319820 (6:46745529 C>T), RS1001424845 (6:46746102 T>C,G), RS1001451783 (6:46759912 G>A), RS1001584183 (6:46751494 T>A,G), RS1001690987 (6:46757558 C>G,T), RS1001855212 (6:46756224 C>A,T), RS1002074491 (6:46756418 AG>A), RS1002405010 (6:46746920 G>A,T)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
Smoke	increases expression, increases abundance	2
bisphenol S	affects cotreatment, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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