ANKRD65

Summary

ANKRD65 (ankyrin repeat domain 65, HGNC:42950) is a protein-coding gene on chromosome 1p36.33, encoding Ankyrin repeat domain-containing protein 65 (E5RJM6).

At a glance

• Clinical variants (ClinVar): 119 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001145210

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:42950
Approved symbol	ANKRD65
Name	ankyrin repeat domain 65
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000235098
Ensembl biotype	protein_coding
Entrez	441869

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000427211, ENST00000442470, ENST00000454272, ENST00000520296, ENST00000537107, ENST00000897624, ENST00000961299

RefSeq mRNA: 5 — MANE Select: NM_001145210 NM_001145210, NM_001243535, NM_001243536, NM_001375659, NM_001375660

CCDS: CCDS55558, CCDS57962, CCDS57963

Canonical transcript exons

ENST00000537107 — 4 exons

Exon	Start	End
ENSE00002204959	1420052	1420592
ENSE00002229397	1418420	1419549
ENSE00003758729	1420797	1421005
ENSE00003913560	1421133	1421276

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 97.16.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6560 / max 114.6501, expressed in 284 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9787	1.3611	255
9788	0.2209	109
9789	0.0740	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.28	gold quality
spinal cord	UBERON:0002240	88.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.01	gold quality
tendon of biceps brachii	UBERON:0008188	87.67	silver quality
right frontal lobe	UBERON:0002810	86.96	gold quality
amygdala	UBERON:0001876	86.86	gold quality
anterior cingulate cortex	UBERON:0009835	85.44	gold quality
putamen	UBERON:0001874	84.12	gold quality
hypothalamus	UBERON:0001898	84.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.28	gold quality
left uterine tube	UBERON:0001303	83.22	gold quality
cerebellar hemisphere	UBERON:0002245	83.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.18	gold quality
cerebellar cortex	UBERON:0002129	83.10	gold quality
prefrontal cortex	UBERON:0000451	82.70	gold quality
caudate nucleus	UBERON:0001873	82.66	gold quality
nucleus accumbens	UBERON:0001882	82.60	gold quality
substantia nigra	UBERON:0002038	82.12	gold quality
cerebellum	UBERON:0002037	81.95	gold quality
tibial nerve	UBERON:0001323	81.81	gold quality
esophagus mucosa	UBERON:0002469	81.72	gold quality
medial globus pallidus	UBERON:0002477	81.05	gold quality
fallopian tube	UBERON:0003889	80.87	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.83	gold quality
esophagus	UBERON:0001043	80.60	gold quality
prostate gland	UBERON:0002367	80.22	gold quality
midbrain	UBERON:0001891	80.20	gold quality
neocortex	UBERON:0001950	79.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.14
E-GEOD-124858	no	2.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting ANKRD65, 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-3064-3P	100.00	70.09	1254
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-6729-3P	96.91	66.79	703

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ankrd65	ENSMUSG00000078487
rattus_norvegicus	Ankrd65	ENSRNOG00000043331
drosophila_melanogaster	rols	FBGN0041096

Paralogs (4): CTTNBP2 (ENSG00000077063), TANC1 (ENSG00000115183), TANC2 (ENSG00000170921), ANKRD63 (ENSG00000230778)

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 65 — E5RJM6 (reviewed: E5RJM6)

All UniProt accessions (1): E5RJM6

Isoforms (3)

UniProt ID	Names	Canonical?
E5RJM6-1	1	yes
E5RJM6-2	2
E5RJM6-3	3

RefSeq proteins (5): NP_001138682, NP_001230464, NP_001230465, NP_001362588, NP_001362589 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR050889	Dendritic_Spine_Reg/Scaffold	Family

Pfam: PF12796

UniProt features (16 total): repeat 10, splice variant 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-E5RJM6-F1	85.07	0.71

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): chr1p36, CAVIN1_TARGET_GENES, PTTG1_TARGET_GENES, ZNF175_TARGET_GENES, ZNF589_TARGET_GENES, ZNF592_TARGET_GENES, ZNF766_TARGET_GENES, MIR6722_3P, MIR6887_3P, GSE12366_PLASMA_CELL_VS_NAIVE_BCELL_UP, MIR214_5P, MURARO_PANCREAS_BETA_CELL, HAY_BONE_MARROW_DENDRITIC_CELL, DESCARTES_FETAL_PLACENTA_SYNCYTIOTROPHOBLASTS_AND_VILLOUS_CYTOTROPHOBLASTS, CREB3_TARGET_GENES

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

664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD65	ZNF570	Q96NI8	480
ANKRD65	C3orf62	Q6ZUJ4	479
ANKRD65	CDCP2	Q5VXM1	476
ANKRD65	TMEM60	Q9H2L4	419
ANKRD65	SLCO6A1	Q86UG4	401
ANKRD65	TMEM232	C9JQI7	400
ANKRD65	TTLL2	Q9BWV7	399
ANKRD65	ZNF394	Q53GI3	397
ANKRD65	MRPL54	Q6P161	372
ANKRD65	EMC6	Q9BV81	349
ANKRD65	LGI2	Q8N0V4	322
ANKRD65	ZBTB7C	A1YPR0	322
ANKRD65	C1QTNF12	Q5T7M4	321
ANKRD65	L1TD1	Q5T7N2	319
ANKRD65	FBXO25	Q8TCJ0	316

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ANKRD65	TTC19	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): ANKRD65 (Affinity Capture-MS), TTC19 (Affinity Capture-MS), ANKRD65 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A2ARS0, A6NE52, A6QPE7, A8MYJ7, A8VU90, C9JTQ0, E1BD59, E5RJM6, O08672, P54777, Q08353, Q0P5G1, Q0V8J4, Q13470, Q13608, Q15653, Q28616, Q2TB02, Q3SWY4, Q3UYR4, Q53GL7, Q58EX7, Q5IJ48, Q5JR98, Q60778, Q62893, Q6EMK4, Q6F5E8, Q6MG64, Q6P7C4, Q6UX07, Q6ZMH5, Q6ZVH7, Q6ZVZ8, Q7RTR2, Q8CDY7, Q8CIE4, Q8K592, Q8NI38

Diamond homologs: A6QPE7, E5RJM6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	104
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1807723	GRCh37/hg19 1p36.33-36.32(chr1:849467-2972435)x1	Pathogenic
1807780	GRCh37/hg19 1p36.33-36.32(chr1:1335011-2302755)x1	Pathogenic
253365	GRCh37/hg19 1p36.33(chr1:1309373-2043694)x4	Likely pathogenic

SpliceAI

508 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1420909:T:TA	donor_gain	1.0000
1:1420047:CGTA:C	donor_loss	0.9900
1:1420048:GTAC:G	donor_loss	0.9900
1:1420049:TA:T	donor_loss	0.9900
1:1420800:T:A	donor_gain	0.9900
1:1421105:AG:A	donor_gain	0.9900
1:1421106:G:C	donor_gain	0.9900
1:1419548:TCCTA:T	acceptor_loss	0.9800
1:1419549:CCTAG:C	acceptor_loss	0.9800
1:1419550:CT:C	acceptor_loss	0.9800
1:1419551:T:G	acceptor_loss	0.9800
1:1421105:AGC:A	donor_gain	0.9800
1:1421099:CCA:C	donor_gain	0.9700
1:1419546:TGTC:T	acceptor_gain	0.9600
1:1420050:A:AC	donor_gain	0.9600
1:1420051:C:CC	donor_gain	0.9600
1:1419550:C:CC	acceptor_gain	0.9500
1:1420770:CCCCT:C	donor_gain	0.9500
1:1420781:C:A	donor_gain	0.9500
1:1420898:AGGCC:A	donor_gain	0.9500
1:1421099:C:CT	donor_gain	0.9400
1:1421105:A:AC	donor_gain	0.9400
1:1419547:GTC:G	acceptor_gain	0.9300
1:1419548:TC:T	acceptor_gain	0.9300
1:1419549:CC:C	acceptor_gain	0.9300
1:1420775:TC:T	donor_gain	0.9300
1:1420819:G:A	donor_gain	0.9200
1:1419545:ATGTC:A	acceptor_gain	0.9000
1:1419673:T:TA	donor_gain	0.9000
1:1420780:C:CA	donor_gain	0.9000

AlphaMissense

2467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1419404:T:A	D299V	0.988
1:1419470:G:T	A277D	0.987
1:1419405:C:G	D299H	0.986
1:1419287:G:T	P338H	0.980
1:1419405:C:A	D299Y	0.979
1:1419471:C:G	A277P	0.979
1:1419503:T:A	D266V	0.979
1:1420560:G:T	A81D	0.978
1:1419386:G:T	P305H	0.977
1:1419404:T:G	D299A	0.977
1:1420359:G:T	A148D	0.976
1:1420462:C:G	A114P	0.975
1:1419504:C:G	D266H	0.973
1:1420071:G:T	A244D	0.970
1:1419374:G:T	A309D	0.969
1:1419375:C:G	A309P	0.969
1:1419403:G:C	D299E	0.968
1:1419403:G:T	D299E	0.968
1:1420248:G:T	A185D	0.965
1:1420458:G:T	A115D	0.965
1:1419474:C:G	A276P	0.963
1:1420561:C:G	A81P	0.963
1:1419372:A:G	S310P	0.962
1:1419461:C:A	G280V	0.959
1:1419473:G:T	A276D	0.959
1:1419371:G:T	S310Y	0.958
1:1420249:C:G	A185P	0.958
1:1420360:C:G	A148P	0.957
1:1419276:C:G	A342P	0.955
1:1419446:A:T	V285D	0.955

dbSNP variants (sampled 300 via entrez): RS1000010885 (1:1422375 G>A,C), RS1000146004 (1:1422527 A>G), RS1000538355 (1:1422481 G>A,C), RS1000843734 (1:1418001 G>A,C), RS1001826682 (1:1421361 G>T), RS1002023131 (1:1420082 C>G,T), RS1002163555 (1:1420263 G>A,T), RS1002329192 (1:1420791 G>C), RS1002547176 (1:1419397 C>T), RS1003072800 (1:1419234 T>C), RS1003835124 (1:1419426 C>T), RS1004054576 (1:1420300 C>T), RS1004425758 (1:1420517 C>T), RS1004672334 (1:1419561 G>A,T), RS1005831533 (1:1423017 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:600669

GenCC curated gene-disease

Mondo (1): idiopathic generalized epilepsy (MONDO:0005579)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562694	Epilepsy, Idiopathic Generalized (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
Aflatoxin B1	increases expression, decreases methylation	2
sotorasib	affects cotreatment, increases expression	1
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
aflatoxin B2	decreases methylation	1
nutlin 3	affects cotreatment, increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	increases expression, affects cotreatment	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Dactinomycin	increases expression, affects cotreatment	1
Estradiol	decreases expression, affects cotreatment	1
Rifampin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation, decreases expression	1
Cyclosporine	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03590197	PHASE4	COMPLETED	Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy
NCT03940326	PHASE4	COMPLETED	Levetiracetam Versus Valproate in Idiopathic Generalized Tonic-clonic Seizures
NCT00150735	PHASE3	COMPLETED	Monotherapy With Levetiracetam in Newly Diagnosed Patients Suffering From Epilepsy
NCT00150748	PHASE3	COMPLETED	Long Term Follow up Treatment With Levetiracetam in Subjects of 4 Years and Older With Generalized Epilepsy
NCT03678753	PHASE3	COMPLETED	Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures
NCT05147571	PHASE3	ACTIVE_NOT_RECRUITING	RNS System NAUTILUS Study
NCT06908356	PHASE2	RECRUITING	An Open Label Trial to Evaluate the Efficacy and Safety of PRAX-628 in Adults With Focal Onset or Tonic-Clonic Seizures
NCT06425159	PHASE2/PHASE3	TERMINATED	A Study to Determine if BHV-7000 is Effective and Safe in Adults With Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures
NCT00001325	Not specified	COMPLETED	Metabolic Abnormalities in Children With Epilepsy
NCT00916903	Not specified	TERMINATED	Genetic Disease Gene Identification
NCT01311440	Not specified	COMPLETED	Modified Atkins Diet Treatment for Adults With Drug-resistant Epilepsy
NCT01432821	Not specified	COMPLETED	Blinking and Yawning in Epilepsy: The Role of Dopamine
NCT03368469	Not specified	WITHDRAWN	Transcranial Direct Current Stimulation (tDCS) in Children and Adolescents With Epilepsy and Depression
NCT03457961	Not specified	UNKNOWN	Post-market Study of AMPA Receptor Antagonists for Epilepsy Patients in Hong Kong
NCT03955432	Not specified	TERMINATED	Long-term Cardiac Monitoring in Epilepsy
NCT04252846	Not specified	COMPLETED	A Study to Investigate Dosage, Effectiveness, and Safety of Perampanel When Used as First Add-on Therapy in Participants >=12 Years With Partial Onset Seizures With or Without Secondary Generalization or With Primary Generalized Tonic-Clonic Seizures Associated With Idiopathic Generalized Epilepsy
NCT04965571	Not specified	COMPLETED	Clinical Features and Outcome of Wilson’s Disease With Generalized Epilepsy in Chinese Patients
NCT05374928	Not specified	ACTIVE_NOT_RECRUITING	Human Epilepsy Project 3
NCT05530109	Not specified	TERMINATED	Study of Attentional Disorders in Patients Suffering From Idiopathic Generalized Epilepsy.
NCT06388174	Not specified	RECRUITING	Idiopathic Generalized Epilepsy Syndromes
NCT06797791	Not specified	COMPLETED	Assessment of Multifocal Continuous Theta Burst Transcranial Magnetic Stimulation (cTBS) Effects in Generalized Epilepsy Patients.