ANKRD39

Summary

ANKRD39 (ankyrin repeat domain 39, HGNC:28640) is a protein-coding gene on chromosome 2q11.2, encoding Ankyrin repeat domain-containing protein 39 (Q53RE8).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 50 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_016466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28640
Approved symbol	ANKRD39
Name	ankyrin repeat domain 39
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC41816
Ensembl gene	ENSG00000213337
Ensembl biotype	protein_coding
Entrez	51239

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000393537, ENST00000443120, ENST00000871181

RefSeq mRNA: 1 — MANE Select: NM_016466 NM_016466

CCDS: CCDS2028

Canonical transcript exons

ENST00000393537 — 4 exons

Exon	Start	End
ENSE00001160852	96853401	96853604
ENSE00001160859	96854338	96854441
ENSE00001515693	96847990	96848444
ENSE00001787891	96857888	96858016

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 95.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2510 / max 77.9198, expressed in 1702 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29774	6.2510	1702

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	95.14	gold quality
gastrocnemius	UBERON:0001388	93.37	gold quality
muscle of leg	UBERON:0001383	92.79	gold quality
prefrontal cortex	UBERON:0000451	89.68	gold quality
apex of heart	UBERON:0002098	88.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.75	gold quality
cerebellar hemisphere	UBERON:0002245	87.60	gold quality
cerebellar cortex	UBERON:0002129	87.47	gold quality
anterior cingulate cortex	UBERON:0009835	87.41	gold quality
right frontal lobe	UBERON:0002810	87.35	gold quality
adenohypophysis	UBERON:0002196	86.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.41	gold quality
cerebellum	UBERON:0002037	86.38	gold quality
pituitary gland	UBERON:0000007	85.48	gold quality
right adrenal gland	UBERON:0001233	85.30	gold quality
hypothalamus	UBERON:0001898	85.16	gold quality
frontal cortex	UBERON:0001870	85.12	gold quality
neocortex	UBERON:0001950	85.11	gold quality
left adrenal gland	UBERON:0001234	84.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.82	gold quality
left adrenal gland cortex	UBERON:0035825	84.79	gold quality
right adrenal gland cortex	UBERON:0035827	84.67	gold quality
heart left ventricle	UBERON:0002084	84.63	gold quality
putamen	UBERON:0001874	84.53	gold quality
amygdala	UBERON:0001876	84.43	gold quality
nucleus accumbens	UBERON:0001882	84.41	gold quality
caudate nucleus	UBERON:0001873	84.19	gold quality
cardiac ventricle	UBERON:0002082	83.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting ANKRD39, 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-4455	100.00	65.48	1587
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-5583-5P	97.85	67.61	1243
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-7161-3P	96.79	68.79	798
HSA-MIR-4654	95.86	65.72	751
HSA-MIR-4769-5P	95.37	66.09	570

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankrd39	ENSDARG00000041350
mus_musculus	Ankrd39	ENSMUSG00000079610
rattus_norvegicus	Ankrd39	ENSRNOG00000064008
drosophila_melanogaster	CG44001	FBGN0264743

Paralogs (2): CDKN2C (ENSG00000123080), CDKN2D (ENSG00000129355)

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 39 — Q53RE8 (reviewed: Q53RE8)

All UniProt accessions (1): Q53RE8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the ANKRD39 family.

RefSeq proteins (1): NP_057550* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF12796

UniProt features (8 total): repeat 4, chain 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53RE8-F1	84.41	0.72

Functional residue map

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

Post-translational modifications (1): 153

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): RNGTGGGC_UNKNOWN, WEI_MYCN_TARGETS_WITH_E_BOX, NKX62_Q2, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, AFP1_Q6, TGGNNNNNNKCCAR_UNKNOWN, IK2_01, E12_Q6, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_UP, SANSOM_APC_MYC_TARGETS, SANSOM_APC_TARGETS_REQUIRE_MYC, chr2q11, RICKMAN_HEAD_AND_NECK_CANCER_F, PILON_KLF1_TARGETS_UP, KASLER_HDAC7_TARGETS_1_UP

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (2): molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (1): cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD39	FAHD2B	Q6P2I3	609
ANKRD39	FAM178B	Q8IXR5	590
ANKRD39	ITPRIPL1	Q6GPH6	509
ANKRD39	FER1L5	A0AVI2	505
ANKRD39	EEIG2	Q5T8I3	497
ANKRD39	LMAN2L	Q9H0V9	447
ANKRD39	UQCC6	Q69YU5	447
ANKRD39	ZNF514	Q96K75	445
ANKRD39	CNNM3	Q8NE01	445
ANKRD39	ASTL	Q6HA08	439
ANKRD39	SLC67A2	Q8NBP5	435
ANKRD39	CLDND2	Q8NHS1	432
ANKRD39	FAHD2A	Q96GK7	417
ANKRD39	SAXO4	Q7Z5V6	415
ANKRD39	STARD7	Q9NQZ5	397
ANKRD39	VWA3B	Q502W6	397

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CUL2	VHL	psi-mi:“MI:0914”(association)	0.940
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790
CUL3	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CUL3	KLHL2	psi-mi:“MI:0914”(association)	0.350
ANKRD39	CDC25C	psi-mi:“MI:0914”(association)	0.350
ANKRD39	UBA6	psi-mi:“MI:0914”(association)	0.350
ANKRD39	COPS2	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): ANKRD39 (Affinity Capture-MS), ANKRD39 (Affinity Capture-MS), ANKRD39 (Two-hybrid), ANKRD39 (Two-hybrid), GLDC (Affinity Capture-MS), LANCL2 (Affinity Capture-MS), CUL1 (Affinity Capture-MS), COPS3 (Affinity Capture-MS), TBCE (Affinity Capture-MS), UBA6 (Affinity Capture-MS), COPS2 (Affinity Capture-MS), PTPN11 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), PITHD1 (Affinity Capture-MS), COPS4 (Affinity Capture-MS)

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: Q0P5B9, Q53RE8, Q54KH3, Q7XUW4, Q9D2X0, Q10225, Q4I8B6, Q4X251, Q5I1X5, Q5M9H0, Q5XIU1, Q7S3M5, Q7Z8U2, Q86WC6, Q8N7Z5, Q8WUF5, Q969K4, Q99LJ2, Q9CZK6, Q9D119, A0A8I3PDQ1, A0JNB0, A1Y2K1, A5GFW5, A6QLK6, O35177, O42287, O43281, P06241, P0C550, P10569, P14234, P19706, P27447, P29355, P34109, P38753, P39688, P56945, P62993

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neddylation	6	28.4×	1e-06
Antigen processing: Ubiquitination & Proteasome degradation	5	18.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	7	26.4×	1e-07
proteasome-mediated ubiquitin-dependent protein catabolic process	5	23.7×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1047904	GRCh37/hg19 2q11.1-11.2(chr2:96755045-98021592)	Pathogenic

SpliceAI

1711 predictions. Top by Δscore:

Variant	Effect	Δscore
2:96839721:ACTC:A	donor_loss	1.0000
2:96839723:TCA:T	donor_loss	1.0000
2:96839724:CA:C	donor_loss	1.0000
2:96839725:A:AG	donor_loss	1.0000
2:96840091:CCGAT:C	acceptor_gain	1.0000
2:96840092:CGAT:C	acceptor_gain	1.0000
2:96840092:CGATC:C	acceptor_gain	1.0000
2:96840094:AT:A	acceptor_gain	1.0000
2:96840094:ATC:A	acceptor_loss	1.0000
2:96840095:TC:T	acceptor_loss	1.0000
2:96840096:C:CC	acceptor_gain	1.0000
2:96840226:CCTCA:C	donor_loss	1.0000
2:96840227:CTCAC:C	donor_loss	1.0000
2:96840228:TCA:T	donor_loss	1.0000
2:96840231:CCTT:C	donor_loss	1.0000
2:96840257:C:CA	donor_gain	1.0000
2:96840327:CCAG:C	acceptor_gain	1.0000
2:96840328:CAG:C	acceptor_gain	1.0000
2:96840328:CAGC:C	acceptor_gain	1.0000
2:96840329:AG:A	acceptor_gain	1.0000
2:96840330:GC:G	acceptor_loss	1.0000
2:96840331:C:CC	acceptor_gain	1.0000
2:96840332:T:G	acceptor_loss	1.0000
2:96840515:C:CC	acceptor_gain	1.0000
2:96840825:A:AC	donor_gain	1.0000
2:96840826:C:CC	donor_gain	1.0000
2:96840919:C:CT	acceptor_gain	1.0000
2:96840920:A:T	acceptor_gain	1.0000
2:96842055:CTCA:C	donor_loss	1.0000
2:96842056:TCACC:T	donor_loss	1.0000

AlphaMissense

1178 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:96853410:A:C	S133R	0.997
2:96853410:A:T	S133R	0.997
2:96853412:T:G	S133R	0.997
2:96853494:G:C	S105R	0.997
2:96853494:G:T	S105R	0.997
2:96853496:T:G	S105R	0.997
2:96853569:G:C	C80W	0.997
2:96853593:G:C	S72R	0.997
2:96853593:G:T	S72R	0.997
2:96853595:T:G	S72R	0.997
2:96853465:A:G	L115P	0.996
2:96853501:C:G	R103P	0.996
2:96853558:A:G	L84P	0.996
2:96853591:C:G	R73P	0.996
2:96848441:C:G	A138P	0.995
2:96853459:A:G	L117P	0.995
2:96853486:C:A	G108V	0.995
2:96853582:T:G	H76P	0.995
2:96853585:C:A	G75V	0.995
2:96854417:C:A	G42V	0.995
2:96848444:C:G	A137P	0.994
2:96853462:A:G	L116P	0.994
2:96853499:C:G	A104P	0.994
2:96853561:A:G	L83P	0.994
2:96853597:G:T	A71D	0.994
2:96853510:G:T	A100D	0.993
2:96853571:A:G	C80R	0.993
2:96853487:C:A	G108W	0.992
2:96853570:C:T	C80Y	0.992
2:96854426:G:T	A39D	0.992

dbSNP variants (sampled 300 via entrez): RS1000220260 (2:96850827 A>AT), RS1000236293 (2:96857066 G>C), RS1000300197 (2:96854041 C>T), RS1000570784 (2:96850492 T>C,G), RS1000649302 (2:96854327 C>T), RS1000684838 (2:96856740 G>A), RS1001140023 (2:96849564 C>T), RS1001480684 (2:96855156 C>G), RS1001555539 (2:96856366 CAGG>C), RS1001701427 (2:96854893 G>C), RS1001818504 (2:96850123 T>G), RS1001822780 (2:96856398 G>A), RS1001938587 (2:96850204 T>C), RS1001994741 (2:96848770 G>A), RS1002036962 (2:96856125 T>C,G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (2): cleft lip (MONDO:0004747), fetal growth restriction (MONDO:0005030)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0410030	Cleft lip

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008839_542	Height	7.000000e-18

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002971	Cleft Lip	C07.465.409.225; C07.465.525.164; C07.650.525.164; C16.131.850.525.164
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
monomethylarsonous acid	increases expression	1
K 7174	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Benzo(a)pyrene	increases expression	1
Catechin	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03480607	PHASE4	COMPLETED	Dexmedetomidine as Adjuvant for Bupivacaine in Ultrasound Guided Infraorbital Nerve Block for Cleft Lip Repair
NCT00347867	PHASE4	UNKNOWN	Viagra for the Treatment of IUGR
NCT00909974	PHASE4	COMPLETED	Effect of Prenatal Nutritional Supplementation on Birth Outcome in Hounde District, Burkina Faso
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01390051	PHASE4	COMPLETED	Can Low Molecular Weight Heparin During Pregnancy With Intrauterine Growth Restriction Increase Birth Weight?
NCT01695070	PHASE4	COMPLETED	Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT05029778	PHASE4	UNKNOWN	Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
NCT05800938	PHASE4	COMPLETED	The Effect of Oral Isosorbide Mononitrate Therapy on Umbilical Artery Doppler Resistance Index in Pregnancies With Intrauterine Growth Restriction: Prospective Randomized Control Trial
NCT07171086	PHASE4	NOT_YET_RECRUITING	AI-POCUS for Maternal and Neonatal Health in Ethiopia
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT03314090	PHASE3	COMPLETED	Silicone Gel in the Treatment of Cleft Lip Scars
NCT00174252	PHASE3	COMPLETED	Study Aimed At Improving Height With Genotonorm In Children Born Little And/Or Light With Growth Retardation At The Age
NCT00197340	PHASE3	COMPLETED	Antepartum Chronic Epidural Therapy (ACET) to Improve Blood Flow to the Uterus, Placenta and Baby in Pre-Eclampsia and Intrauterine Growth Restriction
NCT00452491	PHASE3	COMPLETED	MAXOMAT ® in the Treatment of Severe Early Onset Intrauterine Growth Retardation on Pre-pubertal Children
NCT01073605	PHASE3	COMPLETED	Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation
NCT02336243	PHASE3	UNKNOWN	A Randomized Trial of Docosahexaenoic Acid Supplementation During Pregnancy to Prevent Deep Placentation Disorders
NCT02590536	PHASE3	COMPLETED	A Trial Evaluating the Role of Sildenafil in the Treatment of Fetal Growth Restriction
NCT02672566	PHASE3	COMPLETED	Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction
NCT03177824	PHASE3	UNKNOWN	Sildenafil Citrate for Treatment of Growth-restricted Fetuses
NCT03230162	PHASE3	UNKNOWN	Sildenafil Versus Low Molecular Weight Heparin in Fetal Growth Restriction Treatment
NCT03324139	PHASE3	COMPLETED	Treatment of Intrauterine Growth Restriction With Low Molecular Heparin.
NCT03669185	PHASE3	UNKNOWN	Pentaerithrityl Tetranitrate (PETN) for Secondary Prevention of Intrauterine Growth Restriction
NCT04084990	PHASE3	TERMINATED	Sleep Apnea and Fetal Growth Restriction
NCT04356326	PHASE3	RECRUITING	Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy
NCT04557475	PHASE3	WITHDRAWN	Transplacental Aspirin Therapy for Early Onset Fetal Growth Restriction
NCT04762992	PHASE3	ENROLLING_BY_INVITATION	LMWH for Treatment of Early Fetal Growth Restriction (HepaGrowth)
NCT05253781	PHASE3	COMPLETED	Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE)
NCT05651347	PHASE3	RECRUITING	Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction
NCT05774236	PHASE3	COMPLETED	Cook´s Balloon Versus Dinoprostone for Labor Induction of Term Pregnancies With Fetal Growth Restriction
NCT06497959	PHASE3	RECRUITING	Study of Placental Vascularization Using Contrast Ultrasound
NCT00004639	PHASE2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT06885801	PHASE2	NOT_YET_RECRUITING	Evaluation of a Novel Nasal Conformer in Pediatric Patients
NCT02280031	PHASE2	COMPLETED	Effect of Low Dose Aspirin on Birthweight in Twins: The GAP Trial.
NCT02425436	PHASE2	COMPLETED	Role of Ginkgo Biloba Extract in IUGR
NCT02678221	PHASE2	UNKNOWN	Sildenafil Citrate for the Management of Asymmetrical Intrauterine Growth Restriction
NCT02696577	PHASE2	COMPLETED	The Effect of Omega 3 on Pregnancy Complicated by Asymmetrical Intrauterine Growth Restriction
NCT07098975	PHASE2	RECRUITING	Statin Intervention for Severe Early-Onset Placental Insufficiency. (STATIN-PRE Trial)