ANKDD1A

Summary

ANKDD1A (ankyrin repeat and death domain containing 1A, HGNC:28002) is a protein-coding gene on chromosome 15q22.31, encoding Ankyrin repeat and death domain-containing protein 1A (Q495B1).

Predicted to be involved in signal transduction.

Source: NCBI Gene 348094 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 108 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_182703

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28002
Approved symbol	ANKDD1A
Name	ankyrin repeat and death domain containing 1A
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25870
Ensembl gene	ENSG00000166839
Ensembl biotype	protein_coding
Entrez	348094

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000319580, ENST00000395723, ENST00000483400, ENST00000491145, ENST00000496480, ENST00000496660, ENST00000513267, ENST00000611260, ENST00000620154, ENST00000855784, ENST00000855785, ENST00000965210, ENST00000965211, ENST00000965212, ENST00000965213, ENST00000965214, ENST00000965215, ENST00000965216, ENST00000965217, ENST00000965218

RefSeq mRNA: 1 — MANE Select: NM_182703 NM_182703

CCDS: CCDS10197

Canonical transcript exons

ENST00000319580 — 15 exons

Exon	Start	End
ENSE00001201138	64931487	64931585
ENSE00001364585	64949841	64949972
ENSE00001369188	64943484	64943582
ENSE00001377304	64944652	64944747
ENSE00001384304	64947404	64947593
ENSE00001384956	64934136	64934234
ENSE00003510296	64942467	64942565
ENSE00003550002	64926066	64926170
ENSE00003566575	64926901	64926999
ENSE00003581197	64917386	64917514
ENSE00003657969	64915797	64915900
ENSE00003663536	64930822	64930920
ENSE00003686271	64911902	64911964
ENSE00003734117	64921921	64922019
ENSE00003749459	64957103	64958691

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 90.75.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0526 / max 38.4938, expressed in 370 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147202	1.0270	362
207565	0.0256	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	90.75	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.42	gold quality
left adrenal gland cortex	UBERON:0035825	89.61	gold quality
adrenal cortex	UBERON:0001235	89.57	gold quality
spleen	UBERON:0002106	89.40	gold quality
left adrenal gland	UBERON:0001234	89.35	gold quality
right adrenal gland cortex	UBERON:0035827	89.10	gold quality
right adrenal gland	UBERON:0001233	88.91	gold quality
adrenal gland	UBERON:0002369	88.03	gold quality
saphenous vein	UBERON:0007318	87.99	gold quality
medial globus pallidus	UBERON:0002477	87.20	gold quality
primary visual cortex	UBERON:0002436	86.74	gold quality
middle temporal gyrus	UBERON:0002771	85.18	gold quality
tibial artery	UBERON:0007610	85.05	gold quality
popliteal artery	UBERON:0002250	85.04	gold quality
nucleus accumbens	UBERON:0001882	84.81	gold quality
globus pallidus	UBERON:0001875	84.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.62	gold quality
anterior cingulate cortex	UBERON:0009835	84.58	gold quality
tibia	UBERON:0000979	84.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.20	gold quality
amygdala	UBERON:0001876	84.17	gold quality
cerebellar hemisphere	UBERON:0002245	83.98	gold quality
cerebellar cortex	UBERON:0002129	83.82	gold quality
caudate nucleus	UBERON:0001873	83.70	gold quality
aorta	UBERON:0000947	83.63	gold quality
occipital lobe	UBERON:0002021	83.49	gold quality
cerebellum	UBERON:0002037	83.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.42	gold quality
descending thoracic aorta	UBERON:0002345	83.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.96
E-GEOD-70580	no	105.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting ANKDD1A, 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-4795-3P	100.00	74.62	4024
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-4328	99.57	71.06	4094

Literature-anchored findings (GeneRIF, showing 2)

• ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1alpha by upregulating FIH1. ANKDD1A decreases the half-life of HIF1alpha by upregulating FIH1, decreases glucose uptake and lactate production, inhibits glioblastoma multiforme (GBM) autophagy, and induces apoptosis in GBM cells under hypoxia (PMID:30082910)
• Results provide evidence that rs34988193 is a deleterious germline variant present in ANKDD1a associated with poor outcomes of patients with low grade glioma. (PMID:30651372)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankdd1a	ENSDARG00000098647
mus_musculus	Ankdd1a	ENSMUSG00000066510
rattus_norvegicus	Ankdd1a	ENSRNOG00000015554

Paralogs (1): ANKDD1B (ENSG00000189045)

Protein

Protein identifiers

Ankyrin repeat and death domain-containing protein 1A — Q495B1 (reviewed: Q495B1)

All UniProt accessions (6): Q495B1, A0A0C4DFZ5, A0A0C4DGA8, A0A0C4DGZ7, D6RD28, Q8TAJ8

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (4)

UniProt ID	Names	Canonical?
Q495B1-5	5	yes
Q495B1-2	2
Q495B1-6	3
Q495B1-1	1

RefSeq proteins (1): NP_874362* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00023, PF12796

UniProt features (18 total): repeat 11, splice variant 4, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q495B1-F1	89.79	0.80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, ROZANOV_MMP14_TARGETS_UP, DOUGLAS_BMI1_TARGETS_UP, LIU_PROSTATE_CANCER_DN, MARTENS_BOUND_BY_PML_RARA_FUSION, chr15q22, CBX5_TARGET_GENES, HAND1_TARGET_GENES, MIR4795_3P, MIR548G_3P, MIR450A_1_3P, MIR1303, MIR4768_3P, MIR183_3P, MIR491_3P

GO Biological Process (1): signal transduction (GO:0007165)

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
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
binding	1

Protein interactions and networks

STRING

754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKDD1A	C16orf46	Q6P387	397
ANKDD1A	HIF1A	Q16665	396
ANKDD1A	C22orf42	Q6IC83	396
ANKDD1A	SAMD10	Q9BYL1	370
ANKDD1A	CCDC183	Q5T5S1	351
ANKDD1A	ARMCX5	Q6P1M9	351
ANKDD1A	PCDHA13	Q9Y5I0	336
ANKDD1A	DORIP1	Q4W4Y0	324
ANKDD1A	KLHL28	Q9NXS3	322
ANKDD1A	HIF1AN	Q9NWT6	320
ANKDD1A	C1orf54	Q8WWF1	306
ANKDD1A	BEND6	Q5SZJ8	305
ANKDD1A	LYPD5	Q6UWN5	305
ANKDD1A	NSMCE4A	Q9NXX6	298
ANKDD1A	HHIPL1	Q96JK4	295

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ZNF597	HCFC1	psi-mi:“MI:0914”(association)	0.530
ANKDD1A	HIF1AN	psi-mi:“MI:0915”(physical association)	0.500
ANKDD1A	P3H3	psi-mi:“MI:0914”(association)	0.350
RPGRIP1L	ILVBL	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (10): HIF1AN (Affinity Capture-MS), ANKDD1A (Proximity Label-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), ANKDD1A (Affinity Capture-MS), TTN (Affinity Capture-MS), LEPREL2 (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), ANKDD1A (Affinity Capture-MS), ANKDD1A (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: A6NHY2, Q14DN9, Q495B1, Q9GKW8, A0A0K0PU92, O00221, O54910, P25799, P25963, P69744, P83757, P98150, Q00653, Q03017, Q08353, Q25338, Q2QXZ2, Q2RAQ5, Q3UMT1, Q5EFR1, Q5I144, Q5I148, Q5I149, Q5I156, Q5I159, Q5I160, Q6RI86, Q810B6, Q86WC6, Q8BLA8, Q8C0T1, Q9D119, Q9DBR7, Q9H1D0, Q9JIP0, Q9NQA5, Q9P2R3, Q9WTK5, Q9XSM3, Q9Z1E3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	81
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
58573	GRCh38/hg38 15q22.31(chr15:64448836-65975439)x3	Pathogenic
560063	Single allele	Likely pathogenic

SpliceAI

3529 predictions. Top by Δscore:

Variant	Effect	Δscore
15:64911961:GGCC:G	donor_gain	1.0000
15:64911962:GCC:G	donor_gain	1.0000
15:64911962:GCCG:G	donor_gain	1.0000
15:64911965:G:GG	donor_gain	1.0000
15:64915852:G:GT	donor_gain	1.0000
15:64921919:A:AG	acceptor_gain	1.0000
15:64921920:G:GG	acceptor_gain	1.0000
15:64930818:GCAG:G	acceptor_loss	1.0000
15:64930819:CAGGA:C	acceptor_loss	1.0000
15:64930821:G:A	acceptor_loss	1.0000
15:64930821:GGA:G	acceptor_gain	1.0000
15:64930918:GCG:G	donor_gain	1.0000
15:64930919:CGGTG:C	donor_loss	1.0000
15:64930921:G:C	donor_loss	1.0000
15:64930921:G:GG	donor_gain	1.0000
15:64930922:TGA:T	donor_loss	1.0000
15:64930923:GAG:G	donor_loss	1.0000
15:64934231:TCAT:T	donor_gain	1.0000
15:64934231:TCATG:T	donor_loss	1.0000
15:64934233:AT:A	donor_gain	1.0000
15:64934234:TGTA:T	donor_loss	1.0000
15:64934235:G:GG	donor_gain	1.0000
15:64934237:AA:A	donor_loss	1.0000
15:64942461:CCACA:C	acceptor_loss	1.0000
15:64942462:CACAG:C	acceptor_loss	1.0000
15:64942463:ACAGC:A	acceptor_loss	1.0000
15:64942464:CA:C	acceptor_loss	1.0000
15:64942465:A:AG	acceptor_gain	1.0000
15:64942465:AGCAG:A	acceptor_gain	1.0000
15:64942466:G:GA	acceptor_gain	1.0000

AlphaMissense

3424 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:64947524:T:A	W428R	0.986
15:64947524:T:C	W428R	0.986
15:64926928:G:C	A167P	0.979
15:64921954:T:C	F101L	0.978
15:64921956:C:A	F101L	0.978
15:64921956:C:G	F101L	0.978
15:64947551:T:C	F437L	0.977
15:64947553:C:A	F437L	0.977
15:64947553:C:G	F437L	0.977
15:64947526:G:C	W428C	0.974
15:64947526:G:T	W428C	0.974
15:64943509:C:A	A331D	0.973
15:64926929:C:A	A167D	0.971
15:64943511:G:C	A332P	0.971
15:64947552:T:C	F437S	0.970
15:64944677:C:A	A364D	0.968
15:64926094:C:A	A132D	0.967
15:64944721:G:C	A379P	0.967
15:64949871:G:C	R461P	0.965
15:64926994:G:C	D189H	0.962
15:64926091:C:A	A131E	0.961
15:64949885:T:A	W466R	0.961
15:64949885:T:C	W466R	0.961
15:64942492:C:A	A298D	0.960
15:64926093:G:C	A132P	0.958
15:64926925:G:C	A166P	0.958
15:64943508:G:C	A331P	0.956
15:64930847:C:A	A199D	0.954
15:64926123:T:C	F142L	0.953
15:64926125:C:A	F142L	0.953

dbSNP variants (sampled 300 via entrez): RS1000010587 (15:64949070 G>A), RS1000030077 (15:64929531 A>G), RS1000101617 (15:64929298 C>G), RS1000235854 (15:64926677 T>A), RS1000252451 (15:64913307 A>G), RS1000336442 (15:64932161 G>A), RS1000382529 (15:64923215 G>A,C), RS1000433589 (15:64937588 T>C), RS1000496130 (15:64927906 G>A,T), RS1000569615 (15:64947280 G>A), RS1000609304 (15:64927709 A>C,G), RS1000642246 (15:64955804 T>C), RS1000644530 (15:64933791 G>A), RS1000657428 (15:64935446 C>T), RS1000740784 (15:64913245 A>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:609273

GenCC curated gene-disease

Mondo (1): nemaline myopathy 6 (MONDO:0012237)

Orphanet (1): Childhood-onset nemaline myopathy (Orphanet:171439)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001337_47	Platelet count	1.000000e-11
GCST005991_38	Platelet count	6.000000e-10
GCST009856_32	Leukocyte telomere length	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538398	Nemaline myopathy 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation, affects expression	5
bisphenol A	decreases expression, decreases methylation, increases methylation	2
sodium arsenite	decreases methylation, decreases expression, increases abundance, increases expression	2
propionaldehyde	increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	decreases expression, increases abundance	1
hydroquinone	decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Arsenic	decreases expression, increases abundance	1
Benzene	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Demecolcine	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Nickel	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03211923	Not specified	UNKNOWN	Muscle Relaxation in Myopathies With Positive Muscle Phenomena