ANK1

Summary

ANK1 (ankyrin 1, HGNC:492) is a protein-coding gene on chromosome 8p11.21, encoding Ankyrin-1 (P16157). Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.

Ankyrins are a family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 1, the prototype of this family, was first discovered in the erythrocytes, but since has also been found in brain and muscles. Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis. Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified.

Source: NCBI Gene 286 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary spherocytosis (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 144
• Clinical variants (ClinVar): 1,643 total — 193 pathogenic, 253 likely-pathogenic
• Phenotypes (HPO): 66
• Cancer driver (intOGen): activating (oncogene-like) across 6 cancer types
• MANE Select transcript: NM_000037

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:492
Approved symbol	ANK1
Name	ankyrin 1
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Aliases	SPH1
Ensembl gene	ENSG00000029534
Ensembl biotype	protein_coding
OMIM	612641
Entrez	286

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000265709, ENST00000289734, ENST00000314214, ENST00000335651, ENST00000347528, ENST00000348036, ENST00000518061, ENST00000518715, ENST00000520299, ENST00000521407, ENST00000522231, ENST00000522543, ENST00000524227, ENST00000645531, ENST00000705521, ENST00000705522

RefSeq mRNA: 8 — MANE Select: NM_000037 NM_000037, NM_001142445, NM_001142446, NM_020475, NM_020476, NM_020477, NM_020478, NM_020480

CCDS: CCDS47849, CCDS55227, CCDS6119, CCDS6120, CCDS6121, CCDS6122

Canonical transcript exons

ENST00000289734 — 43 exons

Exon	Start	End
ENSE00000532984	41708778	41708975
ENSE00000532987	41704041	41704139
ENSE00000691945	41672354	41672912
ENSE00000692046	41704374	41704472
ENSE00000692050	41706143	41706241
ENSE00000692080	41715652	41715849
ENSE00001192253	41661876	41661941
ENSE00001192267	41661430	41661564
ENSE00001252137	41698043	41698121
ENSE00001252145	41699452	41699548
ENSE00001252155	41701550	41701622
ENSE00001252162	41702052	41702144
ENSE00001252187	41714156	41714254
ENSE00001252194	41714976	41715074
ENSE00001252199	41716953	41717051
ENSE00001252205	41717604	41717702
ENSE00001252214	41718106	41718204
ENSE00001252224	41719661	41719858
ENSE00001252233	41723125	41723223
ENSE00001252241	41723535	41723633
ENSE00001252247	41724456	41724554
ENSE00001252255	41725761	41725946
ENSE00001252268	41727250	41727348
ENSE00001252279	41727908	41728006
ENSE00001252286	41733971	41734069
ENSE00001252297	41758036	41758137
ENSE00003468411	41694592	41694803
ENSE00003468578	41684544	41684690
ENSE00003471948	41693105	41693201
ENSE00003480301	41695177	41695331
ENSE00003504663	41686152	41686283
ENSE00003541933	41688511	41688589
ENSE00003560787	41696363	41696587
ENSE00003566338	41696676	41696773
ENSE00003571523	41668267	41668564
ENSE00003600622	41690474	41690599
ENSE00003603014	41663659	41663742
ENSE00003603711	41692648	41692876
ENSE00003649005	41693898	41694102
ENSE00003649989	41690227	41690346
ENSE00003653028	41688156	41688230
ENSE00003654289	41653225	41655753
ENSE00003899248	41797512	41797622

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 98.70.

FANTOM5 (CAGE): breadth broad, TPM avg 10.7770 / max 1890.5836, expressed in 409 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92845	6.1835	133
92835	1.5141	67
92833	0.7096	53
92834	0.5863	51
92852	0.3616	78
92844	0.2988	62
92843	0.2622	65
92846	0.2485	68
92836	0.1929	60
92848	0.1828	82

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.70	gold quality
triceps brachii	UBERON:0001509	98.65	gold quality
body of tongue	UBERON:0011876	98.63	gold quality
biceps brachii	UBERON:0001507	98.51	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.31	gold quality
diaphragm	UBERON:0001103	98.13	gold quality
apex of heart	UBERON:0002098	98.12	gold quality
gluteal muscle	UBERON:0002000	97.72	gold quality
gastrocnemius	UBERON:0001388	97.51	gold quality
skeletal muscle tissue	UBERON:0001134	96.51	gold quality
trabecular bone tissue	UBERON:0002483	96.18	gold quality
muscle of leg	UBERON:0001383	96.15	gold quality
muscle organ	UBERON:0001630	95.58	gold quality
skeletal muscle organ	UBERON:0014892	95.58	gold quality
vastus lateralis	UBERON:0001379	93.84	gold quality
heart left ventricle	UBERON:0002084	93.83	gold quality
right atrium auricular region	UBERON:0006631	93.81	gold quality
cardiac ventricle	UBERON:0002082	93.77	gold quality
cerebellar hemisphere	UBERON:0002245	93.69	gold quality
cerebellar cortex	UBERON:0002129	93.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.36	gold quality
cerebellum	UBERON:0002037	92.92	gold quality
deltoid	UBERON:0001476	92.82	gold quality
quadriceps femoris	UBERON:0001377	92.11	gold quality
tongue	UBERON:0001723	91.82	gold quality
substantia nigra pars compacta	UBERON:0001965	91.44	gold quality
cardiac atrium	UBERON:0002081	91.01	gold quality
muscle tissue	UBERON:0002385	90.31	gold quality
heart right ventricle	UBERON:0002080	90.26	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	324.63
E-CURD-112	yes	64.56
E-HCAD-6	yes	59.14
E-HCAD-25	yes	38.20
E-MTAB-10042	yes	25.73
E-ANND-3	yes	10.91
E-MTAB-5061	yes	10.38
E-MTAB-9388	yes	8.87
E-MTAB-9067	yes	7.21
E-HCAD-9	yes	5.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB, MYOD1, NFE2, SRF, TBP

miRNA regulators (miRDB)

83 targeting ANK1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4761-5P	99.51	66.69	804

Literature-anchored findings (GeneRIF, showing 40)

• ankyrin and protein 4.1 are cleaved by native and recombinant falcipain-2 near their C-termini (PMID:12130521)
• interaction of hydrophilic domain with two N-terminal immunoglobulin domains of titin (PMID:12444090)
• A small muscle-specific isoform of the ANK1 gene, ank1.5, interacts with obscurin. Since ank1.5 is localised on the sarcoplasmic reticulum and obscurin on the myofibrils, these two proteins may provide a molecular link between these subcellular regions. (PMID:12527750)
• identification of ankyrin as a target of spectrin’s E2/E3 activity (PMID:15040428)
• The interactions of three protein 4.2-derived recombinant proteins with CDB3 and ankyrin were investigated by using Far-Western blot and pull-down assay. (PMID:16718373)
• off rates of the band 3-ankyrin interaction are sufficiently slow to allow sustained erythrocyte deformation without loss of elasticity (PMID:16762928)
• Allelic and genotypic frequencies were similar in both studied groups for the G199A and Memphis I polymorphismsin Hereditary Spherocytosis among the Mexican population. (PMID:17128827)
• It was shown that the region within beta-spectrin involved in interactions with ankyrin includes a lipid-binding site and binding is inhibited by ankyrin. Our results shows: the ankyrin-sens. lipid-bind. site of beta-spectrin exhibits a helical conform. (PMID:17520478)
• Our results therefore indicate the importance of N-terminal region for lipid-binding activity of the beta-spectrin ankyrin-binding domain and its substantial role in maintaining the spectrin-based skeleton distribution. (PMID:17716929)
• Structural and mutational studies of the binding region on small Ank1 for obscurin suggest that it consists of two ankyrin repeats with very similar structures. (PMID:17720975)
• Ankyrin facilitates intracellular trafficking of alpha1-Na+-K+-ATPase in polarized cells. (PMID:18768923)
• Generated a library of more than 16,000 ANK-1 promoters with degenerate sequence around the dinucleotide deletion mutation and cloned the functional promoter sequences. Identified the wild type and three additional sequences, and derived a consensus. (PMID:20479128)
• The Hereditary Spherocytosis mutation in the human Ankyrin-1 promoter disrupted the binding of the transcription factor TFIID, the major component of the pre-initiation complex. (PMID:21071415)
• a region upstream of the promoter is a barrier insulator. The region exhibited functional and structural characteristics of a barrier, including prevention of gene silencing, appropriate chromatin configuration and occupancy by barrier-associated proteins (PMID:21099109)
• cytoskeletal ankyrin family are substrates for FIH-catalyzed hydroxylations (PMID:21177872)
• Determination of structural models of the complex between the cytoplasmic domain of erythrocyte band 3 and ankyrin-R repeats 13-24. (PMID:21493712)
• results indicate that the ANK1 locus is a new, common susceptibility locus for type 2 diabetes across different ethnic groups (PMID:22456796)
• The interaction of KCTD6 with ankyrin-1 may have implications beyond muscle for hereditary spherocytosis, as KCTD6 is also present in erythrocytes, and erythrocyte ankyrin isoforms contain its mapped minimal binding site. (PMID:22573887)
• A tissue-specific chromatin loop brings NF-E2 and ANK1E into close proximity preventing gene silencing and mutagenesis leading to hereditary spherocytosis. (PMID:22968456)
• The ankyrin-binding site on band 3 is located near the deoxygenated hemoglobin-binding site, therefore following deoxygenation ankyrin is displaced from band 3. (PMID:23013433)
• ANK1 rs516946 confers impaired insulin release. (PMID:23457408)
• The study reports the refinement for a protein heterodimer complex using limited EPR spectroscopic data and a rigid-body docking algorithm: a three-dimensional model for an ankyrin 1-BND3 complex. (PMID:24758720)
• A novel L1340P mutation in the ANK1 gene is associated with hereditary spherocytosis. (PMID:24903897)
• Our analyses suggest that these DNA methylation changes may have a role in the onset of Alzheimer disease given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known susceptibility gene network. (PMID:25129075)
• We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of Alzheimer disease manifestation. (PMID:25129077)
• analysis of a novel p.Q1772X ANK1 mutation in a Korean family with hereditary spherocytosis [case report of two family members] (PMID:26107955)
• rs515071 in ANK1 is a novel genetic risk for late-onset Alzheimer’s disease susceptibility in Han Chinese. (PMID:26611832)
• Mutational characteristics of ANK1 and SPTB genes in Korean hereditary spherocytosis have been described. (PMID:26830532)
• Ankyrin-1 is induced to a greater extent than the embedded miRNA following DNA damage. (PMID:27054339)
• ANK1 rs508419-C type 2 diabetes (T2D)-risk allele alters DNA-protein complex binding leading to increased promoter activity and sAnk1 expression; thus, increased sAnk1 expression in skeletal muscle might contribute to T2D susceptibility. (PMID:27121283)
• The present study demonstrates that ANK1 is aberrantly expressed in pancreatic adenocarcinomas in association with promoter hypomethylation (PMID:27144336)
• Study shows that Ankyrin-1 forms a high-affinity interaction with AE1 tetramers but does not associate with AE1 dimers in erythrocyte membranes. (PMID:27989623)
• These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN’s inhibitory effect on SERCA1 activity. (PMID:28487373)
• Two novel mutations in ANK1 (Y216X and E142X) are responsible for hereditary spherocytosis. (PMID:28694211)
• ANK1 is up-regulated 4-fold in Alzheimer disease microglia, but not in neurons or astrocytes from the same individuals. (PMID:28700589)
• Aberrant ANK1 methylation is highly prevalent in lung cancer, discriminate tumors by histology and patients’ smoking history, and contributes to miR-486-5p repression. (PMID:28965852)
• Our finding suggested that a de novo nonsense mutation in ANK1 may be causative to HS which plays an important role in supplementing the mutational spectrum of the ANK1 and explaining the mechanism of HS. (PMID:29099659)
• Transient Receptor Potential Vanniloid-1 channel (TRPV-1) has a role in the cough reflex and airway expression is increased in patients with chronic cough. The Ankyrin-1 receptor (TRPA-1) is often co-expressed (PMID:29149168)
• ANK1 is characterized by region and disease-specific differential DNA methylation in multiple neurodegenerative diseases. (PMID:30439595)
• The current meta-analysis suggests that ANKK1 Taq1A and DRD2 C957T polymorphisms have limited if any effect on the performance on executive function tasks in healthy adults. (PMID:30836122)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ank1a	ENSDARG00000059093
danio_rerio	ank1b	ENSDARG00000074777
danio_rerio		ENSDARG00000092143
mus_musculus	Ank1	ENSMUSG00000031543
rattus_norvegicus	Ank1	ENSRNOG00000018241
drosophila_melanogaster	Ank	FBGN0011747
drosophila_melanogaster	Ank2	FBGN0261788
caenorhabditis_elegans		WBGENE00006780

Paralogs (3): ANK2 (ENSG00000145362), ANK3 (ENSG00000151150), ASB7 (ENSG00000183475)

Protein

Protein identifiers

Ankyrin-1 — P16157 (reviewed: P16157)

Alternative names: Ankyrin-R, Erythrocyte ankyrin

All UniProt accessions (8): A0A2R8Y4B0, A0A994J4W8, P16157, A0A994J7F8, C9JN86, H0YAY8, H0YBS0, Q6PK32

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane. Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions. Together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils.

Subunit / interactions. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with a number of integral membrane proteins and cytoskeletal proteins. Interacts (via N-terminus) with SPTB/spectrin (beta chain). Also interacts with TTN/titin. Isoform Mu17 interacts with OBSCN isoform 3/obscurin. Interacts with HIF1AN. Interacts (via ANK 1-5 repeats) with RHCE; this interaction mediates the primary membrane attachment site for ANK1. Interacts (via ANK 1-2 repeats) with AQP1 (via the N-terminal). Interacts (via ANK 1-13 repeats) with EPB42. Interacts directly with SLC4A1 (via the cytoplasmic domain); this interaction is mediated by the SLC4A1 Band 3-II and Band 3-III dimers.

Subcellular location. Cytoplasm. Cytoskeleton Membrane. Myofibril. Sarcomere. M line Sarcoplasmic reticulum Sarcoplasmic reticulum Sarcoplasmic reticulum.

Tissue specificity. Isoform Mu17, isoform Mu18, isoform Mu19 and isoform Mu20 are expressed in skeletal muscle. Isoform Br21 is expressed in brain.

Post-translational modifications. Regulated by phosphorylation. Palmitoylated. Hydroxylated by HIF1AN at several asparagine and 1 aspartate residue within ANK repeat region. Hydroxylation seems to increase the conformational stability of this region and may also modulate protein-protein interactions mediated by the ANK repeat region. (Microbial infection) Probably cleaved by P.falciparum SERA6; the cleavage probably causes the disruption of the actin cytoskeleton and the rupture of the erythrocyte cell membrane releasing the merozoites.

Disease relevance. Spherocytosis 1 (SPH1) [MIM:182900] A form of spherocytosis, a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH1 is characterized by severe hemolytic anemia. Inheritance can be autosomal dominant or autosomal recessive. Patients with homozygous mutations have a more severe disorder. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The 55 kDa regulatory domain is involved in regulating binding of SPTB/spectrin (beta chain) and SLC4A1/erythrocyte membrane protein band 3. The ANK repeat region forms a spiral around a large central cavity and is involved in binding of ion transporters. Adopts a T-shaped arrangement, in the ankyrin-1 complex, in which ANK 1-5 repeats are orthogonal to ANK 6-24 repeats, with the peptide binding groove of ANK 1-5 repeats oriented toward the membrane. The rearrangement of the ANK 1-5 repeats orients the canonical protein binding groove to directly face the membrane, to interact the membrane-embedded targets RHCE and AQP1. The tandem configuration of the two ZU5 and the UPA domains forms a structural supramodule termed ZZU. ZU5-1 mediates interaction with beta-spectrin, and the ZU5-1/UPA interface is required for ankyrin’s function other than binding to spectrin.

Miscellaneous. Major erythrocyte-specific isoform. Produced by alternative promoter usage. Predominant form of minor erythrocyte-specific isoforms. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative splicing of isoform Er1. Produced by alternative promoter usage. Produced by alternative splicing of isoform Mu17. Produced by alternative splicing of isoform Mu17. Produced by alternative splicing of isoform Mu17. Produced by alternative splicing of isoform Er1. Produced by alternative splicing.

Isoforms (23)

UniProt ID	Names	Canonical?
P16157-1	Er1, 1, 2.1	yes
P16157-4	Er2, 2, 2.2
P16157-5	Er3, 3
P16157-6	Er4, 4
P16157-3	Er5, 5
P16157-7	Er6, 6
P16157-8	Er7, 7
P16157-9	Er8, 8
P16157-10	Er9, 9
P16157-11	Er10, 10
P16157-12	Er11, 11
P16157-13	Er12, 12
P16157-14	Er13, 13
P16157-15	Er14, 14
P16157-16	Er15, 15
P16157-2	Er16
P16157-17	Mu17, ank1.5, muscle-specific 1
P16157-18	Mu18, ank1.6, muscle-specific 2
P16157-19	Mu19, muscle-specific 3
P16157-20	Mu20, muscle-specific 4
P16157-21	Br21
P16157-22	22
P16157-23	23

RefSeq proteins (8): NP_000028, NP_001135917, NP_001135918, NP_065208, NP_065209, NP_065210, NP_065211, NP_065213 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR000906	ZU5_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR040745	Ankyrin_UPA	Domain
IPR051165	Multifunctional_ANK_Repeat	Family

Pfam: PF00023, PF00531, PF00791, PF12796, PF13637, PF17809

UniProt features (219 total): helix 65, modified residue 34, strand 28, repeat 23, sequence variant 19, splice variant 17, region of interest 9, compositionally biased region 8, sequence conflict 5, mutagenesis site 4, turn 3, domain 3, chain 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
2YVI	X-RAY DIFFRACTION	1.92
3F59	X-RAY DIFFRACTION	2
3UD1	X-RAY DIFFRACTION	2
7UZQ	ELECTRON MICROSCOPY	2.17
3UD2	X-RAY DIFFRACTION	2.21
7UZU	ELECTRON MICROSCOPY	2.3
7V0K	ELECTRON MICROSCOPY	2.4
7V0S	ELECTRON MICROSCOPY	2.5
1N11	X-RAY DIFFRACTION	2.7
7V0M	ELECTRON MICROSCOPY	2.7
8CSV	ELECTRON MICROSCOPY	2.7
8CS9	ELECTRON MICROSCOPY	2.74
3KBT	X-RAY DIFFRACTION	2.75
3KBU	X-RAY DIFFRACTION	2.75
8CTE	ELECTRON MICROSCOPY	2.9
7V0X	ELECTRON MICROSCOPY	3
7TW3	ELECTRON MICROSCOPY	4.4
7TW6	ELECTRON MICROSCOPY	5.6
7TW5	ELECTRON MICROSCOPY	5.7
8CSL	ELECTRON MICROSCOPY	25
2YQF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16157-F1	69.64	0.36

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 (34): 105, 233, 429, 431, 464, 629, 662, 695, 728, 759, 761, 781, 817, 834, 856, 961, 1073, 1082, 1378, 1380 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
1824	abolishes interaction with obscn (in isoform mu17).
1826	abolishes interaction with obscn (in isoform mu17).
1829	abolishes interaction with obscn (in isoform mu17).
1830	abolishes interaction with obscn (in isoform mu17).

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-447038	NrCAM interactions
R-HSA-447041	CHL1 interactions
R-HSA-447043	Neurofascin interactions
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-1266738	Developmental Biology
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-373760	L1CAM interactions
R-HSA-392499	Metabolism of proteins
R-HSA-422475	Axon guidance
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9675108	Nervous system development

MSigDB gene sets: 416 (showing top): CHIBA_RESPONSE_TO_TSA_UP, GNF2_PRDX2, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GCANCTGNY_MYOD_Q6, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, CACCAGC_MIR138, CTATGCA_MIR153, CAGCTG_AP4_Q5, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GNF2_ANK1, BROWNE_HCMV_INFECTION_48HR_DN, MODULE_120, GOBP_EXOCYTOSIS, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP

GO Biological Process (7): exocytosis (GO:0006887), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), cytoskeleton organization (GO:0007010), signal transduction (GO:0007165), maintenance of epithelial cell apical/basal polarity (GO:0045199), protein localization to plasma membrane (GO:0072659), Golgi vesicle transport (GO:0048193)

GO Molecular Function (9): structural molecule activity (GO:0005198), structural constituent of cytoskeleton (GO:0005200), cytoskeletal adaptor activity (GO:0008093), enzyme binding (GO:0019899), protein phosphatase binding (GO:0019903), spectrin binding (GO:0030507), transmembrane transporter binding (GO:0044325), ATPase binding (GO:0051117), protein binding (GO:0005515)

GO Cellular Component (18): cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), spectrin-associated cytoskeleton (GO:0014731), basolateral plasma membrane (GO:0016323), sarcoplasmic reticulum (GO:0016529), Z disc (GO:0030018), axolemma (GO:0030673), M band (GO:0031430), sarcolemma (GO:0042383), neuron projection (GO:0043005), postsynaptic membrane (GO:0045211), ankyrin-1 complex (GO:0170014), cytoplasm (GO:0005737), membrane (GO:0016020), A band (GO:0031672), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
L1CAM interactions	4
ER to Golgi Anterograde Transport	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Axon guidance	1
Nervous system development	1
Post-translational protein modification	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
vesicle-mediated transport	2
cytoplasm	2
cytoskeleton	2
cytoskeletal protein binding	2
protein binding	2
plasma membrane	2
secretion by cell	1
vesicle fusion to plasma membrane	1
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
organelle organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
maintenance of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
protein localization to membrane	1
protein localization to cell periphery	1
molecular_function	1
structural molecule activity	1
cytoskeleton organization	1
protein-macromolecule adaptor activity	1
phosphatase binding	1
protein-containing complex binding	1
enzyme binding	1
binding	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
cytoplasmic side of membrane	1
basal plasma membrane	1
plasma membrane region	1
endoplasmic reticulum	1
sarcoplasm	1
I band	1
neuron projection membrane	1

Protein interactions and networks

STRING

5612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANK1	EPB41	P11171	997
ANK1	ADD1	P35611	986
ANK1	ADD3	Q9UEY8	984
ANK1	SLC4A1	P02730	983
ANK1	ADD2	P35612	976
ANK1	OBSCN	Q5VST9	970
ANK1	TTN	Q8WZ42	966
ANK1	L1CAM	P32004	953
ANK1	SPTB	P11277	926
ANK1	SPTBN4	Q9H254	907
ANK1	TRPV1	Q8NER1	902
ANK1	NFASC	O94856	899
ANK1	SPTBN5	Q9NRC6	886
ANK1	CALM1	P02593	879
ANK1	MAML1	Q92585	878

IntAct

21 interactions, top by confidence:

A	B	Type	Score
OBSCN	ANK1	psi-mi:“MI:0915”(physical association)	0.560
OBSCN	ANK1	psi-mi:“MI:0407”(direct interaction)	0.560
OBSCN	ANK1	psi-mi:“MI:0403”(colocalization)	0.560
CHL1	LGALS1	psi-mi:“MI:0914”(association)	0.530
OBSCN	ANK1	psi-mi:“MI:0915”(physical association)	0.400
MB	ANK1	psi-mi:“MI:0915”(physical association)	0.400
ANK1	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
PPP1R12B	ANKRD28	psi-mi:“MI:0914”(association)	0.350
RAPGEF5	DDHD2	psi-mi:“MI:0914”(association)	0.350
ANK1	VAC14	psi-mi:“MI:0914”(association)	0.350
ANK1	FGFR1	psi-mi:“MI:0914”(association)	0.350
SLC4A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
ZNF800	MED19	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (72): ANK1 (Biochemical Activity), ANK1 (Two-hybrid), RHAG (Two-hybrid), OBSCN (Two-hybrid), ANK1 (Reconstituted Complex), ANK1 (Affinity Capture-MS), ANK1 (Affinity Capture-MS), FIG4 (Affinity Capture-MS), PIKFYVE (Affinity Capture-MS), ANK1 (Affinity Capture-MS), PDS5B (Affinity Capture-MS), VAC14 (Affinity Capture-MS), NELFB (Affinity Capture-MS), ANK1 (Affinity Capture-MS), OBSCN (Two-hybrid)

ESM2 similar proteins: A0PJZ0, A6NGH8, A7E2S9, B2RR83, B7U179, B9DHT4, C7B178, D3J162, D3J163, F4IDQ6, G5E8K5, O22161, O44997, O70511, P16157, P53355, Q01484, Q02357, Q05921, Q08E43, Q12955, Q3EC11, Q4R3S3, Q4R544, Q52T38, Q5R6D7, Q5RCK5, Q5TYM7, Q5VYY1, Q60772, Q641X1, Q7T163, Q80YE7, Q8C8R3, Q91ZT9, Q91ZU0, Q92527, Q94B55, Q9BGT9, Q9CQM6

Diamond homologs: G5E8K5, O70511, P16157, Q01484, Q02357, Q12955, Q8C8R3, Q8IV45, A0A0G2K2P5, O97758, P39447, Q07157, Q6R653

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ANK1	“down-regulates activity”	SLN	binding
ANK1	“form complex”	“Ankyrin complex”	binding
NFASC	“up-regulates quantity”	ANK1	relocalization
NRCAM	“up-regulates quantity”	ANK1	relocalization
CHL1	“up-regulates quantity”	ANK1	relocalization
ANK1	“down-regulates activity”	ATP2A1	binding

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 6 cancer types — ANGS, CHOL, COAD, COADREAD, LUAD, PRAD.

Clinical variants and AI predictions

ClinVar

1643 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	193
Likely pathogenic	253
Uncertain significance	689
Likely benign	211
Benign	101

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1198634	NM_000037.4(ANK1):c.2390_2393del	Pathogenic
1299404	NM_000037.4(ANK1):c.382_386del (p.Lys128fs)	Pathogenic
1299406	NM_000037.4(ANK1):c.3850del (p.Asp1284fs)	Pathogenic
1299410	NM_000037.4(ANK1):c.2393_2403del (p.Val798fs)	Pathogenic
1299414	NM_000037.4(ANK1):c.3629+2T>C	Pathogenic
1300176	NM_000037.4(ANK1):c.2098-1G>T	Pathogenic
1300177	NM_000037.4(ANK1):c.4098C>A (p.Cys1366Ter)	Pathogenic
1323896	NM_000037.4(ANK1):c.3157C>T (p.Arg1053Ter)	Pathogenic
1330541	NM_000037.4(ANK1):c.1124T>G (p.Leu375Ter)	Pathogenic
1330553	NM_000037.4(ANK1):c.2102del (p.Gly701fs)	Pathogenic
1330761	NM_000037.4(ANK1):c.2803C>T (p.Arg935Ter)	Pathogenic
1331044	NM_000037.4(ANK1):c.5436_5437insCAGGG (p.Glu1813fs)	Pathogenic
1369201	NM_000037.4(ANK1):c.1549G>T (p.Glu517Ter)	Pathogenic
1393753	NM_000037.4(ANK1):c.4414C>T (p.Gln1472Ter)	Pathogenic
1406324	NM_000037.4(ANK1):c.358C>T (p.Gln120Ter)	Pathogenic
1435388	NM_000037.4(ANK1):c.3016_3022dup (p.Val1008fs)	Pathogenic
1451985	NM_000037.4(ANK1):c.2947del (p.Ala983fs)	Pathogenic
1455153	NM_000037.4(ANK1):c.856C>T (p.Arg286Ter)	Pathogenic
154596	GRCh38/hg38 8p11.21-11.1(chr8:39960531-43673207)x3	Pathogenic
1676944	NM_000037.4(ANK1):c.5192C>G (p.Ser1731Ter)	Pathogenic
1676945	NM_000037.4(ANK1):c.4157dup (p.Tyr1386Ter)	Pathogenic
1676946	NM_000037.4(ANK1):c.5071C>T (p.Gln1691Ter)	Pathogenic
1676947	NM_000037.4(ANK1):c.1305+1G>A	Pathogenic
1676949	NM_000037.4(ANK1):c.1602+1G>C	Pathogenic
1676950	NM_000037.4(ANK1):c.3629+1G>C	Pathogenic
1676951	NM_000037.4(ANK1):c.886del (p.Ala296fs)	Pathogenic
1676957	NM_000037.4(ANK1):c.319C>T (p.Gln107Ter)	Pathogenic
1676966	NM_000037.4(ANK1):c.1365T>G (p.Tyr455Ter)	Pathogenic
1676985	NM_000037.4(ANK1):c.3639_3649dup (p.Pro1217fs)	Pathogenic
1676995	NM_000037.4(ANK1):c.4204C>T (p.Gln1402Ter)	Pathogenic

SpliceAI

7956 predictions. Top by Δscore:

Variant	Effect	Δscore
8:41661835:T:TA	donor_gain	1.0000
8:41661843:A:AC	donor_gain	1.0000
8:41661844:C:CC	donor_gain	1.0000
8:41661877:T:TA	donor_gain	1.0000
8:41661937:ATGAT:A	acceptor_gain	1.0000
8:41661938:TGAT:T	acceptor_gain	1.0000
8:41661939:GAT:G	acceptor_gain	1.0000
8:41661940:AT:A	acceptor_gain	1.0000
8:41661941:TCTA:T	acceptor_loss	1.0000
8:41661942:C:CC	acceptor_gain	1.0000
8:41661942:CTAG:C	acceptor_loss	1.0000
8:41663654:CCCA:C	donor_loss	1.0000
8:41663656:CAC:C	donor_loss	1.0000
8:41663658:C:CT	donor_loss	1.0000
8:41663658:CCTT:C	donor_gain	1.0000
8:41663738:TTCCC:T	acceptor_gain	1.0000
8:41663740:CCC:C	acceptor_gain	1.0000
8:41663741:CCC:C	acceptor_gain	1.0000
8:41663742:CCTG:C	acceptor_loss	1.0000
8:41663749:T:TC	acceptor_gain	1.0000
8:41668261:TCTCA:T	donor_loss	1.0000
8:41668262:CTCAC:C	donor_loss	1.0000
8:41668263:TCACC:T	donor_loss	1.0000
8:41668264:CAC:C	donor_loss	1.0000
8:41668265:A:T	donor_loss	1.0000
8:41668594:G:T	acceptor_gain	1.0000
8:41668597:C:CT	acceptor_gain	1.0000
8:41668597:C:T	acceptor_gain	1.0000
8:41668598:G:T	acceptor_gain	1.0000
8:41684535:GACAC:G	donor_loss	1.0000

AlphaMissense

12273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:41692872:A:G	W1212R	1.000
8:41692872:A:T	W1212R	1.000
8:41692874:A:G	F1211S	1.000
8:41693126:A:G	F1203S	1.000
8:41693181:A:G	W1185R	1.000
8:41693181:A:T	W1185R	1.000
8:41693915:A:G	L1172P	1.000
8:41693990:A:G	L1147P	1.000
8:41694007:G:C	F1141L	1.000
8:41694007:G:T	F1141L	1.000
8:41694008:A:G	F1141S	1.000
8:41694009:A:G	F1141L	1.000
8:41694035:A:T	V1132D	1.000
8:41717695:A:G	L405P	1.000
8:41718172:T:A	K380N	1.000
8:41718172:T:G	K380N	1.000
8:41718173:T:A	K380I	1.000
8:41718179:G:T	A378D	1.000
8:41718182:A:C	I377S	1.000
8:41718182:A:T	I377N	1.000
8:41718196:A:C	F372L	1.000
8:41718196:A:T	F372L	1.000
8:41718197:A:G	F372S	1.000
8:41718198:A:G	F372L	1.000
8:41719722:C:T	G349E	1.000
8:41719729:G:C	H347D	1.000
8:41719731:G:T	A346D	1.000
8:41719734:G:T	A345D	1.000
8:41719752:A:G	L339P	1.000
8:41719851:A:G	L306P	1.000

dbSNP variants (sampled 300 via entrez): RS1000009928 (8:41783129 T>C), RS1000014156 (8:41721734 T>C), RS1000030265 (8:41868691 T>C), RS1000037598 (8:41705636 C>T), RS1000039355 (8:41820801 G>C), RS1000059768 (8:41858604 G>A), RS1000061548 (8:41868381 C>T), RS1000065151 (8:41652850 T>C), RS1000066317 (8:41722023 G>C), RS1000067415 (8:41830909 C>T), RS1000087511 (8:41863275 C>T), RS1000096767 (8:41827158 C>T), RS1000103477 (8:41678143 T>A,C), RS1000117624 (8:41822356 T>G), RS1000151947 (8:41854065 T>G)

Disease associations

OMIM: gene MIM:612641 | disease phenotypes: MIM:182900, MIM:615592, MIM:618459

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spherocytosis	Definitive	Autosomal dominant
hereditary spherocytosis type 1	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary spherocytosis	Limited	AR
hereditary spherocytosis	Definitive	AD

Mondo (7): hereditary spherocytosis type 1 (MONDO:0008447), severe combined immunodeficiency due to IKK2 deficiency (MONDO:0014267), hereditary spherocytosis (MONDO:0019350), hemolytic anemia (MONDO:0003664), anemia (MONDO:0002280), immunodeficiency 62 (MONDO:0032763), microcephaly (MONDO:0001149)

Orphanet (3): Hereditary spherocytosis (Orphanet:822), Combined immunodeficiency due to IKBKB deficiency (Orphanet:397787), Childhood-onset common variable immunodeficiency due to ARHGEF1 deficiency (Orphanet:696942)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000135	Hypogonadism
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000377	Abnormal pinna morphology
HP:0000458	Anosmia
HP:0000482	Microcornea
HP:0000556	Retinal dystrophy
HP:0000581	Blepharophimosis
HP:0000582	Upslanted palpebral fissure
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0000952	Jaundice
HP:0000960	Sacral dimple
HP:0000980	Pallor
HP:0001081	Cholelithiasis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001510	Growth delay

GWAS associations

144 associations (top):

Study	Trait	p-value
GCST000803_5	Glycated hemoglobin levels	6.000000e-12
GCST000803_8	Glycated hemoglobin levels	1.000000e-08
GCST001444_38	Pulmonary function decline	5.000000e-06
GCST001461_1	Type 2 diabetes	1.000000e-08
GCST002352_36	Type 2 diabetes	2.000000e-07
GCST002390_7	Glycated hemoglobin levels	1.000000e-15
GCST003400_41	Type 2 diabetes	1.000000e-12
GCST004007_18	Mean corpuscular hemoglobin concentration	1.000000e-08
GCST004007_7	Mean corpuscular hemoglobin concentration	3.000000e-10
GCST004602_67	Mean corpuscular volume	1.000000e-16
GCST004605_38	Mean corpuscular hemoglobin concentration	4.000000e-43
GCST004605_39	Mean corpuscular hemoglobin concentration	2.000000e-17
GCST004605_40	Mean corpuscular hemoglobin concentration	4.000000e-62
GCST004608_104	Granulocyte percentage of myeloid white cells	2.000000e-11
GCST004611_32	High light scatter reticulocyte count	1.000000e-12
GCST004611_33	High light scatter reticulocyte count	2.000000e-19
GCST004611_34	High light scatter reticulocyte count	2.000000e-10
GCST004611_35	High light scatter reticulocyte count	8.000000e-30
GCST004612_40	High light scatter reticulocyte percentage of red cells	3.000000e-12
GCST004612_41	High light scatter reticulocyte percentage of red cells	3.000000e-18
GCST004612_42	High light scatter reticulocyte percentage of red cells	9.000000e-10
GCST004612_43	High light scatter reticulocyte percentage of red cells	8.000000e-28
GCST004619_119	Reticulocyte fraction of red cells	2.000000e-86
GCST004619_155	Reticulocyte fraction of red cells	2.000000e-14
GCST004619_175	Reticulocyte fraction of red cells	5.000000e-56
GCST004619_22	Reticulocyte fraction of red cells	3.000000e-40
GCST004619_88	Reticulocyte fraction of red cells	2.000000e-20
GCST004621_122	Red cell distribution width	3.000000e-20
GCST004622_12	Reticulocyte count	4.000000e-14
GCST004622_13	Reticulocyte count	2.000000e-57

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004541	HbA1c measurement
EFO:0004314	forced expiratory volume
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004344	birth weight
EFO:0008473	insulin response measurement
EFO:0004471	insulin sensitivity measurement
EFO:0004509	hemoglobin measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009473	hemolysis
EFO:0005091	monocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000740	Anemia	C15.378.050
D000743	Anemia, Hemolytic	C15.378.050.141
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D013103	Spherocytosis, Hereditary	C15.378.050.141.150.785; C16.320.070.785

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases mutagenesis	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, affects expression, affects methylation	3
bisphenol A	affects methylation, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Doxorubicin	increases expression	2
Lead	affects expression, affects methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression, decreases methylation	2
Aflatoxin B1	affects methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	increases reaction, affects binding	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05777993	PHASE4	ENROLLING_BY_INVITATION	A Study to Provide Continued Access to Mitapivat for Participants Who Previously Completed an Agios-Sponsored Mitapivat Study
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00046969	PHASE4	COMPLETED	Epoetin Beta in Treating Anemia in Patients With Cervical Cancer
NCT00111995	PHASE4	COMPLETED	Evaluating Aranesp® for the Treatment of Anemia in African-American Subjects With Chronic Renal Failure (CRF) Receiving Hemodialysis
NCT00117039	PHASE4	COMPLETED	A Study to Evaluate the Effectiveness of Aranesp® for Cancer Patients With Anemia
NCT00117065	PHASE4	COMPLETED	Study of Transplant Related Anemia Treated With Aranesp® (STRATA)
NCT00117117	PHASE4	COMPLETED	A Study to Assess Symptom Burden in Subjects With Nonmyeloid Malignancies Receiving Chemotherapy and Aranesp®
NCT00126334	PHASE4	COMPLETED	Conservative Versus Liberal Red Cell Transfusion in Myocardial Infarction Trial: The CRIT Pilot
NCT00153868	PHASE4	COMPLETED	A Web-based Study of Quality of Life Benefits Associated Aranesp in Anemic Patients With Cancer
NCT00168948	PHASE4	UNKNOWN	Intermittent Antimalaria Treatment With SP in African Children
NCT00173706	PHASE4	UNKNOWN	Evaluation of the Effects of L-Carnitine Injection in Patients Undergoing Hemodialysis
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00204334	PHASE4	COMPLETED	Effects of Anemia Correction on Vascular and Monocyte Function in Renal Transplant Recipients
NCT00206739	PHASE4	COMPLETED	Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infants
NCT00211120	PHASE4	TERMINATED	Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR)
NCT00216541	PHASE4	COMPLETED	A Study of the Safety and Effectiveness of Epoetin Alfa on Hemoglobin Levels and Blood Transfusions in Cancer Patients Receiving Chemotherapy
NCT00223938	PHASE4	TERMINATED	Study of the Efficacy and Safety of Ferrlecit in the Maintenance Dosing in Hemodialysis Patients.
NCT00223964	PHASE4	COMPLETED	Study of the Efficacy of Two Doses of Ferrlecit in the Treatment of Iron Deficiency in Pediatric Hemodialysis Patients
NCT00224003	PHASE4	COMPLETED	Study of the Safety and Efficacy of Ferrlecit® Maintenance Dosing in Pediatric Hemodialysis Patients
NCT00224068	PHASE4	COMPLETED	Effect of Iron Therapy as an Adjunct to Epoetin Alfa in the Anemia of Cancer Chemotherapy
NCT00239642	PHASE4	COMPLETED	Safety and Efficacy of Iron Sucrose in Children
NCT00247507	PHASE4	UNKNOWN	The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients
NCT00248716	PHASE4	UNKNOWN	Treatment of Anemia in the 2nd Year of Life. Comparison of the Efficacy of Two Different Iron Preparations.
NCT00283465	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Treatment With Epoetin Alfa on Hemoglobin Levels, Red Blood Cell Transfusions, and Quality of Life in Patients With Cancer Receiving Platinum-containing Chemotherapy
NCT00312871	PHASE4	TERMINATED	Effects of Early Correction of Anemia in Patients With Chronic Renal Insufficiency
NCT00315484	PHASE4	COMPLETED	Hematologic Response of Epoetin Alfa (PROCRIT) Versus Darbepoetin Alfa (ARANESP) in Chemotherapy Induced Anemia
NCT00317902	PHASE4	COMPLETED	An Open-Label Study to Evaluate the Effect of Every Other Week PROCRIT� (Epoetin Alfa) Dosing (40,000-60,000 Units) On Maintaining Quality of Life and Target Hemoglobin Levels in Anemic HIV-Infected Patients (CHAMPS II)
NCT00335023	PHASE4	COMPLETED	Well Being of Obstetric Patients on Minimal Blood Transfusions
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00377481	PHASE4	COMPLETED	COMFORT Study: A Crossover Study of NeoRecormon (Epoetin Beta) and Darbepoetin Alfa in Patients With Renal Anemia.
NCT00396435	PHASE4	COMPLETED	Correction of Anaemia and Progression of Renal Failure on Transplanted Patients
NCT00401869	PHASE4	COMPLETED	The Effect of PROCRIT (Epoetin Alfa) on Postoperative Vigor and Handgrip Strength (VIGOR Study)
NCT00413101	PHASE4	COMPLETED	A Study of NeoRecormon (Epoetin Beta) in Patients With End Stage Renal Disease.
NCT00431496	PHASE4	COMPLETED	A Study of Cinacalcet to Improve Achievement of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Targets in Patients With End Stage Renal Disease (ESRD)
NCT00437723	PHASE4	COMPLETED	A Study of NeoRecormon in Patients With Chronic Kidney Disease.
NCT00440063	PHASE4	TERMINATED	A Study of NeoRecormon (Epoetin Beta) in Patients With Renal Anemia.
NCT00470158	PHASE4	COMPLETED	Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes
NCT00479102	PHASE4	UNKNOWN	Prevention of Iron Deficiency in 2nd Year of Life
NCT00495365	PHASE4	TERMINATED	A Dose Conversion Study of Epoetin Alfa in Subjects With the Anemia of Chronic Kidney Disease.