ANKRD26

Summary

ANKRD26 (ankyrin repeat domain 26, HGNC:29186) is a protein-coding gene on chromosome 10p12.1, encoding Ankyrin repeat domain-containing protein 26 (Q9UPS8). Acts as a regulator of adipogenesis.

This gene encodes a protein containing N-terminal ankyrin repeats which function in protein-protein interactions. Mutations in this gene are associated with autosomal dominant thrombocytopenia-2. Pseudogenes of this gene are found on chromosome 7, 10, 13 and 16. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 22852 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombocytopenia 2 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 2,972 total — 2 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 7
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_014915

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29186
Approved symbol	ANKRD26
Name	ankyrin repeat domain 26
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1074
Ensembl gene	ENSG00000107890
Ensembl biotype	protein_coding
OMIM	610855
Entrez	22852

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 11 protein_coding, 10 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000376087, ENST00000436985, ENST00000445828, ENST00000466890, ENST00000473304, ENST00000490015, ENST00000674670, ENST00000674697, ENST00000675116, ENST00000675187, ENST00000675349, ENST00000675439, ENST00000675846, ENST00000675936, ENST00000676232, ENST00000676280, ENST00000676299, ENST00000676361, ENST00000676420, ENST00000921906, ENST00000968139, ENST00000968140, ENST00000968141, ENST00000968142, ENST00000968143

RefSeq mRNA: 2 — MANE Select: NM_014915 NM_001256053, NM_014915

CCDS: CCDS41499, CCDS91225

Canonical transcript exons

ENST00000376087 — 34 exons

Exon	Start	End
ENSE00000816206	27012882	27013110
ENSE00000816207	27014494	27014711
ENSE00001098463	27006917	27006962
ENSE00001368685	27046353	27046523
ENSE00001469350	27004116	27005723
ENSE00001594033	27053320	27053390
ENSE00001635022	27060512	27060540
ENSE00001641466	27093349	27093522
ENSE00001651673	27092406	27092512
ENSE00001671596	27037186	27037323
ENSE00001674939	27029286	27029356
ENSE00001679857	27060345	27060417
ENSE00001680478	27022558	27022687
ENSE00001682972	27037871	27038054
ENSE00001692035	27061144	27061242
ENSE00001694221	27028852	27028945
ENSE00001696306	27034796	27035752
ENSE00001705364	27063988	27064081
ENSE00001715605	27093685	27093799
ENSE00001719325	27017502	27017792
ENSE00001748294	27082803	27082833
ENSE00001769422	27077338	27077540
ENSE00001781104	27086539	27086609
ENSE00001784814	27066487	27066548
ENSE00001792239	27033225	27033377
ENSE00001795617	27048801	27048979
ENSE00001806525	27024447	27024559
ENSE00001918019	27100085	27100494
ENSE00003582454	27043426	27043567
ENSE00003600070	27079089	27079161
ENSE00003639277	27039965	27040178
ENSE00003663416	27067157	27067286
ENSE00003665061	27077633	27077693
ENSE00003665824	27044157	27044190

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 91.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9621 / max 129.1825, expressed in 1665 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108743	5.7065	1596
108742	1.2555	777

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.44	gold quality
calcaneal tendon	UBERON:0003701	90.72	gold quality
sural nerve	UBERON:0015488	90.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.83	gold quality
adrenal tissue	UBERON:0018303	88.84	gold quality
right uterine tube	UBERON:0001302	87.14	gold quality
ventricular zone	UBERON:0003053	85.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.86	gold quality
adenohypophysis	UBERON:0002196	82.79	gold quality
cerebellar hemisphere	UBERON:0002245	82.58	gold quality
cerebellar cortex	UBERON:0002129	82.41	gold quality
gastrocnemius	UBERON:0001388	81.97	gold quality
muscle of leg	UBERON:0001383	81.95	gold quality
ganglionic eminence	UBERON:0004023	81.79	gold quality
tendon	UBERON:0000043	81.78	gold quality
colonic epithelium	UBERON:0000397	81.31	gold quality
right frontal lobe	UBERON:0002810	81.22	gold quality
endothelial cell	CL:0000115	81.02	gold quality
pituitary gland	UBERON:0000007	80.70	gold quality
right ovary	UBERON:0002118	80.28	gold quality
cortical plate	UBERON:0005343	80.26	gold quality
left ovary	UBERON:0002119	80.20	gold quality
endocervix	UBERON:0000458	80.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.72	gold quality
cerebellum	UBERON:0002037	79.53	gold quality
nucleus accumbens	UBERON:0001882	79.47	gold quality
stromal cell of endometrium	CL:0002255	79.25	gold quality
tibial nerve	UBERON:0001323	79.18	gold quality
heart left ventricle	UBERON:0002084	79.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-88	yes	23.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FLI1, RUNX1

miRNA regulators (miRDB)

109 targeting ANKRD26, 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-4713-3P	100.00	65.92	505
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 29)

• mutations in the 5’ UTR of ANKRD26 are implicated in thrombocytopenia 2. (PMID:21211618)
• The ANKRD26-related thrombocytopenia has to be taken into consideration in the differential diagnosis of isolated thrombocytopenias. (PMID:21467542)
• Ubiquitin/proteasome-rich particulate cytoplasmic structures are a characteristic feature of ANKRD26-related thrombocytopenia platelets and megakaryocytes. (PMID:23223974)
• the missense mutations may paly a role in the pathogenesis of Autosomal-dominant nonsyndromic thrombocytopenia-2 (PMID:23869080)
• Studies indicate that ANKRD26-RT is an insidious form of inherited thrombocytopenias that exposes patients to a low risk of bleeding but predisposes them to hematologic myeloid malignancies. (PMID:24030261)
• ANKRD26 regulatory region mutations induce MAPK hyperactivation in familial thrombocytopenia (PMID:24430186)
• The study supports the association of ANKRD26 mutations with thrombocytopenia 2 and a predisposition to myeloid malignancies. (PMID:24628296)
• thrombocytopenia with 5’UTR ANKRD26 gene mutation must be considered in case of a constitutional isolated thrombocytopenia, with a low bleeding tendency, associated with autosomal dominant transmission and normal platelet volume. (PMID:25902755)
• WASP, RUNX1, and ANKRD26 genes are important for normal TPO signaling and the network underlying thrombopoiesis. (PMID:26175287)
• Molecular analysis identified a mutation located in the promoter of the ankyrin repeat domain 26 (ANKRD26) gene, c.-127A>T in normocytic thrombocytopenia. (PMID:27108925)
• The findings of lifelong thrombocytopenia with mild/absent bleeding, family history of thrombocytopenia with normal platelet size and myeloid neoplasms should raise the suspicion of ANKRD26 mutated thrombocytopenia. (PMID:27123948)
• investigation of one patient with the c.3G>A showed that mutation was associated with strong ANKRD26 overexpression in vivo, which is the proposed mechanism for predisposition to AML in THC2 patients (PMID:28100250)
• in a cohort of patients with suspected familial thrombocytopenia, the c.-140C>G mutation seems to be the most frequent ANKRD26 mutation. (PMID:28277066)
• Two cases with mutant ANKRD26 highlight that patients with thrombocytopenia 2 are at risk of being misdiagnosed with myelodysplastic syndrome and receiving undue myelosuppressive treatments. Because dysmegakaryopoiesis is a feature also of other forms of inherited thrombocytopenia, a genetic disorder must always be considered when a patient presents with isolated thrombocytopenia and dysmegakaryopoiesis. (PMID:28976612)
• The overall purpose of this review is to point out that important progresses have been made in understanding the pathogenesis of ANKRD26-Related Thrombocytopenia and MYH9-Related Diseases and new therapeutic approaches have been proposed and tested. (PMID:29545013)
• A novel nucleotide substitution in the 5’ untranslated region of ANKRD26 gene is associated with inherited thrombocytopenia. (PMID:30747248)
• ANKRD26-RET is a novel rearrangement of the RET gene, associated with RET expression in thyroid tissue (PMID:31425920)
• Successful management of a pregnant woman with severe ANKRD26-related thrombocytopenia and anti-HPA-5b alloimmunization. (PMID:31607198)
• Study demonstrates that downregulation of ANKRD26 gene caused by promoter hypermethylation at specific CpGs represents a common abnormality in obese patients. These changes correlate to the pro-inflammatory profile and the cardio-metabolic risk factors of obese individuals, suggesting they mark the adverse health outcome occurring in some of these patients. (PMID:31801613)
• Relation between mutations in the 5’ UTR of ANKRD26 gene and inherited thrombocytopenia with predisposition to myeloid malignancies. An Egyptian study. (PMID:32659145)
• A novel RUNX1 mutation with ANKRD26 dysregulation is related to thrombocytopenia in a sporadic form of myelodysplastic syndrome. (PMID:32944898)
• Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript. (PMID:33857290)
• Clonal hematopoiesis in patients with ANKRD26 or ETV6 germline mutations. (PMID:35537115)
• Prevalence and natural history of variants in the ANKRD26 gene: a short review and update of reported cases. (PMID:35587581)
• ANKRD26-Related Thrombocytopenia and Predisposition to Myeloid Neoplasms. (PMID:35751752)
• Platelet functional abnormalities and clinical presentation in pediatric patients with germline RUNX1, ANKRD26, and ETV6 mutations. (PMID:35796010)
• Hereditary platelet disorders associated with germ line variants in RUNX1, ETV6, and ANKRD26. (PMID:36626254)
• Inherited thrombocytopenia associated with a variant in the FLI1 binding site in the 5’ UTR of ANKRD26. (PMID:38757516)
• Impact of thrombocytopenia-associated c.-118C>T and c.-140C>G ANKRD26 5’UTR variants in three-generational pedigree. (PMID:39212265)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-272n13.3	ENSDARG00000099768
drosophila_melanogaster	CG8679	FBGN0032934
drosophila_melanogaster	CG42391	FBGN0259737
caenorhabditis_elegans	lem-3	WBGENE00002276
caenorhabditis_elegans		WBGENE00019483
caenorhabditis_elegans		WBGENE00206377

Paralogs (7): ANKRD30A (ENSG00000148513), ANKRD30BL (ENSG00000163046), ANKRD18A (ENSG00000180071), ANKRD30B (ENSG00000180777), ANKRD62 (ENSG00000181626), ANKRD18B (ENSG00000230453), ANKRD20A1 (ENSG00000260691)

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 26 — Q9UPS8 (reviewed: Q9UPS8)

All UniProt accessions (15): Q9UPS8, A0A6Q8PF30, A0A6Q8PFU2, A0A6Q8PG48, A0A6Q8PGH2, A0A6Q8PGU7, A0A6Q8PGV3, A0A6Q8PGX8, A0A6Q8PH02, A0A6Q8PHD6, A0A6Q8PHI6, A0A6Q8PHK2, A0A6Q8PHK8, E7ESJ3, H0Y4T9

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a regulator of adipogenesis. Involved in the regulation of the feeding behavior.

Subunit / interactions. Interacts with TRIO. Interacts with GPS2. Interacts with CCDC85B. Interacts with HMMR.

Disease relevance. Thrombocytopenia 2 (THC2) [MIM:188000] A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UPS8-1	1	yes
Q9UPS8-2	2

RefSeq proteins (2): NP_001242982, NP_055730* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR021885	DUF3496	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR039497	CC144C-like_CC_dom	Domain
IPR050657

Pfam: PF00023, PF12001, PF12796, PF14915

UniProt features (38 total): modified residue 7, sequence variant 6, repeat 5, region of interest 5, coiled-coil region 5, compositionally biased region 5, splice variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPS8-F1	62.91	0.08

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 (7): 11, 15, 241, 261, 489, 530, 631

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 146 (showing top): GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, GOBP_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, ZHANG_BREAST_CANCER_PROGENITORS_UP, MODULE_48, MODULE_95, chr10p12, MODULE_104, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, MODULE_41, LEE_BMP2_TARGETS_DN

GO Biological Process (1): negative regulation of fat cell differentiation (GO:0045599)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): centrosome (GO:0005813)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
binding	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

1510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD26	DDX41	Q9UJV9	696
ANKRD26	ETV6	P41212	693
ANKRD26	SRP72	O76094	668
ANKRD26	FBF1	Q8TES7	649
ANKRD26	RUNX1	Q01196	626
ANKRD26	GAS7	O60861	591
ANKRD26	GATA2	P23769	589
ANKRD26	CEP164	Q9UPV0	579
ANKRD26	MYH9	P35579	555
ANKRD26	LACTB	P83096	549
ANKRD26	TUB	P50607	549
ANKRD26	NBEAL2	Q6ZNJ1	507
ANKRD26	SCLT1	Q96NL6	502
ANKRD26	TTBK2	Q6IQ55	496
ANKRD26	C3AR1	Q16581	496

IntAct

55 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
RAB9A	GDI1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
FAM9B	GEMIN2	psi-mi:“MI:0914”(association)	0.530
PRKAR1A	AKAP3	psi-mi:“MI:0914”(association)	0.530
NDEL1	OFD1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
ANKRD26	CANX	psi-mi:“MI:0915”(physical association)	0.400
ANKRD26	CORO1C	psi-mi:“MI:0915”(physical association)	0.400
ANKRD26	RBM26	psi-mi:“MI:0915”(physical association)	0.400
ANKRD26	AHNAK	psi-mi:“MI:0915”(physical association)	0.400
ANKRD26	H1-5	psi-mi:“MI:0915”(physical association)	0.400
JUN		psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
CBX2	TRANK1	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
ARID1A	SS18L1	psi-mi:“MI:0914”(association)	0.350
GOLT1B	NBAS	psi-mi:“MI:0914”(association)	0.350
MIF	BLTP3B	psi-mi:“MI:0914”(association)	0.350
SLC2A8	LAMP1	psi-mi:“MI:0914”(association)	0.350
VPS35	KIF2A	psi-mi:“MI:0914”(association)	0.350
WASF2	HSBP1	psi-mi:“MI:0914”(association)	0.350
WDR3	PRMT5	psi-mi:“MI:0914”(association)	0.350
NDEL1	SHTN1	psi-mi:“MI:0914”(association)	0.350
LURAP1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
SYCE1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
CCDC40	TRAF5	psi-mi:“MI:0914”(association)	0.350
NCKAP5	KIF3C	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): ANKRD26 (Affinity Capture-MS), ANKRD26 (Proximity Label-MS), ANKRD26 (Proximity Label-MS), ANKRD26 (Proximity Label-MS), ANKRD26 (Proximity Label-MS), ANKRD26 (Proximity Label-MS), ANKRD26 (Affinity Capture-MS), ANKRD26 (Affinity Capture-MS), ANKRD26 (Affinity Capture-MS), ANKRD26 (Affinity Capture-MS), ANKRD26 (Proximity Label-MS), ANKRD26 (Affinity Capture-RNA), ANKRD26 (Proximity Label-MS), ANKRD26 (Proximity Label-MS), ANKRD26 (Proximity Label-MS)

ESM2 similar proteins: A0A0A6YYL3, A0JP26, A2A2Z9, A2RUR9, A6NC57, A6NI47, A6QR20, A8MYB1, A9JSR5, A9ZSY0, B2RU33, B7ZQJ9, F1M5M3, H3BUK9, O15050, P51954, P98182, Q19UN5, Q4UJ75, Q501X2, Q5CZ79, Q5DW34, Q5SQ80, Q5TYW2, Q5VUR7, Q66HB6, Q6NSI1, Q6S545, Q6S5H5, Q6S8J7, Q71S21, Q7TPV2, Q7TSC3, Q7ZT11, Q80X59, Q811D2, Q86Y13, Q86YR6, Q8IVF6, Q8IYA2

Diamond homologs: A0A0A6YYL3, A0JP26, A0PJZ0, A2A2Z9, A2RUR9, A5A3E0, A6NC57, A6NI47, A7E2S9, B2RU33, H3BUK9, P0CG38, P0CG39, Q3MJ40, Q4R3S3, Q4UJ75, Q5CZ79, Q5JPF3, Q5SQ80, Q5TYW2, Q5VUR7, Q6NSI1, Q6S545, Q6S5H5, Q6S8J3, Q6S8J7, Q811D2, Q86YR6, Q8IYA2, Q92527, Q9BXX2, Q9BXX3, Q9D504, Q9H560, Q9UPS8, Q8IVF6, A6QL64, Q8N2N9, Q8NF67, Q96IX9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ANKRD26	“up-regulates activity”	PIDD1	relocalization
RUNX1	“down-regulates quantity by repression”	ANKRD26	“transcriptional regulation”
FLI1	“down-regulates quantity by repression”	ANKRD26	“transcriptional regulation”
ANKRD26	down-regulates	Adipogenesis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
Activation of BAD and translocation to mitochondria	7	87.4×	1e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	77.1×	2e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	77.1×	2e-10
Activation of BH3-only proteins	7	57.0×	2e-09
RHO GTPases activate PKNs	7	36.4×	5e-08
Intrinsic Pathway for Apoptosis	7	33.6×	8e-08
FOXO-mediated transcription	5	27.5×	1e-05
Signaling by FGFR1 in disease	5	24.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	24.1×	7e-04
intracellular protein localization	10	13.8×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

2972 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	1890
Likely benign	744
Benign	133

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1684447	NM_014915.3(ANKRD26):c.-126T>G	Pathogenic
1703797	NM_014915.3(ANKRD26):c.2356C>T (p.Arg786Ter)	Pathogenic
1175767	NM_014915.3(ANKRD26):c.-127A>C	Likely pathogenic
2580852	NM_014915.3(ANKRD26):c.-107C>T	Likely pathogenic
626920	NM_014915.3(ANKRD26):c.-128G>C	Likely pathogenic
828130	NM_014915.3(ANKRD26):c.2476G>T (p.Glu826Ter)	Likely pathogenic

SpliceAI

5412 predictions. Top by Δscore:

Variant	Effect	Δscore
10:27005721:CAG:C	acceptor_gain	1.0000
10:27006913:ATAC:A	donor_loss	1.0000
10:27006914:TA:T	donor_loss	1.0000
10:27006915:A:AG	donor_loss	1.0000
10:27006916:CCTT:C	donor_gain	1.0000
10:27017496:GCTAA:G	donor_loss	1.0000
10:27017497:CTAAC:C	donor_loss	1.0000
10:27017498:TAAC:T	donor_loss	1.0000
10:27017499:AACC:A	donor_loss	1.0000
10:27017500:A:AT	donor_loss	1.0000
10:27017501:C:G	donor_loss	1.0000
10:27017521:T:TA	donor_gain	1.0000
10:27017542:T:A	donor_gain	1.0000
10:27017587:TG:T	donor_gain	1.0000
10:27017604:ATT:A	donor_gain	1.0000
10:27017606:T:TA	donor_gain	1.0000
10:27017638:T:TA	donor_gain	1.0000
10:27024441:TCTTA:T	donor_loss	1.0000
10:27024442:CTTAC:C	donor_loss	1.0000
10:27024443:TTA:T	donor_loss	1.0000
10:27024444:TAC:T	donor_loss	1.0000
10:27024445:A:AC	donor_gain	1.0000
10:27024445:AC:A	donor_gain	1.0000
10:27024445:ACCCA:A	donor_loss	1.0000
10:27024446:C:CC	donor_gain	1.0000
10:27024446:CC:C	donor_gain	1.0000
10:27024556:CAGA:C	acceptor_gain	1.0000
10:27024558:GA:G	acceptor_gain	1.0000
10:27024560:C:CC	acceptor_gain	1.0000
10:27024561:T:C	acceptor_gain	1.0000

AlphaMissense

11469 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:27100166:G:T	A54D	0.997
10:27033314:C:G	A1240P	0.996
10:27033337:A:G	L1232P	0.996
10:27093522:C:G	A120P	0.996
10:27093799:C:A	R81S	0.996
10:27093799:C:G	R81S	0.996
10:27100098:C:G	D77H	0.996
10:27033349:A:G	L1228P	0.995
10:27093778:A:C	C88W	0.995
10:27093780:A:G	C88R	0.995
10:27093746:A:G	L99P	0.994
10:27100157:C:A	G57V	0.994
10:27100170:C:G	A53P	0.994
10:27033307:A:G	L1242P	0.993
10:27033347:C:G	A1229P	0.993
10:27033361:A:G	L1224P	0.993
10:27093386:A:G	L165P	0.993
10:27093713:T:A	D110V	0.993
10:27093714:C:G	D110H	0.993
10:27093779:C:T	C88Y	0.993
10:27100085:C:G	R81T	0.993
10:27100097:T:A	D77V	0.993
10:27100167:C:G	A54P	0.993
10:27093434:G:T	A149D	0.992
10:27093791:A:G	L84P	0.992
10:27033333:T:A	K1233N	0.991
10:27033333:T:G	K1233N	0.991
10:27093485:A:G	L132P	0.991
10:27093782:G:T	A87D	0.991
10:27093794:G:T	A83D	0.991

dbSNP variants (sampled 300 via entrez): RS1000017113 (10:26991930 C>A,T), RS1000116123 (10:26990762 A>G), RS1000167135 (10:26990474 T>C), RS1000172375 (10:26948754 G>A,T), RS1000189077 (10:27033649 C>T), RS1000208004 (10:27043119 T>A), RS1000265780 (10:26948364 T>A,G), RS1000269061 (10:26984142 A>G), RS1000274041 (10:27086757 C>A,T), RS1000285270 (10:27002878 A>C,G), RS1000319018 (10:27057419 G>A), RS1000327579 (10:26954761 G>A,C), RS1000354862 (10:27074390 G>A,C), RS1000359743 (10:27046760 A>C), RS1000450028 (10:26991953 T>A,C)

Disease associations

OMIM: gene MIM:610855 | disease phenotypes: MIM:188000, MIM:231200

GenCC curated gene-disease

Disease	Classification	Inheritance
thrombocytopenia 2	Definitive	Autosomal dominant
acute myeloid leukemia	Strong	Autosomal dominant
autosomal thrombocytopenia with normal platelets	Supportive	Autosomal dominant
hereditary thrombocytopenia and hematologic cancer predisposition syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
thrombocytopenia 2	Definitive	AD

Mondo (8): thrombocytopenia 2 (MONDO:0008555), hereditary neoplastic syndrome (MONDO:0015356), breast ductal adenocarcinoma (MONDO:0005590), thrombocytopenia (MONDO:0002049), inherited bleeding disorder, platelet-type (MONDO:0000009), acute myeloid leukemia (MONDO:0018874), (MONDO:0015679), hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Orphanet (3): Hereditary thrombocytopenia with normal platelets (Orphanet:268322), Inherited cancer-predisposing syndrome (Orphanet:140162), Rare hemorrhagic disorder due to a platelet anomaly (Orphanet:248326)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000978	Bruising susceptibility
HP:0001873	Thrombocytopenia
HP:0001974	Increased total leukocyte count
HP:0011876	Abnormal platelet volume
HP:0012524	Abnormal platelet shape
HP:0034010	Increased megakaryocyte colony forming unit count

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008129_20	Body mass index	2.000000e-12
GCST008338_6	Blood cell traits (multivariate analysis)	2.000000e-08
GCST008514_16	Peginterferon alfa-2a treatment response in chronic hepatitis B infection	9.000000e-06
GCST90002402_112	Platelet count	3.000000e-14

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0010103	response to peginterferon alfa-2a

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C563324	Platelet Disorder, Familial, with Associated Myeloid Malignancy (supp.)
C536519	Thrombocytopenia chromosome breakage (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	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
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1DL	SHAMUi001-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	PHASE4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	PHASE4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	PHASE4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	PHASE4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	PHASE4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	PHASE4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	PHASE4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients