Thrombocytopenia 2

Summary

Thrombocytopenia 2 (MONDO:0008555) is a disease caused by ANKRD26 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: ANKRD26 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 266

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombocytopenia 2
Mondo ID	MONDO:0008555
MeSH	C536519
OMIM	188000
NCIT	C129035
UMLS	C1861185
MedGen	349976
GARD	0005191
Is cancer (heuristic)	no

Also known as: THC2 · thrombocytopenia 2 · thrombocytopenia autosomal dominant 2 · thrombocytopenia type 2

Data availability: 266 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood platelet disease › thrombocytopenia › inherited thrombocytopenia › thrombocytopenia 2

Related subtypes (20): thrombocytopenia, cyclic, thrombocytopenia 3, congenital thrombotic thrombocytopenic purpura, thrombocytopenia, X-linked, with or without dyserythropoietic anemia, thrombocytopenia 1, thrombocytopenia 4, thrombocytopenia 5, autosomal dominant macrothrombocytopenia, isolated delta-storage pool disease, syndromic constitutional thrombocytopenia, alpha granule disease, thrombocytopenia 7, macrothrombocytopenia, isolated, congenital autosomal recessive small-platelet thrombocytopenia, congenital amegakaryocytic thrombocytopenia, thrombocytopenia 9, thrombocytopenia 10, thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, thrombocytopenia 12 with or without myopathy, thrombocytopenia 13, syndromic

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

266 retrieved; paginated sample, class counts are floors:

115 uncertain significance, 62 conflicting classifications of pathogenicity, 44 benign, 30 benign/likely benign, 6 pathogenic/likely pathogenic, 4 likely benign, 3 likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1684447	NM_014915.3(ANKRD26):c.-126T>G	ANKRD26	Pathogenic	no assertion criteria provided
1703797	NM_014915.3(ANKRD26):c.2356C>T (p.Arg786Ter)	ANKRD26	Pathogenic	criteria provided, single submitter
30853	NM_014915.3(ANKRD26):c.-134G>A	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
626941	NM_014915.3(ANKRD26):c.-126T>C	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
626943	NM_014915.3(ANKRD26):c.-127A>T	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627410	NM_014915.3(ANKRD26):c.-118C>T	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812727	NM_014915.3(ANKRD26):c.-128G>A	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812728	NM_014915.3(ANKRD26):c.-128G>T	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2580852	NM_014915.3(ANKRD26):c.-107C>T	ANKRD26	Likely pathogenic	criteria provided, single submitter
626920	NM_014915.3(ANKRD26):c.-128G>C	ANKRD26	Likely pathogenic	criteria provided, single submitter
828130	NM_014915.3(ANKRD26):c.2476G>T (p.Glu826Ter)	ANKRD26	Likely pathogenic	criteria provided, single submitter
1033718	NM_014915.3(ANKRD26):c.371A>T (p.Gln124Leu)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1185034	NM_014915.3(ANKRD26):c.2642A>G (p.Asn881Ser)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1301713	NM_014915.3(ANKRD26):c.2260A>T (p.Lys754Ter)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1320286	NM_014915.3(ANKRD26):c.1035_1036insT (p.Lys346Ter)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1337300	NM_014915.3(ANKRD26):c.599A>G (p.Lys200Arg)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1337895	NM_014915.3(ANKRD26):c.3710T>C (p.Met1237Thr)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1337931	NM_014915.3(ANKRD26):c.3761A>G (p.Asp1254Gly)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1691513	NM_014915.3(ANKRD26):c.425C>T (p.Ala142Val)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1703808	NM_014915.3(ANKRD26):c.-125T>G	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210182	NM_014915.3(ANKRD26):c.1571A>G (p.His524Arg)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2170112	NM_014915.3(ANKRD26):c.1667A>G (p.Asn556Ser)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2442443	NM_014915.3(ANKRD26):c.4900T>C (p.Ser1634Pro)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2444878	NM_014915.3(ANKRD26):c.2053G>A (p.Asp685Asn)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2503508	NM_014915.3(ANKRD26):c.5107G>A (p.Val1703Ile)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2577907	NM_014915.3(ANKRD26):c.1495A>G (p.Thr499Ala)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2579772	NM_014915.3(ANKRD26):c.4564A>G (p.Met1522Val)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
260456	NM_014915.3(ANKRD26):c.1269+7_1269+12delinsA	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
299726	NM_014915.3(ANKRD26):c.4879C>T (p.Pro1627Ser)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
299733	NM_014915.3(ANKRD26):c.3704A>T (p.Gln1235Leu)	ANKRD26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ANKRD26	Definitive	Autosomal dominant	thrombocytopenia 2	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANKRD26	Orphanet:168629	Autosomal thrombocytopenia with normal platelets
MASTL	Orphanet:168629	Autosomal thrombocytopenia with normal platelets

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ANKRD26	HGNC:29186	ENSG00000107890	Q9UPS8	Ankyrin repeat domain-containing protein 26	gencc,clinvar
MASTL	HGNC:19042	ENSG00000120539	Q96GX5	Serine/threonine-protein kinase greatwall	clinvar
ACBD5	HGNC:23338	ENSG00000107897	Q5T8D3	Acyl-CoA-binding domain-containing protein 5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANKRD26	Ankyrin repeat domain-containing protein 26	Acts as a regulator of adipogenesis.
MASTL	Serine/threonine-protein kinase greatwall	Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance.
ACBD5	Acyl-CoA-binding domain-containing protein 5	Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	9.2×	0.246
Scaffold/PPI	1	5.8×	0.246
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANKRD26	Scaffold/PPI	no		Ankyrin_rpt, DUF3496, Ankyrin_rpt-contain_sf
MASTL	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
ACBD5	Other/Unknown	no		Acyl-CoA-binding_protein, FERM/acyl-CoA-bd_prot_sf, ACBD5

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1
oocyte	1
secondary oocyte	1
ventricular zone	1
jejunal mucosa	1
lateral globus pallidus	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANKRD26	206	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, sural nerve
MASTL	217	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
ACBD5	253	ubiquitous	marker	jejunal mucosa, left ventricle myocardium, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACBD5	1,814
ANKRD26	1,721
MASTL	1,464

Intra-cohort edges

A	B	Sources
ACBD5	ANKRD26	string_interaction
ACBD5	MASTL	biogrid_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MASTL	Q96GX5	2
ACBD5	Q5T8D3	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANKRD26	Q9UPS8	62.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MASTL Facilitates Mitotic Progression	1	380.7×	0.010	MASTL
RHO GTPase cycle	2	40.1×	0.010	ANKRD26, ACBD5
Signaling by Rho GTPases	2	22.8×	0.010	ANKRD26, ACBD5
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	2	22.3×	0.010	ANKRD26, ACBD5
Peroxisomal lipid metabolism	1	223.9×	0.014	ACBD5
Class I peroxisomal membrane protein import	1	173.0×	0.015	ACBD5
RND1 GTPase cycle	1	88.5×	0.020	ANKRD26
RND3 GTPase cycle	1	86.5×	0.020	ANKRD26
RND2 GTPase cycle	1	86.5×	0.020	ANKRD26
Protein localization	1	63.4×	0.025	ACBD5
RHOC GTPase cycle	1	48.8×	0.030	ACBD5
Fatty acid metabolism	1	43.8×	0.030	ACBD5
Signal Transduction	2	6.8×	0.033	ANKRD26, ACBD5
RHOA GTPase cycle	1	24.9×	0.045	ACBD5
Metabolism of lipids	1	10.5×	0.098	ACBD5
Metabolism	1	3.9×	0.237	ACBD5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
female meiosis II	1	2808.7×	0.004	MASTL
fatty acid catabolic process	1	432.1×	0.010	ACBD5
pexophagy	1	351.1×	0.010	ACBD5
G2/M transition of mitotic cell cycle	1	104.0×	0.021	MASTL
negative regulation of fat cell differentiation	1	104.0×	0.021	ANKRD26
regulation of mitotic cell cycle	1	80.2×	0.023	MASTL
fatty acid metabolic process	1	64.6×	0.024	ACBD5
regulation of cell cycle	1	24.9×	0.055	MASTL
DNA damage response	1	17.8×	0.067	MASTL
cell division	1	15.4×	0.070	MASTL
intracellular signal transduction	1	12.7×	0.077	MASTL

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ANKRD26	0	0
MASTL	0	0
ACBD5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MASTL	44	Binding:44

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MASTL
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ANKRD26, ACBD5

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ANKRD26	0	—
MASTL	44	—
ACBD5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.