Thrombocytopenia 13, syndromic

Summary

Thrombocytopenia 13, syndromic (MONDO:0958333) is a disease caused by GALE (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GALE (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombocytopenia 13, syndromic
Mondo ID	MONDO:0958333
OMIM	620776
UMLS	C5935599
MedGen	1856296
GARD	0027013
Is cancer (heuristic)	no

Data availability: 27 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood platelet disease › thrombocytopenia › inherited thrombocytopenia › thrombocytopenia 13, syndromic

Related subtypes (20): thrombocytopenia 2, 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

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

27 retrieved; paginated sample, class counts are floors:

10 pathogenic/likely pathogenic, 10 likely pathogenic, 4 conflicting classifications of pathogenicity, 2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029823	NM_001008216.2(GALE):c.449C>T (p.Thr150Met)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21171	NM_001008216.2(GALE):c.505C>T (p.Arg169Trp)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21172	NM_001008216.2(GALE):c.715C>T (p.Arg239Trp)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
281922	NM_001008216.2(GALE):c.796-1G>T	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2837803	NM_001008216.2(GALE):c.517del (p.Gln173fs)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2876476	NM_001008216.2(GALE):c.151_154del (p.Arg51fs)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3012577	NM_001008216.2(GALE):c.2T>C (p.Met1Thr)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3067122	NM_001008216.2(GALE):c.230_231insTGTT (p.Lys78fs)	GALE	Pathogenic	no assertion criteria provided
3582025	NM_001008216.2(GALE):c.315_316del (p.Tyr105_Arg106delinsTer)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3582055	NM_001008216.2(GALE):c.142_143del (p.Ser48fs)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3682	NM_001008216.2(GALE):c.280G>A (p.Val94Met)	GALE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066286	NM_001008216.2(GALE):c.351+1G>T	GALE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
21173	NM_001008216.2(GALE):c.905G>A (p.Gly302Asp)	GALE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2868204	NM_001008216.2(GALE):c.643-2A>C	GALE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2876477	NM_001008216.2(GALE):c.122-11_122-1del	GALE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3581951	NM_001008216.2(GALE):c.989_990dup (p.Glu331fs)	GALE	Likely pathogenic	criteria provided, single submitter
3581954	NM_001008216.2(GALE):c.924C>G (p.Tyr308Ter)	GALE	Likely pathogenic	criteria provided, single submitter
3581960	NM_001008216.2(GALE):c.882C>G (p.Tyr294Ter)	GALE	Likely pathogenic	criteria provided, single submitter
3581962	NM_001008216.2(GALE):c.882C>A (p.Tyr294Ter)	GALE	Likely pathogenic	criteria provided, single submitter
3581964	NM_001008216.2(GALE):c.726_729del (p.Ile242fs)	GALE	Likely pathogenic	criteria provided, single submitter
3675	NM_001008216.2(GALE):c.548T>C (p.Leu183Pro)	GALE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1424506	NM_001008216.2(GALE):c.668T>C (p.Leu223Pro)	GALE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3676	NM_001008216.2(GALE):c.101A>G (p.Asn34Ser)	GALE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
592180	NM_001008216.2(GALE):c.658C>T (p.Arg220Trp)	GALE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
984932	NM_001008216.2(GALE):c.151C>T (p.Arg51Trp)	GALE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
596687	NM_001008216.2(GALE):c.382G>A (p.Val128Met)	GALE	Uncertain significance	criteria provided, multiple submitters, no conflicts
596688	NM_001008216.2(GALE):c.710G>A (p.Gly237Asp)	GALE	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
GALE	Strong	Autosomal recessive	thrombocytopenia 13, syndromic	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GALE	Orphanet:308473	Erythrocyte galactose epimerase deficiency
GALE	Orphanet:308487	Generalized galactose epimerase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GALE	HGNC:4116	ENSG00000117308	Q14376	UDP-glucose 4-epimerase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GALE	UDP-glucose 4-epimerase	Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GALE	Enzyme (other)	yes	5.1.3.2	UDP_G4E, NAD(P)-bd_dom, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	1
mucosa of transverse colon	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GALE	248	ubiquitous	marker	lower esophagus mucosa, mucosa of transverse colon, rectum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GALE	2,133

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GALE	Q14376	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective GALE causes EDG	1	11420.0×	2e-04	GALE
Galactose catabolism	1	1631.4×	6e-04	GALE

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	1	3370.4×	4e-04	GALE
galactose catabolic process	1	2808.7×	4e-04	GALE

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GALE	HALOPROGIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GALE	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
HALOPROGIN	4	GALE
DIETHYLSTILBESTROL	4	GALE
ETHACRYNIC ACID	4	GALE
EBSELEN	3	GALE

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GALE	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GALE	5.1.3.2, 5.1.3.7	UDP-glucose 4-epimerase, UDP-N-acetylglucosamine 4-epimerase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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.

Compound	Max phase	Cohort target (bioactivity)
HALOPROGIN	4	GALE
DIETHYLSTILBESTROL	4	GALE
ETHACRYNIC ACID	4	GALE
EBSELEN	3	GALE

Druggability pyramid

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

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

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.