Thrombocytopenia 12 with or without myopathy

Summary

Thrombocytopenia 12 with or without myopathy (MONDO:0958325) is a disease caused by GNE (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GNE (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 43

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombocytopenia 12 with or without myopathy
Mondo ID	MONDO:0958325
OMIM	620757
UMLS	C5935593
MedGen	1861803
GARD	0027007
Is cancer (heuristic)	no

Data availability: 43 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 12 with or without myopathy

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 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

43 retrieved; paginated sample, class counts are floors:

15 pathogenic/likely pathogenic, 10 likely pathogenic, 9 pathogenic, 7 conflicting classifications of pathogenicity, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
188796	NM_005476.7(GNE):c.612G>A (p.Trp204Ter)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188847	NM_005476.7(GNE):c.829C>T (p.Arg277Cys)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188882	NM_005476.7(GNE):c.1760T>C (p.Ile587Thr)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
189156	NM_005476.7(GNE):c.386G>A (p.Arg129Gln)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
197184	NM_005476.7(GNE):c.736C>T (p.Arg246Trp)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218297	NM_005476.7(GNE):c.647T>C (p.Val216Ala)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
283278	NM_005476.7(GNE):c.1132G>T (p.Asp378Tyr)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
285936	NM_005476.7(GNE):c.175C>T (p.Arg59Ter)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
290196	NM_005476.7(GNE):c.484C>T (p.Arg162Cys)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
290224	NM_005476.7(GNE):c.2005G>A (p.Gly669Arg)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
290423	NM_005476.7(GNE):c.1686del (p.Cys563fs)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370285	NM_005476.7(GNE):c.916C>T (p.Arg306Ter)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
370758	NM_005476.7(GNE):c.856C>T (p.Gln286Ter)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
41233	NM_005476.7(GNE):c.527A>T (p.Asp176Val)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
424619	NM_005476.7(GNE):c.1571C>T (p.Ala524Val)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
498582	NM_005476.7(GNE):c.470_471del (p.His157fs)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
552288	NM_005476.7(GNE):c.1258C>T (p.Arg420Ter)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
556674	NM_005476.7(GNE):c.1556A>G (p.Asn519Ser)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
597827	NM_005476.7(GNE):c.1792_1793dup (p.Glu599fs)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6025	NM_005476.7(GNE):c.2135T>C (p.Met712Thr)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
6030	NM_005476.7(GNE):c.737G>A (p.Arg246Gln)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6033	NM_005476.7(GNE):c.1714G>C (p.Val572Leu)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
6035	NM_005476.7(GNE):c.1892C>T (p.Ala631Val)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
861130	NM_005476.7(GNE):c.2023T>C (p.Tyr675His)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2440544	NM_005476.7(GNE):c.557A>G (p.Tyr186Cys)	GNE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3597305	NM_005476.7(GNE):c.1861del (p.Ala621fs)	GNE	Likely pathogenic	criteria provided, single submitter
3597306	NM_005476.7(GNE):c.1593_1597del (p.Lys532fs)	GNE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3597307	NM_005476.7(GNE):c.1595dup (p.Leu534fs)	GNE	Likely pathogenic	criteria provided, single submitter
3597309	NM_005476.7(GNE):c.1237G>T (p.Asp413Tyr)	GNE	Likely pathogenic	criteria provided, single submitter
3597311	NM_005476.7(GNE):c.555dup (p.Tyr186fs)	GNE	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 3 · 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
GNE	Definitive	Autosomal recessive	GNE myopathy	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNE	Orphanet:3166	Sialuria
GNE	Orphanet:438207	Severe autosomal recessive macrothrombocytopenia
GNE	Orphanet:602	GNE myopathy

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
GNE	HGNC:23657	ENSG00000159921	Q9Y223	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNE	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase	Bifunctional enzyme that possesses both UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities, and serves as the initiator of the biosynthetic pathway leading to the production of N-acetylneuraminic acid (NeuAc), a…

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)
GNE	Enzyme (other)	yes	2.7.1.60	ROK, UDP_GlcNAc_Epimerase_2_dom, UDP-GlcNAc_Epase

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
colonic mucosa	1
mucosa of sigmoid colon	1
nasal cavity epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNE	286	ubiquitous	marker	mucosa of sigmoid colon, colonic mucosa, nasal cavity epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNE	2,210

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNE	Q9Y223	5

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 GNE causes sialuria, NK and IBM2	1	11420.0×	2e-04	GNE
Sialic acid metabolism	1	326.3×	0.003	GNE

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
N-acetylglucosamine biosynthetic process	1	8426.0×	4e-04	GNE
N-acetylneuraminate biosynthetic process	1	5617.3×	4e-04	GNE
UDP-N-acetylglucosamine metabolic process	1	2808.7×	4e-04	GNE
CMP-N-acetylneuraminate biosynthetic process	1	2808.7×	4e-04	GNE

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNE	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GNE	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GNE	2.7.1.60, 3.2.1.183, 5.1.3.14	N-acylmannosamine kinase, UDP-N-acetylglucosamine 2-epimerase (hydrolysing), UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)

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

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	GNE
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GNE	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.