arthrogryposis multiplex congenita 7, X-linked

Summary

arthrogryposis multiplex congenita 7, X-linked (MONDO:0975826) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	arthrogryposis multiplex congenita 7, X-linked
Mondo ID	MONDO:0975826
OMIM	301127
UMLS	C5974872
MedGen	1874402
GARD	0027323
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › arthrogryposis multiplex congenita › arthrogryposis multiplex congenita 7, X-linked

Related subtypes (23): prenatal-onset spinal muscular atrophy with congenital bone fractures, adducted thumbs-arthrogryposis syndrome, Christian type, arthrogryposis multiplex congenita 2, neurogenic type, fetal akinesia deformation sequence, arthrogryposis multiplex congenita-whistling face syndrome, arthrogryposis-hyperkeratosis syndrome, lethal form, multiple pterygium-malignant hyperthermia syndrome, Marden-Walker syndrome, arthrogryposis due to muscular dystrophy, infantile-onset X-linked spinal muscular atrophy, van den Ende-Gupta syndrome, lethal arthrogryposis-anterior horn cell disease syndrome, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, arthrogryposis-like syndrome, autosomal recessive myogenic arthrogryposis multiplex congenita, Wieacker-Wolff syndrome (spectrum), arthrogryposis multiplex congenita 6, arthrogryposis multiplex congenita 3, myogenic type, arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum, microphthalmia microtia fetal akinesia, MYBPC1-related autosomal recessive non-lethal arthrogryposis multiplex congenita syndrome, arthrogryposis multiplex congenita 5, hypomyelination neuropathy-arthrogryposis syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4819941	NM_001081550.2(THOC2):c.2899+8G>T	THOC2	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
THOC2	Orphanet:457240	X-linked intellectual disability-short stature-overweight syndrome

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
THOC2	HGNC:19073	ENSG00000125676	Q8NI27	THO complex subunit 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
THOC2	THO complex subunit 2	Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
THOC2	Other/Unknown	no		THO_THOC2_C, THO_THOC2_N, THOC2_N

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
calcaneal tendon	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
THOC2	297	ubiquitous	marker	secondary oocyte, calcaneal tendon, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
THOC2	3,251

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
THOC2	Q8NI27	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Transport of Mature Transcript to Cytoplasm	1	380.7×	0.013	THOC2
RNA Polymerase II Transcription Termination	1	219.6×	0.013	THOC2
mRNA 3’-end processing	1	196.9×	0.013	THOC2
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	152.3×	0.013	THOC2
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.019	THOC2
Metabolism of RNA	1	41.7×	0.032	THOC2
RNA Polymerase II Transcription	1	22.5×	0.051	THOC2
Gene expression (Transcription)	1	17.8×	0.056	THOC2

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
regulation of mRNA export from nucleus	1	2106.5×	0.003	THOC2
stem cell division	1	1872.4×	0.003	THOC2
generation of neurons	1	1532.0×	0.003	THOC2
blastocyst development	1	674.1×	0.004	THOC2
poly(A)+ mRNA export from nucleus	1	674.1×	0.004	THOC2
mRNA export from nucleus	1	295.6×	0.006	THOC2
neuron development	1	255.3×	0.006	THOC2
negative regulation of neuron projection development	1	237.3×	0.006	THOC2
cell morphogenesis	1	157.5×	0.008	THOC2
RNA splicing	1	88.2×	0.013	THOC2
regulation of gene expression	1	83.4×	0.013	THOC2
mRNA processing	1	78.8×	0.013	THOC2

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
THOC2	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
THOC2	1	Binding:1

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	THOC2

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)
THOC2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.