Sprengel deformity

Summary

Sprengel deformity (MONDO:0008482) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 6

Clinical features

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000473	Torticollis	Very frequent (80-99%)
HP:0001435	Abnormality of the shoulder girdle musculature	Very frequent (80-99%)
HP:0003043	Abnormality of the shoulder	Very frequent (80-99%)
HP:0008952	Shoulder muscle hypoplasia	Very frequent (80-99%)
HP:0000175	Cleft palate	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Sprengel deformity
Mondo ID	MONDO:0008482
MeSH	C535802
OMIM	184400
Orphanet	3181
ICD-11	2144522441
SNOMED CT	79120002
UMLS	C0152438
MedGen	56291
GARD	0007693
MedDRA	10010455
NORD	1736
Is cancer (heuristic)	no

Also known as: congenital elevation of the scapula · congenital upward displacement of the scapula · high scapula · Sprengel deformity · Sprengel deformity (disease) · Sprengel’s deformity · Sprengel’s shoulder

Data availability: 1 ClinVar variant · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › respiratory or thoracic malformation › thoracic malformation › Sprengel deformity

Related subtypes (14): Acropectorovertebral dysplasia, congenitally short costocoracoid ligament, thoracolaryngopelvic dysplasia, fetal akinesia deformation sequence, lethal congenital contracture syndrome 1, orofaciodigital syndrome IV, thoracic dysplasia-hydrocephalus syndrome, thoracomelic dysplasia, Matthew-Wood syndrome, NEK9-related lethal skeletal dysplasia, short rib-polydactyly syndrome, shoulder and thorax deformity-congenital heart disease syndrome, sternal cleft, ossification anomalies-psychomotor developmental delay 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 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1684630	NC_000017.11:g.8117792_8126946del	TRG-GCC2-6	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

1 cohort genes, 0 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRG-GCC2-6	HGNC:12273			tRNA-Gly (anticodon GCC) 2-6	clinvar

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)
TRG-GCC2-6	Other/Unknown	no

Expression context

Cohort genes with no expression data: 1.

Breadth distribution (Bgee present_calls)

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

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRG-GCC2-6

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRG-GCC2-6	0

Structural data

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

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRG-GCC2-6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 0; 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	TRG-GCC2-6

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)
TRG-GCC2-6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.