spondyloepimetaphyseal dysplasia, Shohat type

Summary

spondyloepimetaphyseal dysplasia, Shohat type (MONDO:0011252) is a disease caused by DDRGK1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DDRGK1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 33

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

33 HPO clinical features (Orphanet curated; top 33 by frequency):

HPO ID	Term	Frequency
HP:0000926	Platyspondyly	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002829	Arthralgia	Frequent (30-79%)
HP:0003015	Flared metaphysis	Frequent (30-79%)
HP:0003016	Metaphyseal widening	Frequent (30-79%)
HP:0003026	Short long bone	Frequent (30-79%)
HP:0003088	Premature osteoarthritis	Frequent (30-79%)
HP:0003468	Abnormal vertebral morphology	Frequent (30-79%)
HP:0003498	Disproportionate short stature	Frequent (30-79%)
HP:0003510	Severe short stature	Frequent (30-79%)
HP:0005257	Thoracic hypoplasia	Frequent (30-79%)
HP:0005930	Abnormality of epiphysis morphology	Frequent (30-79%)
HP:0006462	Generalized bone demineralization	Frequent (30-79%)
HP:0008463	Central vertebral hypoplasia	Frequent (30-79%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0001433	Hepatosplenomegaly	Occasional (5-29%)
HP:0001602	Laryngeal stenosis	Occasional (5-29%)
HP:0001609	Hoarse voice	Occasional (5-29%)
HP:0002663	Delayed epiphyseal ossification	Occasional (5-29%)
HP:0002777	Tracheal stenosis	Occasional (5-29%)
HP:0002781	Upper airway obstruction	Occasional (5-29%)
HP:0002953	Vertebral compression fracture	Occasional (5-29%)
HP:0002970	Genu varum	Occasional (5-29%)
HP:0002979	Bowing of the legs	Occasional (5-29%)
HP:0003025	Metaphyseal irregularity	Occasional (5-29%)
HP:0003099	Fibular overgrowth	Occasional (5-29%)
HP:0003270	Abdominal distention	Occasional (5-29%)
HP:0003307	Hyperlordosis	Occasional (5-29%)
HP:0008418	Squared-off platyspondyly	Occasional (5-29%)
HP:0008450	Narrow vertebral interpedicular distance	Occasional (5-29%)
HP:0009826	Limb undergrowth	Occasional (5-29%)
HP:0025426	Abnormal bronchus morphology	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepimetaphyseal dysplasia, Shohat type
Mondo ID	MONDO:0011252
MeSH	C566523
OMIM	602557
Orphanet	93352
ICD-11	1389783101
SNOMED CT	719201004
UMLS	C1865185
MedGen	400703
GARD	0004980
Is cancer (heuristic)	no

Also known as: SEMD Shohat type · SEMD, Shohat type · SEMDSH · spondyloepimetaphyseal dysplasia Shohat type · spondyloepimetaphyseal dysplasia, Shohat type

Data availability: 3 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › spondyloepimetaphyseal dysplasia › spondyloepimetaphyseal dysplasia, Shohat type

Related subtypes (22): spondyloepimetaphyseal dysplasia-hypotrichosis syndrome, spondyloepimetaphyseal dysplasia, Maroteaux type, spondyloepimetaphyseal dysplasia, Strudwick type, spondyloepimetaphyseal dysplasia, sponastrime type, spondyloepimetaphyseal dysplasia, Irapa type, spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome, spondyloepimetaphyseal dysplasia, Bieganski type, spondyloepimetaphyseal dysplasia-abnormal dentition syndrome, spondyloepimetaphyseal dysplasia, Missouri type, spondyloepimetaphyseal dysplasia, matrilin-3 type, spondyloepimetaphyseal dysplasia, Genevieve type, spondyloepimetaphyseal dysplasia, aggrecan type, spondyloepimetaphyseal dysplasia, Handigodu type, spondyloepimetaphyseal dysplasia, Isidor type, spondyloepimetaphyseal dysplasia, PAPSS2 type, spondyloepimetaphyseal dysplasia with joint laxity, spondyloepimetaphyseal dysplasia, Krakow type, spondyloepimetaphyseal dysplasia, Isidor-Toutain type, spondyloepimetaphyseal dysplasia, di rocco type, COL2A1-related spondyloepiphyseal dysplasia, spondyloepimetaphyseal dysplasia, Guo-Campeau type, spondyloepimetaphyseal dysplasia, Li-Shao-Li type

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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2073894	NM_023935.3(DDRGK1):c.391C>T (p.Arg131Ter)	DDRGK1	Pathogenic	criteria provided, multiple submitters, no conflicts
487527	NM_023935.3(DDRGK1):c.408+1G>A	DDRGK1	Pathogenic	no assertion criteria provided
1255464	NM_023935.3(DDRGK1):c.511-10A>G	DDRGK1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
DDRGK1	Strong	Autosomal recessive	spondyloepimetaphyseal dysplasia, Shohat type	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DDRGK1	Orphanet:93352	Spondyloepimetaphyseal dysplasia, Shohat type

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
DDRGK1	HGNC:16110	ENSG00000198171	Q96HY6	DDRGK domain-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DDRGK1	DDRGK domain-containing protein 1	Component of the UFM1 ribosome E3 ligase (UREL) complex, a multiprotein complex that catalyzes ufmylation of endoplasmic reticulum-docked proteins.

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)
DDRGK1	Other/Unknown	no		DDRGK_dom-contain, WH-like_DNA-bd_sf, WH_DNA-bd_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
right adrenal gland	1
right adrenal gland cortex	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DDRGK1	271	ubiquitous	marker	tendon of biceps brachii, right adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDRGK1	4,153

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DDRGK1	Q96HY6	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
RHOA GTPase cycle	1	74.6×	0.013	DDRGK1

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
positive regulation of I-kappaB phosphorylation	1	16852.0×	0.001	DDRGK1
positive regulation of reticulophagy	1	5617.3×	0.001	DDRGK1
positive regulation of protein localization to endoplasmic reticulum	1	5617.3×	0.001	DDRGK1
positive regulation of plasma cell differentiation	1	4213.0×	0.001	DDRGK1
obsolete positive regulation of proteolysis involved in protein catabolic process	1	4213.0×	0.001	DDRGK1
protein K69-linked ufmylation	1	3370.4×	0.001	DDRGK1
negative regulation of IRE1-mediated unfolded protein response	1	2808.7×	0.001	DDRGK1
protein ufmylation	1	2407.4×	0.002	DDRGK1
protein localization to endoplasmic reticulum	1	2106.5×	0.002	DDRGK1
regulation of intracellular estrogen receptor signaling pathway	1	1872.4×	0.002	DDRGK1
negative regulation of PERK-mediated unfolded protein response	1	1404.3×	0.002	DDRGK1
positive regulation of cell cycle G1/S phase transition	1	1123.5×	0.002	DDRGK1
ribosome disassembly	1	991.3×	0.002	DDRGK1
positive regulation of proteasomal protein catabolic process	1	991.3×	0.002	DDRGK1
reticulophagy	1	702.2×	0.003	DDRGK1
rescue of stalled cytosolic ribosome	1	481.5×	0.004	DDRGK1
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	1	401.2×	0.004	DDRGK1
cartilage development	1	251.5×	0.006	DDRGK1
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	1	210.7×	0.007	DDRGK1
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.007	DDRGK1
response to endoplasmic reticulum stress	1	166.8×	0.008	DDRGK1
regulation of protein stability	1	125.8×	0.010	DDRGK1
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.017	DDRGK1
negative regulation of gene expression	1	69.1×	0.017	DDRGK1
positive regulation of cell migration	1	61.7×	0.019	DDRGK1
positive regulation of gene expression	1	38.7×	0.029	DDRGK1
negative regulation of apoptotic process	1	34.8×	0.031	DDRGK1
positive regulation of cell population proliferation	1	33.6×	0.031	DDRGK1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	DDRGK1

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
DDRGK1	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
DDRGK1	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	DDRGK1

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)
DDRGK1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.