Schneckenbecken dysplasia

Summary

Schneckenbecken dysplasia (MONDO:0010013) is a disease caused by SLC35D1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC35D1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 143
• Phenotypes (HPO): 26

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

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

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0000256	Macrocephaly	Very frequent (80-99%)
HP:0000272	Malar flattening	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000773	Short ribs	Very frequent (80-99%)
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0000882	Hypoplastic scapulae	Very frequent (80-99%)
HP:0000895	Lateral clavicle hook	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Very frequent (80-99%)
HP:0000946	Hypoplastic ilia	Very frequent (80-99%)
HP:0001004	Lymphedema	Very frequent (80-99%)
HP:0001561	Polyhydramnios	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0003038	Fibular hypoplasia	Very frequent (80-99%)
HP:0003312	Abnormal form of the vertebral bodies	Very frequent (80-99%)
HP:0008479	Hypoplastic vertebral bodies	Very frequent (80-99%)
HP:0008873	Disproportionate short-limb short stature	Very frequent (80-99%)
HP:0012107	Increased fibular diameter	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000268	Dolichocephaly	Frequent (30-79%)
HP:0001231	Abnormal fingernail morphology	Frequent (30-79%)
HP:0001800	Hypoplastic toenails	Frequent (30-79%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000947	Dumbbell-shaped long bone	Occasional (5-29%)
HP:0005019	Diaphyseal thickening	Occasional (5-29%)
HP:0005616	Accelerated skeletal maturation	Occasional (5-29%)
HP:0008108	Advanced tarsal ossification	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	schneckenbecken dysplasia
Mondo ID	MONDO:0010013
MeSH	C536637
OMIM	269250
Orphanet	3144
DOID	DOID:0050775
ICD-11	584032448
SNOMED CT	254049009
UMLS	C0432194
MedGen	98475
GARD	0000169
Is cancer (heuristic)	no

Also known as: chondrodysplasia lethal neonatal with snail like pelvis · chondrodysplasia with snail-like pelvis · schneckenbecken dysplasia · SHNKND · SLC35D1-CDG

Data availability: 143 ClinVar variants · 5 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 › schneckenbecken dysplasia

Related subtypes (49): atelosteogenesis, midface dysplasia, Kashin-Beck disease, achondroplasia, Boomerang dysplasia, campomelic dysplasia, cleidocranial dysplasia 1, Leri-Weill dyschondrosteosis, hypochondroplasia, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, Kniest dysplasia, pseudoachondroplasia, ulna metaphyseal dysplasia syndrome, acheiropody, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, bone dysplasia, lethal Holmgren type, cleidocranial dysplasia, recessive form, diastrophic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, lethal Kniest-like dysplasia, metaphyseal chondrodysplasia, Kaitila type, metaphyseal chondrodysplasia, Spahr type, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, pycnodysostosis, pyknoachondrogenesis, Pyle disease, mesomelia-synostoses syndrome, lethal chondrodysplasia, Seller type, acrocapitofemoral dysplasia, brachyolmia, Desbuquois dysplasia, fibrochondrogenesis, multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, thanatophoric dysplasia, Blount disease, osteogenesis imperfecta, achondrogenesis, acromesomelic dysplasia, neonatal osteosclerotic dysplasia, Akaba Hayasaka syndrome, Fairbank disease, mesomelic dysplasia, spondyloepimetaphyseal dysplasia, cleidocranial dysplasia 2, arterial tortuosity-bone fragility syndrome, linkeropathy

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

143 retrieved; paginated sample, class counts are floors:

68 likely benign, 45 uncertain significance, 10 benign, 9 pathogenic, 5 conflicting classifications of pathogenicity, 5 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1123	NM_015139.3(SLC35D1):c.125del (p.Lys42fs)	SLC35D1	Pathogenic	no assertion criteria provided
1125	NM_015139.3(SLC35D1):c.636+1G>T	SLC35D1	Pathogenic	no assertion criteria provided
1126	NM_015139.3(SLC35D1):c.319C>T (p.Arg107Ter)	SLC35D1	Pathogenic	no assertion criteria provided
1127	NM_015139.3(SLC35D1):c.392+3A>G	SLC35D1	Pathogenic	no assertion criteria provided
1128	NM_015139.3(SLC35D1):c.533+730_637-1766del	SLC35D1	Pathogenic	no assertion criteria provided
1129	NM_015139.3(SLC35D1):c.193A>C (p.Thr65Pro)	SLC35D1	Pathogenic	no assertion criteria provided
2005679	NM_015139.3(SLC35D1):c.64_70del (p.Thr22fs)	SLC35D1	Pathogenic	criteria provided, single submitter
3691465	NM_015139.3(SLC35D1):c.479G>A (p.Trp160Ter)	SLC35D1	Pathogenic	criteria provided, single submitter
4771008	NM_015139.3(SLC35D1):c.850dup (p.Thr284fs)	SLC35D1	Pathogenic	criteria provided, single submitter
1124	NM_015139.3(SLC35D1):c.932G>A (p.Trp311Ter)	SLC35D1	Likely pathogenic	criteria provided, single submitter
1325087	NM_015139.3(SLC35D1):c.496_497del (p.Val166fs)	SLC35D1	Likely pathogenic	criteria provided, single submitter
1499652	NM_015139.3(SLC35D1):c.464+1G>C	SLC35D1	Likely pathogenic	criteria provided, single submitter
3075713	NM_015139.3(SLC35D1):c.919T>A (p.Tyr307Asn)	SLC35D1	Likely pathogenic	criteria provided, single submitter
3652026	NM_015139.3(SLC35D1):c.876+1G>A	SLC35D1	Likely pathogenic	criteria provided, single submitter
1049524	NM_015139.3(SLC35D1):c.707A>G (p.Tyr236Cys)	SLC35D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1702486	NM_015139.3(SLC35D1):c.930G>A (p.Thr310=)	SLC35D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
440280	NM_015139.3(SLC35D1):c.814G>A (p.Ala272Thr)	SLC35D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
502490	NM_015139.3(SLC35D1):c.213C>A (p.Ser71=)	SLC35D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
967179	NM_015139.3(SLC35D1):c.891_892del (p.Ile299fs)	SLC35D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1013855	NM_015139.3(SLC35D1):c.37A>G (p.Lys13Glu)	SLC35D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1038736	NM_015139.3(SLC35D1):c.812A>G (p.Tyr271Cys)	SLC35D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1214190	NM_015139.3(SLC35D1):c.586G>A (p.Val196Ile)	SLC35D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1314773	NM_015139.3(SLC35D1):c.902T>C (p.Met301Thr)	SLC35D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1353875	NM_015139.3(SLC35D1):c.208C>T (p.Pro70Ser)	SLC35D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1377542	NM_015139.3(SLC35D1):c.553_554delinsAC (p.Leu185Thr)	SLC35D1	Uncertain significance	criteria provided, single submitter
1381973	NM_015139.3(SLC35D1):c.376A>G (p.Ser126Gly)	SLC35D1	Uncertain significance	criteria provided, single submitter
1392953	NM_015139.3(SLC35D1):c.776T>A (p.Phe259Tyr)	SLC35D1	Uncertain significance	criteria provided, single submitter
1406521	NM_015139.3(SLC35D1):c.24_26del (p.Gln8del)	SLC35D1	Uncertain significance	criteria provided, single submitter
1413663	NM_015139.3(SLC35D1):c.492G>A (p.Met164Ile)	SLC35D1	Uncertain significance	criteria provided, single submitter
1438609	NM_015139.3(SLC35D1):c.275C>T (p.Ala92Val)	SLC35D1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
SLC35D1	Definitive	Autosomal recessive	schneckenbecken dysplasia	4
INPPL1	Supportive	Autosomal recessive	schneckenbecken dysplasia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC35D1	Orphanet:3144	Schneckenbecken dysplasia
INPPL1	Orphanet:2746	Opsismodysplasia
INPPL1	Orphanet:3144	Schneckenbecken dysplasia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC35D1	HGNC:20800	ENSG00000116704	Q9NTN3	Nucleotide sugar transporter SLC35D1	gencc,clinvar
INPPL1	HGNC:6080	ENSG00000165458	O15357	Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC35D1	Nucleotide sugar transporter SLC35D1	Antiporter that transports nucleotide sugars across the endoplasmic reticulum (ER) membrane in exchange for either their cognate nucleoside monophosphate or another nucleotide sugar.
INPPL1	Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2	Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinas…

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Scaffold/PPI	1	8.6×	0.112

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC35D1	Transporter	yes		Sugar_P_trans_dom, TPT_transporter
INPPL1	Scaffold/PPI	no	3.1.3.56	IPPc, SH2, SAM

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic mucosa	1
mucosa of sigmoid colon	1
secondary oocyte	1
mucosa of stomach	1
right lobe of thyroid gland	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC35D1	282	ubiquitous	marker	secondary oocyte, mucosa of sigmoid colon, colonic mucosa
INPPL1	223	ubiquitous	marker	mucosa of stomach, stromal cell of endometrium, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INPPL1	2,630
SLC35D1	947

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INPPL1	O15357	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC35D1	Q9NTN3	80.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC35D1 causes SCHBCKD	1	5710.0×	0.005	SLC35D1
Formation of the active cofactor, UDP-glucuronate	1	1142.0×	0.011	SLC35D1
Transport of nucleotide sugars	1	571.0×	0.013	SLC35D1
Metabolic disorders of biological oxidation enzymes	1	439.2×	0.013	SLC35D1
Glucuronidation	1	380.7×	0.013	SLC35D1
Interleukin-2 family signaling	1	317.2×	0.013	INPPL1
Inositol phosphate metabolism	1	237.9×	0.013	INPPL1
Synthesis of IP3 and IP4 in the cytosol	1	211.5×	0.013	INPPL1
Interleukin receptor SHC signaling	1	203.9×	0.013	INPPL1
PI Metabolism	1	178.4×	0.013	INPPL1
Signaling by CSF1 (M-CSF) in myeloid cells	1	173.0×	0.013	INPPL1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1	158.6×	0.013	INPPL1
Phase II - Conjugation of compounds	1	139.3×	0.013	SLC35D1
Transport of vitamins, nucleosides, and related molecules	1	135.9×	0.013	SLC35D1
Metabolism	2	11.6×	0.013	SLC35D1, INPPL1
Synthesis of PIPs at the plasma membrane	1	105.7×	0.015	INPPL1
Phospholipid metabolism	1	100.2×	0.015	INPPL1
Biological oxidations	1	64.9×	0.022	SLC35D1
Diseases of metabolism	1	40.2×	0.034	SLC35D1
Signaling by Interleukins	1	32.1×	0.040	INPPL1
SLC-mediated transmembrane transport	1	29.6×	0.041	SLC35D1
Cytokine Signaling in Immune system	1	20.4×	0.057	INPPL1
Metabolism of lipids	1	15.8×	0.071	INPPL1
Transport of small molecules	1	12.6×	0.084	SLC35D1
Disease	1	6.5×	0.148	SLC35D1
Immune System	1	6.5×	0.148	INPPL1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pyrimidine nucleotide-sugar transmembrane transport	1	8426.0×	0.003	SLC35D1
nucleotide-sugar transmembrane transport	1	4213.0×	0.003	SLC35D1
regulation of actin filament organization	1	1203.7×	0.006	INPPL1
negative regulation of insulin-like growth factor receptor signaling pathway	1	1053.2×	0.006	INPPL1
ruffle assembly	1	648.1×	0.008	INPPL1
phosphatidylinositol dephosphorylation	1	324.1×	0.011	INPPL1
chondroitin sulfate proteoglycan biosynthetic process	1	312.1×	0.011	SLC35D1
endochondral ossification	1	271.8×	0.011	INPPL1
regulation of immune response	1	247.8×	0.011	INPPL1
establishment of mitotic spindle orientation	1	240.7×	0.011	INPPL1
immune system process	1	195.9×	0.011	INPPL1
embryonic skeletal system development	1	195.9×	0.011	SLC35D1
phosphatidylinositol biosynthetic process	1	183.2×	0.011	INPPL1
ERK1 and ERK2 cascade	1	159.0×	0.012	INPPL1
glucose metabolic process	1	127.7×	0.013	INPPL1
response to insulin	1	115.4×	0.013	INPPL1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	105.3×	0.013	INPPL1
post-embryonic development	1	102.8×	0.013	INPPL1
regulation of protein localization	1	102.8×	0.013	INPPL1
actin filament organization	1	59.3×	0.022	INPPL1
endocytosis	1	47.6×	0.026	INPPL1
gene expression	1	39.9×	0.029	INPPL1
negative regulation of gene expression	1	34.5×	0.032	INPPL1
negative regulation of cell population proliferation	1	21.1×	0.051	INPPL1
cell adhesion	1	18.7×	0.055	INPPL1
apoptotic process	1	14.3×	0.068	INPPL1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
INPPL1	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
INPPL1	2	4
SLC35D1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ESTRAMUSTINE PHOSPHATE	4	INPPL1
CRIZOTINIB	4	INPPL1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
INPPL1	38	Binding:38

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
INPPL1	3.1.3.56, 3.1.3.86	inositol-polyphosphate 5-phosphatase, phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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)
ESTRAMUSTINE PHOSPHATE	4	INPPL1
CRIZOTINIB	4	INPPL1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	INPPL1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	SLC35D1
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)
SLC35D1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.