Spondyloenchondrodysplasia with immune dysregulation

Summary

Spondyloenchondrodysplasia with immune dysregulation (MONDO:0011939) is a disease caused by ACP5 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ACP5 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 314

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Spondyloenchondrodysplasia with immune dysregulation
Mondo ID	MONDO:0011939
MeSH	C535782, C564307
OMIM	271550, 607944
Orphanet	1855, 50816
SNOMED CT	254079002, 703523004
UMLS	C1842763
MedGen	375009
GARD	0004978
Is cancer (heuristic)	no

Also known as: combined immunodeficiency with autoimmunity and spondylometaphyseal dysplasia · Roifman Immunoskeletal syndrome · SEM · SPENCD · SPENCDI · spondyloenchondrodysplasia · Spondyloenchondrodysplasia with immune dysregulation · spondyloenchondrodysplasia with immune dysregulation · spondyloenchondromatosis · spondylometaphyseal dysplasia with combined immunodeficiency · spondylometaphyseal dysplasia with enchondromatous changes

Data availability: 314 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › spondylometaphyseal dysplasia › Spondyloenchondrodysplasia with immune dysregulation

Related subtypes (18): Kniest dysplasia, spondyloepimetaphyseal dysplasia, Strudwick type, spondylometaphyseal dysplasia, Kozlowski type, spondylometaphyseal dysplasia, Schmidt type, spondylometaphyseal dysplasia, ‘corner fracture’ type, spondylometaphyseal dysplasia, Sedaghatian type, spondylometaphyseal dysplasia, Golden type, axial spondylometaphyseal dysplasia, spondylometaphyseal dysplasia-bowed forearms-facial dysmorphism syndrome, spondylometaphyseal dysplasia-cone-rod dystrophy syndrome, spondylometaphyseal dysplasia, A4 type, spondylometaphyseal dysplasia, East African type, autosomal recessive spondylometaphyseal dysplasia, Megarbane type, spondylometaphyseal dysplasia, Czarny-Ratajczak type, regressive spondylometaphyseal dysplasia, spondylometaphyseal dysplasia, pagnamenta type, odontochondrodysplasia, SBDS-related severe neonatal spondylometaphyseal dysplasia

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

314 retrieved; paginated sample, class counts are floors:

138 uncertain significance, 117 likely benign, 34 pathogenic, 7 conflicting classifications of pathogenicity, 7 benign, 5 benign/likely benign, 4 pathogenic/likely pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031092	NM_001611.5(ACP5):c.736-2A>G	ACP5	Pathogenic	criteria provided, single submitter
1072535	NC_000019.9:g.(?11685805)(11688152_?)del	ACP5	Pathogenic	criteria provided, single submitter
1073554	NM_001611.5(ACP5):c.733C>T (p.Gln245Ter)	ACP5	Pathogenic	criteria provided, single submitter
1075181	NM_001611.5(ACP5):c.257del (p.Phe86fs)	ACP5	Pathogenic	criteria provided, single submitter
1373515	NM_001611.5(ACP5):c.526del (p.Arg176fs)	ACP5	Pathogenic	criteria provided, single submitter
1375674	NM_001611.5(ACP5):c.259del (p.Gln87fs)	ACP5	Pathogenic	criteria provided, single submitter
1401166	NM_001611.5(ACP5):c.375_376insTA (p.Ile126Ter)	ACP5	Pathogenic	criteria provided, single submitter
1403982	NM_001611.5(ACP5):c.222C>A (p.Tyr74Ter)	ACP5	Pathogenic	criteria provided, single submitter
1437995	NM_001611.5(ACP5):c.136del (p.Arg46fs)	ACP5	Pathogenic	criteria provided, single submitter
1452268	NM_001611.5(ACP5):c.361del (p.Ile121fs)	ACP5	Pathogenic	criteria provided, single submitter
1452787	NM_001611.5(ACP5):c.266_272del (p.Thr89fs)	ACP5	Pathogenic	criteria provided, single submitter
1455117	NM_001611.5(ACP5):c.799del (p.Ser267fs)	ACP5	Pathogenic	criteria provided, multiple submitters, no conflicts
1456634	NM_001611.5(ACP5):c.712T>C (p.Cys238Arg)	ACP5	Pathogenic	criteria provided, single submitter
1510689	NM_001611.5(ACP5):c.721G>A (p.Asp241Asn)	ACP5	Pathogenic	criteria provided, single submitter
1897232	NM_001611.5(ACP5):c.372dup (p.Lys125Ter)	ACP5	Pathogenic	criteria provided, single submitter
2030290	NM_001611.5(ACP5):c.654_658del (p.Cys219fs)	ACP5	Pathogenic	criteria provided, single submitter
2110138	NM_001611.5(ACP5):c.628_634delinsCCTACC (p.Ser210fs)	ACP5	Pathogenic	criteria provided, single submitter
2134218	NM_001611.5(ACP5):c.550C>T (p.Gln184Ter)	ACP5	Pathogenic	criteria provided, single submitter
225658	NM_001611.5(ACP5):c.816dup (p.Lys273fs)	ACP5	Pathogenic	no assertion criteria provided
225659	NM_001611.5(ACP5):c.772_790del (p.Ser258fs)	ACP5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2417776	NM_001611.5(ACP5):c.710_718del (p.Leu237_Gly239del)	ACP5	Pathogenic	criteria provided, single submitter
2423723	NC_000019.9:g.(?11685825)(11688132_?)del	ACP5	Pathogenic	criteria provided, single submitter
2736805	NM_001611.5(ACP5):c.618C>A (p.Tyr206Ter)	ACP5	Pathogenic	criteria provided, single submitter
2980611	NM_001611.5(ACP5):c.372_373insC (p.Lys125fs)	ACP5	Pathogenic	criteria provided, single submitter
29829	NM_001611.5(ACP5):c.266C>T (p.Thr89Ile)	ACP5	Pathogenic	no assertion criteria provided
29830	NM_001611.5(ACP5):c.667C>T (p.Gln223Ter)	ACP5	Pathogenic	no assertion criteria provided
29831	NM_001611.5(ACP5):c.791T>A (p.Met264Lys)	ACP5	Pathogenic	criteria provided, single submitter
29832	NM_001611.5(ACP5):c.643G>C (p.Gly215Arg)	ACP5	Pathogenic	no assertion criteria provided
29833	NM_001611.5(ACP5):c.325G>A (p.Gly109Arg)	ACP5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3722995	NM_001611.5(ACP5):c.250_251del (p.Lys84fs)	ACP5	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ACP5	Definitive	Autosomal recessive	Spondyloenchondrodysplasia with immune dysregulation	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACP5	Orphanet:1855	Spondyloenchondrodysplasia

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
ACP5	HGNC:124	ENSG00000102575	P13686	Tartrate-resistant acid phosphatase type 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACP5	Tartrate-resistant acid phosphatase type 5	Involved in osteopontin/bone sialoprotein dephosphorylation.

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)
ACP5	Enzyme (other)	yes	3.1.3.2	Calcineurin-like_PHP, Acid_PPase, Metallo-depent_PP-like

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
periodontal ligament	1
right lung	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACP5	233	broad	marker	periodontal ligament, upper lobe of left lung, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACP5	2,983

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACP5	P13686	2

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
Vitamin B2 (riboflavin) metabolism	1	1631.4×	6e-04	ACP5

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
negative regulation of superoxide anion generation	1	8426.0×	0.002	ACP5
negative regulation of macrophage cytokine production	1	1203.7×	0.003	ACP5
negative regulation of interleukin-12 production	1	1053.2×	0.003	ACP5
negative regulation of nitric oxide biosynthetic process	1	991.3×	0.003	ACP5
nitric oxide biosynthetic process	1	702.2×	0.003	ACP5
superoxide anion generation	1	674.1×	0.003	ACP5
bone morphogenesis	1	601.9×	0.003	ACP5
bone resorption	1	581.1×	0.003	ACP5
negative regulation of interleukin-1 beta production	1	510.7×	0.003	ACP5
response to cytokine	1	374.5×	0.004	ACP5
negative regulation of tumor necrosis factor production	1	251.5×	0.005	ACP5
negative regulation of inflammatory response	1	137.0×	0.008	ACP5
defense response to Gram-positive bacterium	1	127.7×	0.008	ACP5
response to lipopolysaccharide	1	124.8×	0.008	ACP5

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
ACP5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACP5	3.1.3.2	acid phosphatase

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	ACP5
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)
ACP5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.