MASS syndrome

Summary

MASS syndrome (MONDO:0011431) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 332

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	MASS syndrome
Mondo ID	MONDO:0011431
MeSH	C536030
OMIM	604308
Orphanet	99715
UMLS	C1858556
MedGen	346932
GARD	0008489
Is cancer (heuristic)	no

Also known as: MASS phenotype · MASS syndrome · Mitral valve prolapse, Aortic enlargement, Skin and Skeletal findings · OCTD

Data availability: 332 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › overlapping connective tissue disease › MASS syndrome

Related subtypes (1): mixed connective tissue disease

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

332 retrieved; paginated sample, class counts are floors:

135 uncertain significance, 122 conflicting classifications of pathogenicity, 25 pathogenic/likely pathogenic, 17 pathogenic, 13 likely pathogenic, 13 likely benign, 4 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1324391	NM_000138.5(FBN1):c.3338-1G>C	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451231	NM_000138.5(FBN1):c.4121G>A (p.Cys1374Tyr)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
163462	NM_000138.5(FBN1):c.7754T>C (p.Ile2585Thr)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
163480	NM_000138.5(FBN1):c.1879C>T (p.Arg627Cys)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
16434	NM_000138.5(FBN1):c.5134_5137dup (p.Asn1713fs)	FBN1	Pathogenic	no assertion criteria provided
16440	NM_000138.5(FBN1):c.364C>T (p.Arg122Cys)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
16461	NM_000138.5(FBN1):c.718C>T (p.Arg240Cys)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1675081	NM_000138.5(FBN1):c.5836del (p.Gln1946fs)	FBN1	Pathogenic	criteria provided, single submitter
1707834	NM_000138.5(FBN1):c.2753del (p.Pro918fs)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
180351	NM_000138.5(FBN1):c.1285C>T (p.Arg429Ter)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180352	NM_000138.5(FBN1):c.1633C>T (p.Arg545Cys)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
200001	NM_000138.5(FBN1):c.2645C>T (p.Ala882Val)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
200022	NM_000138.5(FBN1):c.3712G>A (p.Asp1238Asn)	FBN1	Pathogenic	reviewed by expert panel
200052	NM_000138.5(FBN1):c.4621C>T (p.Arg1541Ter)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
200191	NM_000138.5(FBN1):c.6388G>A (p.Glu2130Lys)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265401	NM_000138.5(FBN1):c.2581C>T (p.Arg861Ter)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2925582	NM_000138.5(FBN1):c.407G>T (p.Cys136Phe)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
36042	NM_000138.5(FBN1):c.1948C>T (p.Arg650Cys)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
36043	NM_000138.5(FBN1):c.2055C>G (p.Cys685Trp)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
36075	NM_000138.5(FBN1):c.4460-8G>A	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
36078	NM_000138.5(FBN1):c.4588C>T (p.Arg1530Cys)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
36082	NM_000138.5(FBN1):c.4786C>T (p.Arg1596Ter)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
36107	NM_000138.5(FBN1):c.6806T>C (p.Ile2269Thr)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42284	NM_000138.5(FBN1):c.1468+5G>A	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42295	NM_000138.5(FBN1):c.184C>T (p.Arg62Cys)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
42340	NM_000138.5(FBN1):c.368G>A (p.Cys123Tyr)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
42376	NM_000138.5(FBN1):c.4955G>A (p.Cys1652Tyr)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430150	NM_000138.5(FBN1):c.5183C>T (p.Ala1728Val)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4531277	NM_000138.5(FBN1):c.5336dup (p.Asn1779fs)	FBN1	Pathogenic	criteria provided, single submitter
457162	NM_000138.5(FBN1):c.1462T>C (p.Cys488Arg)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 29 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL2A1	Orphanet:137678	Spondyloepiphyseal dysplasia with metatarsal shortening
COL2A1	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL2A1	Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome
COL2A1	Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment
COL2A1	Orphanet:2380	Legg-Calvé-Perthes disease
COL2A1	Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type
COL2A1	Orphanet:485	Kniest dysplasia
COL2A1	Orphanet:85166	Platyspondylic dysplasia, Torrance type
COL2A1	Orphanet:85198	Dysspondyloenchondromatosis
COL2A1	Orphanet:86820	Familial avascular necrosis of femoral head
COL2A1	Orphanet:90653	Stickler syndrome type 1
COL2A1	Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
COL2A1	Orphanet:93296	Achondrogenesis type 2
COL2A1	Orphanet:93297	Hypochondrogenesis
COL2A1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type
COL2A1	Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type
COL2A1	Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type
COL2A1	Orphanet:94068	Spondyloepiphyseal dysplasia congenita
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric 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
COL2A1	HGNC:2200	ENSG00000139219	P02458	Collagen alpha-1(II) chain	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL2A1	Collagen alpha-1(II) chain	Type II collagen is specific for cartilaginous tissues.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL2A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom

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
cartilage tissue	1
corpus epididymis	1
tibia	1
decidua	1
skin of hip	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL2A1	145	broad	marker	tibia, cartilage tissue, corpus epididymis
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBN1	3,640
COL2A1	2,491

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL2A1	P02458	11
FBN1	P35555	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
Integrin cell surface interactions	2	134.3×	0.001	COL2A1, FBN1
Fibronectin matrix formation	1	285.5×	0.017	COL2A1
MET activates PTK2 signaling	1	190.3×	0.017	COL2A1
Elastic fibre formation	1	167.9×	0.017	FBN1
TGF-beta receptor signaling activates SMADs	1	163.1×	0.017	FBN1
Molecules associated with elastic fibres	1	154.3×	0.017	FBN1
Collagen chain trimerization	1	129.8×	0.017	COL2A1
Signaling by PDGF	1	126.9×	0.017	COL2A1
NCAM1 interactions	1	124.1×	0.017	COL2A1
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.017	COL2A1
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.017	COL2A1
Collagen degradation	1	87.8×	0.017	COL2A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.017	COL2A1
Non-integrin membrane-ECM interactions	1	77.2×	0.017	COL2A1
ECM proteoglycans	1	75.1×	0.017	COL2A1
Degradation of the extracellular matrix	1	58.9×	0.020	FBN1
Post-translational protein phosphorylation	1	50.1×	0.022	FBN1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	43.6×	0.023	COL2A1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.023	FBN1

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
skeletal system development	2	125.8×	0.003	COL2A1, FBN1
post-embryonic eye morphogenesis	1	2808.7×	0.004	FBN1
obsolete sequestering of BMP in extracellular matrix	1	2106.5×	0.004	FBN1
obsolete sequestering of TGFbeta in extracellular matrix	1	2106.5×	0.004	FBN1
negative regulation of osteoclast development	1	1685.2×	0.004	FBN1
otic vesicle development	1	1404.3×	0.004	COL2A1
anterior head development	1	1404.3×	0.004	COL2A1
cartilage development involved in endochondral bone morphogenesis	1	1203.7×	0.004	COL2A1
proteoglycan metabolic process	1	936.2×	0.004	COL2A1
notochord development	1	842.6×	0.004	COL2A1
embryonic eye morphogenesis	1	766.0×	0.004	FBN1
limb bud formation	1	766.0×	0.004	COL2A1
embryonic skeletal joint morphogenesis	1	766.0×	0.004	COL2A1
cellular response to insulin-like growth factor stimulus	1	648.1×	0.004	FBN1
cartilage condensation	1	383.0×	0.007	COL2A1
cell adhesion mediated by integrin	1	337.0×	0.007	FBN1
tissue homeostasis	1	280.9×	0.007	COL2A1
cellular response to BMP stimulus	1	280.9×	0.007	COL2A1
endochondral ossification	1	271.8×	0.007	COL2A1
negative regulation of osteoclast differentiation	1	271.8×	0.007	FBN1
metanephros development	1	255.3×	0.007	FBN1
extrinsic apoptotic signaling pathway in absence of ligand	1	234.1×	0.008	COL2A1
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	205.5×	0.008	COL2A1
heart morphogenesis	1	187.2×	0.009	COL2A1
camera-type eye development	1	179.3×	0.009	FBN1
lung alveolus development	1	175.5×	0.009	FBN1
chondrocyte differentiation	1	150.5×	0.009	COL2A1
inner ear morphogenesis	1	150.5×	0.009	COL2A1
cellular response to transforming growth factor beta stimulus	1	138.1×	0.010	FBN1
glucose metabolic process	1	127.7×	0.010	FBN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL2A1	0	0
FBN1	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
COL2A1	2	Binding:2

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

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	2	COL2A1, FBN1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COL2A1	2	—
FBN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.