Synpolydactyly type 2

Summary

Synpolydactyly type 2 (MONDO:0011984) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	synpolydactyly type 2
Mondo ID	MONDO:0011984
MeSH	C564278
OMIM	608180
Orphanet	295197
ICD-11	1370014661
UMLS	C1842422
MedGen	331290
GARD	0017359
Is cancer (heuristic)	no

Also known as: SD2, Debeer type · SD2b · SPD, Debeer type · SPD2 · synpolydactyly 2 · synpolydactyly type 2 · synpolydactyly, 3/3'4, associated with metacarpal and metatarsal synostoses · synpolydactyly, Debeer type

Data availability: 9 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 › syndactyly › non-syndromic syndactyly › non-syndromic synpolydactyly › synpolydactyly type 2

Related subtypes (3): polysyndactyly 4, synpolydactyly type 1, synpolydactyly type 3

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

9 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031049	NM_006486.3(FBLN1):c.32C>A (p.Pro11Gln)	FBLN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1514922	NM_006486.3(FBLN1):c.1685G>A (p.Arg562His)	FBLN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2584812	NM_006486.3(FBLN1):c.451G>A (p.Gly151Arg)	FBLN1	Uncertain significance	criteria provided, single submitter
3376571	NM_006486.3(FBLN1):c.1949G>A (p.Arg650His)	FBLN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382633	NM_006486.3(FBLN1):c.1489C>T (p.Arg497Cys)	FBLN1	Uncertain significance	criteria provided, single submitter
4292493	NM_006486.3(FBLN1):c.1922T>C (p.Leu641Pro)	FBLN1	Uncertain significance	criteria provided, single submitter
1232901	NM_006486.3(FBLN1):c.963C>T (p.Ile321=)	FBLN1	Benign	criteria provided, multiple submitters, no conflicts
1285261	NM_006486.3(FBLN1):c.422A>G (p.Gln141Arg)	FBLN1	Benign	criteria provided, multiple submitters, no conflicts
790781	NM_006486.3(FBLN1):c.1690G>A (p.Ala564Thr)	FBLN1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
FBLN1	Limited	Unknown	synpolydactyly type 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FBLN1	Orphanet:295197	Synpolydactyly type 2
FBLN1	Orphanet:404451	FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome

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
FBLN1	HGNC:3600	ENSG00000077942	P23142	Fibulin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBLN1	Fibulin-1	Incorporated into fibronectin-containing matrix fibers.

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
Complement	1	268.0×	0.004

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FBLN1	Complement	yes		Anaphylatoxin/fibulin, EGF-type_Asp/Asn_hydroxyl_site, EGF

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
endocervix	1
gall bladder	1
pericardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBLN1	264	ubiquitous	marker	endocervix, gall bladder, pericardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBLN1	2,756

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FBLN1	P23142	79.49

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
Molecules associated with elastic fibres	1	308.6×	0.003	FBLN1

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 transformation of host cell by virus	1	16852.0×	8e-04	FBLN1
positive regulation of substrate-dependent cell migration, cell attachment to substrate	1	4213.0×	0.001	FBLN1
negative regulation of transforming growth factor beta production	1	3370.4×	0.001	FBLN1
blood coagulation, fibrin clot formation	1	1685.2×	0.002	FBLN1
negative regulation of cell motility	1	1296.3×	0.002	FBLN1
negative regulation of substrate adhesion-dependent cell spreading	1	1123.5×	0.002	FBLN1
negative regulation of stem cell proliferation	1	842.6×	0.002	FBLN1
negative regulation of protein phosphorylation	1	581.1×	0.003	FBLN1
negative regulation of cell adhesion	1	383.0×	0.004	FBLN1
embryo implantation	1	351.1×	0.004	FBLN1
positive regulation of fibroblast proliferation	1	295.6×	0.004	FBLN1
negative regulation of ERK1 and ERK2 cascade	1	216.1×	0.005	FBLN1
extracellular matrix organization	1	122.1×	0.009	FBLN1
positive regulation of gene expression	1	38.7×	0.026	FBLN1

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
FBLN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	FBLN1
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)
FBLN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.