Syndactyly type 8

Summary

Syndactyly type 8 (MONDO:0010669) is a disease caused by FGF16 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FGF16 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	syndactyly type 8
Mondo ID	MONDO:0010669
MeSH	C564100
OMIM	309630
Orphanet	2498
DOID	DOID:0111813
ICD-11	577712860
SNOMED CT	715442006
UMLS	C1839728
MedGen	333392
GARD	0003559
Is cancer (heuristic)	no

Also known as: FGF16 non-syndromic syndactyly · fusion of metacarpals 4 and 5 · metacarpal 4-5 fusion · metacarpal 4-5 fusion, X-linked recessive · metacarpals 4 and 5 fusion · MF4 · non-syndromic syndactyly caused by mutation in FGF16

Data availability: 3 ClinVar variants · 3 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 › syndactyly type 8

Related subtypes (7): non-syndromic synpolydactyly, syndactyly type 1, syndactyly type 3, syndactyly type 4, syndactyly type 5, mesoaxial synostotic syndactyly with phalangeal reduction, syndactyly type 6

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 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
66059	NM_003868.3(FGF16):c.535C>T (p.Arg179Ter)	FGF16	Pathogenic	no assertion criteria provided
66060	NM_003868.3(FGF16):c.470C>A (p.Ser157Ter)	FGF16	Pathogenic	no assertion criteria provided
160345	NM_003868.2(FGF16):c.275_293dup	FGF16	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
FGF16	Strong	X-linked	syndactyly type 8	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGF16	Orphanet:2498	Syndactyly type 8

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
FGF16	HGNC:3672	ENSG00000196468	O43320	Fibroblast growth factor 16	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGF16	Fibroblast growth factor 16	Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation, and is required for normal cardiomyocyte proliferation and heart development.

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)
FGF16	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF

Expression context

Cohort genes with no expression data: 0.

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
deltoid	1
primordial germ cell in gonad	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGF16	65	tissue_specific	yes	primordial germ cell in gonad, tibialis anterior, deltoid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGF16	3,703

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FGF16	O43320	82.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. 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
Signaling by activated point mutants of FGFR3	1	951.7×	0.003	FGF16
FGFR3c ligand binding and activation	1	878.5×	0.003	FGF16
FGFR2c ligand binding and activation	1	878.5×	0.003	FGF16
Phospholipase C-mediated cascade; FGFR3	1	878.5×	0.003	FGF16
FGFR4 ligand binding and activation	1	815.7×	0.003	FGF16
Phospholipase C-mediated cascade; FGFR4	1	761.3×	0.003	FGF16
Activated point mutants of FGFR2	1	671.8×	0.003	FGF16
Phospholipase C-mediated cascade; FGFR2	1	634.4×	0.003	FGF16
PI-3K cascade:FGFR3	1	634.4×	0.003	FGF16
SHC-mediated cascade:FGFR3	1	601.0×	0.003	FGF16
PI-3K cascade:FGFR4	1	571.0×	0.003	FGF16
FRS-mediated FGFR3 signaling	1	543.8×	0.003	FGF16
SHC-mediated cascade:FGFR4	1	543.8×	0.003	FGF16
PI-3K cascade:FGFR2	1	496.5×	0.003	FGF16
FRS-mediated FGFR4 signaling	1	496.5×	0.003	FGF16
Signaling by FGFR3 in disease	1	496.5×	0.003	FGF16
SHC-mediated cascade:FGFR2	1	475.8×	0.003	FGF16
FRS-mediated FGFR2 signaling	1	439.2×	0.003	FGF16
Negative regulation of FGFR3 signaling	1	439.2×	0.003	FGF16
Negative regulation of FGFR4 signaling	1	407.9×	0.003	FGF16
Negative regulation of FGFR2 signaling	1	368.4×	0.003	FGF16
PI3K Cascade	1	271.9×	0.004	FGF16
Signaling by FGFR2 in disease	1	265.6×	0.004	FGF16
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.009	FGF16
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.011	FGF16
PIP3 activates AKT signaling	1	66.8×	0.016	FGF16
RAF/MAP kinase cascade	1	61.1×	0.016	FGF16

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 endothelial cell chemotaxis to fibroblast growth factor	1	5617.3×	0.002	FGF16
response to temperature stimulus	1	1532.0×	0.003	FGF16
fibroblast growth factor receptor signaling pathway	1	285.6×	0.010	FGF16
neurogenesis	1	208.1×	0.010	FGF16
animal organ morphogenesis	1	191.5×	0.010	FGF16
regulation of cell migration	1	157.5×	0.011	FGF16
positive regulation of MAPK cascade	1	80.6×	0.018	FGF16
cell-cell signaling	1	69.6×	0.018	FGF16
positive regulation of cell population proliferation	1	33.6×	0.033	FGF16
signal transduction	1	16.1×	0.062	FGF16

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
FGF16	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	0
E	Difficult family or no structure, no drug	1	FGF16

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)
FGF16	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.