Familial hypodysfibrinogenemia

Summary

Familial hypodysfibrinogenemia (MONDO:0016638) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial hypodysfibrinogenemia
Mondo ID	MONDO:0016638
Orphanet	248408
UMLS	C1859970
MedGen	347987
GARD	0017202
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › congenital fibrinogen deficiency › familial dysfibrinogenemia › congenital afibrinogenemia › familial hypodysfibrinogenemia

Related subtypes (1): familial hypofibrinogenemia

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16415	NM_021871.4(FGA):c.510+1G>T	FGA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGA	Orphanet:101041	Familial hypofibrinogenemia
FGA	Orphanet:248408	Familial hypodysfibrinogenemia
FGA	Orphanet:93562	AFib amyloidosis
FGA	Orphanet:98880	Familial afibrinogenemia
FGA	Orphanet:98881	Familial dysfibrinogenemia

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
FGA	HGNC:3661	ENSG00000171560	P02671	Fibrinogen alpha chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGA	Fibrinogen alpha chain	Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix.

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)
FGA	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_coil_dom, Fibrinogen_a/b/g_C_1

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
islet of Langerhans	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGA	153	tissue_specific	marker	right lobe of liver, liver, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGA	2,327

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGA	P02671	39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. 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
Aggregated β-amyloid interacts with fibrinogen	1	2855.0×	0.006	FGA
Fibrin formation	1	878.5×	0.006	FGA
p130Cas linkage to MAPK signaling for integrins	1	761.3×	0.006	FGA
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	713.8×	0.006	FGA
MyD88 deficiency (TLR2/4)	1	601.0×	0.006	FGA
IRAK4 deficiency (TLR2/4)	1	571.0×	0.006	FGA
Regulation of TLR by endogenous ligand	1	496.5×	0.006	FGA
Integrin signaling	1	423.0×	0.006	FGA
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.006	FGA
MAP2K and MAPK activation	1	285.5×	0.006	FGA
Signaling by RAF1 mutants	1	278.5×	0.006	FGA
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.006	FGA
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.006	FGA
Signaling downstream of RAS mutants	1	253.8×	0.006	FGA
Signaling by BRAF and RAF1 fusions	1	170.4×	0.009	FGA
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	152.3×	0.009	FGA
Integrin cell surface interactions	1	134.3×	0.009	FGA
ER-Phagosome pathway	1	129.8×	0.009	FGA
Amyloid fiber formation	1	102.9×	0.011	FGA
Post-translational protein phosphorylation	1	100.2×	0.011	FGA
Platelet degranulation	1	87.8×	0.012	FGA
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	FGA

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
blood coagulation, common pathway	1	8426.0×	0.002	FGA
induction of bacterial agglutination	1	2808.7×	0.003	FGA
blood coagulation, fibrin clot formation	1	1685.2×	0.003	FGA
positive regulation of peptide hormone secretion	1	1532.0×	0.003	FGA
plasminogen activation	1	1296.3×	0.003	FGA
positive regulation of heterotypic cell-cell adhesion	1	1296.3×	0.003	FGA
protein polymerization	1	991.3×	0.003	FGA
fibrinolysis	1	842.6×	0.003	FGA
positive regulation of vasoconstriction	1	601.9×	0.003	FGA
positive regulation of exocytosis	1	601.9×	0.003	FGA
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	581.1×	0.003	FGA
negative regulation of endothelial cell apoptotic process	1	495.6×	0.004	FGA
positive regulation of substrate adhesion-dependent cell spreading	1	374.5×	0.004	FGA
positive regulation of protein secretion	1	343.9×	0.004	FGA
platelet aggregation	1	337.0×	0.004	FGA
response to calcium ion	1	318.0×	0.004	FGA
cell-matrix adhesion	1	163.6×	0.008	FGA
protein-containing complex assembly	1	113.9×	0.010	FGA
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.012	FGA
adaptive immune response	1	84.3×	0.012	FGA
innate immune response	1	33.6×	0.030	FGA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGA	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	FGA

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)
FGA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.