Pregnancy loss, recurrent, susceptibility to, 1

Summary

Pregnancy loss, recurrent, susceptibility to, 1 (MONDO:0013727) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pregnancy loss, recurrent, susceptibility to, 1
Mondo ID	MONDO:0013727
OMIM	614389
UMLS	C3280670
MedGen	482300
Is cancer (heuristic)	no

Also known as: F5 pregnancy loss, recurrent, susceptibility · foetal loss, recurrent, susceptibility to · pregnancy loss, recurrent, susceptibility caused by mutation in F5 · pregnancy loss, recurrent, susceptibility to, 1 · pregnancy loss, recurrent, susceptibility to, type 1 · RPRGL1

Data availability: 35 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › pregnancy loss, recurrent, susceptibility › pregnancy loss, recurrent, susceptibility to, 1

Related subtypes (3): pregnancy loss, recurrent, susceptibility to, 2, pregnancy loss, recurrent, susceptibility to, 3, pregnancy loss, recurrent, 4

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

35 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 8 conflicting classifications of pathogenicity, 6 likely pathogenic, 4 pathogenic/likely pathogenic, 3 pathogenic, 3 benign/likely benign, 1 drug response, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
619178	NM_033031.3(CCNB3):c.3752T>A (p.Val1251Asp)	CCNB3	Pathogenic	no assertion criteria provided
2734020	NM_000130.5(F5):c.3799del (p.Leu1267fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734021	NM_000130.5(F5):c.3088C>T (p.Arg1030Ter)	F5	Pathogenic	criteria provided, multiple submitters, no conflicts
2866617	NM_000130.5(F5):c.5453del (p.Leu1818fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2895285	NM_000130.5(F5):c.2021del (p.Lys674fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430053	NM_000130.5(F5):c.5037dup (p.Ser1680fs)	F5	Pathogenic	criteria provided, multiple submitters, no conflicts
627264	NM_000130.5(F5):c.1830_1831dup (p.His611fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2887062	NM_000130.5(F5):c.4962_4971+3del	F5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3600169	NM_000130.5(F5):c.5816T>G (p.Leu1939Ter)	F5	Likely pathogenic	criteria provided, single submitter
3600193	NM_000130.5(F5):c.2846del (p.Leu949fs)	F5	Likely pathogenic	criteria provided, single submitter
3600196	NM_000130.5(F5):c.2079T>G (p.Tyr693Ter)	F5	Likely pathogenic	criteria provided, single submitter
3600213	NM_000130.5(F5):c.1297-1G>C	F5	Likely pathogenic	criteria provided, single submitter
3600215	NM_000130.5(F5):c.1059del (p.Phe353fs)	F5	Likely pathogenic	criteria provided, single submitter
642	NM_000130.4(F5):c.1601G>A (p.Arg534Gln)	F5	drug response	reviewed by expert panel
1771009	NM_000130.5(F5):c.136C>G (p.Arg46Gly)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293607	NM_000130.5(F5):c.3442T>C (p.Ser1148Pro)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
579171	NM_000130.5(F5):c.5265A>G (p.Ile1755Met)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
627181	NM_000130.5(F5):c.5408A>G (p.His1803Arg)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
716054	NM_000130.5(F5):c.3162A>C (p.Glu1054Asp)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
787578	NM_000130.5(F5):c.4589A>C (p.Glu1530Ala)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870845	NM_000130.5(F5):c.3221A>G (p.Asn1074Ser)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
873759	NM_000130.5(F5):c.5923G>C (p.Gly1975Arg)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293581	NM_000130.5(F5):c.5534A>G (p.His1845Arg)	F5	Uncertain significance	criteria provided, multiple submitters, no conflicts
293598	NM_000130.5(F5):c.4309A>T (p.Thr1437Ser)	F5	Uncertain significance	criteria provided, multiple submitters, no conflicts
293640	NM_000130.5(F5):c.437G>A (p.Arg146Gln)	F5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3276991	NM_000130.5(F5):c.6407T>C (p.Ile2136Thr)	F5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3600182	NM_000130.5(F5):c.4796+3T>C	F5	Uncertain significance	criteria provided, single submitter
3891639	NM_000130.5(F5):c.1253T>C (p.Ile418Thr)	F5	Uncertain significance	criteria provided, single submitter
3891657	NM_000130.5(F5):c.478C>T (p.Pro160Ser)	F5	Uncertain significance	criteria provided, single submitter
3891661	NM_000130.5(F5):c.6259T>C (p.Phe2087Leu)	F5	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F5	Orphanet:131	Budd-Chiari syndrome
F5	Orphanet:326	Congenital factor V deficiency
F5	Orphanet:329217	Cerebral sinovenous thrombosis
F5	Orphanet:391320	East Texas bleeding disorder
F5	Orphanet:599579	Factor V Amsterdam bleeding disorder
F5	Orphanet:600194	Factor V Atlanta bleeding disorder

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
CCNB3	HGNC:18709	ENSG00000147082	Q8WWL7	G2/mitotic-specific cyclin-B3	clinvar
F5	HGNC:3542	ENSG00000198734	P12259	Coagulation factor V	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCNB3	G2/mitotic-specific cyclin-B3	Cyclins are positive regulatory subunits of the cyclin-dependent kinases (CDKs), and thereby play an essential role in the control of the cell cycle, notably via their destruction during cell division.
F5	Coagulation factor V	Central regulator of hemostasis.

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)
CCNB3	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
F5	Other/Unknown	no		FA58C, Cupredoxin, Galactose-bd-like_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
secondary oocyte	1
choroid plexus epithelium	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCNB3	156	tissue_specific	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte
F5	206	broad	marker	right lobe of liver, liver, choroid plexus epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCNB3	2,576
F5	1,754

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F5	P12259	18

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCNB3	Q8WWL7	42.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 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
Defective cleavage of FV variant at a.a.534	1	3806.7×	0.001	F5
Defective cleavage of FV variant at R334	1	3806.7×	0.001	F5
Amplification and propagation of coagulation cascade	1	634.4×	0.005	F5
Initiation of coagulation cascade	1	475.8×	0.005	F5
Cargo concentration in the ER	1	335.9×	0.006	F5
Regulation of clotting cascade	1	233.1×	0.007	F5
COPII-mediated vesicle transport	1	163.1×	0.009	F5
Post-translational protein phosphorylation	1	100.2×	0.012	F5
Platelet degranulation	1	87.8×	0.012	F5
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	F5

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
response to vitamin K	1	2808.7×	0.002	F5
blood circulation	1	255.3×	0.012	F5
meiotic cell cycle	1	122.1×	0.014	CCNB3
G1/S transition of mitotic cell cycle	1	100.3×	0.014	CCNB3
blood coagulation	1	86.9×	0.014	F5
cell division	1	23.1×	0.043	CCNB3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CCNB3	PALBOCICLIB
F5	EDOXABAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCNB3	17	4
F5	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PALBOCICLIB	4	CCNB3
EDOXABAN	4	F5
DINACICLIB	3	CCNB3
ALVOCIDIB	3	CCNB3
QUERCETIN	3	CCNB3
SILMITASERTIB	2	CCNB3
INDIRUBIN	2	CCNB3
SELICICLIB	2	CCNB3
LUTEOLIN	2	CCNB3
ASNUCICLIB	2	CCNB3
FISETIN	2	CCNB3
RIVICICLIB	2	CCNB3
AT-7519	2	CCNB3
RAZAXABAN	2	F5
KAEMPFEROL	1	CCNB3
SU-9516	1	CCNB3
HARMINE	1	CCNB3
BMS-387032	1	CCNB3
LADUVIGLUSIB	1	CCNB3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CCNB3	148	Binding:147, Functional:1
F5	10	Binding:10

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CCNB3	148

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

19 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.

Compound	Max phase	Cohort target (bioactivity)
PALBOCICLIB	4	CCNB3
EDOXABAN	4	F5
DINACICLIB	3	CCNB3
ALVOCIDIB	3	CCNB3
QUERCETIN	3	CCNB3
SILMITASERTIB	2	CCNB3
INDIRUBIN	2	CCNB3
SELICICLIB	2	CCNB3
LUTEOLIN	2	CCNB3
ASNUCICLIB	2	CCNB3
FISETIN	2	CCNB3
RIVICICLIB	2	CCNB3
AT-7519	2	CCNB3
RAZAXABAN	2	F5
KAEMPFEROL	1	CCNB3
SU-9516	1	CCNB3
HARMINE	1	CCNB3
BMS-387032	1	CCNB3
LADUVIGLUSIB	1	CCNB3

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CCNB3, F5
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.