factor 5 and Factor VIII, combined deficiency of, 2
diseaseOn this page
Also known as combined deficiency of factor V and factor VIII caused by mutation in MCFD2F5F8D2factor 5 and Factor VIII, combined deficiency of, type 2factor V and factor VIII, combined deficiency offactor V and factor VIII, combined deficiency of, 2MCFD2 combined deficiency of factor V and factor VIII
Summary
factor 5 and Factor VIII, combined deficiency of, 2 (MONDO:0013331) is a disease caused by MCFD2 (GenCC Definitive), with 2 cohort genes.
At a glance
- Causal gene: MCFD2 (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 113
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | factor 5 and Factor VIII, combined deficiency of, 2 |
| Mondo ID | MONDO:0013331 |
| OMIM | 613625 |
| UMLS | C3150889 |
| MedGen | 462239 |
| GARD | 0018632 |
| Is cancer (heuristic) | no |
Also known as: combined deficiency of factor V and factor VIII caused by mutation in MCFD2 · F5F8D2 · factor 5 and Factor VIII, combined deficiency of, 2 · factor 5 and Factor VIII, combined deficiency of, type 2 · factor V and factor VIII, combined deficiency of · factor V and factor VIII, combined deficiency of, 2 · MCFD2 combined deficiency of factor V and factor VIII
Data availability: 113 ClinVar variants · 5 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › combined deficiency of factor V and factor VIII › factor 5 and Factor VIII, combined deficiency of, 2
Related subtypes (2): factor V and factor VIII, combined deficiency of, type 1, factor V and factor VIII, combined deficiency of, with normal protein C and protein C inhibitor
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
113 retrieved; paginated sample, class counts are floors:
71 uncertain significance, 25 benign, 7 pathogenic, 6 likely benign, 2 likely pathogenic, 2 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2866 | NM_139279.6(MCFD2):c.309+1G>A | MCFD2 | Pathogenic | no assertion criteria provided |
| 2867 | NM_139279.6(MCFD2):c.103del (p.Gln35fs) | MCFD2 | Pathogenic | no assertion criteria provided |
| 2868 | NM_139279.6(MCFD2):c.249del (p.Asp83fs) | MCFD2 | Pathogenic | no assertion criteria provided |
| 2869 | NM_139279.6(MCFD2):c.265_272del (p.Asp89fs) | MCFD2 | Pathogenic | no assertion criteria provided |
| 2870 | NM_139279.6(MCFD2):c.387C>G (p.Asp129Glu) | MCFD2 | Pathogenic | no assertion criteria provided |
| 2871 | NM_139279.6(MCFD2):c.407T>C (p.Ile136Thr) | MCFD2 | Pathogenic | no assertion criteria provided |
| 2872 | NM_139279.6(MCFD2):c.241G>T (p.Asp81Tyr) | MCFD2 | Pathogenic | no assertion criteria provided |
| 2865 | NM_139279.6(MCFD2):c.149+5G>A | MCFD2 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 800824 | NM_139279.6(MCFD2):c.47T>C (p.Leu16Pro) | MCFD2 | Likely pathogenic | criteria provided, single submitter |
| 336332 | NM_139279.6(MCFD2):c.*2848C>T | MCFD2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 336385 | NM_139279.6(MCFD2):c.-7+11T>A | MCFD2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 336392 | NM_001171506.2(MCFD2):c.-189C>G | LOC129933675 | Uncertain significance | criteria provided, single submitter |
| 896542 | NM_001171506.2(MCFD2):c.-205G>C | LOC129933675 | Uncertain significance | criteria provided, single submitter |
| 336325 | NM_139279.6(MCFD2):c.*3354A>G | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336327 | NM_139279.6(MCFD2):c.*3293A>C | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336329 | NM_139279.6(MCFD2):c.*3099G>A | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336331 | NM_139279.6(MCFD2):c.*3014G>A | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336333 | NM_139279.6(MCFD2):c.*2789G>C | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336337 | NM_139279.6(MCFD2):c.*2565A>G | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336340 | NM_139279.6(MCFD2):c.*2169G>A | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336342 | NM_139279.6(MCFD2):c.*2141G>C | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336343 | NM_139279.6(MCFD2):c.*2121G>A | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336345 | NM_139279.6(MCFD2):c.*2017C>T | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336346 | NM_139279.6(MCFD2):c.*1995G>A | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336349 | NM_139279.6(MCFD2):c.*1875T>C | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336355 | NM_139279.6(MCFD2):c.*1415C>T | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336356 | NM_139279.6(MCFD2):c.*1354G>T | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336358 | NM_139279.6(MCFD2):c.*1314C>T | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336361 | NM_139279.6(MCFD2):c.*1158C>A | MCFD2 | Uncertain significance | criteria provided, single submitter |
| 336362 | NM_139279.6(MCFD2):c.*1111G>C | MCFD2 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 6 · 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 |
|---|---|---|---|---|
| MCFD2 | Definitive | Autosomal recessive | factor 5 and Factor VIII, combined deficiency of, 2 | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| MCFD2 | Orphanet:35909 | Combined deficiency of factor V and factor VIII |
Cohort genes → proteins
2 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| MCFD2 | HGNC:18451 | ENSG00000180398 | Q8NI22 | Multiple coagulation factor deficiency protein 2 | gencc,clinvar |
| MCFD2-AS1 | HGNC:58223 | ENSG00000228925 | MCFD2 antisense RNA 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| MCFD2 | Multiple coagulation factor deficiency protein 2 | The MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. |
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) |
|---|---|---|---|---|
| MCFD2 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS | |
| MCFD2-AS1 | Other/Unknown | no |
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 |
|---|---|
| adrenal tissue | 1 |
| parotid gland | 1 |
| seminal vesicle | 1 |
| body of pancreas | 1 |
| left adrenal gland cortex | 1 |
| primordial germ cell in gonad | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| MCFD2 | 295 | ubiquitous | marker | parotid gland, seminal vesicle, adrenal tissue |
| MCFD2-AS1 | 133 | marker | primordial germ cell in gonad, body of pancreas, left adrenal gland cortex |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MCFD2 | 881 |
| MCFD2-AS1 | 0 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| MCFD2 | Q8NI22 | 17 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 9. 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 |
|---|---|---|---|---|
| Cargo concentration in the ER | 1 | 335.9× | 0.022 | MCFD2 |
| COPII-mediated vesicle transport | 1 | 163.1× | 0.022 | MCFD2 |
| ER to Golgi Anterograde Transport | 1 | 132.8× | 0.022 | MCFD2 |
| Transport to the Golgi and subsequent modification | 1 | 102.9× | 0.022 | MCFD2 |
| Asparagine N-linked glycosylation | 1 | 60.1× | 0.030 | MCFD2 |
| Membrane Trafficking | 1 | 37.1× | 0.037 | MCFD2 |
| Vesicle-mediated transport | 1 | 34.8× | 0.037 | MCFD2 |
| Post-translational protein modification | 1 | 19.2× | 0.059 | MCFD2 |
| Metabolism of proteins | 1 | 12.4× | 0.081 | MCFD2 |
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 |
|---|---|---|---|---|
| vesicle-mediated transport | 1 | 96.3× | 0.019 | MCFD2 |
| gene expression | 1 | 79.9× | 0.019 | MCFD2 |
| protein transport | 1 | 43.9× | 0.023 | MCFD2 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 0 of 2 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 |
|---|---|---|
| MCFD2 | 0 | 0 |
| MCFD2-AS1 | 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 | 2 | MCFD2, MCFD2-AS1 |
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) |
|---|---|---|
| MCFD2 | 0 | — |
| MCFD2-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.