Vertebral, cardiac, renal, and limb defects syndrome 3
diseaseOn this page
Also known as Congenital Nad Deficiency Disorder 3VCRL3
Summary
Vertebral, cardiac, renal, and limb defects syndrome 3 (MONDO:0030077) is a disease caused by NADSYN1 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: NADSYN1 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 34
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | vertebral, cardiac, renal, and limb defects syndrome 3 |
| Mondo ID | MONDO:0030077 |
| OMIM | 618845 |
| UMLS | C5394250 |
| MedGen | 1709064 |
| GARD | 0018510 |
| Is cancer (heuristic) | no |
Also known as: Congenital Nad Deficiency Disorder 3 · VCRL3 · VERTEBRAL, CARDIAC, RENAL, AND LIMB DEFECTS SYNDROME 3 · vertebral, cardiac, renal, and limb defects syndrome 3
Data availability: 34 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 › autosomal genetic disease › autosomal recessive disease › congenital vertebral-cardiac-renal anomalies syndrome › vertebral, cardiac, renal, and limb defects syndrome 3
Related subtypes (2): vertebral, cardiac, renal, and limb defects syndrome 1, vertebral, cardiac, renal, and limb defects syndrome 2
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
34 retrieved; paginated sample, class counts are floors:
9 benign, 8 uncertain significance, 5 likely pathogenic, 4 conflicting classifications of pathogenicity, 4 pathogenic, 3 pathogenic/likely pathogenic, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1699308 | NM_018161.5(NADSYN1):c.524G>A (p.Cys175Tyr) | NADSYN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 834710 | NM_018161.5(NADSYN1):c.1717G>A (p.Ala573Thr) | NADSYN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 834711 | NM_018161.5(NADSYN1):c.1819del (p.Val607fs) | NADSYN1 | Pathogenic | no assertion criteria provided |
| 834713 | NM_018161.5(NADSYN1):c.735T>A (p.Cys245Ter) | NADSYN1 | Pathogenic | no assertion criteria provided |
| 834715 | NM_018161.5(NADSYN1):c.1839C>G (p.Tyr613Ter) | NADSYN1 | Pathogenic | no assertion criteria provided |
| 869157 | NM_018161.5(NADSYN1):c.145T>C (p.Cys49Arg) | NADSYN1 | Pathogenic | criteria provided, single submitter |
| 998169 | NM_018161.5(NADSYN1):c.1459C>T (p.Arg487Ter) | NADSYN1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2575904 | NM_018161.5(NADSYN1):c.1088C>T (p.Ala363Val) | NADSYN1 | Likely pathogenic | criteria provided, single submitter |
| 3382592 | NM_018161.5(NADSYN1):c.1744C>T (p.Gln582Ter) | NADSYN1 | Likely pathogenic | criteria provided, single submitter |
| 3894573 | NM_018161.5(NADSYN1):c.1036C>T (p.Arg346Ter) | NADSYN1 | Likely pathogenic | criteria provided, single submitter |
| 4845261 | NM_018161.5(NADSYN1):c.475G>A (p.Gly159Arg) | NADSYN1 | Likely pathogenic | no assertion criteria provided |
| 4849287 | NM_018161.5(NADSYN1):c.317+2T>G | NADSYN1 | Likely pathogenic | criteria provided, single submitter |
| 1309754 | NM_018161.5(NADSYN1):c.271del (p.Met91fs) | NADSYN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2342520 | NM_018161.5(NADSYN1):c.379C>T (p.Arg127Cys) | NADSYN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2442205 | NM_018161.5(NADSYN1):c.1765-7T>A | NADSYN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2575903 | NM_018161.5(NADSYN1):c.1759G>A (p.Asp587Asn) | NADSYN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2434022 | NM_018161.5(NADSYN1):c.1621G>A (p.Gly541Arg) | NADSYN1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2434023 | NM_018161.5(NADSYN1):c.1189C>T (p.Gln397Ter) | NADSYN1 | Uncertain significance | criteria provided, single submitter |
| 2434024 | NM_018161.5(NADSYN1):c.-690G>A | NADSYN1 | Uncertain significance | criteria provided, single submitter |
| 2689523 | NM_018161.5(NADSYN1):c.1787C>T (p.Ala596Val) | NADSYN1 | Uncertain significance | criteria provided, single submitter |
| 3067835 | NM_018161.5(NADSYN1):c.1247G>T (p.Cys416Phe) | NADSYN1 | Uncertain significance | criteria provided, single submitter |
| 3382593 | NM_018161.5(NADSYN1):c.87T>A (p.Ser29Arg) | NADSYN1 | Uncertain significance | criteria provided, single submitter |
| 4079354 | NM_018161.5(NADSYN1):c.1047+3A>G | NADSYN1 | Uncertain significance | criteria provided, single submitter |
| 4079355 | NM_018161.5(NADSYN1):c.317+17C>A | NADSYN1 | Uncertain significance | criteria provided, single submitter |
| 1229671 | NM_018161.5(NADSYN1):c.705T>C (p.Cys235=) | NADSYN1 | Benign | criteria provided, multiple submitters, no conflicts |
| 1248202 | NM_018161.5(NADSYN1):c.220G>C (p.Val74Leu) | NADSYN1 | Benign | criteria provided, multiple submitters, no conflicts |
| 1264964 | NM_018161.5(NADSYN1):c.744T>C (p.Ile248=) | NADSYN1 | Benign | criteria provided, multiple submitters, no conflicts |
| 1321836 | NM_018161.5(NADSYN1):c.264-26A>G | NADSYN1 | Benign | criteria provided, multiple submitters, no conflicts |
| 1321837 | NM_018161.5(NADSYN1):c.317+22C>T | NADSYN1 | Benign | criteria provided, multiple submitters, no conflicts |
| 1321838 | NM_018161.5(NADSYN1):c.408-21C>T | NADSYN1 | Benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · 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 |
|---|---|---|---|---|
| NADSYN1 | Strong | Autosomal recessive | vertebral, cardiac, renal, and limb defects syndrome 3 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| NADSYN1 | Orphanet:521438 | Congenital vertebral-cardiac-renal anomalies 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 |
|---|---|---|---|---|---|
| NADSYN1 | HGNC:29832 | ENSG00000172890 | Q6IA69 | Glutamine-dependent NAD(+) synthetase | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| NADSYN1 | Glutamine-dependent NAD(+) synthetase | Catalyzes the final step of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway, the ATP-dependent amidation of deamido-NAD using L-glutamine as a nitrogen source. |
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 |
|---|---|---|---|
| Enzyme (other) | 1 | 12.0× | 0.083 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| NADSYN1 | Enzyme (other) | yes | 6.3.5.1 | C-N_Hydrolase, NAD_synthase, Gln-dep_NAD_synthase |
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 |
|---|---|
| granulocyte | 1 |
| mucosa of transverse colon | 1 |
| right uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| NADSYN1 | 258 | ubiquitous | marker | right uterine tube, granulocyte, mucosa of transverse colon |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| NADSYN1 | 2,114 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| NADSYN1 | Q6IA69 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 4. 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 |
|---|---|---|---|---|
| Nicotinate metabolism | 1 | 393.8× | 0.010 | NADSYN1 |
| Metabolism of water-soluble vitamins and cofactors | 1 | 181.3× | 0.011 | NADSYN1 |
| Metabolism of vitamins and cofactors | 1 | 116.5× | 0.011 | NADSYN1 |
| Metabolism | 1 | 11.6× | 0.086 | NADSYN1 |
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 |
|---|---|---|---|---|
| NAD+ biosynthetic process | 1 | 1872.4× | 5e-04 | NADSYN1 |
| ‘de novo’ NAD+ biosynthetic process from L-tryptophan | 1 | 1872.4× | 5e-04 | NADSYN1 |
| NAD+ biosynthetic process via the salvage pathway | 1 | 1872.4× | 5e-04 | NADSYN1 |
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 |
|---|---|---|
| NADSYN1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| NADSYN1 | 6.3.5.1 | NAD+ synthase (glutamine-hydrolysing) |
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 | 1 | NADSYN1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| 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) |
|---|---|---|
| NADSYN1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: NADSYN1