Nonsyndromic congenital nail disorder 3

Summary

Nonsyndromic congenital nail disorder 3 (MONDO:0007900) is a disease caused by PLCD1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PLCD1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nonsyndromic congenital nail disorder 3
Mondo ID	MONDO:0007900
MeSH	C537289
OMIM	151600
DOID	DOID:0080081
SNOMED CT	74102009
UMLS	C0544855
MedGen	107463
GARD	0002555
Is cancer (heuristic)	no

Also known as: Gorlin Bushkell Jensen syndrome · inherited isolated nail anomaly caused by mutation in PLCD1 · leukonychia totalis multiple sebaceous cysts renal calculi · nail disorder, nonsyndromic congenital, 3 · nail disorder, nonsyndromic congenital, 3, (leukonychia) · nail disorder, nonsyndromic congenital, type 3 · NDNC3 · nonsyndromic congenital nail disorder type 3 · PLCD1 inherited isolated nail anomaly

Data availability: 14 ClinVar variants · 7 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › nail disorder › inherited isolated nail anomaly › nonsyndromic congenital nail disorder 3

Related subtypes (8): isolated congenital digital clubbing, nonsyndromic congenital nail disorder 2, nonsyndromic congenital nail disorder 1, nonsyndromic congenital nail disorder 5, nonsyndromic congenital nail disorder 7, nonsyndromic congenital nail disorder 8, leukonychia totalis, isolated congenital anonychia

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

14 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 3 pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2064069	NM_006225.4(PLCD1):c.1588C>T (p.Arg530Ter)	PLCD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30239	NM_006225.4(PLCD1):c.1246C>T (p.Arg416Ter)	PLCD1	Pathogenic	no assertion criteria provided
30240	NM_006225.4(PLCD1):c.1724-5_1728del	PLCD1	Pathogenic	no assertion criteria provided
30242	NM_006225.4(PLCD1):c.562T>C (p.Cys188Arg)	PLCD1	Pathogenic	no assertion criteria provided
4849409	NM_006225.4(PLCD1):c.1597C>T (p.Gln533Ter)	PLCD1	Likely pathogenic	criteria provided, single submitter
30241	NM_006225.4(PLCD1):c.1657G>A (p.Ala553Thr)	PLCD1	Conflicting classifications of pathogenicity	no assertion criteria provided
1333358	NM_006225.4(PLCD1):c.1016G>T (p.Cys339Phe)	PLCD1	Uncertain significance	criteria provided, single submitter
2455046	NM_006225.4(PLCD1):c.1427G>A (p.Arg476His)	PLCD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2508913	NM_006225.4(PLCD1):c.179G>A (p.Arg60Gln)	PLCD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065867	NM_006225.4(PLCD1):c.1118T>C (p.Ile373Thr)	PLCD1	Uncertain significance	criteria provided, single submitter
3065906	NM_006225.4(PLCD1):c.1205C>T (p.Ala402Val)	PLCD1	Uncertain significance	criteria provided, single submitter
3068029	NM_006225.4(PLCD1):c.1137+5G>C	PLCD1	Uncertain significance	criteria provided, single submitter
3307322	NM_006225.4(PLCD1):c.413G>A (p.Arg138His)	PLCD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892102	NM_006225.4(PLCD1):c.1606G>C (p.Gly536Arg)	PLCD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
PLCD1	Strong	Autosomal recessive	nonsyndromic congenital nail disorder 3	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLCD1	Orphanet:2387	Leukonychia totalis

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
PLCD1	HGNC:9060	ENSG00000187091	P51178	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLCD1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLCD1	Scaffold/PPI	no	3.1.4.11	C2_dom, PLipase_C_PInositol-sp_X_dom, PI-PLC_fam

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
mucosa of transverse colon	1
olfactory bulb	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLCD1	274	ubiquitous	marker	olfactory bulb, type B pancreatic cell, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLCD1	1,399

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLCD1	P51178	89.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Synthesis of IP3 and IP4 in the cytosol	1	423.0×	0.002	PLCD1

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
phospholipase C/protein kinase C signal transduction	1	2808.7×	0.001	PLCD1
phosphatidylinositol metabolic process	1	887.0×	0.002	PLCD1
phospholipid metabolic process	1	343.9×	0.004	PLCD1
lipid catabolic process	1	244.2×	0.004	PLCD1

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
PLCD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PLCD1	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLCD1	3.1.4.11	phosphoinositide phospholipase C

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	PLCD1

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)
PLCD1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.