Noonan syndrome-like disorder with loose anagen hair 2

Summary

Noonan syndrome-like disorder with loose anagen hair 2 (MONDO:0054588) is a disease caused by PPP1CB (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PPP1CB (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Noonan syndrome-like disorder with loose anagen hair 2
Mondo ID	MONDO:0054588
OMIM	617506
DOID	DOID:0080693
NCIT	C176940
UMLS	C4479577
MedGen	1376945
GARD	0025953
Is cancer (heuristic)	no

Also known as: Noonan syndrome-like disorder with loose anagen hair 2 · NSLH2

Data availability: 15 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hair anomaly › alopecia › loose anagen syndrome › Noonan syndrome-like disorder with loose anagen hair › Noonan syndrome-like disorder with loose anagen hair 2

Related subtypes (1): Noonan syndrome-like disorder with loose anagen hair 1

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

15 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 4 likely pathogenic, 3 pathogenic, 2 pathogenic/likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
254648	NM_002709.3(PPP1CB):c.146C>G (p.Pro49Arg)	PPP1CB	Pathogenic	reviewed by expert panel
254651	NM_002709.3(PPP1CB):c.548A>T (p.Glu183Val)	PPP1CB	Pathogenic	reviewed by expert panel
254652	NM_002709.3(PPP1CB):c.548A>C (p.Glu183Ala)	PPP1CB	Pathogenic	reviewed by expert panel
449872	NM_002709.3(PPP1CB):c.658C>T (p.Arg220Cys)	PPP1CB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
974912	NM_002709.3(PPP1CB):c.545T>A (p.Met182Lys)	PPP1CB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1727054	NM_002709.3(PPP1CB):c.493G>C (p.Asp165His)	PPP1CB	Likely pathogenic	criteria provided, single submitter
254653	NM_002709.3(PPP1CB):c.820G>A (p.Glu274Lys)	PPP1CB	Likely pathogenic	reviewed by expert panel
3256555	NM_002709.3(PPP1CB):c.493G>A (p.Asp165Asn)	PPP1CB	Likely pathogenic	criteria provided, single submitter
427633	NM_002709.3(PPP1CB):c.166G>C (p.Ala56Pro)	PPP1CB	Likely pathogenic	reviewed by expert panel
1328162	NM_002709.3(PPP1CB):c.434T>A (p.Ile145Asn)	PPP1CB	Uncertain significance	criteria provided, single submitter
2964846	NM_002709.3(PPP1CB):c.943G>A (p.Val315Ile)	PPP1CB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3586395	NM_002709.3(PPP1CB):c.381_383dup (p.Ser128_Ile129insSer)	PPP1CB	Uncertain significance	criteria provided, single submitter
4279746	NM_002709.3(PPP1CB):c.806C>G (p.Pro269Arg)	PPP1CB	Uncertain significance	criteria provided, single submitter
667025	NM_002709.3(PPP1CB):c.201A>G (p.Gln67=)	PPP1CB	Benign	reviewed by expert panel
747303	NM_002709.3(PPP1CB):c.53-9G>A	PPP1CB	Benign	reviewed by expert panel

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
PPP1CB	Definitive	Autosomal dominant	Noonan syndrome-like disorder with loose anagen hair	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PPP1CB	Orphanet:2701	Noonan syndrome-like disorder with loose anagen hair

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
PPP1CB	HGNC:9282	ENSG00000213639	P62140	Serine/threonine-protein phosphatase PP1-beta catalytic subunit	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PPP1CB	Serine/threonine-protein phosphatase PP1-beta catalytic subunit	Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PPP1CB	Phosphatase	yes	3.1.3.16	Calcineurin-like_PHP, Ser/Thr-sp_prot-phosphatase, Metallo-depent_PP-like

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
amniotic fluid	1
buccal mucosa cell	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PPP1CB	295	ubiquitous	marker	calcaneal tendon, amniotic fluid, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PPP1CB	1,044

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PPP1CB	P62140	91.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
SHOC2 M1731 mutant abolishes MRAS complex function	1	1427.5×	0.003	PPP1CB
Gain-of-function MRAS complexes activate RAF signaling	1	1427.5×	0.003	PPP1CB
Phosphorylation and nuclear translocation of the CRY:PER:kinase complex	1	815.7×	0.003	PPP1CB
Maturation of hRSV A proteins	1	761.3×	0.003	PPP1CB
RHO GTPases activate CIT	1	601.0×	0.003	PPP1CB
RHO GTPases Activate ROCKs	1	601.0×	0.003	PPP1CB
RHO GTPases activate PAKs	1	543.8×	0.003	PPP1CB
Triglyceride catabolism	1	475.8×	0.003	PPP1CB
Downregulation of TGF-beta receptor signaling	1	407.9×	0.004	PPP1CB
RAF activation	1	335.9×	0.004	PPP1CB
RHO GTPases activate PKNs	1	317.2×	0.004	PPP1CB
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.009	PPP1CB
mRNA Polyadenylation	1	87.8×	0.011	PPP1CB

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
entrainment of circadian clock by photoperiod	1	732.7×	0.006	PPP1CB
glycogen metabolic process	1	526.6×	0.006	PPP1CB
regulation of cell adhesion	1	306.4×	0.006	PPP1CB
regulation of circadian rhythm	1	259.3×	0.006	PPP1CB
circadian regulation of gene expression	1	234.1×	0.006	PPP1CB
protein dephosphorylation	1	221.7×	0.006	PPP1CB
MAPK cascade	1	153.2×	0.007	PPP1CB
cell division	1	46.2×	0.022	PPP1CB

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
PPP1CB	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
PPP1CB	9	Binding:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PPP1CB	3.1.3.16	protein-serine/threonine phosphatase

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	1	PPP1CB
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)
PPP1CB	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.