Nevus comedonicus syndrome

Summary

Nevus comedonicus syndrome (MONDO:0014873) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 16

Clinical features

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0010566	Hamartoma	Very frequent (80-99%)
HP:0025249	Comedo	Very frequent (80-99%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0001052	Nevus flammeus	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001595	Abnormality of the hair	Occasional (5-29%)
HP:0001760	Abnormal foot morphology	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0002414	Spina bifida	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0003298	Spina bifida occulta	Occasional (5-29%)
HP:0003468	Abnormal vertebral morphology	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)
HP:0008064	Ichthyosis	Occasional (5-29%)
HP:0100258	Preaxial polydactyly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	nevus comedonicus syndrome
Mondo ID	MONDO:0014873
OMIM	617025
Orphanet	64754
NCIT	C3946
SNOMED CT	35962006
UMLS	C0265987
MedGen	75592
GARD	0013073
Is cancer (heuristic)	no

Also known as: acne Nevus · acneiform Nevus · comedo Nevus · NC · Nevus comedonicus · nevus comedonicus, somatic · pilosebaceous nevoid disorder

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › integumentary system benign neoplasm › benign neoplasm of skin › melanocytic nevus › nevus comedonicus syndrome

Related subtypes (27): conjunctival nevus, blue nevus, halo nevus, intradermal nevus, pigmented spindle cell nevus, nevus, epidermal, neurocutaneous melanocytosis, neutrophil actin dysfunction, CHILD syndrome, Becker nevus syndrome, CLOVES syndrome, segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome, congenital panfollicular nevus, porokeratotic eccrine ostial and dermal duct nevus, hereditary mucosal leukokeratosis, linear verrucous nevus syndrome, nevus of Ota, nevus of Ito, phakomatosis pigmentokeratotica, PENS syndrome, Angora hair nevus, didymosis aplasticosebacea, scalp syndrome, Nevada syndrome, palpebral nevus, large congenital melanocytic nevus, benign melanocytic skin nevus

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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
242987	NM_033116.4(NEK9):c.[1715G>T;1731+1G>T]		Pathogenic	no assertion criteria provided
242988	NM_033116.4(NEK9):c.1817T>C (p.Ile573Thr)	NEK9	Pathogenic	no assertion criteria provided
243002	NM_033116.6(NEK9):c.500T>C (p.Ile167Thr)	NEK9	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEK9	Orphanet:464366	NEK9-related lethal skeletal dysplasia
NEK9	Orphanet:64754	Nevus comedonicus 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
NEK9	HGNC:18591	ENSG00000119638	Q8TD19	Serine/threonine-protein kinase Nek9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEK9	Serine/threonine-protein kinase Nek9	Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NEK9	Kinase	yes		Reg_chr_condens, Prot_kinase_dom, Ser/Thr_kinase_AS

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
left ovary	1
right uterine tube	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEK9	296	ubiquitous	marker	tibia, right uterine tube, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEK9	2,341

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NEK9	Q8TD19	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Activation of NIMA Kinases NEK9, NEK6, NEK7	1	1427.5×	0.006	NEK9
Nuclear Envelope Breakdown	1	456.8×	0.007	NEK9
Mitotic Prophase	1	368.4×	0.007	NEK9
Nuclear Pore Complex (NPC) Disassembly	1	308.6×	0.007	NEK9
EML4 and NUDC in mitotic spindle formation	1	92.8×	0.019	NEK9
Mitotic Prometaphase	1	69.2×	0.019	NEK9
M Phase	1	66.0×	0.019	NEK9
Cell Cycle, Mitotic	1	48.2×	0.023	NEK9
Cell Cycle	1	36.0×	0.028	NEK9

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
regulation of mitotic cell cycle	1	240.7×	0.011	NEK9
mitotic cell cycle	1	133.8×	0.011	NEK9
cell division	1	46.2×	0.022	NEK9

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
NEK9	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NEK9	21	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	NEK9
FEDRATINIB	4	NEK9
DABRAFENIB	4	NEK9
PACRITINIB	4	NEK9
FOSTAMATINIB	4	NEK9
CRIZOTINIB	4	NEK9
DOVITINIB	3	NEK9
LESTAURTINIB	3	NEK9
FORETINIB	2	NEK9
REBASTINIB	2	NEK9
DANUSERTIB	2	NEK9
R-406	2	NEK9
ENMD-2076	2	NEK9
AT-9283	2	NEK9
MILCICLIB	2	NEK9
BMS-754807	2	NEK9
GSK-461364	1	NEK9
KW-2449	1	NEK9
XL-019	1	NEK9
CYC-116	1	NEK9
AST-487	1	NEK9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NEK9	254	Binding:254

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
NEK9	254

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

21 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)
MOMELOTINIB	4	NEK9
FEDRATINIB	4	NEK9
DABRAFENIB	4	NEK9
PACRITINIB	4	NEK9
FOSTAMATINIB	4	NEK9
CRIZOTINIB	4	NEK9
DOVITINIB	3	NEK9
LESTAURTINIB	3	NEK9
FORETINIB	2	NEK9
REBASTINIB	2	NEK9
DANUSERTIB	2	NEK9
R-406	2	NEK9
ENMD-2076	2	NEK9
AT-9283	2	NEK9
MILCICLIB	2	NEK9
BMS-754807	2	NEK9
GSK-461364	1	NEK9
KW-2449	1	NEK9
XL-019	1	NEK9
CYC-116	1	NEK9
AST-487	1	NEK9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NEK9
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.