Skin creases, congenital symmetric circumferential, 2

Summary

Skin creases, congenital symmetric circumferential, 2 (MONDO:0014755) is a disease caused by MAPRE2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MAPRE2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	skin creases, congenital symmetric circumferential, 2
Mondo ID	MONDO:0014755
OMIM	616734
DOID	DOID:0112243
UMLS	C4225225
MedGen	902880
GARD	0016156
Is cancer (heuristic)	no

Also known as: CSCSC2 · MAPRE2 multiple benign circumferential skin creases on limbs · multiple benign circumferential skin creases on limbs caused by mutation in MAPRE2 · skin creases, congenital symmetric circumferential, 2 · skin creases, congenital symmetric circumferential, 2; CSCSC2 · skin creases, congenital symmetric circumferential, type 2 · symmetric circumferential skin creases, congenital, 2

Data availability: 14 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › multiple benign circumferential skin creases on limbs › skin creases, congenital symmetric circumferential, 2

Related subtypes (1): multiple benign circumferential skin creases on limbs 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

14 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
218927	NM_014268.4(MAPRE2):c.260A>G (p.Tyr87Cys)	MAPRE2	Pathogenic	no assertion criteria provided
218928	NM_014268.4(MAPRE2):c.454C>T (p.Gln152Ter)	MAPRE2	Pathogenic	no assertion criteria provided
218929	NM_014268.4(MAPRE2):c.203A>G (p.Asn68Ser)	MAPRE2	Pathogenic	no assertion criteria provided
218930	NM_014268.4(MAPRE2):c.427C>T (p.Arg143Cys)	MAPRE2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705433	NM_014268.4(MAPRE2):c.518G>A (p.Arg173Gln)	MAPRE2	Likely pathogenic	criteria provided, single submitter
633295	NM_014268.4(MAPRE2):c.169_176del (p.Thr57fs)	MAPRE2	Likely pathogenic	criteria provided, single submitter
633596	NM_014268.4(MAPRE2):c.380G>A (p.Arg127Gln)	MAPRE2	Likely pathogenic	no assertion criteria provided
2672722	NC_000018.10:g.34978519_34978522del	LOC126862725	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2498212	NM_014268.4(MAPRE2):c.517C>T (p.Arg173Ter)	MAPRE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3543249	NM_014268.4(MAPRE2):c.868G>A (p.Val290Met)	MAPRE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705460	NM_014268.4(MAPRE2):c.367G>A (p.Ala123Thr)	MAPRE2	Uncertain significance	criteria provided, single submitter
3236062	NM_014268.4(MAPRE2):c.473A>G (p.Tyr158Cys)	MAPRE2	Uncertain significance	criteria provided, single submitter
4292656	NM_014268.4(MAPRE2):c.70G>A (p.Gly24Arg)	MAPRE2	Uncertain significance	criteria provided, single submitter
4819824	NM_014268.4(MAPRE2):c.285C>G (p.Phe95Leu)	MAPRE2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · 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
MAPRE2	Definitive	Autosomal recessive	skin creases, congenital symmetric circumferential, 2	18

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAPRE2	Orphanet:2505	Multiple benign circumferential skin creases on limbs

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
MAPRE2	HGNC:6891	ENSG00000166974	Q15555	Microtubule-associated protein RP/EB family member 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAPRE2	Microtubule-associated protein RP/EB family member 2	Adapter protein that is involved in microtubule polymerization, and spindle function by stabilizing microtubules and anchoring them at centrosomes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAPRE2	Other/Unknown	no		CH_dom, EB1_C, MAPRE

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
corpus callosum	1
cortical plate	1
dorsal root ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAPRE2	300	ubiquitous	marker	cortical plate, dorsal root ganglion, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPRE2	2,195

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAPRE2	Q15555	75.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
positive regulation of ARF protein signal transduction	1	5617.3×	0.001	MAPRE2
positive regulation of focal adhesion disassembly	1	1872.4×	0.001	MAPRE2
protein localization to microtubule	1	1296.3×	0.001	MAPRE2
positive regulation of keratinocyte migration	1	1296.3×	0.001	MAPRE2
regulation of microtubule polymerization or depolymerization	1	1053.2×	0.001	MAPRE2
spindle assembly	1	443.5×	0.003	MAPRE2
cell division	1	46.2×	0.022	MAPRE2

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
MAPRE2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MAPRE2	1	Binding:1

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	MAPRE2

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)
MAPRE2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.