Multiple benign circumferential skin creases on limbs 1

Summary

Multiple benign circumferential skin creases on limbs 1 (MONDO:0020738) is a disease caused by TUBB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TUBB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple benign circumferential skin creases on limbs 1
Mondo ID	MONDO:0020738
OMIM	156610
DOID	DOID:0112242
UMLS	C4551592
MedGen	1631916
GARD	0025231
Is cancer (heuristic)	no

Also known as: CSCSC1 · symmetric circumferential skin creases, congenital, 1

Data availability: 11 ClinVar variants · 2 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 › multiple benign circumferential skin creases on limbs 1

Related subtypes (1): skin creases, congenital symmetric circumferential, 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

11 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 pathogenic, 2 likely pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
127190	NM_178014.4(TUBB):c.1057G>A (p.Val353Ile)	TUBB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127191	NM_178014.4(TUBB):c.1201G>A (p.Glu401Lys)	TUBB	Pathogenic	criteria provided, multiple submitters, no conflicts
218925	NM_178014.4(TUBB):c.43C>A (p.Gln15Lys)	TUBB	Pathogenic	no assertion criteria provided
218926	NM_178014.4(TUBB):c.665A>T (p.Tyr222Phe)	TUBB	Pathogenic	no assertion criteria provided
1172521	NM_178014.4(TUBB):c.316T>G (p.Tyr106Asp)	TUBB	Likely pathogenic	criteria provided, single submitter
1685467	NM_178014.4(TUBB):c.45G>C (p.Gln15His)	TUBB	Likely pathogenic	criteria provided, single submitter
1207471	NM_178014.4(TUBB):c.361C>T (p.Arg121Trp)	TUBB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
438586	NM_178014.4(TUBB):c.860C>T (p.Pro287Leu)	TUBB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031753	NM_178014.4(TUBB):c.161C>T (p.Ala54Val)	TUBB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3237496	NM_178014.4(TUBB):c.801G>T (p.Met267Ile)	TUBB	Uncertain significance	criteria provided, single submitter
985193	NM_178014.4(TUBB):c.244G>C (p.Gly82Arg)	TUBB	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
TUBB	Strong	Autosomal dominant	multiple benign circumferential skin creases on limbs 1	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUBB	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
TUBB	HGNC:20778	ENSG00000196230	P07437	Tubulin beta chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUBB	Tubulin beta chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

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)
TUBB	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase

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
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBB	133	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUBB	1,512

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TUBB	P07437	21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
Centrosome maturation	1	253.8×	0.018	TUBB
Loss of Nlp from mitotic centrosomes	1	158.6×	0.018	TUBB
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.018	TUBB
AURKA Activation by TPX2	1	152.3×	0.018	TUBB
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.018	TUBB
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.018	TUBB
Mitotic G2-G2/M phases	1	126.9×	0.018	TUBB
G2/M Transition	1	126.9×	0.018	TUBB
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.018	TUBB
Potential therapeutics for SARS	1	114.2×	0.018	TUBB
Anchoring of the basal body to the plasma membrane	1	113.1×	0.018	TUBB
Cilium Assembly	1	108.8×	0.018	TUBB
Mitotic Prometaphase	1	69.2×	0.024	TUBB
Organelle biogenesis and maintenance	1	66.0×	0.024	TUBB
M Phase	1	66.0×	0.024	TUBB
SARS-CoV Infections	1	55.4×	0.027	TUBB
Cell Cycle, Mitotic	1	48.2×	0.029	TUBB
Cell Cycle	1	36.0×	0.037	TUBB
Viral Infection Pathways	1	30.8×	0.041	TUBB
Innate Immune System	1	25.5×	0.046	TUBB
Infectious disease	1	24.8×	0.046	TUBB
Neutrophil degranulation	1	23.1×	0.047	TUBB
Disease	1	13.1×	0.077	TUBB
Immune System	1	13.0×	0.077	TUBB

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
odontoblast differentiation	1	2106.5×	0.003	TUBB
microtubule-based process	1	991.3×	0.003	TUBB
cytoskeleton-dependent intracellular transport	1	936.2×	0.003	TUBB
regulation of synapse organization	1	648.1×	0.003	TUBB
spindle assembly	1	443.5×	0.003	TUBB
natural killer cell mediated cytotoxicity	1	432.1×	0.003	TUBB
mitotic cell cycle	1	133.8×	0.009	TUBB
microtubule cytoskeleton organization	1	121.2×	0.009	TUBB
cell division	1	46.2×	0.022	TUBB

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
TUBB	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBB	22	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBB
VINBLASTINE	4	TUBB
LEVOFLOXACIN ANHYDROUS	4	TUBB
DOCETAXEL	4	TUBB
NOSCAPINE	4	TUBB
VINBLASTINE SULFATE	4	TUBB
PACLITAXEL	4	TUBB
LEVOFLOXACIN	4	TUBB
VINORELBINE	4	TUBB
TIRBANIBULIN	4	TUBB
PODOFILOX	4	TUBB
VINCRISTINE	4	TUBB
DOCETAXEL ANHYDROUS	4	TUBB
PATUPILONE	3	TUBB
ABT-751	2	TUBB
MAYTANSINE	2	TUBB
DOLASTATIN-10	2	TUBB
INDIBULIN	2	TUBB
PARBENDAZOLE	2	TUBB
NOCODAZOLE	2	TUBB
MOLIBRESIB	2	TUBB
COMBRETASTATIN	1	TUBB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TUBB	1,780	Binding:1740, Functional:34, ADMET:6

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TUBB	1,780

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

22 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)
COLCHICINE	4	TUBB
VINBLASTINE	4	TUBB
LEVOFLOXACIN ANHYDROUS	4	TUBB
DOCETAXEL	4	TUBB
NOSCAPINE	4	TUBB
VINBLASTINE SULFATE	4	TUBB
PACLITAXEL	4	TUBB
LEVOFLOXACIN	4	TUBB
VINORELBINE	4	TUBB
TIRBANIBULIN	4	TUBB
PODOFILOX	4	TUBB
VINCRISTINE	4	TUBB
DOCETAXEL ANHYDROUS	4	TUBB
PATUPILONE	3	TUBB
ABT-751	2	TUBB
MAYTANSINE	2	TUBB
DOLASTATIN-10	2	TUBB
INDIBULIN	2	TUBB
PARBENDAZOLE	2	TUBB
NOCODAZOLE	2	TUBB
MOLIBRESIB	2	TUBB
COMBRETASTATIN	1	TUBB

Druggability pyramid

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

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