Epidermodysplasia verruciformis, susceptibility to, 3

Summary

Epidermodysplasia verruciformis, susceptibility to, 3 (MONDO:0032644) is a disease caused by CIB1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CIB1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermodysplasia verruciformis, susceptibility to, 3
Mondo ID	MONDO:0032644
OMIM	618267
UMLS	C4748876
MedGen	1648390
Is cancer (heuristic)	no

Also known as: epidermodysplasia verruciformis 3 · EV3

Data availability: 8 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › epidermodysplasia verruciformis, susceptibility to › epidermodysplasia verruciformis, susceptibility to, 3

Related subtypes (4): epidermodysplasia verruciformis, susceptibility to, 2, epidermodysplasia verruciformis, susceptibility to, 4, epidermodysplasia verruciformis, susceptibility to, 5, epidermodysplasia verruciformis, susceptibility to, 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

8 retrieved; paginated sample, class counts are floors:

3 risk factor, 2 likely pathogenic, 2 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
599257	NM_006384.4(CIB1):c.214C>T (p.Arg72Ter)	CIB1	Pathogenic	criteria provided, single submitter
599258	NM_006384.4(CIB1):c.52-2A>G	CIB1	Pathogenic	criteria provided, single submitter
3065461	NM_006384.4(CIB1):c.465+1G>A	CIB1	Likely pathogenic	criteria provided, single submitter
3779081	NM_006384.4(CIB1):c.7_8del (p.Gly3fs)	CIB1	Likely pathogenic	criteria provided, single submitter
599254	NM_006384.4(CIB1):c.248_249del (p.Lys83fs)	CIB1	risk factor	no assertion criteria provided
599255	NM_006384.4(CIB1):c.465+1dup	CIB1	risk factor	no assertion criteria provided
599256	NM_006384.4(CIB1):c.548_549dup (p.Ala184fs)	CIB1	risk factor	no assertion criteria provided
4796739	NM_006384.4(CIB1):c.436G>A (p.Ala146Thr)	CIB1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CIB1	Definitive	Autosomal recessive	epidermodysplasia verruciformis, susceptibility to, 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CIB1	Orphanet:302	Inherited epidermodysplasia verruciformis

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
CIB1	HGNC:16920	ENSG00000185043	Q99828	Calcium and integrin-binding protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CIB1	Calcium and integrin-binding protein 1	Calcium-binding protein that plays a role in the regulation of numerous cellular processes, such as cell differentiation, cell division, cell proliferation, cell migration, thrombosis, angiogenesis, cardiac hypertrophy and apoptosis.

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)
CIB1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS

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
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CIB1	289	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CIB1	2,642

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CIB1	Q99828	9

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 male germ cell proliferation	1	16852.0×	0.002	CIB1
endomitotic cell cycle	1	5617.3×	0.004	CIB1
positive regulation of catalytic activity	1	2407.4×	0.005	CIB1
thrombopoietin-mediated signaling pathway	1	2106.5×	0.005	CIB1
positive regulation of protein serine/threonine kinase activity	1	1296.3×	0.005	CIB1
positive regulation of cell adhesion mediated by integrin	1	1053.2×	0.005	CIB1
negative regulation of megakaryocyte differentiation	1	887.0×	0.005	CIB1
positive regulation of calcineurin-NFAT signaling cascade	1	802.5×	0.005	CIB1
regulation of cell division	1	766.0×	0.005	CIB1
positive regulation of cell migration involved in sprouting angiogenesis	1	732.7×	0.005	CIB1
platelet formation	1	702.2×	0.005	CIB1
positive regulation of cell-matrix adhesion	1	674.1×	0.005	CIB1
negative regulation of protein phosphorylation	1	581.1×	0.005	CIB1
positive regulation of protein targeting to membrane	1	561.7×	0.005	CIB1
negative regulation of microtubule depolymerization	1	495.6×	0.005	CIB1
cellular response to nerve growth factor stimulus	1	468.1×	0.005	CIB1
positive regulation of substrate adhesion-dependent cell spreading	1	374.5×	0.006	CIB1
cytoplasmic microtubule organization	1	343.9×	0.007	CIB1
cellular response to growth factor stimulus	1	318.0×	0.007	CIB1
extrinsic apoptotic signaling pathway	1	306.4×	0.007	CIB1
positive regulation of protein phosphorylation	1	276.3×	0.007	CIB1
positive regulation of protein localization to plasma membrane	1	271.8×	0.007	CIB1
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	263.3×	0.007	CIB1
response to ischemia	1	251.5×	0.007	CIB1
negative regulation of neuron projection development	1	237.3×	0.007	CIB1
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.007	CIB1
double-strand break repair	1	203.0×	0.007	CIB1
positive regulation of cell growth	1	183.2×	0.008	CIB1
cellular response to tumor necrosis factor	1	163.6×	0.009	CIB1
spermatid development	1	145.3×	0.009	CIB1

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
CIB1	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
CIB1	12	Binding:12

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	CIB1

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)
CIB1	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.