Immunodeficiency-centromeric instability-facial anomalies syndrome 3

Summary

Immunodeficiency-centromeric instability-facial anomalies syndrome 3 (MONDO:0014828) is a disease caused by CDCA7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CDCA7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency-centromeric instability-facial anomalies syndrome 3
Mondo ID	MONDO:0014828
OMIM	616910
DOID	DOID:0090010
UMLS	C4310799
MedGen	934766
GARD	0016168
Is cancer (heuristic)	no

Also known as: CDCA7 immunodeficiency-centromeric instability-facial anomalies syndrome · ICF3 · immunodeficiency-centromeric instability-Facial anomalies syndrome 3 · immunodeficiency-centromeric instability-facial anomalies syndrome caused by mutation in CDCA7 · immunodeficiency-centromeric instability-Facial anomalies syndrome type 3 · immunodeficiency-centromeric instability-facial anomalies syndrome type 3

Data availability: 17 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › immunodeficiency-centromeric instability-facial anomalies syndrome › immunodeficiency-centromeric instability-facial anomalies syndrome 3

Related subtypes (3): immunodeficiency-centromeric instability-facial anomalies syndrome 1, immunodeficiency-centromeric instability-facial anomalies syndrome 2, immunodeficiency-centromeric instability-facial anomalies syndrome 4

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

17 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 benign, 2 likely benign, 2 likely pathogenic, 1 benign/likely benign, 1 no classifications from unflagged records, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
225529	NM_031942.5(CDCA7):c.1057C>T (p.Arg353Cys)	CDCA7	Likely pathogenic	criteria provided, single submitter
225532	NM_031942.5(CDCA7):c.1058G>A (p.Arg353His)	CDCA7	Likely pathogenic	criteria provided, single submitter
225531	NM_031942.5(CDCA7):c.1148G>A (p.Arg383His)	CDCA7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1357119	NM_031942.5(CDCA7):c.1172C>G (p.Ala391Gly)	CDCA7	Uncertain significance	criteria provided, multiple submitters, no conflicts
225530	NM_031942.5(CDCA7):c.1118del (p.Gly373fs)	CDCA7	no classifications from unflagged records	no classifications from unflagged records
2431847	NM_031942.5(CDCA7):c.1314_1319del (p.Tyr438_Lys440delinsTer)	CDCA7	Uncertain significance	criteria provided, single submitter
2921138	NM_031942.5(CDCA7):c.547T>C (p.Ser183Pro)	CDCA7	Uncertain significance	criteria provided, single submitter
3893033	NM_031942.5(CDCA7):c.22-2A>C	CDCA7	Uncertain significance	criteria provided, single submitter
4846985	NM_031942.5(CDCA7):c.1020dup (p.Tyr341fs)	CDCA7	Uncertain significance	criteria provided, single submitter
964462	NM_031942.5(CDCA7):c.731C>T (p.Pro244Leu)	CDCA7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1167455	NM_031942.5(CDCA7):c.22-17G>T	CDCA7	Benign	criteria provided, multiple submitters, no conflicts
1192545	NM_031942.5(CDCA7):c.895-27C>G	CDCA7	Benign	criteria provided, multiple submitters, no conflicts
1192713	NM_031942.5(CDCA7):c.622-128C>T	CDCA7	Benign	criteria provided, multiple submitters, no conflicts
1656996	NM_031942.5(CDCA7):c.1322+19dup	CDCA7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1672916	NM_031942.5(CDCA7):c.993C>T (p.Asn331=)	CDCA7	Likely benign	criteria provided, multiple submitters, no conflicts
707884	NM_031942.5(CDCA7):c.745A>C (p.Arg249=)	CDCA7	Likely benign	criteria provided, multiple submitters, no conflicts
785981	NM_031942.5(CDCA7):c.1077C>G (p.Thr359=)	CDCA7	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
CDCA7	Strong	Autosomal recessive	immunodeficiency-centromeric instability-facial anomalies syndrome 3	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDCA7	Orphanet:2268	ICF 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
CDCA7	HGNC:14628	ENSG00000144354	Q9BWT1	Cell division cycle-associated protein 7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDCA7	Cell division cycle-associated protein 7	Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDCA7	Transcription factor	no		Znf-4CXXC_R1, CDCA7/CDA7L

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
embryo	1
ileal mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDCA7	215	ubiquitous	marker	ileal mucosa, ventricular zone, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDCA7	1,875

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDCA7	Q9BWT1	2

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
regulation of cell population proliferation	1	115.4×	0.026	CDCA7
regulation of DNA-templated transcription	1	31.6×	0.035	CDCA7
apoptotic process	1	28.7×	0.035	CDCA7

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDCA7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CDCA7

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)
CDCA7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.