3M syndrome 3

Summary

3M syndrome 3 (MONDO:0013627) is a disease caused by CCDC8 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CCDC8 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	3M syndrome 3
Mondo ID	MONDO:0013627
OMIM	614205
UMLS	C3280146
MedGen	481776
GARD	0015772
Is cancer (heuristic)	no

Also known as: 3-M syndrome 3 · 3-M syndrome caused by mutation in CCDC8 · 3M syndrome 3 · 3M3 · CCDC8 3-M syndrome · three M syndrome 3 · three M syndrome type 3

Data availability: 22 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › 3-M syndrome › 3M syndrome 3

Related subtypes (2): 3M syndrome 1, 3M syndrome 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

22 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 7 likely pathogenic, 5 conflicting classifications of pathogenicity, 1 pathogenic, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
31105	NM_032040.5(CCDC8):c.84dup (p.Lys29Ter)	CCDC8	Pathogenic	no assertion criteria provided
3338259	NM_032040.5(CCDC8):c.980del (p.Gln327fs)	CCDC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1028424	NM_032040.5(CCDC8):c.803_807delinsT (p.Lys268fs)	CCDC8	Likely pathogenic	criteria provided, single submitter
3065843	NM_032040.5(CCDC8):c.324_331del (p.Ser108fs)	CCDC8	Likely pathogenic	criteria provided, single submitter
31104	NM_032040.5(CCDC8):c.612dup (p.Lys205fs)	CCDC8	Likely pathogenic	criteria provided, single submitter
3374708	NM_032040.5(CCDC8):c.1057del (p.Ala353fs)	CCDC8	Likely pathogenic	criteria provided, single submitter
4293702	NM_032040.5(CCDC8):c.83_86dup (p.Lys29delinsAsnTer)	CCDC8	Likely pathogenic	criteria provided, single submitter
931927	NM_032040.5(CCDC8):c.203_204del (p.Gln68fs)	CCDC8	Likely pathogenic	criteria provided, single submitter
993034	NM_032040.5(CCDC8):c.963del (p.Ala323fs)	CCDC8	Likely pathogenic	criteria provided, single submitter
2429292	NM_032040.5(CCDC8):c.4_22dup (p.Val8fs)	CCDC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2429294	NM_032040.5(CCDC8):c.1027C>T (p.Gln343Ter)	CCDC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779009	NM_032040.5(CCDC8):c.1491G>A (p.Trp497Ter)	CCDC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
714026	NM_032040.5(CCDC8):c.43C>T (p.Arg15Trp)	CCDC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
932012	NM_032040.5(CCDC8):c.817_829del (p.Ser273fs)	CCDC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028422	NM_032040.5(CCDC8):c.287C>G (p.Thr96Arg)	CCDC8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1319607	NM_032040.5(CCDC8):c.1010_1033del (p.Glu337_Arg344del)	CCDC8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1420267	NM_032040.5(CCDC8):c.1094A>C (p.Asp365Ala)	CCDC8	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439805	NM_032040.5(CCDC8):c.917_924delinsTCCTATG (p.Glu306fs)	CCDC8	Uncertain significance	criteria provided, single submitter
2502306	NM_032040.5(CCDC8):c.43C>G (p.Arg15Gly)	CCDC8	Uncertain significance	criteria provided, single submitter
3064906	NM_032040.5(CCDC8):c.807del (p.Asn270fs)	CCDC8	Uncertain significance	criteria provided, single submitter
3779008	NM_032040.5(CCDC8):c.1075C>T (p.Gln359Ter)	CCDC8	Uncertain significance	criteria provided, single submitter
781490	NM_032040.5(CCDC8):c.1045G>C (p.Ala349Pro)	CCDC8	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
CCDC8	Strong	Autosomal recessive	3M syndrome 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCDC8	Orphanet:2616	3M 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
CCDC8	HGNC:25367	ENSG00000169515	Q9H0W5	Coiled-coil domain-containing protein 8	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCDC8	Coiled-coil domain-containing protein 8	Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity.

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)
CCDC8	Other/Unknown	no		CCDC8

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
cardiac muscle of right atrium	1
kidney epithelium	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCDC8	213	ubiquitous	marker	kidney epithelium, upper arm skin, cardiac muscle of right atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCDC8	3,061

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCDC8	Q9H0W5	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Neddylation	1	47.4×	0.063	CCDC8
Post-translational protein modification	1	19.2×	0.078	CCDC8
Metabolism of proteins	1	12.4×	0.081	CCDC8

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 nuclear division	1	624.1×	0.003	CCDC8
microtubule cytoskeleton organization	1	121.2×	0.008	CCDC8

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
CCDC8	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	CCDC8

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)
CCDC8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.