3MC syndrome 2

Summary

3MC syndrome 2 (MONDO:0009927) is a disease caused by COLEC11 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: COLEC11 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	3MC syndrome 2
Mondo ID	MONDO:0009927
EFO	EFO:1001977
MeSH	C535586
OMIM	265050
Orphanet	2998
DOID	DOID:0060576
UMLS	C0796279
MedGen	167115
GARD	0018428
Is cancer (heuristic)	no

Also known as: 3MC syndrome 2 · 3MC syndrome caused by mutation in COLEC11 · 3MC syndrome type 2 · 3Mc syndrome type 2 · 3MC2 · Carnevale syndrome · COLEC11 3MC syndrome

Data availability: 20 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › 3MC syndrome › 3MC syndrome 2

Related subtypes (2): 3MC syndrome 3, 3MC syndrome 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

20 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 8 pathogenic, 2 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2637568	NC_000002.11:g.(3660973_3685122)(3692235?)del	COLEC11	Pathogenic	criteria provided, single submitter
30968	NM_024027.5(COLEC11):c.505T>C (p.Ser169Pro)	COLEC11	Pathogenic	no assertion criteria provided
30969	NM_024027.5(COLEC11):c.45del (p.Phe16fs)	COLEC11	Pathogenic	no assertion criteria provided
30970	NM_024027.5(COLEC11):c.610G>A (p.Gly204Ser)	COLEC11	Pathogenic	criteria provided, single submitter
30971	NM_024027.5(COLEC11):c.648_650del (p.Ser217del)	COLEC11	Pathogenic	no assertion criteria provided
30973	COLEC11, EX1-3DEL	COLEC11	Pathogenic	no assertion criteria provided
4089	NM_000112.4(SLC26A2):c.835C>T (p.Arg279Trp)	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4092	NM_000112.4(SLC26A2):c.532C>T (p.Arg178Ter)	SLC26A2	Pathogenic	criteria provided, multiple submitters, no conflicts
4097	NM_000112.4(SLC26A2):c.-26+2T>C	SLC26A2	Pathogenic	criteria provided, multiple submitters, no conflicts
4098	NM_000112.4(SLC26A2):c.1957T>A (p.Cys653Ser)	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1186047	NM_024027.5(COLEC11):c.240_241insGA (p.Arg81fs)	COLEC11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3495847	NM_024027.5(COLEC11):c.192G>A (p.Thr64=)	COLEC11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028290	NM_024027.5(COLEC11):c.307C>T (p.Pro103Ser)	COLEC11	Uncertain significance	criteria provided, single submitter
2440502	NM_024027.5(COLEC11):c.508T>C (p.Cys170Arg)	COLEC11	Uncertain significance	criteria provided, single submitter
2585097	NM_024027.5(COLEC11):c.284G>T (p.Gly95Val)	COLEC11	Uncertain significance	criteria provided, single submitter
2585460	NM_024027.5(COLEC11):c.440G>A (p.Arg147His)	COLEC11	Uncertain significance	criteria provided, single submitter
30972	NM_024027.5(COLEC11):c.309del (p.Gly104fs)	COLEC11	Uncertain significance	criteria provided, single submitter
3901920	NM_024027.5(COLEC11):c.496G>A (p.Ala166Thr)	COLEC11	Uncertain significance	criteria provided, single submitter
638367	NM_024027.5(COLEC11):c.433G>A (p.Gly145Ser)	COLEC11	Uncertain significance	criteria provided, single submitter
992511	NM_024027.5(COLEC11):c.28G>T (p.Val10Phe)	COLEC11	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 5 · 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
COLEC11	Definitive	Autosomal recessive	3MC syndrome 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COLEC11	Orphanet:293843	3MC syndrome
SLC26A2	Orphanet:56304	Atelosteogenesis type II
SLC26A2	Orphanet:628	Diastrophic dysplasia
SLC26A2	Orphanet:93298	Achondrogenesis type 1B
SLC26A2	Orphanet:93307	Multiple epiphyseal dysplasia type 4

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COLEC11	HGNC:17213	ENSG00000118004	Q9BWP8	Collectin-11	gencc,clinvar
SLC26A2	HGNC:10994	ENSG00000155850	P50443	Sulfate transporter	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COLEC11	Collectin-11	Lectin that plays a role in innate immunity, apoptosis and embryogenesis.
SLC26A2	Sulfate transporter	Sulfate transporter which mediates sulfate uptake into chondrocytes in order to maintain adequate sulfation of proteoglycans which is needed for cartilage development.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COLEC11	Other/Unknown	no		C-type_lectin-like, Collagen, C-type_lectin-like/link_sf
SLC26A2	Transporter	yes		SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gall bladder	1
liver	1
right lobe of liver	1
colonic mucosa	1
mucosa of sigmoid colon	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COLEC11	180	tissue_specific	marker	right lobe of liver, gall bladder, liver
SLC26A2	282	ubiquitous	marker	colonic mucosa, mucosa of sigmoid colon, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC26A2	1,793
COLEC11	844

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC26A2	P50443	4
COLEC11	Q9BWP8	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC26A2 causes chondrodysplasias	1	5710.0×	0.004	SLC26A2
Transport and metabolism of PAPS	1	815.7×	0.008	SLC26A2
Lectin pathway of complement activation	1	634.4×	0.008	COLEC11
Inorganic anion exchange by SLC26 transporters	1	634.4×	0.008	SLC26A2
Diseases associated with glycosaminoglycan metabolism	1	380.7×	0.010	SLC26A2
Initial triggering of complement	1	300.5×	0.010	COLEC11
Scavenging by Class A Receptors	1	300.5×	0.010	COLEC11
Cytosolic sulfonation of small molecules	1	259.6×	0.010	SLC26A2
Phase II - Conjugation of compounds	1	139.3×	0.017	SLC26A2
Glycosaminoglycan metabolism	1	109.8×	0.019	SLC26A2
SLC transporter disorders	1	102.0×	0.019	SLC26A2
Disorders of transmembrane transporters	1	69.6×	0.021	SLC26A2
Diseases of glycosylation	1	65.6×	0.021	SLC26A2
Biological oxidations	1	64.9×	0.021	SLC26A2
R-HSA-425393	1	64.9×	0.021	SLC26A2
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.022	SLC26A2
Diseases of metabolism	1	40.2×	0.031	SLC26A2
SLC-mediated transmembrane transport	1	29.6×	0.039	SLC26A2
Transport of small molecules	1	12.6×	0.086	SLC26A2
Disease	1	6.5×	0.154	SLC26A2
Metabolism	1	5.8×	0.165	SLC26A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
oxalate transport	1	1203.7×	0.004	SLC26A2
complement activation, lectin pathway	1	842.6×	0.004	COLEC11
positive regulation of opsonization	1	842.6×	0.004	COLEC11
antimicrobial humoral response	1	766.0×	0.004	COLEC11
cell surface pattern recognition receptor signaling pathway	1	702.2×	0.004	COLEC11
sulfate transmembrane transport	1	601.9×	0.004	SLC26A2
chondrocyte proliferation	1	526.6×	0.004	SLC26A2
execution phase of apoptosis	1	383.0×	0.004	COLEC11
developmental process	1	337.0×	0.004	COLEC11
complement activation	1	312.1×	0.004	COLEC11
chondrocyte differentiation	1	150.5×	0.008	SLC26A2
chloride transmembrane transport	1	118.7×	0.009	SLC26A2
proteolysis	1	17.1×	0.058	COLEC11

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
COLEC11	0	0
SLC26A2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	SLC26A2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	COLEC11

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COLEC11	0	—
SLC26A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.