COLEC11

protein-coding

collectin subfamily member 11, the group of C-type lectin domain containing|Complement system activation components|Collectins

Gene summary

This gene encodes a member of the collectin family of C-type lectins that possess collagen-like sequences and carbohydrate recognition domains. Collectins are secreted proteins that play important roles in the innate immune system by binding to carbohydrate antigens on microorganisms, facilitating their recognition and removal. The encoded protein binds to multiple sugars with a preference for fucose and mannose. Mutations in this gene are a cause of 3MC syndrome-2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

MANE transcript

NM_024027.5

Inheritance

ClinVar variants

P:8U:58B:42

Top phenotype

3MC syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr2:3,594,832-3,644,644

External References & Databases

Ensembl (ENSG00000118004)

Transcript & Mutation Effects

hg38 • Region Span ~49.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

3MC syndrome 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009927

Submitter: G2P

3MC syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009927

Submitter: Labcorp Genetics (formerly Invitae)

3MC syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017398

Submitter: Orphanet

Clinical Genomic Database (CGD)

3MC syndrome 2AR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 2569826; 8933348; 21258343

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COLEC11 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 63

Inborn genetic diseasesTotal: 43

not specifiedTotal: 37

COLEC11-related disorderTotal: 25

3MC syndrome 2Total: 14

3MC syndromeTotal: 1

Multiple congenital anomalies/dysmorphic syndrome-intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024027.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	32 clinvar	4 clinvar	39
missense	2 clinvar	1 clinvar	52 clinvar	6 clinvar		61
nonsense						0
start loss						0
frameshift	2 clinvar	3 clinvar	2 clinvar			7
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	4	4	58	38	4	108

Highest pathogenic variant AF is 0.000016727588

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 99 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024027.5	RefSeq	NP_076932.1	6	MANE Select
ENST00000349077.9	Ensembl	ENSP00000339168.4	6	MANE Select
NM_001255982.2	RefSeq	NP_001242911.1	5	Standard
NM_001255983.2	RefSeq	NP_001242912.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
colec11	Danio rerio	Structure: neural crest cell Quality: mislocalised abnormal

Gene / Model

Organism

Observed Phenotype

colec11

Danio rerio

Structure: neural crest cell

Quality: mislocalised

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phagosome - Homo sapiens (human)
Vitamin D Receptor Pathway
Vesicle-mediated transport
Innate Immune System
Immune System

Biological Process

complement activation, lectin pathway
proteolysis
receptor-mediated endocytosis
complement activation
multicellular organism development

Molecular Function

DNA binding
serine-type endopeptidase activity
calcium ion binding
protein binding
mannose binding

Cellular Component

extracellular region
collagen trimer
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000418971
Coding exons: 7
Length: 49623
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.564	159	180	0.882	0.0000131	1844
Missense (PolyPhen)		60	84.026	0.71406		814
Synonymous	-0.903	87	76.9	1.13	0.00000668	563
Loss of Function	2.04	5	12.9	0.388	5.62e-7	157

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000065	0.000062	rare
South Asian	0.000065	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lectin that plays a role in innate immunity, apoptosis and embryogenesis (PubMed:23954398, PubMed:25912189, PubMed:21258343). Calcium-dependent lectin that binds self and non-self glycoproteins presenting high mannose oligosaccharides with at least one terminal alpha-1,2-linked mannose epitope (PubMed:25912189). Primarily recognizes the terminal disaccharide of the glycan (PubMed:25912189). Also recognizes a subset of fucosylated glycans and lipopolysaccharides (PubMed:17179669, PubMed:25912189). Plays a role in innate immunity through its ability to bind non-self sugars presented by microorganisms and to activate the complement through the recruitment of MAPS1 (PubMed:20956340, PubMed:25912189). Also plays a role in apoptosis through its ability to bind in a calcium-independent manner the DNA present at the surface of apoptotic cells and to activate the complement in response to this binding (Probable). Finally, plays a role in development, probably serving as a guidance cue during the migration of neural crest cells and other cell types during embryogenesis (PubMed:21258343, PubMed:28301481). {ECO:0000269|PubMed:17179669, ECO:0000269|PubMed:20956340, ECO:0000269|PubMed:21258343, ECO:0000269|PubMed:23954398, ECO:0000269|PubMed:25912189, ECO:0000269|PubMed:28301481, ECO:0000305|PubMed:20956340, ECO:0000305|PubMed:23954398}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.322
RVIS EVS: -0.11
RVIS percentile EVS: 45.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.267

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium