COLEC11

Summary

COLEC11 (collectin subfamily member 11, HGNC:17213) is a protein-coding gene on chromosome 2p25.3, encoding Collectin-11 (Q9BWP8). Lectin that plays a role in innate immunity, apoptosis and embryogenesis.

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.

Source: NCBI Gene 78989 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 3MC syndrome 2 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 13
• Clinical variants (ClinVar): 141 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_024027

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17213
Approved symbol	COLEC11
Name	collectin subfamily member 11
Location	2p25.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC3279, CL-K1, CL-11
Ensembl gene	ENSG00000118004
Ensembl biotype	protein_coding
OMIM	612502
Entrez	78989

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 43 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000236693, ENST00000349077, ENST00000382062, ENST00000402794, ENST00000402922, ENST00000403096, ENST00000404205, ENST00000416132, ENST00000418971, ENST00000419002, ENST00000438814, ENST00000460971, ENST00000487365, ENST00000856326, ENST00000856327, ENST00000856328, ENST00000856329, ENST00000856330, ENST00000856331, ENST00000856332, ENST00000856333, ENST00000856334, ENST00000856335, ENST00000856336, ENST00000856337, ENST00000856338, ENST00000856339, ENST00000856340, ENST00000856341, ENST00000856342, ENST00000856343, ENST00000856344, ENST00000856345, ENST00000856346, ENST00000856347, ENST00000856348, ENST00000856349, ENST00000856350, ENST00000856351, ENST00000856352, ENST00000856353, ENST00000856354, ENST00000856355, ENST00000856356, ENST00000856357, ENST00000856358, ENST00000922248

RefSeq mRNA: 10 — MANE Select: NM_024027 NM_001255982, NM_001255983, NM_001255984, NM_001255985, NM_001255986, NM_001255987, NM_001255988, NM_001255989, NM_024027, NM_199235

CCDS: CCDS1649, CCDS1650, CCDS58689, CCDS58690, CCDS58691, CCDS58692, CCDS58693, CCDS58694

Canonical transcript exons

ENST00000349077 — 7 exons

Exon	Start	End
ENSE00000999153	3643727	3644644
ENSE00001829192	3595112	3595168
ENSE00003492033	3643444	3643539
ENSE00003537658	3613311	3613382
ENSE00003580209	3604315	3604470
ENSE00003582592	3637533	3637604
ENSE00003785362	3640278	3640331

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 96.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2975 / max 856.8242, expressed in 125 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18641	1.2975	125

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.19	gold quality
gall bladder	UBERON:0002110	96.08	gold quality
liver	UBERON:0002107	94.21	gold quality
right atrium auricular region	UBERON:0006631	92.12	gold quality
cardiac atrium	UBERON:0002081	91.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.59	gold quality
left adrenal gland cortex	UBERON:0035825	91.55	gold quality
left adrenal gland	UBERON:0001234	91.35	gold quality
adrenal cortex	UBERON:0001235	91.17	gold quality
left ovary	UBERON:0002119	90.21	gold quality
adrenal gland	UBERON:0002369	89.99	gold quality
right adrenal gland cortex	UBERON:0035827	89.92	gold quality
right adrenal gland	UBERON:0001233	89.72	gold quality
right ovary	UBERON:0002118	87.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.33	gold quality
decidua	UBERON:0002450	85.78	gold quality
adult mammalian kidney	UBERON:0000082	85.74	gold quality
ovary	UBERON:0000992	85.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.73	gold quality
apex of heart	UBERON:0002098	83.83	gold quality
nephron tubule	UBERON:0001231	83.43	gold quality
left lobe of thyroid gland	UBERON:0001120	82.51	gold quality
omental fat pad	UBERON:0010414	82.03	gold quality
myocardium	UBERON:0002349	81.98	silver quality
peritoneum	UBERON:0002358	81.96	gold quality
kidney epithelium	UBERON:0004819	81.69	gold quality
heart	UBERON:0000948	81.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.21	gold quality
right lobe of thyroid gland	UBERON:0001119	81.15	gold quality
kidney	UBERON:0002113	81.04	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	3705.77
E-CURD-98	yes	3493.02
E-ANND-5	yes	685.73
E-MTAB-9388	yes	11.72
E-HCAD-9	yes	8.52
E-GEOD-81547	yes	8.28
E-MTAB-10553	yes	5.95
E-ANND-3	yes	4.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting COLEC11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-15A-3P	97.47	65.08	527
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-4529-3P	96.40	66.46	582
HSA-MIR-6861-5P	96.23	67.19	800
HSA-MIR-4453	95.61	65.84	436
HSA-MIR-4538	95.61	65.34	449
HSA-MIR-3914	94.91	65.77	643
HSA-MIR-4793-3P	94.87	65.85	896

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 22)

• CL-11 plays a role in activation of the complement system and in the defense against invading microorganisms (PMID:20956340)
• these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome. (PMID:21258343)
• Data show that the concentration of collectin kidney 1 (CL-K1, COLEC11) in plasma was 0.34 +/- 0.13 microg/ml and that in mannan-binding lectin (MBL) was 1.72 +/- 1.51 microg/ml. (PMID:21893516)
• collectin-11 associates with all the known MBL-associated serine proteases (MASP-1, MASP-2 and MASP-3) as well as the lectin complement pathway regulator MAP-1. (PMID:23220946)
• Data suggest that collectin 11 (CL-11), e.g. via complement, may play a role in response to particles and surfaces presenting extracellular DNA, such as apopototic cells. (PMID:23954398)
• Most plasma CL-K1 was found in complex with CL-L1 in a ratio suggesting a heteromeric subunit of 1 CL-L1 & 2 CL-K1 polypeptides. It associated with MASPs 1, 2 & 3. On binding mannan or DNA in the presence of MASP-2, the complex deposited C4b. (PMID:24174618)
• These results suggest that specific diseases may affect CL-K1 synthesis in an organ dependent manner and that elevated plasma CL-K1 levels are associated with the presence of DIC. (PMID:24474086)
• promoter polymorphism COLEC11-9570C>T (rs3820897) was associated with decreased levels of CL-K1. (PMID:25710878)
• the sugar specificity of CL-K1 was established. (PMID:25912189)
• Data indicate differences in the plasma concentrations of collectin liver 1 and collectin kidney 1, M-ficolin and H-ficol in systemic lupus erythematosus (SLE) patients compared to a group of healthy controls. (PMID:26154564)
• identify collectin CL-LK as a novel soluble C-type lectin able to bind M. tuberculosis, and characterize mycobacterial mannose-capped lipoarabinomannan as a primary ligand for CL-LK (PMID:26173080)
• The exclusion of the MASP1 and COLEC11 Loci in two individuals from different consanguineous families and the absence of mutations in four further individuals sequenced for both genes raises the possibility that that there is further genetic heterogeneity of 3MC syndrome (PMID:26789649)
• High CLK1 expression is associated with cardiovascular disease. (PMID:27341702)
• this study demonstrates the role of CL-11 and the molecular mechanisms involved in modulating retinal pigment epithelial cell phagocytosis and cytokine production (PMID:28772263)
• Collectin liver 1 (CL-L1, collectin 10) and collectin kidney 1 (CL-K1, collectin 11) were found widespread and almost identical tissue with a high expression in epithelial cells in endo-/exocrine secretory tissues and mucosa. (PMID:30108587)
• this review discuss the role of collectin-11 as a pattern recognition molecule in complement-mediated ischemic kidney injury (PMID:30237800)
• The allele rs7567833G, the genotypes rs7567833AG and rs7567833GG, and the COLEC11*GGC haplotype were related to T. cruzi infection and clinical progression towards symptomatic Chagas Disease (CD). COLEC11 and MASP2*CD risk genotypes were associated with cardiomyopathy, suggesting that both loci act synergistically in immune modulation of the disease. (PMID:30995222)
• C1q/TNF-Related Protein 6 Is a Pattern Recognition Molecule That Recruits Collectin-11 from the Complement System to Ligands. (PMID:32041782)
• Importance of glycosylation in the interaction of Tamm-Horsfall protein with collectin-11 and acute kidney injury. (PMID:32045104)
• Association of Polymorphisms of MASP1/3, COLEC10, and COLEC11 Genes with 3MC Syndrome. (PMID:32751929)
• Collectin11 and Complement Activation in IgA Nephropathy. (PMID:34615657)
• Collectin-11 promotes cancer cell proliferation and tumor growth. (PMID:36883567)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	colec11	ENSDARG00000013266
mus_musculus	Colec11	ENSMUSG00000036655
rattus_norvegicus	Colec11	ENSRNOG00000008373

Paralogs (4): SFTPA1 (ENSG00000122852), SFTPD (ENSG00000133661), COLEC10 (ENSG00000184374), SFTPA2 (ENSG00000185303)

Protein

Protein identifiers

Collectin-11 — Q9BWP8 (reviewed: Q9BWP8)

Alternative names: Collectin kidney protein 1

All UniProt accessions (3): C9JWT5, Q9BWP8, F8WB29

UniProt curated annotations — full annotation on UniProt →

Function. Lectin that plays a role in innate immunity, apoptosis and embryogenesis. 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. Primarily recognizes the terminal disaccharide of the glycan. Also recognizes a subset of fucosylated glycans and lipopolysaccharides. 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. 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. 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.

Subunit / interactions. Homotrimer; disulfide-linked. Interacts with MASP1; probably triggers the lectin pathway of complement.

Subcellular location. Secreted.

Tissue specificity. Ubiquitous. Detected in adrenal gland, kidney, liver, ovaries and testis (at protein level).

Disease relevance. 3MC syndrome 2 (3MC2) [MIM:265050] A form of 3MC syndrome, an autosomal recessive disorder characterized by facial dysmorphism, craniosynostosis, learning disability, and genital, limb and vesicorenal anomalies. Facial features include hypertelorism, blepharophimosis, blepharoptosis and highly arched eyebrows, cleft lip and/or palate. The term 3MC syndrome includes Carnevale, Mingarelli, Malpuech, and Michels syndromes. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the COLEC10/COLEC11 family.

Isoforms (10)

UniProt ID	Names	Canonical?
Q9BWP8-1	1, CL-K1-I	yes
Q9BWP8-2	2, CL-K1-Ia
Q9BWP8-3	3, CL-K1-Ib
Q9BWP8-4	4, CL-K1-II
Q9BWP8-5	5, CL-K1-Ic
Q9BWP8-6	6, CL-K1-IIa
Q9BWP8-7	7, CL-K1-IIb
Q9BWP8-8	8, CL-K1-IIc
Q9BWP8-9	9
Q9BWP8-10	10

RefSeq proteins (10): NP_001242911, NP_001242912, NP_001242913, NP_001242914, NP_001242915, NP_001242916, NP_001242917, NP_001242918, NP_076932, NP_954705 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR008160	Collagen	Repeat
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR033990	Collectin_CTLD	Domain
IPR051077	Ca-dependent_lectin	Family

Pfam: PF00059, PF01391

UniProt features (54 total): binding site 17, splice variant 10, strand 6, sequence variant 5, helix 4, domain 2, disulfide bond 2, sequence conflict 2, compositionally biased region 2, signal peptide 1, chain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9SRK	X-RAY DIFFRACTION	1.8
4YLI	X-RAY DIFFRACTION	2.45
4YMD	X-RAY DIFFRACTION	2.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWP8-F1	79.64	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (17): 211; 211; 232; 234; 235; 238; 240; 240; 240; 241; 241; 244 …

Disulfide bonds (2): 170–264, 242–256

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-166662	Lectin pathway of complement activation
R-HSA-166663	Initial triggering of complement
R-HSA-3000480	Scavenging by Class A Receptors

MSigDB gene sets: 263 (showing top): chr2p25, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOCC_COLLAGEN_TRIMER, REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_COMPLEMENT_ACTIVATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN

GO Biological Process (10): complement activation, lectin pathway (GO:0001867), cell surface pattern recognition receptor signaling pathway (GO:0002752), proteolysis (GO:0006508), complement activation (GO:0006956), antimicrobial humoral response (GO:0019730), developmental process (GO:0032502), execution phase of apoptosis (GO:0097194), positive regulation of opsonization (GO:1903028), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (10): DNA binding (GO:0003677), calcium ion binding (GO:0005509), D-mannose binding (GO:0005537), identical protein binding (GO:0042802), fucose binding (GO:0042806), oligosaccharide binding (GO:0070492), calcium-dependent carbohydrate binding (GO:0120153), protein binding (GO:0005515), carbohydrate binding (GO:0030246), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), external side of plasma membrane (GO:0009897), serine-type endopeptidase complex (GO:1905370), endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Creation of C4 and C2 activators	1
Complement cascade	1
Binding and Uptake of Ligands by Scavenger Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
humoral immune response	2
defense response to symbiont	2
biological_process	2
monosaccharide binding	2
carbohydrate binding	2
binding	2
complement activation	1
innate immune response	1
innate immune response activating cell surface receptor signaling pathway	1
pattern recognition receptor signaling pathway	1
protein metabolic process	1
immune effector process	1
activation of immune response	1
protein activation cascade	1
apoptotic process	1
cellular process	1
bleb assembly	1
positive regulation of immune effector process	1
opsonization	1
positive regulation of phagocytosis	1
regulation of opsonization	1
immune response	1
nucleic acid binding	1
metal ion binding	1
protein binding	1
cation binding	1
cellular anatomical structure	1
protein-containing complex	1
plasma membrane	1
cell surface	1
side of membrane	1
serine-type peptidase complex	1
endopeptidase complex	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COLEC11	MASP2	O00187	892
COLEC11	COLEC10	Q9Y6Z7	874
COLEC11	MBL2	P11226	874
COLEC11	FCN3	O75636	862
COLEC11	CLEC12A	Q5QGZ9	860
COLEC11	F8W876	F8W876	770
COLEC11	C1S	P09871	754
COLEC11	C1R	P00736	753
COLEC11	FCN1	O00602	738
COLEC11	FCN2	Q15485	711
COLEC11	KIR3DL1	P43629	691
COLEC11	PRSS2	P07478	636
COLEC11	C3	P01024	581
COLEC11	CFP	P27918	542
COLEC11	C4A	P01028	514

IntAct

28 interactions, top by confidence:

A	B	Type	Score
COLEC11	COLEC11	psi-mi:“MI:0407”(direct interaction)	0.680
COLEC11	COLEC11	psi-mi:“MI:0915”(physical association)	0.680
COLEC11	MASP1	psi-mi:“MI:0915”(physical association)	0.560
COLEC11	MASP1	psi-mi:“MI:0915”(physical association)	0.520
COLEC11	MASP2	psi-mi:“MI:0915”(physical association)	0.520
MASP2	COLEC11	psi-mi:“MI:0915”(physical association)	0.520
MASP1	COLEC11	psi-mi:“MI:0915”(physical association)	0.520
COLEC11	COLEC11	psi-mi:“MI:0914”(association)	0.460
N	COLEC11	psi-mi:“MI:0915”(physical association)	0.400
S	COLEC11	psi-mi:“MI:0915”(physical association)	0.400
	COLEC11	psi-mi:“MI:0915”(physical association)	0.400
COLEC11	COLEC10	psi-mi:“MI:0915”(physical association)	0.400
COLEC10	COLEC11	psi-mi:“MI:0915”(physical association)	0.400
COLEC11	MASP1	psi-mi:“MI:0915”(physical association)	0.400
	MASP1	psi-mi:“MI:0914”(association)	0.350
COLEC11	ALB	psi-mi:“MI:0914”(association)	0.350
COLEC11	PLOD3	psi-mi:“MI:0914”(association)	0.350
COLEC11	PLOD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): ASB7 (Affinity Capture-MS), NELL2 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), CDC6 (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), RPL23 (Affinity Capture-MS), TIMP3 (Affinity Capture-MS), COL6A1 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), MTFR1 (Affinity Capture-MS), KLHDC2 (Affinity Capture-MS), FBXO21 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), NELL2 (Affinity Capture-MS), TIMP3 (Affinity Capture-MS)

ESM2 similar proteins: A4KWA1, O88200, O88201, P02706, P07306, P07307, P08290, P18519, P21854, P24721, P26951, P27471, P27812, P27814, P34927, P49300, P49301, P78380, P79391, Q0VCS6, Q2HXU8, Q3LUH2, Q3SXB8, Q49BZ4, Q5NKN2, Q5NKN4, Q5RBQ8, Q61190, Q6QLQ4, Q6UX15, Q6UXB4, Q8BNX1, Q8BWY2, Q8C1T8, Q8HZR8, Q8IUN9, Q8NC01, Q8VBX4, Q8VD98, Q8WTT0

Diamond homologs: A7X3Z0, P0C6B8, P14151, P16109, P16581, P18337, P19070, P22897, P27113, P30836, P33730, P42201, P98105, P98106, P98107, P98109, P98110, P98131, Q00690, Q01102, Q09101, Q17QH6, Q28768, Q2LK94, Q3SXB8, Q4LDE5, Q61830, Q6ZS10, Q7Z407, Q80T79, Q8AV98, Q8CJ91, Q8JGT6, Q923L3, Q95198, Q95235, Q95237, Q95LG1, Q9BWP8, A1XXJ9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PAMPs	“up-regulates activity”	COLEC11	binding
COLEC11	“up-regulates activity”	MASP1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

141 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	56
Likely benign	51
Benign	11

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
2637568	NC_000002.11:g.(3660973_3685122)(3692235?)del	Pathogenic
3068586	NM_024027.5(COLEC11):c.82_94del (p.Ala28fs)	Pathogenic
30968	NM_024027.5(COLEC11):c.505T>C (p.Ser169Pro)	Pathogenic
30969	NM_024027.5(COLEC11):c.45del (p.Phe16fs)	Pathogenic
30970	NM_024027.5(COLEC11):c.610G>A (p.Gly204Ser)	Pathogenic
30971	NM_024027.5(COLEC11):c.648_650del (p.Ser217del)	Pathogenic
30973	COLEC11, EX1-3DEL	Pathogenic
2499839	NM_024027.5(COLEC11):c.241del (p.Arg81fs)	Likely pathogenic

SpliceAI

1560 predictions. Top by Δscore:

Variant	Effect	Δscore
2:3640275:CAG:C	acceptor_loss	1.0000
2:3640276:A:AG	acceptor_gain	1.0000
2:3640277:G:GA	acceptor_gain	1.0000
2:3640277:GGT:G	acceptor_gain	1.0000
2:3640277:GGTGA:G	acceptor_gain	1.0000
2:3643535:GAATG:G	donor_gain	1.0000
2:3643537:ATGGT:A	donor_loss	1.0000
2:3643539:GGTA:G	donor_loss	1.0000
2:3643540:G:GA	donor_loss	1.0000
2:3643540:G:GG	donor_gain	1.0000
2:3643541:T:A	donor_loss	1.0000
2:3643719:C:G	acceptor_gain	1.0000
2:3643723:ACAG:A	acceptor_loss	1.0000
2:3643724:CAGCT:C	acceptor_loss	1.0000
2:3643725:A:AG	acceptor_gain	1.0000
2:3643725:AGCT:A	acceptor_gain	1.0000
2:3643726:G:GT	acceptor_gain	1.0000
2:3643726:GC:G	acceptor_gain	1.0000
2:3643726:GCT:G	acceptor_gain	1.0000
2:3643726:GCTG:G	acceptor_gain	1.0000
2:3595165:TCAG:T	donor_loss	0.9900
2:3595166:CAG:C	donor_loss	0.9900
2:3595167:AG:A	donor_loss	0.9900
2:3595168:GG:G	donor_loss	0.9900
2:3595169:G:GC	donor_loss	0.9900
2:3595170:T:G	donor_loss	0.9900
2:3624778:G:T	donor_gain	0.9900
2:3637527:CTACA:C	acceptor_loss	0.9900
2:3637528:TACA:T	acceptor_loss	0.9900
2:3637532:G:GC	acceptor_loss	0.9900

AlphaMissense

1773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:3643986:G:C	W228C	1.000
2:3643986:G:T	W228C	1.000
2:3643984:T:A	W228R	0.999
2:3643984:T:C	W228R	0.999
2:3644053:T:A	W251R	0.999
2:3644053:T:C	W251R	0.999
2:3644055:G:C	W251C	0.999
2:3644055:G:T	W251C	0.999
2:3644092:T:A	C264S	0.999
2:3644093:G:C	C264S	0.999
2:3643810:T:A	C170S	0.998
2:3643811:G:A	C170Y	0.998
2:3643811:G:C	C170S	0.998
2:3644026:T:A	C242S	0.998
2:3644026:T:C	C242R	0.998
2:3644027:G:C	C242S	0.998
2:3644092:T:C	C264R	0.998
2:3637587:G:A	G86D	0.997
2:3643812:C:G	C170W	0.997
2:3644027:G:A	C242Y	0.997
2:3644028:C:G	C242W	0.997
2:3644054:G:C	W251S	0.997
2:3644093:G:A	C264Y	0.997
2:3644094:T:G	C264W	0.997
2:3637578:G:A	G83E	0.996
2:3643766:T:C	L155P	0.996
2:3643798:G:C	A166P	0.996
2:3643799:C:A	A166D	0.996
2:3643810:T:C	C170R	0.996
2:3643841:C:A	P180H	0.996

dbSNP variants (sampled 300 via entrez): RS1000006306 (2:3598906 A>C,G), RS1000026153 (2:3612968 G>A,C), RS1000071902 (2:3623952 T>C), RS1000139399 (2:3608735 G>T), RS1000174470 (2:3640423 A>C,G), RS1000191702 (2:3621916 C>G,T), RS1000213095 (2:3608472 C>T), RS1000286878 (2:3593993 G>T), RS1000431094 (2:3627475 G>C), RS1000439151 (2:3635900 G>C,T), RS1000454499 (2:3616333 C>G), RS1000536105 (2:3631944 G>A), RS1000580752 (2:3631918 C>G), RS1000588196 (2:3631724 C>A), RS1000613851 (2:3600190 G>A,C,T)

Disease associations

OMIM: gene MIM:612502 | disease phenotypes: MIM:265050, MIM:257920

GenCC curated gene-disease

Disease	Classification	Inheritance
3MC syndrome 2	Definitive	Autosomal recessive
3MC syndrome	Supportive	Autosomal recessive

Mondo (2): 3MC syndrome 2 (MONDO:0009927), 3MC syndrome (MONDO:0017398)

Orphanet (2): 3MC syndrome (Orphanet:293843), Carnevale syndrome (Orphanet:2998)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000289	Broad philtrum
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000437	Depressed nasal tip
HP:0000473	Torticollis
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000537	Epicanthus inversus
HP:0000581	Blepharophimosis
HP:0000593	Abnormal anterior chamber morphology
HP:0000925	Abnormality of the vertebral column
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST003194_23	Fibrinogen levels	1.000000e-08
GCST006630_91	Diastolic blood pressure	5.000000e-09
GCST007998_8	Intraocular pressure	7.000000e-10
GCST008758_29	Pre-treatment viral load in HIV-1 infection	8.000000e-17
GCST009286_1	Chronic kidney disease (reduced eGFR or end stage renal disease) in type 1 diabetes	9.000000e-09
GCST010241_146	Apolipoprotein A1 levels	1.000000e-20
GCST010242_414	HDL cholesterol levels	2.000000e-23
GCST010244_330	Triglyceride levels	4.000000e-14
GCST010245_20	LDL cholesterol levels	7.000000e-09
GCST90000025_790	Appendicular lean mass	1.000000e-13
GCST90011900_137	Serum alkaline phosphatase levels	2.000000e-12
GCST90013406_125	Liver enzyme levels (alkaline phosphatase)	3.000000e-23
GCST90013407_190	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-34

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004695	intraocular pressure measurement
EFO:0010125	viral load
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535586	Carnevale syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression, decreases methylation	3
bisphenol A	decreases methylation, affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
ferrous chloride	decreases expression	1
resorcinol	decreases expression	1
beta-methylcholine	affects expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.