COLEC12

Summary

COLEC12 (collectin subfamily member 12, HGNC:16016) is a protein-coding gene on chromosome 18p11.32, encoding Collectin-12 (Q5KU26). Scavenger receptor that displays several functions associated with host defense.

This gene encodes a member of the C-lectin family, proteins that possess collagen-like sequences and carbohydrate recognition domains. This protein is a scavenger receptor that displays several functions associated with host defense. It can bind to carbohydrate antigens on microorganisms, facilitating their recognition and removal. It also mediates the recognition, internalization, and degradation of oxidatively modified low density lipoprotein by vascular endothelial cells.

Source: NCBI Gene 81035 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 114 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_130386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16016
Approved symbol	COLEC12
Name	collectin subfamily member 12
Location	18p11.32
Locus type	gene with protein product
Status	Approved
Aliases	SRCL, CL-P1, SCARA4
Ensembl gene	ENSG00000158270
Ensembl biotype	protein_coding
OMIM	607621
Entrez	81035

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000400256, ENST00000580242, ENST00000582147, ENST00000851798, ENST00000851799

RefSeq mRNA: 1 — MANE Select: NM_130386 NM_130386

CCDS: CCDS32782

Canonical transcript exons

ENST00000400256 — 10 exons

Exon	Start	End
ENSE00001208502	334742	335230
ENSE00001240712	333007	333143
ENSE00003526793	357400	357522
ENSE00003533028	500508	500701
ENSE00003544566	346295	347341
ENSE00003565310	348065	348163
ENSE00003567962	331668	331777
ENSE00003593507	316737	320064
ENSE00003606445	321662	321807
ENSE00003613443	480707	480757

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0412 / max 298.4823, expressed in 1111 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170940	14.5079	1103
170938	0.4005	225
170939	0.1328	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	98.93	gold quality
tibia	UBERON:0000979	98.52	gold quality
layer of synovial tissue	UBERON:0007616	97.34	gold quality
tendon of biceps brachii	UBERON:0008188	96.71	gold quality
pigmented layer of retina	UBERON:0001782	96.64	gold quality
placenta	UBERON:0001987	95.39	gold quality
skin of hip	UBERON:0001554	94.66	gold quality
periodontal ligament	UBERON:0008266	94.52	gold quality
pericardium	UBERON:0002407	94.39	gold quality
cartilage tissue	UBERON:0002418	94.23	gold quality
lower lobe of lung	UBERON:0008949	93.75	gold quality
parietal pleura	UBERON:0002400	93.27	gold quality
cranial nerve II	UBERON:0000941	93.11	gold quality
choroid plexus epithelium	UBERON:0003911	92.78	gold quality
endocervix	UBERON:0000458	91.92	gold quality
pleura	UBERON:0000977	91.11	gold quality
heart right ventricle	UBERON:0002080	90.51	gold quality
decidua	UBERON:0002450	90.42	gold quality
calcaneal tendon	UBERON:0003701	90.35	gold quality
tendon	UBERON:0000043	89.94	gold quality
mammary duct	UBERON:0001765	89.73	gold quality
trigeminal ganglion	UBERON:0001675	89.66	gold quality
lung	UBERON:0002048	89.48	gold quality
germinal epithelium of ovary	UBERON:0001304	87.52	gold quality
cauda epididymis	UBERON:0004360	87.43	gold quality
epithelium of mammary gland	UBERON:0003244	87.36	gold quality
upper lobe of lung	UBERON:0008948	87.09	gold quality
upper lobe of left lung	UBERON:0008952	86.69	gold quality
visceral pleura	UBERON:0002401	86.64	gold quality
thoracic mammary gland	UBERON:0005200	86.38	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	698.51
E-MTAB-9388	yes	266.00
E-HCAD-35	yes	11.47
E-CURD-112	yes	6.06
E-MTAB-5061	yes	3.01
E-CURD-135	no	878.96
E-MTAB-9467	no	29.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2

miRNA regulators (miRDB)

80 targeting COLEC12, 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-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700

Literature-anchored findings (GeneRIF, showing 14)

• haplotype structure of the CL-P1 gene obtained from six single-nucleotide polymorphisms that were genotyped with 108 alleles in Japanese subjects (PMID:12601552)
• SRCL is expressed in some but not all nurse-like cells; its C-type lectin domain binds specifically to several carbohydrates including GalNAc, T and Tn antigen in a Ca2+-dependent manner. (PMID:12761161)
• SRCL might be involved in selective clearance of specific desialylated glycoproteins from circulation and/or interaction of cells bearing Lewis(x)-type structures with the vascular endothelium (PMID:15845541)
• CL-P1 is not a common membrane protein on endothelial cells found in normal tissues under steady state conditions. (PMID:18423602)
• CL-P1 predominantly mediated phagocytosis for fungi in vascular endothelia. (PMID:19073604)
• The Le(x) residues of both, CEACAM1 and CEA, interact with the human Le(x)-binding glycan receptors DC-SIGN and SRCL. (PMID:20034698)
• The common presence of Lewis(x) groups in granule protein glycans can thus target granule proteins for clearance by SRCL. (PMID:21561871)
• rs17684886 (ZNRF1) and rs599019 (COLEC12) are associated with diabetic retinopathy and rs6427247 (SCYL1BP1) and rs899036 (API5) are associated with severe diabetic retinopathy in Chinese patients with type 2 diabetes (PMID:25819896)
• CL-P1 is a novel receptor involved in myelin uptake by phagocytes and likely plays a role in multiple sclerosis lesion development. (PMID:28317919)
• COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases (PMID:29491476)
• COLEC12 regulates apoptosis of osteosarcoma through Toll-like receptor 4-activated inflammation. (PMID:32822099)
• Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement. (PMID:32909942)
• COLEC12 Promotes Tumor Progression and Is Correlated With Poor Prognosis in Gastric Cancer. (PMID:38112409)
• Dysregulated AEBP1 and COLEC12 Genes in Late-Onset Alzheimer’s Disease: Insights from Brain Cortex and Peripheral Blood Analysis. (PMID:38568322)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	colec12	ENSDARG00000061140
mus_musculus	Colec12	ENSMUSG00000036103
rattus_norvegicus	Colec12	ENSRNOG00000016366

Paralogs (3): MARCO (ENSG00000019169), MSR1 (ENSG00000038945), SCARA5 (ENSG00000168079)

Protein

Protein identifiers

Collectin-12 — Q5KU26 (reviewed: Q5KU26)

Alternative names: Collectin placenta protein 1, Nurse cell scavenger receptor 2, Scavenger receptor class A member 4, Scavenger receptor with C-type lectin

All UniProt accessions (1): Q5KU26

UniProt curated annotations — full annotation on UniProt →

Function. Scavenger receptor that displays several functions associated with host defense. Promotes binding and phagocytosis of Gram-positive, Gram-negative bacteria and yeast. Mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. Binds to several carbohydrates including Gal-type ligands, D-galactose, L- and D-fucose, GalNAc, T and Tn antigens in a calcium-dependent manner and internalizes specifically GalNAc in nurse-like cells. Also binds to sialyl Lewis X or a trisaccharide and asialo-orosomucoid (ASOR). May also play a role in the clearance of amyloid-beta in Alzheimer disease.

Subunit / interactions. The extracellular domain forms a stable trimer. The extracellular domain interacts with fibrillar amyloid-beta peptide.

Subcellular location. Membrane.

Tissue specificity. Expressed in perivascular macrophages. Expressed in plaques-surrounding reactive astrocytes and in perivascular astrocytes associated with cerebral amyloid angiopathy (CAA) in the temporal cortex of Alzheimer patient (at protein level). Strongly expressed in placenta. Moderately expressed in heart, skeletal muscle, small intestine and lung. Weakly expressed in brain, colon, thymus and kidney. Expressed in nurse-like cells. Expressed in reactive astrocytes and vascular/perivascular cells in the brain of Alzheimer patient.

RefSeq proteins (1): NP_569057* (*=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
IPR033989	CD209-like_CTLD	Domain
IPR050111	C-type_lectin/snaclec_domain	Family
IPR058762	COLEC12_dom	Domain

Pfam: PF00059, PF01391, PF26004

UniProt features (61 total): binding site 20, strand 7, sequence conflict 6, glycosylation site 4, domain 4, sequence variant 4, compositionally biased region 3, disulfide bond 3, topological domain 2, coiled-coil region 2, helix 2, chain 1, transmembrane region 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2OX8	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5KU26-F1	70.53	0.16

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 (20): 644; 646; 650; 670; 674; 691; 694; 694; 696; 696; 697; 706 …

Disulfide bonds (3): 607–618, 635–730, 708–722

Glycosylation sites (4): 67, 159, 168, 271

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-3000480	Scavenging by Class A Receptors

MSigDB gene sets: 202 (showing top): TAATAAT_MIR126, BENPORATH_ES_WITH_H3K27ME3, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_COLLAGEN_TRIMER, MODULE_418, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_PLASMA_MEMBRANE_ORGANIZATION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MEMBRANE_RAFT_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, CAGCTG_AP4_Q5, PATIL_LIVER_CANCER

GO Biological Process (8): regulation of immune system process (GO:0002682), phagocytosis, recognition (GO:0006910), defense response (GO:0006952), carbohydrate mediated signaling (GO:0009756), defense response to bacterium (GO:0042742), plasma membrane raft organization (GO:0044857), innate immune response (GO:0045087), immune response (GO:0006955)

GO Molecular Function (7): scavenger receptor activity (GO:0005044), galactose binding (GO:0005534), low-density lipoprotein particle binding (GO:0030169), pattern recognition receptor activity (GO:0038187), metal ion binding (GO:0046872), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (5): collagen trimer (GO:0005581), plasma membrane (GO:0005886), membrane (GO:0016020), endocytic vesicle membrane (GO:0030666), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Binding and Uptake of Ligands by Scavenger Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune system process	2
cargo receptor activity	2
binding	2
regulation of biological process	1
phagocytosis	1
cell recognition	1
response to stress	1
signal transduction	1
cellular response to carbohydrate stimulus	1
defense response	1
response to bacterium	1
plasma membrane organization	1
membrane raft organization	1
immune response	1
defense response to symbiont	1
response to stimulus	1
monosaccharide binding	1
lipoprotein particle binding	1
signaling receptor activity	1
cation binding	1
protein-containing complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
external encapsulating structure	1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COLEC12	LIMK2	P53671	922
COLEC12	CLUL1	Q15846	509
COLEC12	ENOSF1	Q7L5Y1	507
COLEC12	MARCO	Q9UEW3	506
COLEC12	PILRA	Q9UKJ1	472
COLEC12	RHNO1	Q9BSD3	434
COLEC12	SCARF1	Q14162	419
COLEC12	SCAF4	O95104	414
COLEC12	AKAIN1	P0CW23	412
COLEC12	CETN1	Q12798	405
COLEC12	EGR1	P18146	402
COLEC12	THOC1	Q96FV9	399
COLEC12	C22orf39	Q6P5X5	397
COLEC12	CCN1	O00622	393
COLEC12	CEACAM1	P13688	392

IntAct

82 interactions, top by confidence:

A	B	Type	Score
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
MMP9	TIMP1	psi-mi:“MI:0914”(association)	0.640
COLEC12	SCARA3	psi-mi:“MI:0915”(physical association)	0.620
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
CGRRF1	B4GALT3	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
FRMD5	FAM234B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
COLEC12	CSPG5	psi-mi:“MI:0914”(association)	0.530
CSPG5	HIRA	psi-mi:“MI:0914”(association)	0.530
LAIR2	LAMA5	psi-mi:“MI:0914”(association)	0.530
COLEC12	CRP	psi-mi:“MI:0407”(direct interaction)	0.490
COLEC12	CRP	psi-mi:“MI:0403”(colocalization)	0.490
COLEC12	PILRA	psi-mi:“MI:0407”(direct interaction)	0.440
COLEC12	HSPA8	psi-mi:“MI:0915”(physical association)	0.400
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350

BioGRID (113): COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), ZC4H2 (Affinity Capture-MS)

ESM2 similar proteins: A2VE00, A2VE53, A2XW69, A5PMY6, A6QP79, B2RPV6, F1QC17, F7DP49, O75071, Q07065, Q0II90, Q13201, Q2LK54, Q32L59, Q3UIJ9, Q4V7C8, Q4V885, Q53EZ4, Q5BIX7, Q5EAJ6, Q5EB94, Q5KU26, Q5R6R3, Q5R923, Q5RI56, Q5ZM60, Q61595, Q640L3, Q6AZY7, Q6NRC9, Q6P6L0, Q70UQ0, Q7XU27, Q7Z7B0, Q84VY2, Q8BGQ6, Q8BIS8, Q8BMK4, Q8BT07, Q8BVC4

Diamond homologs: A5PMY6, A6QP79, P07307, P08290, P24721, P49259, P49260, Q2LK54, Q4V885, Q5KU26, Q8HZR8, Q8K4Q8, Q8MI05, D3ZWT9, O14594, P02706, P02707, P05451, P06734, P07306, P07897, P07898, P08661, P10716, P10758, P11226, P13608, P13611, P16112, P19999, P20693, P22897, P34927, P41317, P43137, P48304, P49300, P49301, P55066, P55067

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Collagen biosynthesis and modifying enzymes	5	15.2×	2e-03
Interleukin-4 and Interleukin-13 signaling	7	12.9×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	91
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1711456	GRCh37/hg19 18p11.32-11.22(chr18:1-8638260)x1	Pathogenic
545223	NC_000018.10:g.(?10000)(1543845_?)del	Likely pathogenic
625805	GRCh37/hg19 18p11.32(chr18:13034-547239)	Likely pathogenic

SpliceAI

2116 predictions. Top by Δscore:

Variant	Effect	Δscore
18:320060:CAGTA:C	acceptor_gain	1.0000
18:320065:C:CC	acceptor_gain	1.0000
18:321809:T:C	acceptor_gain	1.0000
18:321811:T:TC	acceptor_gain	1.0000
18:321815:C:CT	acceptor_gain	1.0000
18:331664:TTACT:T	donor_loss	1.0000
18:331665:TACTT:T	donor_loss	1.0000
18:331666:A:AC	donor_gain	1.0000
18:331666:A:T	donor_loss	1.0000
18:331667:C:CT	donor_gain	1.0000
18:331667:CT:C	donor_gain	1.0000
18:331773:CATTG:C	acceptor_gain	1.0000
18:331775:TTG:T	acceptor_gain	1.0000
18:331776:TG:T	acceptor_gain	1.0000
18:333140:CAGC:C	acceptor_gain	1.0000
18:346290:CTTA:C	donor_loss	1.0000
18:346291:TTACC:T	donor_loss	1.0000
18:346292:TA:T	donor_loss	1.0000
18:346294:C:A	donor_loss	1.0000
18:348085:T:A	donor_gain	1.0000
18:348161:CAA:C	acceptor_gain	1.0000
18:348164:C:CC	acceptor_gain	1.0000
18:480701:ACT:A	donor_loss	1.0000
18:480702:CTC:C	donor_loss	1.0000
18:480703:TCA:T	donor_loss	1.0000
18:480704:CACC:C	donor_loss	1.0000
18:480705:A:AC	donor_gain	1.0000
18:480706:C:CC	donor_gain	1.0000
18:480706:C:CT	donor_loss	1.0000
18:480706:CCAAA:C	donor_gain	1.0000

AlphaMissense

4900 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:321720:C:A	W717C	0.999
18:321720:C:G	W717C	0.999
18:321722:A:G	W717R	0.999
18:321722:A:T	W717R	0.999
18:321801:C:A	W690C	0.999
18:321801:C:G	W690C	0.999
18:331700:C:A	W677C	0.999
18:331700:C:G	W677C	0.999
18:321748:C:G	C708S	0.998
18:321749:A:G	C708R	0.998
18:321749:A:T	C708S	0.998
18:321803:A:G	W690R	0.998
18:321803:A:T	W690R	0.998
18:331702:A:G	W677R	0.998
18:331702:A:T	W677R	0.998
18:331736:C:A	W665C	0.998
18:331736:C:G	W665C	0.998
18:346552:A:G	L357P	0.998
18:346954:A:G	L223P	0.998
18:357442:A:G	C47R	0.998
18:321682:C:G	C730S	0.997
18:321683:A:T	C730S	0.997
18:321706:C:G	C722S	0.997
18:321707:A:T	C722S	0.997
18:321721:C:G	W717S	0.997
18:321747:A:C	C708W	0.997
18:331694:C:A	W679C	0.997
18:331694:C:G	W679C	0.997
18:331728:A:G	L668P	0.997
18:331738:A:G	W665R	0.997

dbSNP variants (sampled 300 via entrez): RS1000014768 (18:454009 C>T), RS1000018784 (18:365972 G>A), RS1000028344 (18:459996 G>T), RS1000085093 (18:413039 A>G), RS1000096828 (18:399329 AG>A), RS1000123144 (18:493525 G>A), RS1000147886 (18:320525 T>C), RS1000160716 (18:342285 CA>C), RS1000169597 (18:468929 T>C), RS1000198648 (18:329383 A>T), RS1000205460 (18:463051 G>C), RS1000226774 (18:323169 T>G), RS1000232775 (18:422435 TC>T), RS1000247636 (18:374985 A>G), RS1000247864 (18:501427 G>A,C)

Disease associations

OMIM: gene MIM:607621 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000641_8	Bipolar disorder or major depressive disorder	4.000000e-06
GCST001762_491	Obesity-related traits	4.000000e-06
GCST001762_513	Obesity-related traits	3.000000e-06
GCST003523_22	Coenzyme Q10 levels	1.000000e-08
GCST005871_2	Metabolic syndrome	1.000000e-06
GCST006585_2239	Blood protein levels	6.000000e-09
GCST006865_17	Bipolar disorder	7.000000e-06
GCST006865_5	Bipolar disorder	7.000000e-06
GCST007327_67	Smoking status (ever vs never smokers)	4.000000e-08
GCST012310_23	Schizophrenia x sex interaction	9.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005109	energy expenditure
EFO:0004578	homocysteine measurement
EFO:0007836	coenzyme Q10 measurement
EFO:0000195	metabolic syndrome
EFO:0004318	smoking behavior
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	6
Valproic Acid	affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
methylmercuric chloride	decreases expression	2
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Cadmium	affects cotreatment, decreases expression, increases abundance	2
Calcitriol	affects cotreatment, decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	increases expression	2
propionaldehyde	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
butyraldehyde	increases expression	1
chloroquine diphosphate	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
zinc sulfide	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
fumaronitrile	affects response to substance	1
rofecoxib	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
belinostat	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms