COLGALT1

Summary

COLGALT1 (collagen beta(1-O)galactosyltransferase 1, HGNC:26182) is a protein-coding gene on chromosome 19p13.11, encoding Procollagen galactosyltransferase 1 (Q8NBJ5). Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of type I collagen.

The protein encoded by this gene is one of two enzymes that transfers galactose moieties to hydroxylysine residues of collagen and mannose binding lectin. This gene is constitutively expressed and encodes a soluble protein that localizes to the endoplasmic reticulum.

Source: NCBI Gene 79709 — RefSeq curated summary.

At a glance

• Gene–disease (curated): brain small vessel disease 3 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 337 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 12
• Druggable target: yes
• MANE Select transcript: NM_024656

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26182
Approved symbol	COLGALT1
Name	collagen beta(1-O)galactosyltransferase 1
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22329
Ensembl gene	ENSG00000130309
Ensembl biotype	protein_coding
OMIM	617531
Entrez	79709

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000252599, ENST00000593832, ENST00000597075, ENST00000597147, ENST00000600474, ENST00000601354, ENST00000690106, ENST00000690841, ENST00000690947, ENST00000692764, ENST00000886053, ENST00000886054, ENST00000886055, ENST00000912419, ENST00000970586

RefSeq mRNA: 1 — MANE Select: NM_024656 NM_024656

CCDS: CCDS12363

Canonical transcript exons

ENST00000252599 — 12 exons

Exon	Start	End
ENSE00000895576	17580699	17580905
ENSE00001113465	17572483	17572602
ENSE00001113471	17577195	17577271
ENSE00001600195	17560348	17560465
ENSE00002206399	17555649	17555973
ENSE00003047586	17581177	17583157
ENSE00003482989	17567406	17567540
ENSE00003484626	17568509	17568713
ENSE00003515250	17577957	17578089
ENSE00003651706	17577361	17577467
ENSE00003671549	17559311	17559421
ENSE00003686391	17579482	17579609

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 96.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.3717 / max 436.4262, expressed in 1829 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174529	63.9032	1829
174533	2.2514	1068
174531	0.5978	304
174532	0.4233	193
174530	0.1961	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	96.92	gold quality
granulocyte	CL:0000094	95.80	gold quality
monocyte	CL:0000576	95.48	gold quality
mononuclear cell	CL:0000842	95.41	gold quality
spleen	UBERON:0002106	95.36	gold quality
leukocyte	CL:0000738	95.32	gold quality
omental fat pad	UBERON:0010414	95.29	gold quality
peritoneum	UBERON:0002358	95.27	gold quality
right coronary artery	UBERON:0001625	94.81	gold quality
upper lobe of left lung	UBERON:0008952	94.76	gold quality
endocervix	UBERON:0000458	94.64	gold quality
left coronary artery	UBERON:0001626	94.43	gold quality
upper lobe of lung	UBERON:0008948	94.29	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.21	gold quality
lower esophagus	UBERON:0013473	94.19	gold quality
coronary artery	UBERON:0001621	94.11	gold quality
smooth muscle tissue	UBERON:0001135	94.06	gold quality
apex of heart	UBERON:0002098	94.06	gold quality
peripheral nervous system	UBERON:0000010	94.05	gold quality
nerve	UBERON:0001021	94.05	gold quality
tibial nerve	UBERON:0001323	94.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.01	gold quality
right ovary	UBERON:0002118	93.74	gold quality
ascending aorta	UBERON:0001496	93.70	gold quality
thoracic aorta	UBERON:0001515	93.70	gold quality
left uterine tube	UBERON:0001303	93.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.66	gold quality
body of uterus	UBERON:0009853	93.62	gold quality
lymph node	UBERON:0000029	93.49	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	39.14
E-GEOD-83139	yes	7.44
E-GEOD-124858	no	1103.83
E-MTAB-7303	no	387.74
E-MTAB-6911	no	243.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting COLGALT1, 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-10401-5P	99.99	65.79	948
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-873-5P	98.84	66.90	1348

Literature-anchored findings (GeneRIF, showing 6)

• Two collagen beta(1-O)galactosyltransferases corresponding to the GLT25D1 and GLT25D2 proteins were identified. (PMID:19075007)
• Data indicate that galactosylation of collagenous proteins by the soluble GLT25D1 occurs in the early secretory pathway (PMID:20470363)
• introduced substitution Q471R-V472M-N473Q-P474V in the CEECAM1-C-terminal construct, which is found in most animal GLT25D1 and GLT25D2 isoforms but not in CEECAM1. This substitution was shown to partially restore collagen galactosyltransferase activity (PMID:22216269)
• Loss of GLT25D1 led to increased expression and intracellular accumulation of collagen type I, whereas loss of GLT25D2 had no effect on collagen secretion. Inactivation of the GLT25D1 gene resulted in a compensatory induction of GLT25D2 expression. (PMID:27402836)
• GLT25D1 regulates HMW adiponectin secretion. (PMID:28428430)
• Involvement of LH3 and GLT25D1 for glucosyl-galactosyl-hydroxylation on non-collagen-like domain of FGL1. (PMID:33984770)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Colgalt1	ENSMUSG00000034807
rattus_norvegicus	Colgalt1	ENSRNOG00000023317
caenorhabditis_elegans		WBGENE00008426

Paralogs (5): PLOD1 (ENSG00000083444), PLOD3 (ENSG00000106397), PLOD2 (ENSG00000152952), CERCAM (ENSG00000167123), COLGALT2 (ENSG00000198756)

Protein

Protein identifiers

Procollagen galactosyltransferase 1 — Q8NBJ5 (reviewed: Q8NBJ5)

Alternative names: Collagen beta(1-O)galactosyltransferase 1, Glycosyltransferase 25 family member 1, Hydroxylysine galactosyltransferase 1

All UniProt accessions (4): Q8NBJ5, A0A8I5QKL8, A0A8I5QL08, M0QX72

UniProt curated annotations — full annotation on UniProt →

Function. Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of type I collagen. By acting on collagen glycosylation, facilitates the formation of collagen triple helix. Also involved in the biosynthesis of collagen type IV.

Subcellular location. Endoplasmic reticulum lumen.

Tissue specificity. Ubiquitous with higher levels in placenta, heart, lung and spleen.

Post-translational modifications. N-glycosylated.

Disease relevance. Brain small vessel disease 3 (BSVD3) [MIM:618360] An autosomal recessive form of brain small vessel disease, a cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD3 patients may have disease onset in utero or early infancy with subsequent global developmental delay, spasticity, and porencephaly on brain imaging. Other patients may have normal or mildly delayed development with sudden onset of intracranial hemorrhage causing acute neurologic deterioration. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the glycosyltransferase 25 family.

RefSeq proteins (1): NP_078932* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002654	Glyco_trans_25	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR050757	Collagen_mod_GT25	Family

Pfam: PF01755, PF13704

Enzyme classification (BRENDA):

• EC 2.4.1.50 — procollagen galactosyltransferase (BRENDA: 7 organisms, 62 substrates, 25 inhibitors, 19 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
COLLAGEN	0.0008–0.0072	2
UDP-GALACTOSE	0.0188–0.0335	2
UDPGALACTOSE	0.03–0.049	2
CALF SKIN COLLAGEN	0.028	1
ICHTHYOCOL	0.28	1

Catalyzed reactions (Rhea), 1 shown:

• (5R)-5-hydroxy-L-lysyl-[collagen] + UDP-alpha-D-galactose = (5R)-5-O-(beta-D-galactosyl)-5-hydroxy-L-lysyl-[collagen] + UDP + H(+) (RHEA:12637)

UniProt features (21 total): mutagenesis site 8, sequence variant 3, glycosylation site 3, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9EVJ	X-RAY DIFFRACTION	2.7
9EVL	X-RAY DIFFRACTION	2.8
9EVK	X-RAY DIFFRACTION	3
9U7H	ELECTRON MICROSCOPY	3.08
9U7I	ELECTRON MICROSCOPY	3.3
9U7J	ELECTRON MICROSCOPY	3.3
8ZGE	ELECTRON MICROSCOPY	3.4
8ZGC	ELECTRON MICROSCOPY	3.58
8ZGG	ELECTRON MICROSCOPY	3.75
8ZGH	ELECTRON MICROSCOPY	3.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBJ5-F1	88.31	0.74

Functional residue map

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

Glycosylation sites (3): 96, 184, 381

Mutagenesis-validated functional residues (8):

Position	Phenotype
166	loss of galactosyltransferase activity; when associated with a-168.
168	loss of galactosyltransferase activity; when associated with a-166.
292	small decrease of galactosyltransferase activity.
336	small decrease of galactosyltransferase activity.
461	loss of galactosyltransferase activity; when associated with a-463.
463	loss of galactosyltransferase activity; when associated with a-461.
585	no effect on galactosyltransferase activity; when associated with a-587.
587	no effect on galactosyltransferase activity; when associated with a-585.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes

MSigDB gene sets: 162 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BONOME_OVARIAN_CANCER_POOR_SURVIVAL_DN, LIEN_BREAST_CARCINOMA_METAPLASTIC_VS_DUCTAL_UP, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, SANSOM_APC_MYC_TARGETS, chr19p13

GO Biological Process (3): protein O-linked glycosylation (GO:0006493), collagen fibril organization (GO:0030199), positive regulation of collagen fibril organization (GO:1904028)

GO Molecular Function (3): procollagen galactosyltransferase activity (GO:0050211), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): endoplasmic reticulum lumen (GO:0005788), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Collagen formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoprotein biosynthetic process	1
extracellular matrix organization	1
collagen fibril organization	1
positive regulation of extracellular matrix organization	1
regulation of collagen fibril organization	1
UDP-galactosyltransferase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
transferase activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COLGALT1	COL5A2	P05997	551
COLGALT1	COL5A1	P20908	551
COLGALT1	COL1A2	P02464	533
COLGALT1	COL1A1	P02452	527
COLGALT1	P3H4	Q92791	514
COLGALT1	SH2D3A	Q9BRG2	430
COLGALT1	P3H1	Q32P28	415
COLGALT1	MTOR	P42345	408
COLGALT1	PLOD3	O60568	388
COLGALT1	COL4A2	P08572	377
COLGALT1	ERO1A	Q96HE7	377
COLGALT1	FKBP10	Q96AY3	375
COLGALT1	CNDP2	Q96KP4	374
COLGALT1	PLOD1	Q02809	371
COLGALT1	FBP2	O00757	370

IntAct

76 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
COL1A1	P4HA2	psi-mi:“MI:0915”(physical association)	0.710
rep	POLA1	psi-mi:“MI:0914”(association)	0.670
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
COLGALT2	COL1A1	psi-mi:“MI:0914”(association)	0.530
PLOD3	PLOD2	psi-mi:“MI:0914”(association)	0.530
CNPY3	LRIG2	psi-mi:“MI:0914”(association)	0.530
COLQ	PLOD3	psi-mi:“MI:0914”(association)	0.530
COL21A1	PLOD3	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
EHMT2	KDM1A	psi-mi:“MI:0914”(association)	0.460
Cenpe	BBX	psi-mi:“MI:0914”(association)	0.350
Itgb1	SSR3	psi-mi:“MI:0914”(association)	0.350
Anxa2	PPL	psi-mi:“MI:0914”(association)	0.350
TGM2	SRGAP3	psi-mi:“MI:0914”(association)	0.350
Fbxw11	CTNNB1	psi-mi:“MI:0914”(association)	0.350
Ktn1	ESYT2	psi-mi:“MI:0914”(association)	0.350
Lgals3bp	CS	psi-mi:“MI:0914”(association)	0.350
PML	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
PDHA1		psi-mi:“MI:0914”(association)	0.350
FBXO6	GNS	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
lpqN	SOWAHD	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (202): COLGALT1 (Affinity Capture-MS), PLOD1 (Co-fractionation), PLOD2 (Co-fractionation), PLOD3 (Co-fractionation), PRPF40A (Co-fractionation), PYGL (Co-fractionation), COLGALT1 (Affinity Capture-MS), COLGALT1 (Proximity Label-MS), COLGALT1 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS)

ESM2 similar proteins: A4IID1, A5D7I4, A5PK45, A9X1C8, G5E897, O12971, O60568, O77783, O95803, P52848, P52849, P52850, P70428, P97464, Q02353, Q16394, Q3UHN9, Q5F407, Q5IGR6, Q5IGR7, Q5IGR8, Q5M854, Q5R6K5, Q5RBC3, Q5U367, Q5U4X8, Q6EV56, Q6GMK0, Q6GQI7, Q6GQK9, Q6IS24, Q6UW63, Q6ZQ11, Q7TT15, Q7Z4H8, Q812F8, Q86X52, Q8K297, Q8NBJ5, Q8VHI3

Diamond homologs: A0JPH3, A3KGW5, A5PK45, A5PMF6, A7MB73, O77588, Q17FB8, Q29NU5, Q5T4B2, Q5U309, Q5U367, Q5U483, Q6NVG7, Q7Q021, Q811A3, Q8IPK4, Q8IYK4, Q8K297, Q8NBJ5, Q9R0E1, Q9R0E2, P57033, P71398, Q50947, Q50950, Q51116, Q51117, Q57394, Q5UQ62, Q5UQC3, Q02809, Q5R9N3, Q9VTH0, Q03974, Q63321, O00469, O60568, P24802, Q20679, Q5R6K5

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
COLGALT1	“up-regulates activity”	ADIPOQ	palmitoylation
COLGALT1	“up-regulates activity”	COL1A1	glycosylation
COLGALT1	“up-regulates activity”	COL1A2	glycosylation
COLGALT1	“up-regulates activity”	COL3A1	glycosylation
COLGALT1	“up-regulates activity”	COL4A1	glycosylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 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	8	23.9×	7e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	196
Likely benign	89
Benign	15

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
2243995	NM_024656.4(COLGALT1):c.25_37del (p.Arg9fs)	Pathogenic
2906025	NM_024656.4(COLGALT1):c.553_556dup (p.Thr186fs)	Pathogenic
3242663	NC_000019.9:g.(?17666523)(17887515_?)del	Pathogenic
623638	NM_024656.4(COLGALT1):c.452T>G (p.Leu151Arg)	Pathogenic
623639	NM_024656.4(COLGALT1):c.1096del (p.Glu366fs)	Pathogenic
623640	NM_024656.4(COLGALT1):c.460G>C (p.Ala154Pro)	Pathogenic
623641	NM_024656.4(COLGALT1):c.1129G>C (p.Gly377Arg)	Pathogenic
3242710	NC_000019.9:g.(?17670100)(17679542_?)dup	Likely pathogenic
917942	NM_024656.4(COLGALT1):c.173T>C (p.Leu58Pro)	Likely pathogenic

SpliceAI

2286 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17555972:TG:T	donor_gain	1.0000
19:17555973:GG:G	donor_gain	1.0000
19:17555974:G:C	donor_loss	1.0000
19:17555974:G:GG	donor_gain	1.0000
19:17559309:A:AG	acceptor_gain	1.0000
19:17559309:AG:A	acceptor_gain	1.0000
19:17559309:AGGGT:A	acceptor_gain	1.0000
19:17559310:G:GA	acceptor_gain	1.0000
19:17559310:GG:G	acceptor_gain	1.0000
19:17559310:GGGT:G	acceptor_gain	1.0000
19:17559310:GGGTG:G	acceptor_gain	1.0000
19:17559418:CCAG:C	donor_gain	1.0000
19:17559419:CAG:C	donor_gain	1.0000
19:17559420:AG:A	donor_gain	1.0000
19:17559421:GG:G	donor_gain	1.0000
19:17559421:GGTG:G	donor_loss	1.0000
19:17559422:G:C	donor_loss	1.0000
19:17559422:G:GG	donor_gain	1.0000
19:17560466:G:C	donor_loss	1.0000
19:17567404:A:AG	acceptor_gain	1.0000
19:17567405:G:A	acceptor_loss	1.0000
19:17567405:G:GG	acceptor_gain	1.0000
19:17567405:GT:G	acceptor_gain	1.0000
19:17567405:GTTT:G	acceptor_gain	1.0000
19:17567537:CCAG:C	donor_loss	1.0000
19:17567538:CAGG:C	donor_loss	1.0000
19:17567539:AGGTA:A	donor_loss	1.0000
19:17567540:GGTAG:G	donor_loss	1.0000
19:17568504:CACA:C	acceptor_loss	1.0000
19:17568505:ACAG:A	acceptor_gain	1.0000

AlphaMissense

4043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17567516:C:A	N200K	1.000
19:17567516:C:G	N200K	1.000
19:17567520:T:A	W202R	1.000
19:17567520:T:C	W202R	1.000
19:17567517:T:C	F201L	0.999
19:17567519:C:A	F201L	0.999
19:17567519:C:G	F201L	0.999
19:17567522:G:C	W202C	0.999
19:17567522:G:T	W202C	0.999
19:17568576:T:A	V231D	0.999
19:17578066:A:C	S415R	0.999
19:17578068:C:A	S415R	0.999
19:17578068:C:G	S415R	0.999
19:17579519:A:T	E435V	0.999
19:17579521:G:C	D436H	0.999
19:17579522:A:T	D436V	0.999
19:17579525:A:C	D437A	0.999
19:17579525:A:T	D437V	0.999
19:17580714:G:C	K470N	0.999
19:17580714:G:T	K470N	0.999
19:17580787:T:A	W495R	0.999
19:17580787:T:C	W495R	0.999
19:17580868:G:C	D522H	0.999
19:17580869:A:C	D522A	0.999
19:17580869:A:T	D522V	0.999
19:17581280:A:C	S569R	0.999
19:17581282:T:A	S569R	0.999
19:17581282:T:G	S569R	0.999
19:17560425:C:A	A150D	0.998
19:17567482:C:A	A189D	0.998

dbSNP variants (sampled 300 via entrez): RS1000092675 (19:17579057 C>G,T), RS1000152465 (19:17554237 T>C), RS1000210078 (19:17554537 A>G), RS1000215364 (19:17563435 T>C), RS1000332474 (19:17566087 G>A,C), RS1000340929 (19:17558962 C>G,T), RS1000448567 (19:17562502 A>C), RS1000669567 (19:17564862 A>C), RS1000719213 (19:17577092 C>G,T), RS1000730951 (19:17557702 A>G), RS1000784339 (19:17560170 G>A,C,T), RS1000821204 (19:17559522 C>A), RS1000950707 (19:17564565 C>T), RS1001124974 (19:17569985 C>T), RS1001154301 (19:17567787 A>AG)

Disease associations

OMIM: gene MIM:617531 | disease phenotypes: MIM:618360, MIM:615916

GenCC curated gene-disease

Disease	Classification	Inheritance
brain small vessel disease 3	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
brain small vessel disease 3	Moderate	AR

Mondo (3): vascular dementia (MONDO:0004648), brain small vessel disease 3 (MONDO:0100105), dilated cardiomyopathy 1NN (MONDO:0014396)

Orphanet (1): Familial isolated dilated cardiomyopathy (Orphanet:154)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0002059	Cerebral atrophy
HP:0002132	Porencephalic cyst
HP:0002352	Leukoencephalopathy
HP:0002510	Spastic tetraplegia
HP:0002514	Cerebral calcification
HP:0003593	Infantile onset
HP:0010864	Severe intellectual disability
HP:0032325	Lacunar stroke

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_675	Blood protein levels	4.000000e-06
GCST90002407_369	White blood cell count	1.000000e-10

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067420 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.11	Kd	7700	nM	CHEMBL5653589
5.11	ED50	7700	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148112: Binding affinity to human COLGALT1 incubated for 45 mins by Kinobead based pull down assay	kd	7.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	affects expression, decreases expression	2
2,4,6-tribromophenol	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases expression	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Mustard Gas	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651154	Binding	Binding affinity to human COLGALT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2UV	Abcam HEK293T COLGALT1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00165763	PHASE4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	PHASE4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	PHASE4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT00099216	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00130338	PHASE3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00209456	PHASE3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00249158	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia
NCT00261573	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine Versus Placebo in the Treatment of Patients With Vascular Dementia or Mixed Dementia
NCT00621647	PHASE3	COMPLETED	Seroquel- Agitation Associated With Dementia
NCT02453932	PHASE3	COMPLETED	Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT03789760	PHASE3	COMPLETED	The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
NCT03804229	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
NCT03986424	PHASE3	COMPLETED	Local Study of Akatinol Memantine in VaD in Russia
NCT04552041	PHASE3	COMPLETED	Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.
NCT01466543	PHASE2	UNKNOWN	Effect of Zydena (Udenafil) on Cerebral Blood Flow and Peripheral Blood Viscosity
NCT01475578	PHASE2	COMPLETED	Study of STA-1 Capsule in Patients With Vascular Dementia (Marrow-Sea Deficiency)
NCT01608217	PHASE2	COMPLETED	Delta-THC in Dementia
NCT01761227	PHASE2	COMPLETED	Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia
NCT01953705	PHASE2	UNKNOWN	n-3 PUFA for Vascular Cognitive Aging
NCT01965756	PHASE2	COMPLETED	Effect of Insulin Sensitizer Metformin on AD Biomarkers
NCT01978730	PHASE2	UNKNOWN	The Clinical Trial of Chinese Herbal Medicine SaiLuoTong Capsule
NCT02467413	PHASE2	WITHDRAWN	BAC in Patient With Alzheimer’s Disease or Vascular Dementia
NCT03230071	PHASE2	COMPLETED	Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia
NCT04109963	PHASE2	UNKNOWN	Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
NCT05371639	PHASE2	UNKNOWN	Efficacy and Safety of Tian Ma Bian Chun Zhi Gan Tablets in Mild to Moderate Vascular Dementia
NCT00457769	PHASE1	UNKNOWN	Aricept to Improve Functional Tasks in Vascular Dementia
NCT03702543	PHASE1	UNKNOWN	Managing Vascular Dementia Risk Factors With SymTrend
NCT04567745	PHASE1	COMPLETED	Automated Retinal Image Analysis System (EyeQuant) for Computation of Vascular Biomarkers
NCT02098824	PHASE2/PHASE3	UNKNOWN	Symptomatic Treatment of Vascular Cognitive Impairment
NCT04248270	PHASE1/PHASE2	UNKNOWN	A Noval Tau Tracer in Young Onset Dementia
NCT00172900	Not specified	UNKNOWN	MRS and DTI of White Matter in Alzheimer’s Disease
NCT00506818	Not specified	COMPLETED	Cognitive and Emotional Impairment After Stroke
NCT00889603	Not specified	COMPLETED	Non-Interventional Study With Aricept® Evess
NCT01208675	Not specified	COMPLETED	The Swedish BioFINDER Study
NCT01345110	Not specified	COMPLETED	A Longitudinal Multidimensional Population Study on Brain Aging
NCT01370954	Not specified	COMPLETED	NAC-003 P.L.U.S. Program (Progress Through Learning Understanding & Support)
NCT01465360	Not specified	COMPLETED	Performance of AclarusDx™, a Blood-Based Transcriptomic Test for AD, in US Patients Newly Referred to a Memory Center
NCT01815112	Not specified	TERMINATED	Early Diagnosis of Alzheimer-like Dementia: Benefit of MRI and PET Imaging