COLGALT1

protein-coding

collagen beta(1-O)galactosyltransferase 1, the group of Collagen beta(1-O)galactosyltransferases

Gene summary

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. [provided by RefSeq, Dec 2015]

Previous symbols:

GLT25D1

MANE transcript

NM_024656.4

Inheritance

ClinVar variants

P:7U:189B:81

Top phenotype

Brain small vessel disease 3

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr19:17,555,649-17,583,162

External References & Databases

Ensembl (ENSG00000130309)

Transcript & Mutation Effects

hg38 • Region Span ~27.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

brain small vessel disease 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100105

Submitter: Ambry Genetics

brain small vessel disease 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100105

Submitter: Labcorp Genetics (formerly Invitae)

brain small vessel disease 3LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100105

Submitter: Ambry Genetics

brain small vessel disease 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100105

Submitter: ClinGen

COLGALT1 was first reported in relation to autosomal recessive brain small vessel disease 3 (BSVD3) in 2018 (Miyatake et al., PMID: 30412317). BSVD3 results from fragility of cerebral vessels causing an increased risk for intracranial bleeding. The clinical findings depend on the timing and location of the intracranial bleed and have been observed in utero and early infancy. Symptoms include developmental delay, spasticity, and porencephaly on brain imaging (Miyatake et al., PMID: 30412317). The COLGALT1 gene encodes the collagen beta galactosyltransferase 1 (ColGalT1) protein. This protein initiates glycosylation of CoL4a1, an important step in the formation of the triple helix of collagen IV (Teunissen et al., PMID: 33709034). At least 5 biallelic COLGALT1 variants (4 missense, 1 splice site) have been reported in humans. This gene-disease relationship is supported by functional evidence including expression studies and rescue experiments (Miyatake et al., PMID: 30412317; Teunissen et al., PMID: 33709034). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on March 6, 2025 (SOP Version 11).

Clinical Genomic Database (CGD)

Brain small vessel disease 3AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30412317

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COLGALT1 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 180

Inborn genetic diseasesTotal: 144

COLGALT1-related disorderTotal: 30

not specifiedTotal: 29

Brain small vessel disease 3Total: 10

Vascular dementiaTotal: 1

Dilated cardiomyopathy 1NNTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024656.4. 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			2 clinvar	65 clinvar	8 clinvar	75
missense	3 clinvar	1 clinvar	183 clinvar	8 clinvar		195
nonsense			2 clinvar			2
start loss						0
frameshift	3 clinvar					3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	6	1	189	73	8	277

Highest pathogenic variant AF is 0.000006565902

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024656.4	RefSeq	NP_078932.2	12	MANE Select
ENST00000252599.9	Ensembl	ENSP00000252599.3	12	MANE Select
ENST00000597147.2	Ensembl	ENSP00000468947.2	10	Standard
ENST00000690106.1	Ensembl	ENSP00000508762.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysine degradation - Homo sapiens (human)
Other types of O-glycan biosynthesis - Homo sapiens (human)
Collagen biosynthesis and modifying enzymes
Collagen formation
Extracellular matrix organization

Biological Process

positive regulation of collagen fibril organization

Molecular Function

procollagen galactosyltransferase activity

Cellular Component

endoplasmic reticulum lumen
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252599
Coding exons: 12
Length: 27569
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 41
Defined: 125748
p: 0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.523	337	365	0.923	0.0000253	3993
Missense (PolyPhen)		107	113.27	0.94464		1087
Synonymous	0.221	146	149	0.977	0.0000105	1254
Loss of Function	2.06	16	27.7	0.578	0.00000134	321

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of type I collagen (PubMed:19075007, PubMed:22216269, PubMed:27402836). By acting on collagen glycosylation, facilitates the formation of collagen triple helix (PubMed:27402836). {ECO:0000269|PubMed:19075007, ECO:0000269|PubMed:22216269, ECO:0000269|PubMed:27402836}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

RVIS EVS: -1.5
RVIS percentile EVS: 3.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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