Larsen-like syndrome, B3GAT3 type

Summary

Larsen-like syndrome, B3GAT3 type (MONDO:0009511) is a disease caused by B3GAT3 (GenCC Strong), with 4 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: B3GAT3 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 252

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		14	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Larsen-like syndrome, B3GAT3 type
Mondo ID	MONDO:0009511
MeSH	C537874
OMIM	245600
Orphanet	284139
DOID	DOID:0080575
UMLS	C3278404
MedGen	480034
GARD	0017308
Is cancer (heuristic)	no

Also known as: JDSCD · Larsen syndrome, autosomal recessive · multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects · multiple joint dislocations-short stature-craniofacial dysmorphism-congenital heart defects syndrome

Data availability: 252 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › Larsen-like syndrome, B3GAT3 type

Related subtypes (24): congenital disorder of glycosylation type I, congenital disorder of glycosylation type II, Ehlers-Danlos syndrome, musculocontractural type, temtamy preaxial brachydactyly syndrome, progressive myoclonic epilepsy type 3, autosomal recessive limb-girdle muscular dystrophy type 2P, seizures-scoliosis-macrocephaly syndrome, disorder of protein N-glycosylation, disorder of protein O-glycosylation, inborn disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation, disorder of multiple glycosylation, XYLT1-congenital disorder of glycosylation, congenital muscular dystrophy with intellectual disability, congenital disorder of glycosylation syndrome type 4, congenital disorder of glycosylation with defective fucosylation, SLC10A7-congenital disorder of glycosylation, ALG14-congenital disorder of glycosylation, B3GALT6-congenital disorder of glycosylation, A4GALT-congenital disorder of glycosylation, FAM20B-congenital disorder of glycosylation, ALG10-congenital disorder of glycosylation, congenital disorder of glycosylation, type Ibb, congenital disorder of glycosylation, type Iw, autosomal dominant, congenital disorder of glycosylation, type 1DD

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

252 retrieved; paginated sample, class counts are floors:

109 likely benign, 96 uncertain significance, 14 pathogenic, 9 pathogenic/likely pathogenic, 9 conflicting classifications of pathogenicity, 8 likely pathogenic, 4 benign, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1076368	NM_012200.4(B3GAT3):c.516_517insT (p.Gly173fs)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1174609	NM_012200.4(B3GAT3):c.1A>T (p.Met1Leu)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1252005	NM_012200.4(B3GAT3):c.245C>T (p.Pro82Leu)	B3GAT3	Pathogenic	no assertion criteria provided
1455919	NM_012200.4(B3GAT3):c.283C>T (p.Arg95Ter)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1991628	NM_012200.4(B3GAT3):c.604G>T (p.Glu202Ter)	B3GAT3	Pathogenic	criteria provided, single submitter
1995805	NM_012200.4(B3GAT3):c.135del (p.Gln46fs)	B3GAT3	Pathogenic	criteria provided, single submitter
1998893	NM_012200.4(B3GAT3):c.126_154dup (p.Ser52delinsCysSerTyrGlyArgArgIleTer)	B3GAT3	Pathogenic	criteria provided, single submitter
225924	NM_012200.4(B3GAT3):c.667G>A (p.Gly223Ser)	B3GAT3	Pathogenic	criteria provided, single submitter
2683666	NM_012200.4(B3GAT3):c.85C>T (p.Gln29Ter)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2797326	NM_012200.4(B3GAT3):c.36C>A (p.Tyr12Ter)	B3GAT3	Pathogenic	criteria provided, single submitter
2844231	NM_012200.4(B3GAT3):c.150del (p.Ile51fs)	B3GAT3	Pathogenic	criteria provided, single submitter
2890773	NM_012200.4(B3GAT3):c.334G>T (p.Glu112Ter)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2996858	NM_012200.4(B3GAT3):c.298_301del (p.Leu100fs)	B3GAT3	Pathogenic	criteria provided, single submitter
30573	NM_012200.4(B3GAT3):c.830G>A (p.Arg277Gln)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3681718	NM_012200.4(B3GAT3):c.231_234del (p.Ile77fs)	B3GAT3	Pathogenic	criteria provided, single submitter
3685902	NM_012200.4(B3GAT3):c.246del (p.Thr83fs)	B3GAT3	Pathogenic	criteria provided, single submitter
4715364	NM_012200.4(B3GAT3):c.631del (p.Arg211fs)	B3GAT3	Pathogenic	criteria provided, single submitter
4813555	NM_012200.4(B3GAT3):c.277C>G (p.Leu93Val)	B3GAT3	Pathogenic	criteria provided, single submitter
577885	NM_012200.4(B3GAT3):c.175C>T (p.Arg59Ter)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620480	NM_012200.4(B3GAT3):c.673C>T (p.Arg225Ter)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
978467	NM_012200.4(B3GAT3):c.889C>T (p.Arg297Trp)	B3GAT3	Pathogenic	criteria provided, single submitter
981501	NM_012200.4(B3GAT3):c.505C>T (p.Arg169Trp)	B3GAT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5613	NM_007255.3(B4GALT7):c.808C>T (p.Arg270Cys)	B4GALT7	Pathogenic	criteria provided, multiple submitters, no conflicts
1503077	NM_012200.4(B3GAT3):c.619-1G>A	B3GAT3	Likely pathogenic	criteria provided, single submitter
2137125	NM_012200.4(B3GAT3):c.1A>G (p.Met1Val)	B3GAT3	Likely pathogenic	criteria provided, single submitter
2578426	NM_012200.4(B3GAT3):c.986C>G (p.Ser329Ter)	B3GAT3	Likely pathogenic	criteria provided, single submitter
2906193	NM_012200.4(B3GAT3):c.82+1G>A	B3GAT3	Likely pathogenic	criteria provided, single submitter
3599828	NM_012200.4(B3GAT3):c.729G>A (p.Trp243Ter)	B3GAT3	Likely pathogenic	criteria provided, single submitter
3706964	NM_012200.4(B3GAT3):c.2T>G (p.Met1Arg)	B3GAT3	Likely pathogenic	criteria provided, single submitter
4713959	NM_012200.4(B3GAT3):c.257+1G>A	B3GAT3	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
B3GAT3	Strong	Autosomal recessive	Larsen-like syndrome, B3GAT3 type	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
B3GAT3	Orphanet:284139	Larsen-like syndrome, B3GAT3 type
CHST3	Orphanet:263463	CHST3-related skeletal dysplasia
COL11A2	Orphanet:1427	Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:2021	Fibrochondrogenesis
COL11A2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
B4GALT7	Orphanet:75496	B4GALT7-related spondylodysplastic Ehlers-Danlos syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
B3GAT3	HGNC:923	ENSG00000149541	O94766	Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3	gencc,clinvar
CHST3	HGNC:1971	ENSG00000122863	Q7LGC8	Carbohydrate sulfotransferase 3	clinvar
COL11A2	HGNC:2187	ENSG00000204248	P13942	Collagen alpha-2(XI) chain	clinvar
B4GALT7	HGNC:930	ENSG00000027847	Q9UBV7	Beta-1,4-galactosyltransferase 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
B3GAT3	Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3	Glycosaminoglycans biosynthesis.
CHST3	Carbohydrate sulfotransferase 3	Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin.
COL11A2	Collagen alpha-2(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
B4GALT7	Beta-1,4-galactosyltransferase 7	Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.75

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	3	9.0×	0.004
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
B3GAT3	Enzyme (other)	yes	2.4.1.135	Glyco_trans_43, Nucleotide-diphossugar_trans
CHST3	Enzyme (other)	yes	2.8.2.17	Sulfotransferase_dom, Carbohydrate_sulfotransferase, P-loop_NTPase
COL11A2	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
B4GALT7	Enzyme (other)	yes	2.4.1.133	Galactosyl_T, Galactosyl_T_C, Galactosyl_T_N

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	2
cerebellar hemisphere	1
right hemisphere of cerebellum	1
cartilage tissue	1
tibia	1
ventricular zone	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1
left adrenal gland	1
right adrenal gland	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
B3GAT3	215	ubiquitous	marker	right hemisphere of cerebellum, adenohypophysis, cerebellar hemisphere
CHST3	233	ubiquitous	marker	tibia, cartilage tissue, ventricular zone
COL11A2	134	broad	yes	pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis
B4GALT7	259	ubiquitous	marker	tendon of biceps brachii, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
B4GALT7	1,645
COL11A2	1,583
B3GAT3	1,333
CHST3	579

Intra-cohort edges

A	B	Sources
B3GAT3	B4GALT7	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
B3GAT3	O94766	3
B4GALT7	Q9UBV7	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CHST3	Q7LGC8	80.58
COL11A2	P13942	50.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 4 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chondroitin sulfate/dermatan sulfate metabolism	2	475.8×	1e-04	B3GAT3, B4GALT7
Diseases associated with glycosaminoglycan metabolism	2	380.7×	1e-04	B3GAT3, B4GALT7
Heparan sulfate/heparin (HS-GAG) metabolism	2	271.9×	1e-04	B3GAT3, B4GALT7
Glycosaminoglycan-protein linkage region biosynthesis	2	196.9×	2e-04	B3GAT3, B4GALT7
Glycosaminoglycan metabolism	2	109.8×	5e-04	B3GAT3, B4GALT7
Diseases of glycosylation	2	65.6×	0.001	B3GAT3, B4GALT7
Metabolism of carbohydrates and carbohydrate derivatives	2	60.1×	0.001	B3GAT3, B4GALT7
Diseases of metabolism	2	40.2×	0.002	B3GAT3, B4GALT7
Defective CHST3 causes SEDCJD	1	356.9×	0.007	CHST3
Defective B4GALT7 causes EDS, progeroid type	1	142.8×	0.013	B4GALT7
Defective B3GAT3 causes JDSSDHD	1	142.8×	0.013	B3GAT3
CS-GAG biosynthesis	1	135.9×	0.013	CHST3
Keratan sulfate biosynthesis	1	95.2×	0.016	CHST3
MET activates PTK2 signaling	1	95.2×	0.016	COL11A2
Collagen chain trimerization	1	64.9×	0.022	COL11A2
Developmental Lineage of Pancreatic Ductal Cells	1	57.1×	0.024	COL11A2
Assembly of collagen fibrils and other multimeric structures	1	50.1×	0.026	COL11A2
Collagen degradation	1	43.9×	0.027	COL11A2
Collagen biosynthesis and modifying enzymes	1	42.6×	0.027	COL11A2
Non-integrin membrane-ECM interactions	1	38.6×	0.028	COL11A2
Disease	2	6.5×	0.033	B3GAT3, B4GALT7
Metabolism	2	5.8×	0.039	B3GAT3, B4GALT7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
carbohydrate metabolic process	3	101.9×	4e-05	B3GAT3, CHST3, B4GALT7
glycosaminoglycan biosynthetic process	2	421.3×	1e-04	B3GAT3, B4GALT7
chondroitin sulfate proteoglycan biosynthetic process	2	312.1×	1e-04	B3GAT3, CHST3
glycosaminoglycan-protein linkage region biosynthetic process	1	1053.2×	0.006	B4GALT7
soft palate development	1	842.6×	0.006	COL11A2
positive regulation of catalytic activity	1	601.9×	0.007	B3GAT3
proteoglycan metabolic process	1	468.1×	0.007	B4GALT7
dermatan sulfate proteoglycan biosynthetic process	1	421.3×	0.007	B3GAT3
N-acetylglucosamine metabolic process	1	300.9×	0.008	CHST3
sulfur compound metabolic process	1	280.9×	0.008	CHST3
supramolecular fiber organization	1	263.3×	0.008	B4GALT7
keratan sulfate proteoglycan biosynthetic process	1	247.8×	0.008	CHST3
proteoglycan biosynthetic process	1	210.7×	0.009	B4GALT7
positive regulation of intracellular protein transport	1	168.5×	0.010	B3GAT3
heparan sulfate proteoglycan biosynthetic process	1	140.4×	0.011	B3GAT3
negative regulation of fibroblast proliferation	1	123.9×	0.012	B4GALT7
T cell homeostasis	1	113.9×	0.012	CHST3
protein N-linked glycosylation	1	65.8×	0.019	B4GALT7
cartilage development	1	62.9×	0.019	COL11A2
roof of mouth development	1	62.0×	0.019	COL11A2
protein modification process	1	61.1×	0.019	B4GALT7
collagen fibril organization	1	56.2×	0.019	COL11A2
skeletal system development	1	31.4×	0.033	COL11A2
sensory perception of sound	1	25.2×	0.039	COL11A2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
B3GAT3	0	0
CHST3	0	0
COL11A2	0	0
B4GALT7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
B3GAT3	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
B3GAT3	2.4.1.135	galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase
CHST3	2.8.2.17	chondroitin 6-sulfotransferase
B4GALT7	2.4.1.133, 2.4.1.38	xylosylprotein 4-beta-galactosyltransferase, beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	B3GAT3, B4GALT7
D	Druggable family + AlphaFold only, no drug	1	CHST3
E	Difficult family or no structure, no drug	1	COL11A2

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
B3GAT3	4	—
CHST3	0	—
COL11A2	0	—
B4GALT7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.