Adams-Oliver syndrome 4

Summary

Adams-Oliver syndrome 4 (MONDO:0014124) is a disease caused by EOGT (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: EOGT (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 152

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Adams-Oliver syndrome 4
Mondo ID	MONDO:0014124
OMIM	615297
UMLS	C3809092
MedGen	815422
GARD	0015941
Is cancer (heuristic)	no

Also known as: Adams-Oliver syndrome 4 · Adams-Oliver syndrome caused by mutation in EOGT · Adams-Oliver syndrome type 4 · AOS4 · EOGT Adams-Oliver syndrome

Data availability: 152 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › Adams-Oliver syndrome › Adams-Oliver syndrome 4

Related subtypes (5): Adams-Oliver syndrome 2, Adams-Oliver syndrome 3, Adams-Oliver syndrome 5, Adams-Oliver syndrome 6, Adams-Oliver syndrome 1

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

152 retrieved; paginated sample, class counts are floors:

70 likely benign, 47 uncertain significance, 12 benign, 9 pathogenic, 6 benign/likely benign, 3 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1989739	NM_001278689.2(EOGT):c.1234C>T (p.Gln412Ter)	EOGT	Pathogenic	criteria provided, single submitter
2054176	NM_001278689.2(EOGT):c.621-2A>T	EOGT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3246930	NC_000003.11:g.(?69058895)(69061253_?)del	EOGT	Pathogenic	criteria provided, single submitter
4692486	NM_001278689.2(EOGT):c.196_199del (p.Leu66fs)	EOGT	Pathogenic	criteria provided, single submitter
523579	NM_001278689.2(EOGT):c.311+1G>T	EOGT	Pathogenic	criteria provided, single submitter
523580	NM_001278689.2(EOGT):c.404G>A (p.Cys135Tyr)	EOGT	Pathogenic	criteria provided, single submitter
523593	NM_001278689.2(EOGT):c.78_81del (p.His27fs)	EOGT	Pathogenic	criteria provided, multiple submitters, no conflicts
523612	NM_001278689.2(EOGT):c.1335-1G>A	EOGT	Pathogenic	criteria provided, single submitter
55816	NM_001278689.2(EOGT):c.620G>C (p.Trp207Ser)	EOGT	Pathogenic	no assertion criteria provided
55817	NM_001278689.2(EOGT):c.1074del (p.Gly359fs)	EOGT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
55818	NM_001278689.2(EOGT):c.1130G>A (p.Arg377Gln)	EOGT	Pathogenic	no assertion criteria provided
2741011	NM_001278689.2(EOGT):c.831+1G>A	EOGT	Likely pathogenic	criteria provided, single submitter
4845664	NM_001278689.2(EOGT):c.924+1del	EOGT	Likely pathogenic	criteria provided, single submitter
567459	NM_001278689.2(EOGT):c.831+2T>C	EOGT	Likely pathogenic	criteria provided, single submitter
445341	NM_001278689.2(EOGT):c.562A>T (p.Lys188Ter)	EOGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
639398	NM_001278689.2(EOGT):c.176C>G (p.Thr59Ser)	EOGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
946321	NM_001278689.2(EOGT):c.1387G>A (p.Val463Ile)	EOGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1010701	NM_001278689.2(EOGT):c.1114C>T (p.Arg372Trp)	EOGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1021870	NM_001278689.2(EOGT):c.1153-3C>T	EOGT	Uncertain significance	criteria provided, single submitter
1035062	NM_001278689.2(EOGT):c.308G>T (p.Gly103Val)	EOGT	Uncertain significance	criteria provided, single submitter
1050810	NM_001278689.2(EOGT):c.548T>A (p.Ile183Asn)	EOGT	Uncertain significance	criteria provided, single submitter
1054717	NM_001278689.2(EOGT):c.1404G>A (p.Trp468Ter)	EOGT	Uncertain significance	criteria provided, single submitter
1324332	NM_001278689.2(EOGT):c.912delinsAC (p.Tyr304Ter)	EOGT	Uncertain significance	criteria provided, single submitter
1367713	NM_001278689.2(EOGT):c.305T>C (p.Met102Thr)	EOGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1377716	NM_001278689.2(EOGT):c.1129C>T (p.Arg377Trp)	EOGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1386378	NM_001278689.2(EOGT):c.1411C>T (p.Gln471Ter)	EOGT	Uncertain significance	criteria provided, single submitter
1408115	NM_001278689.2(EOGT):c.334G>A (p.Glu112Lys)	EOGT	Uncertain significance	criteria provided, single submitter
1418697	NM_001278689.2(EOGT):c.1355G>A (p.Arg452His)	EOGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1420213	NM_001278689.2(EOGT):c.730G>T (p.Val244Phe)	EOGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1425835	NM_001278689.2(EOGT):c.50G>A (p.Ser17Asn)	EOGT	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
EOGT	Definitive	Autosomal recessive	Adams-Oliver syndrome 4	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EOGT	Orphanet:974	Adams-Oliver syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EOGT	HGNC:28526	ENSG00000163378	Q5NDL2	EGF domain-specific O-linked N-acetylglucosamine transferase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EOGT	EGF domain-specific O-linked N-acetylglucosamine transferase	Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in extracellular proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EOGT	Enzyme (other)	yes	2.4.1.255	Glycosyltransferase_61, Glyco_transf_61_cat

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ascending aorta	1
blood vessel layer	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EOGT	270	ubiquitous	marker	blood vessel layer, thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EOGT	891

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EOGT	Q5NDL2	91.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein O-linked glycosylation	1	224.7×	0.004	EOGT

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EOGT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EOGT	2.4.1.255	protein O-GlcNAc transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0
D	Druggable family + AlphaFold only, no drug	1	EOGT
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EOGT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.