Gillessen-Kaesbach-Nishimura syndrome

Summary

Gillessen-Kaesbach-Nishimura syndrome (MONDO:0009890) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 77

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Gillessen-Kaesbach-Nishimura syndrome
Mondo ID	MONDO:0009890
MeSH	C564881
OMIM	263210
UMLS	C1849762
MedGen	376653
GARD	0015223
Is cancer (heuristic)	no

Also known as: GIKANIS · Gillessen-Kaesbach-Nishimura syndrome

Data availability: 77 ClinVar variants · 1 GenCC gene-disease record.

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 › congenital disorder of glycosylation type I › ALG9-congenital disorder of glycosylation › Gillessen-Kaesbach-Nishimura syndrome

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

77 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 14 likely pathogenic, 6 likely benign, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 4 pathogenic/likely pathogenic, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1524100	NM_024740.2(ALG9):c.566-1G>A	ALG9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2086914	NM_024740.2(ALG9):c.744G>A (p.Trp248Ter)	ALG9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3749	NM_024740.2(ALG9):c.860A>G (p.Tyr287Cys)	ALG9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4705323	NM_024740.2(ALG9):c.427C>T (p.Arg143Ter)	ALG9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179143	NM_024740.2(ALG9):c.701+1G>A	ALG9	Likely pathogenic	criteria provided, single submitter
2007716	NM_024740.2(ALG9):c.896-2A>G	ALG9	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3598953	NM_024740.2(ALG9):c.1651G>T (p.Glu551Ter)	ALG9	Likely pathogenic	criteria provided, single submitter
3598955	NM_024740.2(ALG9):c.1605_1608del	ALG9	Likely pathogenic	criteria provided, single submitter
3598956	NM_024740.2(ALG9):c.1602+1G>A	ALG9	Likely pathogenic	criteria provided, single submitter
3598959	NM_024740.2(ALG9):c.1496C>G (p.Ser499Ter)	ALG9	Likely pathogenic	criteria provided, single submitter
3598964	NM_024740.2(ALG9):c.1324+2T>C	ALG9	Likely pathogenic	criteria provided, single submitter
3598966	NM_024740.2(ALG9):c.1209dup (p.Val404fs)	ALG9	Likely pathogenic	criteria provided, single submitter
3598976	NM_024740.2(ALG9):c.789+1G>A	ALG9	Likely pathogenic	criteria provided, single submitter
3598981	NM_024740.2(ALG9):c.704del (p.Leu235fs)	ALG9	Likely pathogenic	criteria provided, single submitter
3598990	NM_024740.2(ALG9):c.530T>A (p.Leu177Ter)	ALG9	Likely pathogenic	criteria provided, single submitter
3598992	NM_024740.2(ALG9):c.563C>G (p.Ser188Ter)	ALG9	Likely pathogenic	criteria provided, single submitter
4813467	NM_024740.2(ALG9):c.1097A>G (p.His366Arg)	ALG9	Likely pathogenic	criteria provided, single submitter
4845743	NM_024740.2(ALG9):c.230_236delinsGT (p.Asn77fs)	ALG9	Likely pathogenic	criteria provided, single submitter
1314309	NM_024740.2(ALG9):c.1363C>T (p.Arg455Ter)	ALG9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1366237	NM_024740.2(ALG9):c.1489A>G (p.Ile497Val)	ALG9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162619	NM_024740.2(ALG9):c.1173+2T>A	ALG9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
598383	NM_024740.2(ALG9):c.741G>T (p.Arg247Ser)	ALG9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
96135	NM_024740.2(ALG9):c.694G>C (p.Ala232Pro)	ALG9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1042960	NM_024740.2(ALG9):c.1166C>T (p.Ala389Val)	ALG9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1325628	NM_024740.2(ALG9):c.1502T>A (p.Phe501Tyr)	ALG9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1349412	NM_024740.2(ALG9):c.326A>G (p.Tyr109Cys)	ALG9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1807449	NM_024740.2(ALG9):c.1768T>C (p.Phe590Leu)	ALG9	Uncertain significance	criteria provided, multiple submitters, no conflicts
2140708	NM_024740.2(ALG9):c.1820G>A (p.Arg607Gln)	ALG9	Uncertain significance	criteria provided, multiple submitters, no conflicts
2170861	NM_024740.2(ALG9):c.888T>G (p.Asp296Glu)	ALG9	Uncertain significance	criteria provided, multiple submitters, no conflicts
2413262	NM_024740.2(ALG9):c.1753G>A (p.Ala585Thr)	ALG9	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
ALG9	Moderate	Autosomal recessive	Gillessen-Kaesbach-Nishimura syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALG9	Orphanet:730	Autosomal dominant polycystic kidney disease
ALG9	Orphanet:79328	ALG9-CDG

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
ALG9	HGNC:15672	ENSG00000086848	Q9H6U8	Alpha-1,2-mannosyltransferase ALG9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALG9	Alpha-1,2-mannosyltransferase ALG9	Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.

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)
ALG9	Enzyme (other)	yes	2.4.1.259	GPI_mannosylTrfase

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
body of pancreas	1
endothelial cell	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALG9	240	ubiquitous	marker	endothelial cell, body of pancreas, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALG9	1,167

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALG9	Q9H6U8	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ALG9 causes CDG-1l	1	11420.0×	8e-04	ALG9
Diseases associated with N-glycosylation of proteins	1	634.4×	0.007	ALG9
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.014	ALG9
Diseases of glycosylation	1	131.3×	0.017	ALG9
Diseases of metabolism	1	80.4×	0.022	ALG9
Asparagine N-linked glycosylation	1	60.1×	0.025	ALG9
Post-translational protein modification	1	19.2×	0.067	ALG9
Disease	1	13.1×	0.081	ALG9
Metabolism of proteins	1	12.4×	0.081	ALG9

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
dolichol-linked oligosaccharide biosynthetic process	1	842.6×	0.002	ALG9
protein N-linked glycosylation	1	263.3×	0.004	ALG9

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
ALG9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALG9	2.4.1.259, 2.4.1.261	dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase, dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase

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	1	ALG9
D	Druggable family + AlphaFold only, no drug	0
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)
ALG9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.