Zimmermann-Laband syndrome 3

Summary

Zimmermann-Laband syndrome 3 (MONDO:0032854) is a disease caused by KCNN3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: KCNN3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Zimmermann-Laband syndrome 3
Mondo ID	MONDO:0032854
OMIM	618658
UMLS	C5231447
MedGen	1684740
GARD	0016371
Is cancer (heuristic)	no

Also known as: ZIMMERMANN-LABAND SYNDROME 3 · ZLS3

Data availability: 26 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 › Zimmermann-Laband syndrome › Zimmermann-Laband syndrome 3

Related subtypes (2): Zimmermann-Laband syndrome 2, Zimmermann-Laband 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

26 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 4 pathogenic, 3 benign, 2 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1064423	NM_002249.6(KCNN3):c.1606G>A (p.Ala536Thr)	KCNN3	Pathogenic	criteria provided, single submitter
804200	NM_002249.6(KCNN3):c.1306A>T (p.Ser436Cys)	KCNN3	Pathogenic	no assertion criteria provided
804201	NM_002249.6(KCNN3):c.805A>G (p.Lys269Glu)	KCNN3	Pathogenic	no assertion criteria provided
804202	NM_002249.6(KCNN3):c.1049G>A (p.Gly350Asp)	KCNN3	Pathogenic	no assertion criteria provided
1685389	NM_002249.6(KCNN3):c.200AGC[12] (p.Gln79_Gln80del)	KCNN3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3113453	NM_002249.6(KCNN3):c.2141T>C (p.Ile714Thr)	KCNN3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3891452	NM_052917.4(GALNT13):c.142+41082_142+41090dup	GALNT13	Uncertain significance	criteria provided, single submitter
3891453	NM_052917.4(GALNT13):c.142+41089_142+41091dup	GALNT13	Uncertain significance	criteria provided, single submitter
1029428	NM_002249.6(KCNN3):c.1343G>A (p.Arg448His)	KCNN3	Uncertain significance	criteria provided, single submitter
1098591	NM_002249.6(KCNN3):c.2080G>A (p.Glu694Lys)	KCNN3	Uncertain significance	criteria provided, single submitter
1333820	NM_002249.6(KCNN3):c.504C>A (p.Asn168Lys)	KCNN3	Uncertain significance	criteria provided, single submitter
1679705	NM_002249.6(KCNN3):c.1701+3059C>T	KCNN3	Uncertain significance	criteria provided, single submitter
1804639	NM_002249.6(KCNN3):c.650C>T (p.Pro217Leu)	KCNN3	Uncertain significance	no assertion criteria provided
2431680	NM_002249.6(KCNN3):c.682C>T (p.His228Tyr)	KCNN3	Uncertain significance	criteria provided, single submitter
2433011	NM_002249.6(KCNN3):c.2059C>T (p.Gln687Ter)	KCNN3	Uncertain significance	criteria provided, single submitter
2572455	NM_002249.6(KCNN3):c.1259G>A (p.Arg420Gln)	KCNN3	Uncertain significance	criteria provided, single submitter
3234017	NM_002249.6(KCNN3):c.1786A>G (p.Lys596Glu)	KCNN3	Uncertain significance	criteria provided, single submitter
3362408	NM_002249.6(KCNN3):c.1192C>T (p.Arg398Trp)	KCNN3	Uncertain significance	criteria provided, single submitter
3381255	NM_002249.6(KCNN3):c.1124T>G (p.Ile375Ser)	KCNN3	Uncertain significance	criteria provided, single submitter
3779782	NM_002249.6(KCNN3):c.1449-3921del	KCNN3	Uncertain significance	criteria provided, single submitter
4277701	NM_002249.6(KCNN3):c.1942C>T (p.Arg648Trp)	KCNN3	Uncertain significance	criteria provided, single submitter
4819827	NM_002249.6(KCNN3):c.1612G>C (p.Val538Leu)	KCNN3	Uncertain significance	criteria provided, single submitter
1290509	NM_002249.6(KCNN3):c.200AGC[19] (p.Gln76_Gln80dup)	KCNN3	Benign	criteria provided, multiple submitters, no conflicts
403001	NM_002249.6(KCNN3):c.1092G>C (p.Leu364=)	KCNN3	Benign	criteria provided, multiple submitters, no conflicts
403002	NM_002249.6(KCNN3):c.1047T>C (p.Asn349=)	KCNN3	Benign	criteria provided, multiple submitters, no conflicts
403005	NM_002249.6(KCNN3):c.200AGC[20] (p.Gln75_Gln80dup)	KCNN3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
KCNN3	Strong	Autosomal dominant	Zimmermann-Laband syndrome 3	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNN3	Orphanet:3473	Zimmermann-Laband syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNN3	HGNC:6292	ENSG00000143603	Q9UGI6	Small conductance calcium-activated potassium channel protein 3	gencc,clinvar
GALNT13	HGNC:23242	ENSG00000144278	Q8IUC8	Polypeptide N-acetylgalactosaminyltransferase 13	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNN3	Small conductance calcium-activated potassium channel protein 3	Small conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calci…
GALNT13	Polypeptide N-acetylgalactosaminyltransferase 13	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor.

Protein-family classification

Druggable: 2 · 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
Ion channel	1	55.8×	0.036
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNN3	Ion channel	yes		CaM-bd_dom, K_chnl_dom, K_chnl_Ca-activ_SK
GALNT13	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lateral globus pallidus	1
medial globus pallidus	1
substantia nigra pars reticulata	1
cerebellar cortex	1
cerebellar hemisphere	1
cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNN3	227	broad	marker	lateral globus pallidus, substantia nigra pars reticulata, medial globus pallidus
GALNT13	184	broad	marker	cerebellar cortex, cerebellar hemisphere, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNN3	1,407
GALNT13	977

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GALNT13	Q8IUC8	93.06
KCNN3	Q9UGI6	68.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Ca2+ activated K+ channels	1	571.0×	0.007	KCNN3
O-linked glycosylation of mucins	1	92.1×	0.020	GALNT13
Potassium Channels	1	67.2×	0.020	KCNN3
Neuronal System	1	22.1×	0.045	KCNN3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 via N-acetylgalactosamine	1	216.1×	0.013	GALNT13
protein O-linked glycosylation	1	112.3×	0.013	GALNT13
potassium ion transmembrane transport	1	68.0×	0.015	KCNN3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
KCNN3	DEQUALINIUM CHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNN3	2	4
GALNT13	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DEQUALINIUM CHLORIDE	4	KCNN3
CEPHARANTHINE	2	KCNN3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KCNN3	51	Binding:51
GALNT13	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GALNT13	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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.

Compound	Max phase	Cohort target (bioactivity)
DEQUALINIUM CHLORIDE	4	KCNN3
CEPHARANTHINE	2	KCNN3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KCNN3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	GALNT13
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)
GALNT13	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.