Zimmermann-Laband syndrome 2

Summary

Zimmermann-Laband syndrome 2 (MONDO:0014646) is a disease caused by ATP6V1B2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATP6V1B2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Zimmermann-Laband syndrome 2
Mondo ID	MONDO:0014646
OMIM	616455
UMLS	C4225321
MedGen	897567
GARD	0016115
Is cancer (heuristic)	no

Also known as: ATP6V1B2 Zimmermann-Laband syndrome · Zimmermann-Laband syndrome 2 · Zimmermann-Laband syndrome caused by mutation in ATP6V1B2 · Zimmermann-Laband syndrome type 2 · ZLS2

Data availability: 19 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 › Zimmermann-Laband syndrome › Zimmermann-Laband syndrome 2

Related subtypes (2): Zimmermann-Laband syndrome 1, Zimmermann-Laband syndrome 3

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

19 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 5 pathogenic, 4 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1334193	NM_001693.4(ATP6V1B2):c.1121A>G (p.Glu374Gly)	ATP6V1B2	Pathogenic	criteria provided, single submitter
183414	NM_001693.4(ATP6V1B2):c.1454G>C (p.Arg485Pro)	ATP6V1B2	Pathogenic	no assertion criteria provided
203442	NM_001693.4(ATP6V1B2):c.1516C>T (p.Arg506Ter)	ATP6V1B2	Pathogenic	criteria provided, multiple submitters, no conflicts
3362385	NM_001693.4(ATP6V1B2):c.1192C>G (p.Leu398Val)	ATP6V1B2	Pathogenic	no assertion criteria provided
3377165	NM_001693.4(ATP6V1B2):c.1443G>A (p.Trp481Ter)	ATP6V1B2	Pathogenic	criteria provided, single submitter
2572643	NM_001693.4(ATP6V1B2):c.124C>T (p.Gln42Ter)	ATP6V1B2	Likely pathogenic	criteria provided, single submitter
3254713	NM_001693.4(ATP6V1B2):c.487C>G (p.Arg163Gly)	ATP6V1B2	Likely pathogenic	criteria provided, single submitter
4056414	NM_001693.4(ATP6V1B2):c.1057A>T (p.Ile353Phe)	ATP6V1B2	Likely pathogenic	criteria provided, single submitter
431094	NM_001693.4(ATP6V1B2):c.1120G>C (p.Glu374Gln)	ATP6V1B2	Likely pathogenic	criteria provided, single submitter
2683930	NM_001693.4(ATP6V1B2):c.1241A>T (p.Asp414Val)	ATP6V1B2	Uncertain significance	criteria provided, single submitter
3131899	NM_001693.4(ATP6V1B2):c.14C>A (p.Ala5Glu)	ATP6V1B2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382980	NM_001693.4(ATP6V1B2):c.1018C>T (p.Arg340Ter)	ATP6V1B2	Uncertain significance	criteria provided, single submitter
3595460	NM_001693.4(ATP6V1B2):c.631G>C (p.Gly211Arg)	ATP6V1B2	Uncertain significance	criteria provided, single submitter
4086189	NM_001693.4(ATP6V1B2):c.529A>G (p.Ile177Val)	ATP6V1B2	Uncertain significance	criteria provided, single submitter
4086196	NM_001693.4(ATP6V1B2):c.1108G>A (p.Gly370Ser)	ATP6V1B2	Uncertain significance	criteria provided, single submitter
4526431	NM_001693.4(ATP6V1B2):c.503A>G (p.Glu168Gly)	ATP6V1B2	Uncertain significance	criteria provided, single submitter
4819729	NM_001693.4(ATP6V1B2):c.1124G>C (p.Gly375Ala)	ATP6V1B2	Uncertain significance	criteria provided, single submitter
930988	NM_001693.4(ATP6V1B2):c.1437T>G (p.Ile479Met)	ATP6V1B2	Uncertain significance	criteria provided, single submitter
1192466	NM_001693.4(ATP6V1B2):c.463+6T>G	ATP6V1B2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
ATP6V1B2	Strong	Autosomal dominant	Zimmermann-Laband syndrome 2	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP6V1B2	Orphanet:3473	Zimmermann-Laband syndrome
ATP6V1B2	Orphanet:79499	Autosomal dominant deafness-onychodystrophy syndrome
ATP6V1B2	Orphanet:79500	DOORS 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
ATP6V1B2	HGNC:854	ENSG00000147416	P21281	V-type proton ATPase subunit B, brain isoform	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP6V1B2	V-type proton ATPase subunit B, brain isoform	Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP6V1B2	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_bsu

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
lateral nuclear group of thalamus	1
monocyte	1
pons	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP6V1B2	300	ubiquitous	marker	pons, monocyte, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP6V1B2	2,898

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP6V1B2	P21281	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	671.8×	0.004	ATP6V1B2
Insulin receptor recycling	1	380.7×	0.004	ATP6V1B2
Transferrin endocytosis and recycling	1	368.4×	0.004	ATP6V1B2
ROS and RNS production in phagocytes	1	335.9×	0.004	ATP6V1B2
Amino acids regulate mTORC1	1	200.3×	0.006	ATP6V1B2
Ion channel transport	1	96.0×	0.010	ATP6V1B2

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
synaptic vesicle lumen acidification	1	936.2×	0.003	ATP6V1B2
vacuolar acidification	1	732.7×	0.003	ATP6V1B2
ATP metabolic process	1	468.1×	0.003	ATP6V1B2
proton transmembrane transport	1	312.1×	0.003	ATP6V1B2
regulation of macroautophagy	1	295.6×	0.003	ATP6V1B2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
ATP6V1B2	ENOXACIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATP6V1B2	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ENOXACIN	4	ATP6V1B2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATP6V1B2	3	Binding:3

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

1 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)
ENOXACIN	4	ATP6V1B2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATP6V1B2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.