Lethal congenital contracture syndrome 6

disease

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Also known as LCCS6lethal congenital contracture syndrome caused by mutation in ZBTB42lethal congenital contracture syndrome type 6ZBTB42 lethal congenital contracture syndrome

Summary

Lethal congenital contracture syndrome 6 (MONDO:0014549) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lethal congenital contracture syndrome 6
Mondo ID	MONDO:0014549
OMIM	616248
DOID	DOID:0061262
UMLS	C4015686
MedGen	864123
GARD	0025001
Is cancer (heuristic)	no

Also known as: LCCS6 · lethal congenital contracture syndrome 6 · lethal congenital contracture syndrome caused by mutation in ZBTB42 · lethal congenital contracture syndrome type 6 · ZBTB42 lethal congenital contracture syndrome

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › lethal congenital contracture syndrome › lethal congenital contracture syndrome 6

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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031875	NM_001137601.3(ZBTB42):c.1088C>G (p.Thr363Arg)	ZBTB42	Uncertain significance	criteria provided, multiple submitters, no conflicts
183176	NM_001137601.3(ZBTB42):c.1190G>A (p.Arg397His)	ZBTB42	Uncertain significance	criteria provided, single submitter
1246843	NM_001137601.3(ZBTB42):c.45A>G (p.Arg15=)	ZBTB42	Benign	criteria provided, multiple submitters, no conflicts
803053	NM_001137601.3(ZBTB42):c.694G>A (p.Glu232Lys)	ZBTB42	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
ZBTB42	Moderate	Autosomal recessive	lethal congenital contracture syndrome 6	2

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
ZBTB42	HGNC:32550	ENSG00000179627	B2RXF5	Zinc finger and BTB domain-containing protein 42	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZBTB42	Zinc finger and BTB domain-containing protein 42	Transcriptional repressor.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZBTB42	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type

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
esophagus squamous epithelium	1
parotid gland	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZBTB42	163	ubiquitous	marker	parotid gland, esophagus squamous epithelium, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZBTB42	613

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZBTB42	B2RXF5	50.03

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
muscle organ development	1	166.8×	0.018	ZBTB42
negative regulation of transcription by RNA polymerase II	1	17.7×	0.085	ZBTB42
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ZBTB42

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
ZBTB42	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	1	ZBTB42

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)
ZBTB42	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ZBTB42