Carey-Fineman-Ziter syndrome 1

Summary

Carey-Fineman-Ziter syndrome 1 (MONDO:0800437) is a disease caused by MYMK (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MYMK (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Carey-Fineman-Ziter syndrome 1
Mondo ID	MONDO:0800437
MeSH	C536102
OMIM	254940
DOID	DOID:0061115, DOID:0080194
SNOMED CT	429753001
UMLS	C5676876
MedGen	1804638
GARD	0026558
Is cancer (heuristic)	no

Also known as: Carey Fineman Ziter syndrome · Carey-Fineman-Ziter syndrome 1 · CFZS · CFZS1 · congenital nonprogressive myopathy with Moebius and Robin sequences · Moebius sequence, Robin complex, and hypotonia · myopathy, congenital nonprogressive with Moebius and Robin sequences · myopathy, congenital nonprogressive, with Moebius sequence and Robin sequence · myopathy-Moebius-Robin syndrome

Data availability: 6 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 › Carey-Fineman-Ziter syndrome › Carey-Fineman-Ziter syndrome 1

Related subtypes (1): Carey-Fineman-Ziter syndrome 2

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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
430839	NM_001080483.3(MYMK):c.271C>A (p.Pro91Thr)	MYMK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4759237	NM_001080483.3(MYMK):c.457C>T (p.Gln153Ter)	MYMK	Pathogenic	criteria provided, single submitter
4532817	NM_001080483.3(MYMK):c.586C>T (p.Pro196Ser)	MYMK	Likely pathogenic	criteria provided, single submitter
2433959	NM_001080483.3(MYMK):c.8C>T (p.Thr3Met)	MYMK	Uncertain significance	criteria provided, single submitter
3251986	NM_001080483.3(MYMK):c.428T>C (p.Leu143Pro)	MYMK	Uncertain significance	criteria provided, multiple submitters, no conflicts
3778721	NM_001080483.3(MYMK):c.539A>T (p.His180Leu)	MYMK	Uncertain significance	criteria provided, single submitter

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
MYMK	Definitive	Autosomal recessive	Carey-Fineman-Ziter syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYMK	Orphanet:1358	Carey-Fineman-Ziter 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
MYMK	HGNC:33778	ENSG00000187616	A6NI61	Protein myomaker	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYMK	Protein myomaker	Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers.

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)
MYMK	Other/Unknown	no		NGX6/PGAP6/MYMK

Expression context

Cohort genes with no expression data: 0.

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
metanephros cortex	1
putamen	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYMK	70	tissue_specific	yes	tibial nerve, metanephros cortex, putamen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYMK	421

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYMK	A6NI61	91.14

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
positive regulation of skeletal muscle hypertrophy	1	16852.0×	3e-04	MYMK
obsolete plasma membrane fusion	1	4213.0×	5e-04	MYMK
myoblast fusion involved in skeletal muscle regeneration	1	3370.4×	5e-04	MYMK
myoblast fusion	1	601.9×	0.002	MYMK
muscle organ development	1	166.8×	0.006	MYMK

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
MYMK	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	MYMK

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)
MYMK	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.