Carney complex - trismus - pseudocamptodactyly syndrome

Summary

Carney complex - trismus - pseudocamptodactyly syndrome (MONDO:0012137) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Carney complex - trismus - pseudocamptodactyly syndrome
Mondo ID	MONDO:0012137
OMIM	608837
Orphanet	319340
UMLS	C1837245
MedGen	332400
GARD	0017448
Is cancer (heuristic)	no

Also known as: Carney complex variant

Data availability: 13 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 › autosomal genetic disease › autosomal dominant disease › Carney complex › Carney complex - trismus - pseudocamptodactyly syndrome

Related subtypes (2): Carney complex, type 1, Carney complex type 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

13 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 2 benign/likely benign, 2 conflicting classifications of pathogenicity, 2 likely benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14136	NM_002472.3(MYH8):c.2021G>A (p.Arg674Gln)	MYH8	Pathogenic	criteria provided, multiple submitters, no conflicts
4849476	NM_002472.3(MYH8):c.4528+1G>A	MYHAS	Likely pathogenic	criteria provided, single submitter
211563	NM_002472.3(MYH8):c.3532C>T (p.Arg1178Cys)	MYHAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
397646	NM_002472.3(MYH8):c.3320del (p.Leu1107fs)	MYHAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225416	NM_002472.3(MYH8):c.3874C>T (p.Arg1292Ter)	MYH8	Uncertain significance	criteria provided, multiple submitters, no conflicts
3401010	NM_002472.3(MYH8):c.4094C>G (p.Ser1365Cys)	MYH8	Uncertain significance	criteria provided, multiple submitters, no conflicts
931773	NM_002472.3(MYH8):c.4724T>C (p.Val1575Ala)	MYH8	Uncertain significance	criteria provided, single submitter
931774	NM_002472.3(MYH8):c.1640C>T (p.Thr547Met)	MYH8	Uncertain significance	criteria provided, single submitter
634583	NM_002472.3(MYH8):c.977T>C (p.Ile326Thr)	MYHAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
129675	NM_002472.3(MYH8):c.3686T>C (p.Met1229Thr)	MYH8	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
775109	NM_002472.3(MYH8):c.1632T>C (p.Pro544=)	MYH8	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
321623	NM_002472.3(MYH8):c.5435A>G (p.Lys1812Arg)	MYHAS	Likely benign	criteria provided, multiple submitters, no conflicts
739199	NM_002472.3(MYH8):c.479T>A (p.Ile160Asn)	MYHAS	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
MYH8	Strong	Autosomal dominant	trismus-pseudocamptodactyly syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYH8	Orphanet:319340	Carney complex-trismus-pseudocamptodactyly syndrome
MYH8	Orphanet:3377	Trismus-pseudocamptodactyly syndrome

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYH8	HGNC:7578	ENSG00000133020	P13535	Myosin-8	gencc,clinvar
MYHAS	HGNC:50609	ENSG00000272975		myosin heavy chain gene cluster antisense RNA	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYH8	Myosin-8	Muscle contraction.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYH8	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
MYHAS	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
quadriceps femoris	1
skeletal muscle tissue of rectus abdominis	1
vastus lateralis	1
hindlimb stylopod muscle	1
muscle of leg	1
skeletal muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH8	67	tissue_specific	marker	vastus lateralis, quadriceps femoris, skeletal muscle tissue of rectus abdominis
MYHAS	65	tissue_specific	yes	skeletal muscle tissue, hindlimb stylopod muscle, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH8	1,719
MYHAS	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYH8	P13535	75.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Striated Muscle Contraction	1	308.6×	0.006	MYH8
Muscle contraction	1	77.2×	0.013	MYH8

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 filament sliding	1	1053.2×	0.003	MYH8
skeletal muscle contraction	1	510.7×	0.003	MYH8
ATP metabolic process	1	468.1×	0.003	MYH8
muscle contraction	1	208.1×	0.005	MYH8

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
MYH8	0	0
MYHAS	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	2	MYH8, MYHAS

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYH8	0	—
MYHAS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.