Carney complex, type 1

Summary

Carney complex, type 1 (MONDO:0008057) is a disease caused by PRKAR1A (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: PRKAR1A (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 1,005

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Carney complex, type 1
Mondo ID	MONDO:0008057
OMIM	160980
UMLS	C2607929
MedGen	388559
GARD	0015090
Is cancer (heuristic)	no

Also known as: Carney complex caused by mutation in PRKAR1A · Carney complex, type 1 · CNC1 · PRKAR1A Carney complex

Data availability: 1,005 ClinVar variants · 5 GenCC gene-disease records.

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, type 1

Related subtypes (2): Carney complex type 2, Carney complex - trismus - pseudocamptodactyly syndrome

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

600 retrieved; paginated sample, class counts are floors:

289 likely benign, 225 uncertain significance, 37 pathogenic, 20 conflicting classifications of pathogenicity, 13 benign, 8 benign/likely benign, 5 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1076354	NC_000017.10:g.(?66508520)(66533875_?)del	FAM20A	Pathogenic	criteria provided, single submitter
2424527	NC_000017.10:g.(?66508520)(66548013_?)del	FAM20A	Pathogenic	criteria provided, single submitter
1069150	NM_002734.5(PRKAR1A):c.330_338dup (p.Tyr113Ter)	PRKAR1A	Pathogenic	criteria provided, single submitter
1074600	NM_002734.5(PRKAR1A):c.340del (p.Val114fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
1075863	NM_002734.5(PRKAR1A):c.590dup (p.Gly198fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
1253843	NM_002734.5(PRKAR1A):c.957del (p.Pro320fs)	PRKAR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
12662	NM_002734.5(PRKAR1A):c.491_492del (p.Val164fs)	PRKAR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
12663	NM_002734.5(PRKAR1A):c.786_787delinsCT (p.Trp262_Glu263delinsCysTer)	PRKAR1A	Pathogenic	no assertion criteria provided
12667	NM_002734.5(PRKAR1A):c.761_762del (p.Ser254fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
12669	NM_002734.5(PRKAR1A):c.1A>G (p.Met1Val)	PRKAR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
12672	NM_002734.5(PRKAR1A):c.708+1G>T	PRKAR1A	Pathogenic	no assertion criteria provided
12675	NM_002734.5(PRKAR1A):c.709-7_709-2del	PRKAR1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1352652	NM_002734.5(PRKAR1A):c.190_203del (p.Gln64fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
1368681	NM_002734.5(PRKAR1A):c.718dup (p.Leu240fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
1377787	NM_002734.5(PRKAR1A):c.479del (p.Ala160fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
1393898	NM_002734.5(PRKAR1A):c.97del (p.Asp33fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
1399779	NM_002734.5(PRKAR1A):c.502+1G>C	PRKAR1A	Pathogenic	criteria provided, single submitter
1421058	NM_002734.5(PRKAR1A):c.440+1G>A	PRKAR1A	Pathogenic	criteria provided, single submitter
1451227	NM_002734.5(PRKAR1A):c.545dup (p.Asp183fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
1452556	NM_002734.5(PRKAR1A):c.926_930del (p.Asn309fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
1456695	NM_002734.5(PRKAR1A):c.629del (p.Pro210fs)	PRKAR1A	Pathogenic	criteria provided, single submitter
164995	NM_002734.5(PRKAR1A):c.623del (p.Gly208fs)	PRKAR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
2017377	NM_002734.5(PRKAR1A):c.877T>A (p.Phe293Ile)	PRKAR1A	Pathogenic	criteria provided, single submitter
2018571	NM_002734.5(PRKAR1A):c.502+2T>G	PRKAR1A	Pathogenic	criteria provided, single submitter
2021392	NM_002734.5(PRKAR1A):c.786G>A (p.Trp262Ter)	PRKAR1A	Pathogenic	criteria provided, single submitter
2033429	NM_002734.5(PRKAR1A):c.763_766del (p.Ser254_Ile255insTer)	PRKAR1A	Pathogenic	criteria provided, single submitter
2135778	NM_002734.5(PRKAR1A):c.787G>T (p.Glu263Ter)	PRKAR1A	Pathogenic	criteria provided, single submitter
2182961	NM_002734.5(PRKAR1A):c.932_933del (p.Glu311fs)	PRKAR1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2424526	NC_000017.10:g.(?66518887)(66519967_?)del	PRKAR1A	Pathogenic	criteria provided, single submitter
2736638	NM_002734.5(PRKAR1A):c.715A>G (p.Thr239Ala)	PRKAR1A	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 19 · Orphanet: 8 · 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
PRKAR1A	Definitive	Autosomal dominant	Carney complex, type 1	19

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRKAR1A	Orphanet:1359	Carney complex
PRKAR1A	Orphanet:1501	Adrenocortical carcinoma
PRKAR1A	Orphanet:520	Acute promyelocytic leukemia
PRKAR1A	Orphanet:615	Familial atrial myxoma
PRKAR1A	Orphanet:647772	Isolated primary pigmented nodular adrenocortical disease
PRKAR1A	Orphanet:950	Acrodysostosis
FAM20A	Orphanet:1031	Enamel-renal syndrome
MYO15A	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRKAR1A	HGNC:9388	ENSG00000108946	P10644	cAMP-dependent protein kinase type I-alpha regulatory subunit	gencc,clinvar
FAM20A	HGNC:23015	ENSG00000108950	Q96MK3	Pseudokinase FAM20A	clinvar
MYO15A	HGNC:7594	ENSG00000091536	Q9UKN7	Unconventional myosin-XV	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRKAR1A	cAMP-dependent protein kinase type I-alpha regulatory subunit	Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.
FAM20A	Pseudokinase FAM20A	Pseudokinase that acts as an allosteric activator of the Golgi serine/threonine protein kinase FAM20C and is involved in biomineralization of teeth.
MYO15A	Unconventional myosin-XV	Myosins are actin-based motor molecules with ATPase activity.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRKAR1A	Other/Unknown	no		cNMP-bd_dom, cAMP_dep_PK_reg_su_I/II_a/b, cAMP_dep_PK_reg_su
FAM20A	Other/Unknown	no		FAM20_C, FAM20
MYO15A	Scaffold/PPI	no		IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	1
lateral nuclear group of thalamus	1
mucosa of paranasal sinus	1
right lobe of liver	1
smooth muscle tissue	1
upper lobe of left lung	1
adenohypophysis	1
left testis	1
pituitary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRKAR1A	295	ubiquitous	marker	mucosa of paranasal sinus, germinal epithelium of ovary, lateral nuclear group of thalamus
FAM20A	196	broad	marker	right lobe of liver, smooth muscle tissue, upper lobe of left lung
MYO15A	170	tissue_specific	marker	pituitary gland, adenohypophysis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKAR1A	3,586
MYO15A	1,256
FAM20A	736

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FAM20A	Q96MK3	4
PRKAR1A	P10644	3
MYO15A	Q9UKN7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 58. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
ALK mutants bind TKIs	1	317.2×	0.027	PRKAR1A
CREB1 phosphorylation through the activation of Adenylate Cyclase	1	292.8×	0.027	PRKAR1A
PKA activation in glucagon signalling	1	223.9×	0.027	PRKAR1A
PKA activation	1	211.5×	0.027	PRKAR1A
PKA-mediated phosphorylation of CREB	1	190.3×	0.027	PRKAR1A
DARPP-32 events	1	158.6×	0.027	PRKAR1A
Anti-inflammatory response favouring Leishmania parasite infection	1	131.3×	0.027	PRKAR1A
Leishmania parasite growth and survival	1	131.3×	0.027	PRKAR1A
Calmodulin induced events	1	126.9×	0.027	PRKAR1A
CaM pathway	1	126.9×	0.027	PRKAR1A
Ca-dependent events	1	122.8×	0.027	PRKAR1A
Aquaporin-mediated transport	1	122.8×	0.027	PRKAR1A
Glucagon signaling in metabolic regulation	1	115.3×	0.027	PRKAR1A
G-protein mediated events	1	108.8×	0.027	PRKAR1A
DAG and IP3 signaling	1	105.7×	0.027	PRKAR1A
Sensory processing of sound	1	102.9×	0.027	MYO15A
Response of endothelial cells to shear stress	1	100.2×	0.027	PRKAR1A
FCGR3A-mediated IL10 synthesis	1	97.6×	0.027	PRKAR1A
Signaling by ALK in cancer	1	90.6×	0.027	PRKAR1A
Opioid Signalling	1	88.5×	0.027	PRKAR1A
PLC beta mediated events	1	88.5×	0.027	PRKAR1A
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	88.5×	0.027	PRKAR1A
Vasopressin regulates renal water homeostasis via Aquaporins	1	88.5×	0.027	PRKAR1A
Cellular responses to mechanical stimuli	1	86.5×	0.027	PRKAR1A
ADORA2B mediated anti-inflammatory cytokines production	1	84.6×	0.027	PRKAR1A
GPER1 signaling	1	82.8×	0.027	PRKAR1A
Regulation of insulin secretion	1	73.2×	0.029	PRKAR1A
Post NMDA receptor activation events	1	68.0×	0.029	PRKAR1A
Sensory processing of sound by outer hair cells of the cochlea	1	68.0×	0.029	MYO15A
Activation of NMDA receptors and postsynaptic events	1	61.4×	0.029	PRKAR1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tooth eruption	1	1123.5×	0.014	FAM20A
enamel mineralization	1	401.2×	0.014	FAM20A
negative regulation of activated T cell proliferation	1	351.1×	0.014	PRKAR1A
response to light stimulus	1	295.6×	0.014	MYO15A
cellular response to glucagon stimulus	1	280.9×	0.014	PRKAR1A
vascular endothelial cell response to laminar fluid shear stress	1	244.2×	0.014	PRKAR1A
biomineral tissue development	1	216.1×	0.014	FAM20A
negative regulation of inflammatory response to antigenic stimulus	1	200.6×	0.014	PRKAR1A
negative regulation of cAMP/PKA signal transduction	1	200.6×	0.014	PRKAR1A
cardiac muscle cell proliferation	1	193.7×	0.014	PRKAR1A
renal water homeostasis	1	170.2×	0.014	PRKAR1A
mesoderm formation	1	165.2×	0.014	PRKAR1A
calcium ion homeostasis	1	147.8×	0.014	FAM20A
sarcomere organization	1	127.7×	0.015	PRKAR1A
inner ear morphogenesis	1	100.3×	0.018	MYO15A
positive regulation of protein phosphorylation	1	92.1×	0.018	FAM20A
positive regulation of insulin secretion	1	85.1×	0.019	PRKAR1A
response to bacterium	1	64.6×	0.023	FAM20A
locomotory behavior	1	59.8×	0.024	MYO15A
actin filament organization	1	39.6×	0.034	MYO15A
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	37.7×	0.034	PRKAR1A
sensory perception of sound	1	33.6×	0.036	MYO15A
endocytosis	1	31.7×	0.037	MYO15A
chemical synaptic transmission	1	25.8×	0.043	PRKAR1A
negative regulation of gene expression	1	23.0×	0.046	PRKAR1A
intracellular signal transduction	1	12.7×	0.080	PRKAR1A
regulation of transcription by RNA polymerase II	1	3.9×	0.236	PRKAR1A

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKAR1A	0	0
FAM20A	0	0
MYO15A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PRKAR1A	2	Binding:2
MYO15A	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	PRKAR1A, FAM20A, MYO15A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRKAR1A	2	—
FAM20A	0	—
MYO15A	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.