autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Summary

autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (MONDO:8000024) is a disease caused by PRKCD (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PRKCD (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 552

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD
Mondo ID	MONDO:8000024
OMIM	615559
Orphanet	664711
DOID	DOID:0110119
UMLS	C3809928
MedGen	816258
GARD	0015987
Is cancer (heuristic)	no

Data availability: 552 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › hypersensitivity reaction disease › type IV hypersensitivity disease › autoimmune lymphoproliferative syndrome › autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Related subtypes (8): autoimmune lymphoproliferative syndrome type 1, autoimmune lymphoproliferative syndrome type 2A, autoimmune lymphoproliferative syndrome type 2B, autoimmune lymphoproliferative syndrome type 4, autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency, Castleman-Kojima disease, FAS-related autoimmune lymphoproliferative immune disorder, type 3 autoimmune lymphoproliferative 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

552 retrieved; paginated sample, class counts are floors:

290 likely benign, 205 uncertain significance, 20 benign, 14 conflicting classifications of pathogenicity, 13 pathogenic, 7 likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070386	NC_000003.11:g.(?53125899)(53226302_?)del	PRKCD	Pathogenic	criteria provided, single submitter
1072331	NM_006254.4(PRKCD):c.1301del (p.Asp434fs)	PRKCD	Pathogenic	criteria provided, single submitter
1320322	NM_006254.4(PRKCD):c.571+2dup	PRKCD	Pathogenic	no assertion criteria provided
1320323	NM_006254.4(PRKCD):c.1384C>T (p.Gln462Ter)	PRKCD	Pathogenic	no assertion criteria provided
1320324	NM_006254.4(PRKCD):c.642del (p.Asn214fs)	PRKCD	Pathogenic	no assertion criteria provided
1454573	NM_006254.4(PRKCD):c.285C>A (p.Cys95Ter)	PRKCD	Pathogenic	criteria provided, single submitter
1458167	NM_006254.4(PRKCD):c.1300dup (p.Asp434fs)	PRKCD	Pathogenic	criteria provided, single submitter
157674	NM_006254.4(PRKCD):c.1528G>A (p.Gly510Ser)	PRKCD	Pathogenic	no assertion criteria provided
2128407	NM_006254.4(PRKCD):c.1182del (p.Met395fs)	PRKCD	Pathogenic	criteria provided, single submitter
3650412	NM_006254.4(PRKCD):c.1542T>G (p.Tyr514Ter)	PRKCD	Pathogenic	criteria provided, single submitter
4713023	NM_006254.4(PRKCD):c.1318C>T (p.Gln440Ter)	PRKCD	Pathogenic	criteria provided, single submitter
89076	NM_006254.4(PRKCD):c.1352+1G>A	PRKCD	Pathogenic	criteria provided, single submitter
958249	NM_006254.4(PRKCD):c.571C>T (p.Gln191Ter)	PRKCD	Pathogenic	criteria provided, single submitter
2028257	NM_006254.4(PRKCD):c.1743+2T>A	PRKCD	Likely pathogenic	criteria provided, single submitter
2068571	NM_006254.4(PRKCD):c.788-1G>T	PRKCD	Likely pathogenic	criteria provided, single submitter
2909516	NM_006254.4(PRKCD):c.571+1G>A	PRKCD	Likely pathogenic	criteria provided, single submitter
3391052	NM_006254.4(PRKCD):c.1073G>A (p.Gly358Asp)	PRKCD	Likely pathogenic	criteria provided, single submitter
3652522	NM_006254.4(PRKCD):c.657+1G>A	PRKCD	Likely pathogenic	criteria provided, single submitter
4845698	NM_006254.4(PRKCD):c.769C>T (p.Gln257Ter)	PRKCD	Likely pathogenic	criteria provided, single submitter
541623	NM_006254.4(PRKCD):c.788-2A>G	PRKCD	Likely pathogenic	criteria provided, single submitter
1446696	NM_006254.4(PRKCD):c.1511G>A (p.Arg504Gln)	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1454501	NM_006254.4(PRKCD):c.315G>A (p.Trp105Ter)	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
157675	NM_006254.4(PRKCD):c.1840C>T (p.Arg614Trp)	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
252661	NM_006254.4(PRKCD):c.1448G>A (p.Arg483Gln)	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
440191	NM_006254.4(PRKCD):c.1043A>G (p.Asn348Ser)	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626154	NM_006254.4(PRKCD):c.889-9C>T	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
639035	NM_006254.4(PRKCD):c.1691C>T (p.Thr564Met)	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
642091	NM_006254.4(PRKCD):c.657+3G>A	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
648341	NM_006254.4(PRKCD):c.1213G>A (p.Ala405Thr)	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
657119	NM_006254.4(PRKCD):c.1705C>T (p.Arg569Cys)	PRKCD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
PRKCD	Strong	Autosomal recessive	autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRKCD	Orphanet:664711	EBV-induced lymphoproliferative disease due to PRKCD deficiency

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
PRKCD	HGNC:9399	ENSG00000163932	Q05655	Protein kinase C delta type	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRKCD	Protein kinase C delta type	Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosi…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRKCD	Kinase	yes	2.7.11.13	C2_dom, Prot_kinase_dom, AGC-kinase_C

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRKCD	229	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKCD	3,286

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKCD	Q05655	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. 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
HuR (ELAVL1) binds and stabilizes mRNA	1	1268.9×	0.010	PRKCD
Regulation of mRNA stability by proteins that bind AU-rich elements	1	761.3×	0.010	PRKCD
VEGFR2 mediated cell proliferation	1	571.0×	0.010	PRKCD
Apoptotic cleavage of cellular proteins	1	475.8×	0.010	PRKCD
SHC1 events in ERBB2 signaling	1	475.8×	0.010	PRKCD
Apoptotic execution phase	1	475.8×	0.010	PRKCD
Effects of PIP2 hydrolysis	1	456.8×	0.010	PRKCD
Role of phospholipids in phagocytosis	1	456.8×	0.010	PRKCD
RHO GTPases Activate NADPH Oxidases	1	456.8×	0.010	PRKCD
Calmodulin induced events	1	380.7×	0.010	PRKCD
CaM pathway	1	380.7×	0.010	PRKCD
Ca-dependent events	1	368.4×	0.010	PRKCD
Signaling by ERBB2	1	346.1×	0.010	PRKCD
G-protein mediated events	1	326.3×	0.010	PRKCD
DAG and IP3 signaling	1	317.2×	0.010	PRKCD
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.010	PRKCD
Opioid Signalling	1	265.6×	0.010	PRKCD
PLC beta mediated events	1	265.6×	0.010	PRKCD
C-type lectin receptors (CLRs)	1	237.9×	0.010	PRKCD
G alpha (z) signalling events	1	233.1×	0.010	PRKCD
Signaling by VEGF	1	219.6×	0.010	PRKCD
Apoptosis	1	167.9×	0.013	PRKCD
Programmed Cell Death	1	146.4×	0.013	PRKCD
CLEC7A (Dectin-1) signaling	1	142.8×	0.013	PRKCD
Cellular response to chemical stress	1	142.8×	0.013	PRKCD
VEGFA-VEGFR2 Pathway	1	139.3×	0.013	PRKCD
Interferon gamma signaling	1	125.5×	0.014	PRKCD
Interferon Signaling	1	120.2×	0.014	PRKCD
KEAP1-NFE2L2 pathway	1	120.2×	0.014	PRKCD
Platelet activation, signaling and aggregation	1	105.7×	0.015	PRKCD

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 phospholipid scramblase activity	1	16852.0×	0.001	PRKCD
positive regulation of glucosylceramide catabolic process	1	16852.0×	0.001	PRKCD
positive regulation of sphingomyelin catabolic process	1	8426.0×	0.001	PRKCD
termination of signal transduction	1	5617.3×	0.001	PRKCD
regulation of ceramide biosynthetic process	1	5617.3×	0.001	PRKCD
protein kinase C signaling	1	4213.0×	0.002	PRKCD
negative regulation of filopodium assembly	1	3370.4×	0.002	PRKCD
phospholipase C/protein kinase C signal transduction	1	2808.7×	0.002	PRKCD
positive regulation of ceramide biosynthetic process	1	2407.4×	0.002	PRKCD
cellular response to hydroperoxide	1	2106.5×	0.002	PRKCD
negative regulation of glial cell apoptotic process	1	1872.4×	0.002	PRKCD
negative regulation of platelet aggregation	1	1404.3×	0.002	PRKCD
neutrophil activation	1	991.3×	0.003	PRKCD
negative regulation of actin filament polymerization	1	936.2×	0.003	PRKCD
cellular response to angiotensin	1	936.2×	0.003	PRKCD
peptidyl-threonine phosphorylation	1	887.0×	0.003	PRKCD
positive regulation of superoxide anion generation	1	887.0×	0.003	PRKCD
intrinsic apoptotic signaling pathway in response to oxidative stress	1	842.6×	0.003	PRKCD
immunoglobulin mediated immune response	1	702.2×	0.003	PRKCD
Fc-gamma receptor signaling pathway involved in phagocytosis	1	702.2×	0.003	PRKCD
cellular response to fatty acid	1	702.2×	0.003	PRKCD
positive regulation of apoptotic signaling pathway	1	581.1×	0.003	PRKCD
peptidyl-serine phosphorylation	1	495.6×	0.004	PRKCD
B cell proliferation	1	481.5×	0.004	PRKCD
positive regulation of protein import into nucleus	1	421.3×	0.004	PRKCD
regulation of mRNA stability	1	421.3×	0.004	PRKCD
negative regulation of insulin receptor signaling pathway	1	374.5×	0.004	PRKCD
positive regulation of DNA repair	1	358.6×	0.004	PRKCD
negative regulation of MAPK cascade	1	300.9×	0.005	PRKCD
cellular response to UV	1	295.6×	0.005	PRKCD

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
PRKCD	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKCD	49	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKCD
MIDOSTAURIN	4	PRKCD
TAMOXIFEN	4	PRKCD
TOFACITINIB CITRATE	4	PRKCD
BARICITINIB	4	PRKCD
TOFACITINIB	4	PRKCD
CAPIVASERTIB	4	PRKCD
BOSUTINIB	4	PRKCD
ABEMACICLIB	4	PRKCD
SURAMIN	3	PRKCD
FASUDIL	3	PRKCD
ALVOCIDIB	3	PRKCD
CURCUMIN	3	PRKCD
CRENOLANIB	3	PRKCD
ENZASTAURIN	3	PRKCD
RIPASUDIL	3	PRKCD
DOVITINIB	3	PRKCD
LESTAURTINIB	3	PRKCD
RUBOXISTAURIN	3	PRKCD
PHORBOL MYRISTATE ACETATE	2	PRKCD
EDELFOSINE	2	PRKCD
UPROSERTIB	2	PRKCD
UCN-01	2	PRKCD
DORAMAPIMOD	2	PRKCD
SAR-407899 FREE BASE	2	PRKCD
ZOTIRACICLIB	2	PRKCD
CENISERTIB	2	PRKCD
ILORASERTIB	2	PRKCD
LAUROGUADINE	2	PRKCD
SCH-900776	2	PRKCD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRKCD	804	Binding:790, Functional:14

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRKCD	2.7.11.13	protein kinase C

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PRKCD	804

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

30 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)
INGENOL MEBUTATE	4	PRKCD
MIDOSTAURIN	4	PRKCD
TAMOXIFEN	4	PRKCD
TOFACITINIB CITRATE	4	PRKCD
BARICITINIB	4	PRKCD
TOFACITINIB	4	PRKCD
CAPIVASERTIB	4	PRKCD
BOSUTINIB	4	PRKCD
ABEMACICLIB	4	PRKCD
SURAMIN	3	PRKCD
FASUDIL	3	PRKCD
ALVOCIDIB	3	PRKCD
CURCUMIN	3	PRKCD
CRENOLANIB	3	PRKCD
ENZASTAURIN	3	PRKCD
RIPASUDIL	3	PRKCD
DOVITINIB	3	PRKCD
LESTAURTINIB	3	PRKCD
RUBOXISTAURIN	3	PRKCD
PHORBOL MYRISTATE ACETATE	2	PRKCD
EDELFOSINE	2	PRKCD
UPROSERTIB	2	PRKCD
UCN-01	2	PRKCD
DORAMAPIMOD	2	PRKCD
SAR-407899 FREE BASE	2	PRKCD
ZOTIRACICLIB	2	PRKCD
CENISERTIB	2	PRKCD
ILORASERTIB	2	PRKCD
LAUROGUADINE	2	PRKCD
SCH-900776	2	PRKCD

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKCD
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.