Psoriasis 2

Summary

Psoriasis 2 (MONDO:0011269) is a disease caused by CARD14 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: CARD14 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 1,237

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	psoriasis 2
Mondo ID	MONDO:0011269
OMIM	602723
DOID	DOID:0080475
UMLS	C1864497
MedGen	351141
Is cancer (heuristic)	no

Also known as: CARD14 psoriasis · psoriasis 2 · psoriasis caused by mutation in CARD14 · psoriasis type 2 · PSORS2

Data availability: 1,237 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › psoriasis › psoriasis 2

Related subtypes (2): pustular psoriasis, guttate psoriasis

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:

295 uncertain significance, 235 likely benign, 33 benign, 28 conflicting classifications of pathogenicity, 7 benign/likely benign, 1 benign/likely benign; association, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
280130	NM_001366385.1(CARD14):c.349+1G>A	CARD14	Pathogenic	criteria provided, multiple submitters, no conflicts
1002660	NM_001366385.1(CARD14):c.1198C>T (p.Arg400Cys)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1081608	NM_001366385.1(CARD14):c.1358C>G (p.Ser453Cys)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1119427	NM_001366385.1(CARD14):c.1098C>T (p.Ser366=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1121019	NM_001366385.1(CARD14):c.931C>T (p.Arg311Trp)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1139961	NM_001366385.1(CARD14):c.249C>T (p.Asn83=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1141622	NM_001366385.1(CARD14):c.694G>A (p.Glu232Lys)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1152307	NM_001366385.1(CARD14):c.1188C>G (p.Val396=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1157166	NM_001366385.1(CARD14):c.2196C>T (p.His732=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1159232	NM_001366385.1(CARD14):c.921G>A (p.Ser307=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1163113	NM_001366385.1(CARD14):c.1660G>A (p.Gly554Ser)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1170164	NM_001366385.1(CARD14):c.2808-19C>A	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1192693	NM_001366385.1(CARD14):c.675+26G>A	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1441466	NM_001366385.1(CARD14):c.646G>A (p.Ala216Thr)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1476693	NM_001366385.1(CARD14):c.1012A>G (p.Met338Val)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1509202	NM_001366385.1(CARD14):c.2210A>G (p.Asn737Ser)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1562156	NM_001366385.1(CARD14):c.570G>A (p.Glu190=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1588901	NM_001366385.1(CARD14):c.1178C>T (p.Thr393Met)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1592658	NM_001366385.1(CARD14):c.90C>T (p.Ile30=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1613140	NM_001366385.1(CARD14):c.1590G>C (p.Thr530=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1639357	NM_001366385.1(CARD14):c.45C>T (p.Asp15=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1639376	NM_001366385.1(CARD14):c.1356+8del	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1672021	NM_001366385.1(CARD14):c.932G>A (p.Arg311Gln)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1694238	NM_001366385.1(CARD14):c.288C>T (p.Asn96=)	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1694242	NM_001366385.1(CARD14):c.350-4A>G	CARD14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1138039	NM_001366385.1(CARD14):c.2535G>A (p.Leu845=)	LOC126862662	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1062002	NM_001366385.1(CARD14):c.2354G>A (p.Arg785His)	SGSH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1124694	NM_001366385.1(CARD14):c.2019G>A (p.Ala673=)	SGSH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1347490	NM_001366385.1(CARD14):c.2884C>T (p.Arg962Trp)	SGSH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000985	NM_001366385.1(CARD14):c.2924G>C (p.Trp975Ser)	CARD14	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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
CARD14	Definitive	Autosomal dominant	psoriasis 2	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CARD14	Orphanet:2897	Pityriasis rubra pilaris
SGSH	Orphanet:79269	Sanfilippo syndrome type A
CCDC40	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CARD14	HGNC:16446	ENSG00000141527	Q9BXL6	Caspase recruitment domain-containing protein 14	gencc,clinvar
SGSH	HGNC:10818	ENSG00000181523	P51688	N-sulphoglucosamine sulphohydrolase	clinvar
CBX4	HGNC:1554	ENSG00000141582	O00257	E3 SUMO-protein ligase CBX4	clinvar
CCDC40	HGNC:26090	ENSG00000141519	Q4G0X9	Coiled-coil domain-containing protein 40	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CARD14	Caspase recruitment domain-containing protein 14	Acts as a scaffolding protein that can activate the inflammatory transcription factor NF-kappa-B and p38/JNK MAP kinase signaling pathways.
SGSH	N-sulphoglucosamine sulphohydrolase	Catalyzes a step in lysosomal heparan sulfate degradation.
CBX4	E3 SUMO-protein ligase CBX4	E3 SUMO-protein ligase that catalyzes sumoylation of target proteins by promoting the transfer of SUMO from the E2 enzyme to the substrate.
CCDC40	Coiled-coil domain-containing protein 40	Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
Phosphatase	1	21.0×	0.141
Scaffold/PPI	1	4.3×	0.318
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CARD14	Scaffold/PPI	no		CARD, PDZ, Guanylate_kin-like_dom
SGSH	Phosphatase	yes	3.10.1.1	Sulfatase_N, Alkaline_phosphatase_core_sf, Sulfatase_CS
CBX4	Other/Unknown	no		Chromo/chromo_shadow_dom, Chromo-like_dom_sf, Chromo_dom_subgr
CCDC40	Other/Unknown	no		CCDC40

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	1
skin of abdomen	1
skin of leg	1
adrenal cortex	1
left adrenal gland	1
left adrenal gland cortex	1
mucosa of paranasal sinus	1
penis	1
upper leg skin	1
bronchial epithelial cell	1
right uterine tube	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CARD14	179	tissue_specific	yes	lower esophagus mucosa, skin of leg, skin of abdomen
SGSH	272	ubiquitous	marker	left adrenal gland, left adrenal gland cortex, adrenal cortex
CBX4	264	ubiquitous	marker	upper leg skin, penis, mucosa of paranasal sinus
CCDC40	184	ubiquitous	marker	right uterine tube, bronchial epithelial cell, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CARD14	1,902
CBX4	1,848
CCDC40	1,527
SGSH	1,151

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CBX4	O00257	3
SGSH	P51688	2
CCDC40	Q4G0X9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CARD14	Q9BXL6	75.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 4 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MPS IIIA - Sanfilippo syndrome A	1	5710.0×	0.006	SGSH
Mucopolysaccharidoses	1	951.7×	0.018	SGSH
Diseases of carbohydrate metabolism	1	407.9×	0.023	SGSH
SUMOylation of DNA methylation proteins	1	335.9×	0.023	CBX4
Heparan sulfate/heparin (HS-GAG) metabolism	1	271.9×	0.023	SGSH
HS-GAG degradation	1	248.3×	0.023	SGSH
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	150.3×	0.026	CBX4
SUMOylation of transcription cofactors	1	121.5×	0.026	CBX4
SUMOylation of RNA binding proteins	1	119.0×	0.026	CBX4
PTEN Regulation	1	114.2×	0.026	CBX4
Glycosaminoglycan metabolism	1	109.8×	0.026	SGSH
SUMO E3 ligases SUMOylate target proteins	1	89.2×	0.026	CBX4
Regulation of PTEN gene transcription	1	89.2×	0.026	CBX4
SUMOylation	1	81.6×	0.026	CBX4
SUMOylation of chromatin organization proteins	1	79.3×	0.026	CBX4
SUMOylation of DNA damage response and repair proteins	1	73.2×	0.026	CBX4
Transcriptional regulation by RUNX1	1	73.2×	0.026	CBX4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	73.2×	0.026	CBX4
Cellular Senescence	1	68.8×	0.026	CBX4
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.028	SGSH
Intracellular signaling by second messengers	1	45.7×	0.034	CBX4
Oxidative Stress Induced Senescence	1	45.3×	0.034	CBX4
Diseases of metabolism	1	40.2×	0.037	SGSH
PIP3 activates AKT signaling	1	33.4×	0.042	CBX4
Cellular responses to stress	1	18.4×	0.073	CBX4
Cellular responses to stimuli	1	15.7×	0.082	CBX4
RNA Polymerase II Transcription	1	11.3×	0.109	CBX4
Post-translational protein modification	1	9.6×	0.123	CBX4
Gene expression (Transcription)	1	8.9×	0.128	CBX4
Generic Transcription Pathway	1	7.5×	0.145	CBX4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
determination of pancreatic left/right asymmetry	1	842.6×	0.012	CCDC40
determination of digestive tract left/right asymmetry	1	702.2×	0.012	CCDC40
determination of liver left/right asymmetry	1	702.2×	0.012	CCDC40
glycosaminoglycan catabolic process	1	601.9×	0.012	SGSH
regulation of cilium beat frequency	1	526.6×	0.012	CCDC40
heparan sulfate proteoglycan catabolic process	1	468.1×	0.012	SGSH
activation of NF-kappaB-inducing kinase activity	1	421.3×	0.012	CARD14
epithelial cilium movement involved in determination of left/right asymmetry	1	324.1×	0.013	CCDC40
axonemal dynein complex assembly	1	263.3×	0.014	CCDC40
positive regulation of brown fat cell differentiation	1	247.8×	0.014	CBX4
inner dynein arm assembly	1	221.7×	0.014	CCDC40
negative regulation of apoptotic process	2	17.4×	0.014	CARD14, CBX4
epithelial cilium movement involved in extracellular fluid movement	1	191.5×	0.014	CCDC40
cilium organization	1	150.5×	0.015	CCDC40
motile cilium assembly	1	145.3×	0.015	CCDC40
motor behavior	1	140.4×	0.015	SGSH
axoneme assembly	1	135.9×	0.015	CCDC40
regulation of immune response	1	123.9×	0.015	CARD14
determination of adult lifespan	1	108.0×	0.016	SGSH
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	1	100.3×	0.016	CBX4
protein localization to cilium	1	100.3×	0.016	CCDC40
cilium movement	1	98.0×	0.016	CCDC40
tumor necrosis factor-mediated signaling pathway	1	82.6×	0.017	CARD14
protein sumoylation	1	81.0×	0.017	CBX4
positive regulation of protein phosphorylation	1	69.1×	0.019	CARD14
heart looping	1	66.9×	0.019	CCDC40
obsolete positive regulation of NF-kappaB transcription factor activity	1	51.4×	0.024	CARD14
lung development	1	49.6×	0.024	CCDC40
flagellated sperm motility	1	29.3×	0.040	CCDC40
positive regulation of canonical NF-kappaB signal transduction	1	18.2×	0.061	CARD14

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CARD14	0	0
SGSH	0	0
CBX4	0	0
CCDC40	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CBX4	11	Binding:11

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SGSH	3.10.1.1	N-sulfoglucosamine sulfohydrolase

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	1	SGSH
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	CARD14, CBX4, CCDC40

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CARD14	0	—
SGSH	0	—
CBX4	11	—
CCDC40	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.