Immunodeficiency 35

Summary

Immunodeficiency 35 (MONDO:0012682) is a disease caused by TYK2 (GenCC Strong), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TYK2 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 948

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 35
Mondo ID	MONDO:0012682
MeSH	C566928
OMIM	611521
Orphanet	331226
DOID	DOID:0111989
UMLS	C1969086
MedGen	409751
GARD	0017514
Is cancer (heuristic)	no

Also known as: autosomal recessive hyper-IgE syndrome due to TYK2 deficiency · autosomal recessive mendelian susceptibility to mycobacterial diseases due to a partial deficiency caused by mutation in TYK2 · HIES with atypical Mycobacteriosis, autosomal recessive · hyper-IgE syndrome with atypical Mycobacteriosis, autosomal recessive · IMD35 · immunodeficiency 35 · immunodeficiency type 35 · susceptibility to infection due to TYK2 deficiency · TYK2 autosomal recessive mendelian susceptibility to mycobacterial diseases due to a partial deficiency · TYK2 deficiency · tyrosine kinase 2 deficiency

Data availability: 948 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › immunodeficiency 35

Related subtypes (94): B cell deficiency, T-cell immunodeficiency, complement deficiency, myalgic encephalomeyelitis/chronic fatigue syndrome, hypoproteinemia, hypercatabolic, X-linked lymphoproliferative syndrome, Wiskott-Aldrich syndrome, autosomal dominant form, immunodeficiency due to CD25 deficiency, immunodeficiency 67, primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency, pyogenic bacterial infections due to MyD88 deficiency, lymphoproliferative syndrome 1, FADD-related immunodeficiency, immunodeficiency 31B, Wiskott-Aldrich syndrome 2, cryptosporidiosis-chronic cholangitis-liver disease syndrome, idiopathic CD4 lymphocytopenia, immunodeficiency 23, DOCK2 deficiency, immunodeficiency 45, TFRC-related combined immunodeficiency, combined immunodeficiency, autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome, immunodeficiency due to selective anti-polysaccharide antibody deficiency, immunodeficiency 57, immunodeficiency 14b, autosomal recessive, immunodeficiency 98 with autoinflammation, X-linked, immunodeficiency 102, immunodeficiency 74, COVID-19-related, X-linked, immunodeficiency 66, immunodeficiency 80 with or without congenital cardiomyopathy, immunodeficiency 81, immunodeficiency 82 with systemic inflammation, immunodeficiency 84, immunodeficiency 85 and autoimmunity, immunodeficiency 86, immunodeficiency 87 and autoimmunity, immunodeficiency 88, immunodeficiency 89 and autoimmunity, immunodeficiency 91 and hyperinflammation, immunodeficiency 92, immunodeficiency 93 and hypertrophic cardiomyopathy, immunodeficiency 95, immunodeficiency 96, immunodeficiency 97 with autoinflammation, immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, immunodeficiency 101 (varicella zoster virus-specific), immunodeficiency 75, immunodeficiency 76, immunodeficiency 106, susceptibility to viral infections, immunodeficiency 78 with autoimmunity and developmental delay, immunodeficiency 77, immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, immunodeficiency 15a, immunodeficiency 60, immunodeficiency 62, immunodeficiency 63 with lymphoproliferation and autoimmunity, immunodeficiency 64, immunodeficiency 65, susceptibility to viral infections, immunodeficiency 69, immunodeficiency 70, immunodeficiency 72 with autoinflammation, GATA2 deficiency with susceptibility to MDS/AML, Shwachman-Diamond syndrome 1, immunodeficiency 53, immunodeficiency 11b with atopic dermatitis, IKBKG-related immunodeficiency with or without ectodermal dysplasia, FNIP1-associated syndrome, FASLG-related immunodeficiency, TNFRSF9-related immunodeficiency, DNAJC21-related Shwachman Diamond syndrome, IRF4-related immune disorder, PTEN harmartoma tumor syndrome with immune disorder, primary immunodeficiency due to calcium channel deficiency, chronic mucocutaneous candidiasis and connective tissue disease due to JNK1 haploinsufficiency, immune deficiency due to impaired neutrophil phagocytosis and migration, hatipoglu immunodeficiency syndrome, immunodeficiency 112, immunodeficiency 113 with autoimmunity and autoinflammation, immunodeficiency 114, folate-responsive, immunodeficiency 115 with autoinflammation, immunodeficiency 117, immunodeficiency 118, immunodeficiency 119, immunodeficiency 121 with autoinflammation, immunodeficiency 122, immunodeficiency 123 with HPV-related verrucosis, immunodeficiency 125, immunodeficiency 126, susceptibility to, immunodeficiency 127, immunodeficiency 128, immunodeficiency 132b, immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy, immunodeficiency 134 (Epstein-Barr virus-specific)

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:

275 likely benign, 247 uncertain significance, 27 benign, 24 pathogenic, 13 conflicting classifications of pathogenicity, 9 likely pathogenic, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3248456	NC_000019.9:g.(?10244343)(10610709_?)del	MRPL4	Pathogenic	criteria provided, single submitter
1069417	NM_003331.5(TYK2):c.2573C>G (p.Ser858Ter)	TYK2	Pathogenic	criteria provided, single submitter
1425910	NM_003331.5(TYK2):c.2393G>A (p.Trp798Ter)	TYK2	Pathogenic	criteria provided, multiple submitters, no conflicts
1459846	NC_000019.9:g.(?10463090)(10465305_?)del	TYK2	Pathogenic	criteria provided, single submitter
155930	NM_003331.5(TYK2):c.2303_2311del (p.Ser768_Glu771delinsTer)	TYK2	Pathogenic	no assertion criteria provided
1703747	NM_003331.5(TYK2):c.2269C>G (p.Leu757Val)	TYK2	Pathogenic	no assertion criteria provided
1703748	NM_003331.5(TYK2):c.3041T>C (p.Leu1014Pro)	TYK2	Pathogenic	no assertion criteria provided
1703749	NM_003331.5(TYK2):c.1253C>A (p.Ser418Ter)	TYK2	Pathogenic	no assertion criteria provided
1703750	NM_003331.5(TYK2):c.2395G>A (p.Gly799Arg)	TYK2	Pathogenic	no assertion criteria provided
2022602	NM_003331.5(TYK2):c.1148dup (p.Thr384fs)	TYK2	Pathogenic	criteria provided, single submitter
224885	NM_003331.4(TYK2):c.3318_3319insC	TYK2	Pathogenic	no assertion criteria provided
224886	NM_003331.5(TYK2):c.460G>T (p.Glu154Ter)	TYK2	Pathogenic	no assertion criteria provided
224887	NM_003331.5(TYK2):c.149del (p.Ser50fs)	TYK2	Pathogenic	no assertion criteria provided
224888	NM_003331.5(TYK2):c.1912C>T (p.Arg638Ter)	TYK2	Pathogenic	criteria provided, single submitter
225508	NM_003331.5(TYK2):c.209_212del (p.Cys70fs)	TYK2	Pathogenic	criteria provided, multiple submitters, no conflicts
2704548	NM_003331.5(TYK2):c.2488C>T (p.Gln830Ter)	TYK2	Pathogenic	criteria provided, single submitter
2739687	NM_003331.5(TYK2):c.1904dup (p.Glu636fs)	TYK2	Pathogenic	criteria provided, single submitter
2761990	NM_003331.5(TYK2):c.2920_2941del (p.Leu974fs)	TYK2	Pathogenic	criteria provided, single submitter
2764448	NM_003331.5(TYK2):c.424C>T (p.Gln142Ter)	TYK2	Pathogenic	criteria provided, single submitter
2911814	NM_003331.5(TYK2):c.463C>T (p.Gln155Ter)	TYK2	Pathogenic	criteria provided, single submitter
2971918	NM_003331.5(TYK2):c.1825C>T (p.Arg609Ter)	TYK2	Pathogenic	criteria provided, single submitter
3248457	NC_000019.9:g.(?10469831)(10469998_?)del	TYK2	Pathogenic	criteria provided, single submitter
3619403	NM_003331.5(TYK2):c.905del (p.Asp302fs)	TYK2	Pathogenic	criteria provided, single submitter
3659006	NM_003331.5(TYK2):c.2873_2874insTGTA (p.Ile959fs)	TYK2	Pathogenic	criteria provided, single submitter
1067902	NM_003331.5(TYK2):c.2047+1G>T	TYK2	Likely pathogenic	criteria provided, single submitter
1514893	NM_003331.5(TYK2):c.1773+1G>T	TYK2	Likely pathogenic	criteria provided, single submitter
2068667	NM_003331.5(TYK2):c.2311+1G>T	TYK2	Likely pathogenic	criteria provided, single submitter
2701324	NM_003331.5(TYK2):c.629+2T>C	TYK2	Likely pathogenic	criteria provided, single submitter
2974814	NM_003331.5(TYK2):c.1011+2T>G	TYK2	Likely pathogenic	criteria provided, single submitter
3064089	NM_003331.5(TYK2):c.2466+1G>T	TYK2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
TYK2	Strong	Autosomal recessive	immunodeficiency 35	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TYK2	Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma
TYK2	Orphanet:331226	Susceptibility to infection due to TYK2 deficiency
TYK2	Orphanet:98842	Lymphomatoid papulosis

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
TYK2	HGNC:12440	ENSG00000105397	P29597	Non-receptor tyrosine-protein kinase TYK2	gencc,clinvar
MRPL4	HGNC:14276	ENSG00000105364	Q9BYD3	Large ribosomal subunit protein uL4m	clinvar
CDC37	HGNC:1735	ENSG00000105401	Q16543	Hsp90 co-chaperone Cdc37	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TYK2	Non-receptor tyrosine-protein kinase TYK2	Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity.
CDC37	Hsp90 co-chaperone Cdc37	Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TYK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
MRPL4	Other/Unknown	no		Ribosomal_uL4, Ribosomal_uL4-like, Ribosomal_uL4_dom_sf
CDC37	Other/Unknown	no		Cdc37, Cdc37_N_dom, Cdc37_C

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
granulocyte	2
apex of heart	2
adenohypophysis	1
right hemisphere of cerebellum	1
lower esophagus mucosa	1
mucosa of transverse colon	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TYK2	288	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, adenohypophysis
MRPL4	271	ubiquitous	marker	apex of heart, mucosa of transverse colon, lower esophagus mucosa
CDC37	293	broad	marker	sural nerve, apex of heart, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MRPL4	5,173
CDC37	4,773
TYK2	3,932

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MRPL4	Q9BYD3	87
TYK2	P29597	52
CDC37	Q16543	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 64. 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
Drug resistance in ERBB2 KD mutants	1	3806.7×	0.006	CDC37
Drug-mediated inhibition of ERBB2 signaling	1	951.7×	0.006	CDC37
Resistance of ERBB2 KD mutants to trastuzumab	1	951.7×	0.006	CDC37
Resistance of ERBB2 KD mutants to sapitinib	1	951.7×	0.006	CDC37
Resistance of ERBB2 KD mutants to tesevatinib	1	951.7×	0.006	CDC37
Resistance of ERBB2 KD mutants to neratinib	1	951.7×	0.006	CDC37
Resistance of ERBB2 KD mutants to osimertinib	1	951.7×	0.006	CDC37
Resistance of ERBB2 KD mutants to afatinib	1	951.7×	0.006	CDC37
Resistance of ERBB2 KD mutants to AEE788	1	951.7×	0.006	CDC37
Resistance of ERBB2 KD mutants to lapatinib	1	951.7×	0.006	CDC37
Drug resistance in ERBB2 TMD/JMD mutants	1	951.7×	0.006	CDC37
Signaling by ERBB2 in Cancer	1	761.3×	0.006	CDC37
Signaling by EGFRvIII in Cancer	1	761.3×	0.006	CDC37
Signaling by Ligand-Responsive EGFR Variants in Cancer	1	634.4×	0.007	CDC37
Interleukin-23 signaling	1	423.0×	0.009	TYK2
MAPK1 (ERK2) activation	1	380.7×	0.009	TYK2
Signaling by EGFR in Cancer	1	380.7×	0.009	CDC37
MAPK3 (ERK1) activation	1	346.1×	0.009	TYK2
Interleukin-27 signaling	1	346.1×	0.009	TYK2
Interleukin-6 signaling	1	317.2×	0.009	TYK2
Interleukin-35 Signalling	1	317.2×	0.009	TYK2
Constitutive Signaling by Overexpressed ERBB2	1	317.2×	0.009	CDC37
RHOBTB GTPase Cycle	1	271.9×	0.010	CDC37
Regulated Necrosis	1	237.9×	0.011	CDC37
Constitutive Signaling by EGFRvIII	1	237.9×	0.011	CDC37
Signaling by ERBB2 ECD mutants	1	223.9×	0.011	CDC37
IL-6-type cytokine receptor ligand interactions	1	211.5×	0.011	TYK2
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	190.3×	0.012	CDC37
Signaling by CSF3 (G-CSF)	1	190.3×	0.012	TYK2
Other interleukin signaling	1	158.6×	0.012	TYK2

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
regulation of type II interferon-mediated signaling pathway	1	2808.7×	0.006	CDC37
regulation of type I interferon-mediated signaling pathway	1	1404.3×	0.006	CDC37
interleukin-23-mediated signaling pathway	1	936.2×	0.006	TYK2
positive regulation of NK T cell proliferation	1	936.2×	0.006	TYK2
interleukin-12-mediated signaling pathway	1	624.1×	0.006	TYK2
type III interferon-mediated signaling pathway	1	510.7×	0.006	TYK2
growth hormone receptor signaling pathway via JAK-STAT	1	510.7×	0.006	TYK2
positive regulation of type 2 mitophagy	1	510.7×	0.006	CDC37
positive regulation of natural killer cell proliferation	1	468.1×	0.006	TYK2
interleukin-10-mediated signaling pathway	1	468.1×	0.006	TYK2
positive regulation of T-helper 17 type immune response	1	468.1×	0.006	TYK2
type II interferon-mediated signaling pathway	1	401.2×	0.007	TYK2
regulation of cyclin-dependent protein serine/threonine kinase activity	1	244.2×	0.010	CDC37
post-transcriptional regulation of gene expression	1	216.1×	0.011	CDC37
positive regulation of interleukin-17 production	1	200.6×	0.011	TYK2
positive regulation of receptor signaling pathway via JAK-STAT	1	144.0×	0.014	TYK2
positive regulation of protein localization to nucleus	1	130.6×	0.014	TYK2
protein targeting	1	122.1×	0.015	CDC37
type I interferon-mediated signaling pathway	1	114.6×	0.015	TYK2
cell surface receptor signaling pathway via JAK-STAT	1	96.8×	0.016	TYK2
positive regulation of T cell proliferation	1	86.4×	0.018	TYK2
positive regulation of type II interferon production	1	74.9×	0.019	TYK2
cellular response to virus	1	66.9×	0.021	TYK2
mitochondrial translation	1	57.9×	0.023	MRPL4
cytokine-mediated signaling pathway	1	43.5×	0.029	TYK2
protein folding	1	34.5×	0.034	CDC37
cell population proliferation	1	34.2×	0.034	TYK2
protein phosphorylation	1	22.6×	0.049	TYK2
protein stabilization	1	22.3×	0.049	CDC37
immune response	1	15.7×	0.067	TYK2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
TYK2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYK2	72	4
MRPL4	0	0
CDC37	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	TYK2
RUXOLITINIB	4	TYK2
TOFACITINIB	4	TYK2
UPADACITINIB	4	TYK2
BARICITINIB	4	TYK2
FILGOTINIB	4	TYK2
ABROCITINIB	4	TYK2
DEUCRAVACITINIB	4	TYK2
MOMELOTINIB	4	TYK2
AXITINIB	4	TYK2
RUXOLITINIB PHOSPHATE	4	TYK2
INFIGRATINIB PHOSPHATE	4	TYK2
INFIGRATINIB	4	TYK2
PACRITINIB	4	TYK2
TOFACITINIB CITRATE	4	TYK2
BOSUTINIB	4	TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	TYK2
NINTEDANIB	4	TYK2
SUNITINIB	4	TYK2
DASATINIB	4	TYK2
ERLOTINIB	4	TYK2
CRIZOTINIB	4	TYK2
MIDOSTAURIN	4	TYK2
IMATINIB	4	TYK2
DELGOCITINIB	3	TYK2
DEFACTINIB	3	TYK2
ITACITINIB	3	TYK2
ALVOCIDIB	3	TYK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TYK2	1,083	Binding:1043, Functional:39, ADMET:1
CDC37	51	Binding:51

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TYK2	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TYK2	1,083

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

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)
FEDRATINIB	4	TYK2
RUXOLITINIB	4	TYK2
TOFACITINIB	4	TYK2
UPADACITINIB	4	TYK2
BARICITINIB	4	TYK2
FILGOTINIB	4	TYK2
ABROCITINIB	4	TYK2
DEUCRAVACITINIB	4	TYK2
MOMELOTINIB	4	TYK2
AXITINIB	4	TYK2
RUXOLITINIB PHOSPHATE	4	TYK2
INFIGRATINIB PHOSPHATE	4	TYK2
INFIGRATINIB	4	TYK2
PACRITINIB	4	TYK2
TOFACITINIB CITRATE	4	TYK2
BOSUTINIB	4	TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	TYK2
NINTEDANIB	4	TYK2
SUNITINIB	4	TYK2
DASATINIB	4	TYK2
ERLOTINIB	4	TYK2
CRIZOTINIB	4	TYK2
MIDOSTAURIN	4	TYK2
IMATINIB	4	TYK2
DELGOCITINIB	3	TYK2
DEFACTINIB	3	TYK2
ITACITINIB	3	TYK2
ALVOCIDIB	3	TYK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TYK2
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	MRPL4, CDC37

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)
MRPL4	0	—
CDC37	51	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.