MHC class II deficiency

Summary

MHC class II deficiency (MONDO:0008855) is a disease (an umbrella term covering 5 Mondo subtypes) caused by variants in RFX5, CIITA, RFXANK, and 1 other genes, with 8 cohort genes and 3 clinical trials. Top therapeutic interventions include fludarabine phosphate.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal genes: RFX5 (GenCC Definitive), CIITA (GenCC Strong), RFXANK (GenCC Strong), RFXAP (GenCC Strong)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 8
• ClinVar variants: 2,630
• Phenotypes (HPO): 38
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		179	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

38 HPO clinical features (Orphanet curated; top 38 by frequency):

HPO ID	Term	Frequency
HP:0031390	Reduced MHC II surface expression	Obligate (100%)
HP:0002205	Recurrent respiratory infections	Very frequent (80-99%)
HP:0004798	Recurrent infection of the gastrointestinal tract	Very frequent (80-99%)
HP:0005354	Lack of T cell function	Very frequent (80-99%)
HP:0000246	Sinusitis	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0002014	Diarrhea	Frequent (30-79%)
HP:0002718	Recurrent bacterial infections	Frequent (30-79%)
HP:0002726	Recurrent Staphylococcus aureus infections	Frequent (30-79%)
HP:0002728	Chronic mucocutaneous candidiasis	Frequent (30-79%)
HP:0002841	Recurrent fungal infections	Frequent (30-79%)
HP:0004313	Decreased circulating antibody level	Frequent (30-79%)
HP:0004385	Protracted diarrhea	Frequent (30-79%)
HP:0004429	Recurrent viral infections	Frequent (30-79%)
HP:0005353	Recurrent herpes	Frequent (30-79%)
HP:0005368	Abnormality of humoral immunity	Frequent (30-79%)
HP:0005386	Recurrent protozoan infections	Frequent (30-79%)
HP:0005401	Recurrent candida infections	Frequent (30-79%)
HP:0012384	Rhinitis	Frequent (30-79%)
HP:0025347	Decreased circulating beta-2-microglobulin level	Frequent (30-79%)
HP:0030991	Sclerosing cholangitis	Frequent (30-79%)
HP:0200124	Chronic hepatitis due to cryptosporidium infection	Frequent (30-79%)
HP:0032218	Decreased proportion of CD4-positive T cells	Frequent (30-79%)
HP:0000371	Acute otitis media	Occasional (5-29%)
HP:0000988	Skin rash	Occasional (5-29%)
HP:0001875	Decreased total neutrophil count	Occasional (5-29%)
HP:0001876	Pancytopenia	Occasional (5-29%)
HP:0001890	Autoimmune hemolytic anemia	Occasional (5-29%)
HP:0001904	Neutropenia in presence of anti-neutropil antibodies	Occasional (5-29%)
HP:0001973	Autoimmune thrombocytopenia	Occasional (5-29%)
HP:0002960	Autoimmunity	Occasional (5-29%)
HP:0003139	Panhypogammaglobulinemia	Occasional (5-29%)
HP:0005403	Decreased total T cell count	Occasional (5-29%)
HP:0031381	Decreased lymphocyte proliferation in response to mitogen	Occasional (5-29%)
HP:0031394	Abnormal CD4:CD8 ratio	Occasional (5-29%)
HP:0001260	Dysarthria	Very rare (<1-4%)
HP:0001999	Abnormal facial shape	Very rare (<1-4%)
HP:0002066	Gait ataxia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	MHC class II deficiency
Mondo ID	MONDO:0008855
MeSH	C537079
OMIM	209920
Orphanet	572
DOID	DOID:5812
ICD-11	2021339495
NCIT	C176823, C3895
SNOMED CT	71904008
UMLS	C5447452
MedGen	1781237
GARD	0000824
Is cancer (heuristic)	no

Also known as: BARE lymphocyte syndrome · Bare lymphocyte syndrome 2 · Bare lymphocyte syndrome type 2 · Bare lymphocyte syndrome, type II · BARE lymphocyte syndrome, type II, complementation group B, included · BARE lymphocyte syndrome, type II, complementation group C, included · BARE lymphocyte syndrome, type II, complementation group D, included · BARE lymphocyte syndrome, type II, complementation group E, included · BLS · BLS 2 · BLS type II · BLS, type II · BLSII · HLA class 2-negative SCID · HLA class 2-negative severe combined immunodeficiency · immunodeficiency by defective expression of HLA class type 2 · major histocompatibility complex class II expression deficiency · MHC class II expression deficiency · SCID, HLA Class 2-negative · SCID, HLA Class II-negative (+2 more)

Data availability: 2,630 ClinVar variants · 10 GenCC gene-disease records · 35 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › combined immunodeficiency › severe combined immunodeficiency › familial severe combined immunodeficiency › MHC class II deficiency

Related subtypes (13): severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency, reticular dysgenesis, T-B+ severe combined immunodeficiency due to gamma chain deficiency, T-B+ severe combined immunodeficiency due to JAK3 deficiency, severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive, severe combined immunodeficiency due to DCLRE1C deficiency, Omenn syndrome, immunodeficiency 104, Cernunnos-XLF deficiency, immunodeficiency 18, immunodeficiency 19, immunodeficiency 49, immunodeficiency 105

Subtypes (5): MHC class II deficiency 1, MHC class II deficiency 2, MHC class II deficiency 3, MHC class II deficiency 4, MHC class II deficiency 5

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, 257 uncertain significance, 30 pathogenic, 17 benign, 11 likely pathogenic, 6 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071007	NC_000016.9:g.(?10971168)(10971259_?)del	CIITA	Pathogenic	criteria provided, single submitter
1072600	NM_000246.4(CIITA):c.1240C>T (p.Arg414Ter)	CIITA	Pathogenic	criteria provided, single submitter
1072919	NM_000246.4(CIITA):c.1717C>T (p.Gln573Ter)	CIITA	Pathogenic	criteria provided, single submitter
1073259	NM_000246.4(CIITA):c.2014C>T (p.Gln672Ter)	CIITA	Pathogenic	criteria provided, single submitter
1076559	NM_000246.4(CIITA):c.632del (p.Pro211fs)	CIITA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076860	NM_000246.4(CIITA):c.36C>A (p.Tyr12Ter)	CIITA	Pathogenic	criteria provided, single submitter
1360274	NM_000246.4(CIITA):c.1383dup (p.Ala462fs)	CIITA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1396255	NM_000246.4(CIITA):c.1389T>G (p.Tyr463Ter)	CIITA	Pathogenic	criteria provided, single submitter
1400898	NC_000016.9:g.(?11000336)(11017160_?)del	CIITA	Pathogenic	criteria provided, single submitter
1412942	NM_000246.4(CIITA):c.3361C>T (p.Gln1121Ter)	CIITA	Pathogenic	criteria provided, single submitter
1415818	NM_000246.4(CIITA):c.2740A>T (p.Lys914Ter)	CIITA	Pathogenic	criteria provided, single submitter
1416680	NM_000246.4(CIITA):c.1536_1537insTTGCGGTC (p.Ser513fs)	CIITA	Pathogenic	criteria provided, single submitter
1452318	NM_000246.4(CIITA):c.1962del (p.Ala656fs)	CIITA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454206	NM_000246.4(CIITA):c.2479C>T (p.Gln827Ter)	CIITA	Pathogenic	criteria provided, single submitter
1454398	NM_000246.4(CIITA):c.2526del (p.Pro843fs)	CIITA	Pathogenic	criteria provided, single submitter
1455424	NM_000246.4(CIITA):c.1863dup (p.Glu622fs)	CIITA	Pathogenic	criteria provided, single submitter
1458041	NM_000246.4(CIITA):c.802_803dup (p.Pro269fs)	CIITA	Pathogenic	criteria provided, single submitter
1458155	NM_000246.4(CIITA):c.682C>T (p.Gln228Ter)	CIITA	Pathogenic	criteria provided, multiple submitters, no conflicts
1459331	NM_000246.4(CIITA):c.1502_1511del (p.Phe501fs)	CIITA	Pathogenic	criteria provided, single submitter
1459361	NM_000246.4(CIITA):c.2828_2829insTG (p.Ser944fs)	CIITA	Pathogenic	criteria provided, single submitter
1460015	NM_000246.4(CIITA):c.2490del (p.Gly831fs)	CIITA	Pathogenic	criteria provided, single submitter
1497267	NM_000246.4(CIITA):c.2889-1G>T	CIITA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072890	NM_001025603.2(RFX5):c.273T>G (p.Tyr91Ter)	RFX5	Pathogenic	criteria provided, single submitter
1380120	NM_001025603.2(RFX5):c.602del (p.Val201fs)	RFX5	Pathogenic	criteria provided, single submitter
1385971	NM_001025603.2(RFX5):c.56dup (p.Gly20fs)	RFX5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1414875	NM_001025603.2(RFX5):c.445C>T (p.Arg149Ter)	RFX5	Pathogenic	criteria provided, single submitter
1431893	NM_001025603.2(RFX5):c.880C>T (p.Arg294Ter)	RFX5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1496062	NM_001025603.2(RFX5):c.1016C>G (p.Ser339Ter)	RFX5	Pathogenic	criteria provided, single submitter
1072999	NM_003721.4(RFXANK):c.383del (p.Leu128fs)	RFXANK	Pathogenic	criteria provided, single submitter
1074711	NM_003721.4(RFXANK):c.634C>T (p.Arg212Ter)	RFXANK	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 7 · 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
RFX5	Definitive	Autosomal recessive	MHC class II deficiency	5
CIITA	Strong	Autosomal recessive	MHC class II deficiency	2
RFXANK	Strong	Autosomal recessive	MHC class II deficiency	4
RFXAP	Strong	Autosomal recessive	MHC class II deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CIITA	Orphanet:572	Immunodeficiency by defective expression of MHC class II
RFX5	Orphanet:572	Immunodeficiency by defective expression of MHC class II
RFXANK	Orphanet:572	Immunodeficiency by defective expression of MHC class II
RFXAP	Orphanet:572	Immunodeficiency by defective expression of MHC class II
ALG5	Orphanet:730	Autosomal dominant polycystic kidney disease
ABAT	Orphanet:2066	Gamma-aminobutyric acid transaminase deficiency
ECM1	Orphanet:530	Lipoid proteinosis

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CIITA	HGNC:7067	ENSG00000179583	P33076	MHC class II transactivator	gencc,clinvar
RFX5	HGNC:9986	ENSG00000143390	P48382	DNA-binding protein RFX5	gencc,clinvar
RFXANK	HGNC:9987	ENSG00000064490	O14593	DNA-binding protein RFXANK	gencc,clinvar
RFXAP	HGNC:9988	ENSG00000133111	O00287	Regulatory factor X-associated protein	gencc,clinvar
ALG5	HGNC:20266	ENSG00000120697	Q9Y673	Dolichyl-phosphate beta-glucosyltransferase	clinvar
ABAT	HGNC:23	ENSG00000183044	P80404	4-aminobutyrate aminotransferase, mitochondrial	clinvar
NR2C2AP	HGNC:30763	ENSG00000184162	Q86WQ0	Nuclear receptor 2C2-associated protein	clinvar
ECM1	HGNC:3153	ENSG00000143369	Q16610	Extracellular matrix protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CIITA	MHC class II transactivator	Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter.
RFX5	DNA-binding protein RFX5	Activates transcription from class II MHC promoters.
RFXANK	DNA-binding protein RFXANK	Activates transcription from class II MHC promoters.
RFXAP	Regulatory factor X-associated protein	Part of the RFX complex that binds to the X-box of MHC II promoters.
ALG5	Dolichyl-phosphate beta-glucosyltransferase	Dolichyl-phosphate beta-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
ABAT	4-aminobutyrate aminotransferase, mitochondrial	Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively.
NR2C2AP	Nuclear receptor 2C2-associated protein	May act as a repressor of NR2C2-mediated transactivation by suppressing the binding between NR2C2/TR4 and the TR4-response element in target genes.
ECM1	Extracellular matrix protein 1	Involved in endochondral bone formation as negative regulator of bone mineralization.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.12

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	2.2×	0.502
Enzyme (other)	1	1.5×	0.502
Other/Unknown	6	1.3×	0.502

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CIITA	Other/Unknown	no		Leu-rich_rpt, NACHT_NTPase, MHC_II_transact
RFX5	Other/Unknown	no		DNA-bd_RFX, RFX5_C, WH-like_DNA-bd_sf
RFXANK	Scaffold/PPI	no		Ankyrin_rpt, DNA-bd_RFXANK, Ankyrin_rpt-contain_sf
RFXAP	Other/Unknown	no		RFXAP_RFXANK-bd, RFXAP_C_sf
ALG5	Other/Unknown	no		Glyco_trans_2-like, Nucleotide-diphossugar_trans, DPG_synthase
ABAT	Enzyme (other)	yes	2.6.1.19	4NH2But_aminotransferase_euk, Aminotrans_3, PyrdxlP-dep_Trfase_major
NR2C2AP	Other/Unknown	no		Galactose-bd-like_sf
ECM1	Other/Unknown	no		ECM1, Serum_albumin-like

Expression context

Cohort genes with no expression data: 0.

7 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	2
lower esophagus mucosa	2
mucosa of transverse colon	2
tendon of biceps brachii	2
granulocyte	1
mononuclear cell	1
epithelium of nasopharynx	1
lymph node	1
right uterine tube	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
body of pancreas	1
corpus epididymis	1
parotid gland	1
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1
cortical plate	1
buccal mucosa cell	1
pharyngeal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CIITA	200	broad	marker	monocyte, granulocyte, mononuclear cell
RFX5	289	ubiquitous	marker	epithelium of nasopharynx, lymph node, monocyte
RFXANK	270	ubiquitous	marker	lower esophagus mucosa, mucosa of transverse colon, right uterine tube
RFXAP	231	ubiquitous	yes	primordial germ cell in gonad, tendon of biceps brachii, male germ line stem cell (sensu Vertebrata) in testis
ALG5	285	ubiquitous	marker	parotid gland, body of pancreas, corpus epididymis
ABAT	289	ubiquitous	marker	Brodmann (1909) area 23, endothelial cell, middle temporal gyrus
NR2C2AP	217	ubiquitous	marker	cortical plate, mucosa of transverse colon, tendon of biceps brachii
ECM1	253	ubiquitous	marker	lower esophagus mucosa, buccal mucosa cell, pharyngeal mucosa

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALG5	2,785
CIITA	2,388
RFXANK	1,957
ECM1	1,835
ABAT	1,711
RFX5	1,103
NR2C2AP	1,012
RFXAP	539

Intra-cohort edges

A	B	Sources
CIITA	RFX5	biogrid_interaction, intact, string_interaction
CIITA	RFXANK	biogrid_interaction, string_interaction
CIITA	RFXAP	string_interaction
NR2C2AP	RFXANK	string_interaction
RFX5	RFXANK	biogrid_interaction, intact, string_interaction
RFX5	RFXAP	biogrid_interaction, intact, string_interaction
RFXANK	RFXAP	biogrid_interaction, intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RFX5	P48382	3
RFXANK	O14593	3
RFXAP	O00287	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NR2C2AP	Q86WQ0	96.58
ABAT	P80404	93.91
ALG5	Q9Y673	92.29
CIITA	P33076	69.10
ECM1	Q16610	69.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 8 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of dolichyl-phosphate-glucose	1	1142.0×	0.006	ALG5
Degradation of GABA	1	1142.0×	0.006	ABAT
Synthesis of substrates in N-glycan biosythesis	1	58.6×	0.064	ALG5
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	41.5×	0.064	ALG5
Nuclear Receptor transcription pathway	1	40.1×	0.064	NR2C2AP
Interferon gamma signaling	1	25.1×	0.076	CIITA
Interferon Signaling	1	24.0×	0.076	CIITA
Platelet degranulation	1	17.6×	0.090	ECM1
Asparagine N-linked glycosylation	1	12.0×	0.116	ALG5
Cytokine Signaling in Immune system	1	8.2×	0.152	CIITA
Post-translational protein modification	1	3.8×	0.277	ALG5
Immune System	1	2.6×	0.344	CIITA
Metabolism of proteins	1	2.5×	0.344	ALG5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 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 MHC class II biosynthetic process	4	687.8×	6e-10	CIITA, RFX5, RFXANK, RFXAP
regulation of type 2 immune response	1	2407.4×	0.005	ECM1
copulation	1	1203.7×	0.005	ABAT
obsolete GABA metabolic process	1	1203.7×	0.005	ABAT
GABA catabolic process	1	1203.7×	0.005	ABAT
negative regulation of peptidase activity	1	1203.7×	0.005	ECM1
negative regulation of gamma-aminobutyric acid secretion	1	1203.7×	0.005	ABAT
positive regulation of prolactin secretion	1	1203.7×	0.005	ABAT
positive regulation of aspartate secretion	1	1203.7×	0.005	ABAT
positive regulation of transcription by RNA polymerase II	4	8.5×	0.005	CIITA, RFX5, RFXANK, RFXAP
negative regulation of dopamine secretion	1	601.9×	0.008	ABAT
positive regulation of dopamine metabolic process	1	601.9×	0.008	ABAT
positive regulation of heat generation	1	481.5×	0.009	ABAT
positive regulation of MHC class I biosynthetic process	1	401.2×	0.009	CIITA
positive regulation of inhibitory postsynaptic potential	1	401.2×	0.009	ABAT
regulation of T cell migration	1	343.9×	0.010	ECM1
GABA biosynthetic process	1	300.9×	0.010	ABAT
positive regulation of uterine smooth muscle contraction	1	300.9×	0.010	ABAT
negative regulation of cytokine-mediated signaling pathway	1	267.5×	0.011	ECM1
endochondral bone growth	1	240.7×	0.012	ECM1
nervous system process	1	172.0×	0.015	ABAT
type II interferon-mediated signaling pathway	1	172.0×	0.015	CIITA
negative regulation of collagen biosynthetic process	1	160.5×	0.015	CIITA
chondrocyte development	1	133.8×	0.016	ECM1
response to iron ion	1	133.8×	0.016	ABAT
negative regulation of bone mineralization	1	133.8×	0.016	ECM1
dolichol-linked oligosaccharide biosynthetic process	1	120.4×	0.017	ALG5
regulation of bone mineralization	1	104.7×	0.018	ECM1
host-mediated suppression of symbiont invasion	1	100.3×	0.018	CIITA
response to antibiotic	1	100.3×	0.018	CIITA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8

Druggability breadth: 1 of 8 evidence-associated genes (12%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CIITA	0	0
RFX5	0	0
RFXANK	0	0
RFXAP	0	0
ALG5	0	0
ABAT	0	0
NR2C2AP	0	0
ECM1	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
ABAT	41	Binding:41

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABAT	2.6.1.19	4-aminobutyrate-2-oxoglutarate transaminase

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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	1	ABAT
E	Difficult family or no structure, no drug	7	CIITA, RFX5, RFXANK, RFXAP, ALG5, NR2C2AP, ECM1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CIITA	0	—
RFX5	0	—
RFXANK	0	—
RFXAP	0	—
ALG5	0	—
ABAT	41	—
NR2C2AP	0	—
ECM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT04251325	Not specified	UNKNOWN	Socio-demographic Characteristics of Basic Life Support Course Participants
NCT04353089	Not specified	UNKNOWN	Geographical Association Between Basic Life Support Courses, Bystander Cardiopulmonary Resuscitation and Survival

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	1