Immunodeficiency 51

Summary

Immunodeficiency 51 (MONDO:0013500) is a disease caused by IL17RA (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: IL17RA (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 879

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 51
Mondo ID	MONDO:0013500
OMIM	613953
DOID	DOID:0111996
UMLS	C4310803
MedGen	934770
GARD	0015732
Is cancer (heuristic)	no

Also known as: CANDF5 · candidiasis, familial chronic mucocutaneous, autosomal recessive · candidiasis, familial, 5 · candidiasis, familial, type 5 · IMD51 · immunodeficiency 51

Data availability: 879 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › chronic mucocutaneous candidiasis › immunodeficiency 51

Related subtypes (11): candidiasis, familial, 1, chronic mucocutaneous candidiasis due to inhibition of lymphoblastic transformation, chronic mucocutaneous candidiasis due to intrinsic defect in lymphoblastic transformation, chronic mucocutaneous candidiasis due to lymphokine deficiency, chronic mucocutaneous candidiasis due to monocyte chemotactic disorder, candidiasis, familial, 3, candidiasis, familial, 4, candidiasis, familial, 6, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, candidiasis, familial, 8, candidiasis, familial, 9

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:

265 likely benign, 256 uncertain significance, 30 benign, 26 conflicting classifications of pathogenicity, 12 pathogenic, 7 likely pathogenic, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2424095	NC_000022.10:g.(?17565982)(20052185_?)del	ADA2	Pathogenic	criteria provided, single submitter
1375868	NM_014339.7(IL17RA):c.213dup (p.Ser72fs)	IL17RA	Pathogenic	criteria provided, single submitter
1386866	NM_014339.7(IL17RA):c.186G>A (p.Trp62Ter)	IL17RA	Pathogenic	criteria provided, single submitter
2000048	NM_014339.7(IL17RA):c.205del (p.Thr69fs)	IL17RA	Pathogenic	criteria provided, single submitter
2085281	NM_014339.7(IL17RA):c.680_681insG (p.Thr228fs)	IL17RA	Pathogenic	criteria provided, single submitter
2794701	NM_014339.7(IL17RA):c.185G>A (p.Trp62Ter)	IL17RA	Pathogenic	criteria provided, single submitter
2998290	NM_014339.7(IL17RA):c.705del (p.Ser236fs)	IL17RA	Pathogenic	criteria provided, single submitter
30486	NM_014339.7(IL17RA):c.850C>T (p.Gln284Ter)	IL17RA	Pathogenic	no assertion criteria provided
372204	NM_014339.7(IL17RA):c.1302_1318dup (p.Asn440fs)	IL17RA	Pathogenic	no assertion criteria provided
372205	NM_014339.7(IL17RA):c.1159G>A (p.Asp387Asn)	IL17RA	Pathogenic	no assertion criteria provided
372206	NM_014339.7(IL17RA):c.196C>T (p.Arg66Ter)	IL17RA	Pathogenic	criteria provided, single submitter
372207	NM_014339.7(IL17RA):c.268del (p.Leu90fs)	IL17RA	Pathogenic	no assertion criteria provided
1067524	NM_014339.7(IL17RA):c.163+2T>C	IL17RA	Likely pathogenic	criteria provided, single submitter
1518224	NM_014339.7(IL17RA):c.598+1G>T	IL17RA	Likely pathogenic	criteria provided, single submitter
2671780	NM_014339.7(IL17RA):c.805_808del (p.Thr269fs)	IL17RA	Likely pathogenic	criteria provided, single submitter
3235884	NM_014339.7(IL17RA):c.292T>C (p.Trp98Arg)	IL17RA	Likely pathogenic	criteria provided, single submitter
3362564	NM_014339.7(IL17RA):c.721del (p.Glu241fs)	IL17RA	Likely pathogenic	criteria provided, single submitter
3362583	NM_014339.7(IL17RA):c.112_119del (p.His38fs)	IL17RA	Likely pathogenic	criteria provided, single submitter
3658695	NM_014339.7(IL17RA):c.931+2T>G	IL17RA	Likely pathogenic	criteria provided, single submitter
1008332	NM_014339.7(IL17RA):c.1531G>A (p.Gly511Ser)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1047270	NM_014339.7(IL17RA):c.2200A>G (p.Met734Val)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1359178	NM_014339.7(IL17RA):c.456C>A (p.Asp152Glu)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1469957	NM_014339.7(IL17RA):c.281C>T (p.Ala94Val)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683660	NM_014339.7(IL17RA):c.582G>A (p.Thr194=)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2052119	NM_014339.7(IL17RA):c.1955C>G (p.Pro652Arg)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3109151	NM_014339.7(IL17RA):c.2418G>C (p.Glu806Asp)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340563	NM_014339.7(IL17RA):c.36G>T (p.Pro12=)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340565	NM_014339.7(IL17RA):c.152C>T (p.Thr51Met)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340572	NM_014339.7(IL17RA):c.427C>T (p.Arg143Cys)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340573	NM_014339.7(IL17RA):c.465G>C (p.Gln155His)	IL17RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 4 · 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
IL17RA	Strong	Autosomal recessive	immunodeficiency 51	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL17RA	Orphanet:1334	Chronic mucocutaneous candidiasis
ADA2	Orphanet:124	Diamond-Blackfan anemia
ADA2	Orphanet:404553	Deficiency of adenosine deaminase 2
ADA2	Orphanet:820	Sneddon syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IL17RA	HGNC:5985	ENSG00000177663	Q96F46	Interleukin-17 receptor A	gencc,clinvar
ADA2	HGNC:1839	ENSG00000093072	Q9NZK5	Adenosine deaminase 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL17RA	Interleukin-17 receptor A	Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.
ADA2	Adenosine deaminase 2	Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL17RA	Other/Unknown	no		SEFIR_dom, IL17R_A/B_N, IL17RA/B_FnIII-like_1_sf
ADA2	Enzyme (other)	yes	3.5.4.4	A_deaminase_dom, Ado/ade_deaminase, ADGF

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	2
monocyte	2
blood	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL17RA	262	ubiquitous	marker	blood, monocyte, leukocyte
ADA2	254	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL17RA	2,226
ADA2	1,808

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL17RA	Q96F46	10
ADA2	Q9NZK5	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 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
Surfactant metabolism	1	184.2×	0.028	ADA2
Interleukin-17 signaling	1	126.9×	0.028	IL17RA
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	44.6×	0.052	IL17RA
Innate Immune System	1	12.8×	0.119	ADA2
Neutrophil degranulation	1	11.5×	0.119	ADA2
Immune System	1	6.5×	0.155	ADA2
Metabolism of proteins	1	6.2×	0.155	ADA2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
inosine biosynthetic process	1	2808.7×	0.002	ADA2
adenosine catabolic process	1	2106.5×	0.002	ADA2
granulocyte chemotaxis	1	1685.2×	0.002	IL17RA
T-helper 17 type immune response	1	1685.2×	0.002	IL17RA
interleukin-17A-mediated signaling pathway	1	1404.3×	0.002	IL17RA
positive regulation of chemokine (C-X-C motif) ligand 1 production	1	1404.3×	0.002	IL17RA
positive regulation of interleukin-23 production	1	1203.7×	0.002	IL17RA
fibroblast activation	1	1203.7×	0.002	IL17RA
interleukin-17-mediated signaling pathway	1	842.6×	0.003	IL17RA
positive regulation of interleukin-5 production	1	702.2×	0.003	IL17RA
positive regulation of interleukin-13 production	1	561.7×	0.003	IL17RA
positive regulation of cytokine production involved in inflammatory response	1	271.8×	0.006	IL17RA
defense response to fungus	1	221.7×	0.007	IL17RA
protein catabolic process	1	118.7×	0.012	IL17RA
positive regulation of interleukin-6 production	1	83.4×	0.016	IL17RA
positive regulation of inflammatory response	1	72.6×	0.016	IL17RA
response to virus	1	72.0×	0.016	IL17RA
cell surface receptor signaling pathway	1	32.0×	0.034	IL17RA
inflammatory response	1	18.9×	0.055	IL17RA
innate immune response	1	16.8×	0.059	IL17RA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IL17RA	0	0
ADA2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADA2	3.5.4.4	adenosine deaminase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	ADA2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	IL17RA

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)
IL17RA	0	—
ADA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.