Immunodeficiency 62

Summary

Immunodeficiency 62 (MONDO:0032763) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 62
Mondo ID	MONDO:0032763
OMIM	618459
Orphanet	696942
DOID	DOID:0111991
UMLS	C5193109
MedGen	1673905
Is cancer (heuristic)	no

Also known as: IMD62 · immunodeficiency 62

Data availability: 12 ClinVar variants · 2 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 62

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, immunodeficiency 35, 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 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

12 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 2 conflicting classifications of pathogenicity, 2 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
810949	NM_000037.4(ANK1):c.1153C>T (p.Arg385Cys)	ANK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2084226	NM_004706.4(ARHGEF1):c.2522C>T (p.Ala841Val)	ARHGEF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1370813	NM_004706.4(ARHGEF1):c.2149G>A (p.Glu717Lys)	ARHGEF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1451068	NM_004706.4(ARHGEF1):c.-20+1180T>A	ARHGEF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431777	NM_004706.4(ARHGEF1):c.130A>G (p.Ser44Gly)	ARHGEF1	Uncertain significance	criteria provided, single submitter
2431903	NM_004706.4(ARHGEF1):c.424G>A (p.Val142Met)	ARHGEF1	Uncertain significance	criteria provided, single submitter
3901068	NM_004706.4(ARHGEF1):c.205C>T (p.Gln69Ter)	ARHGEF1	Uncertain significance	criteria provided, single submitter
4071544	NM_004706.4(ARHGEF1):c.1480G>T (p.Asp494Tyr)	ARHGEF1	Uncertain significance	criteria provided, single submitter
633649	NM_004706.4(ARHGEF1):c.853C>T (p.Arg285Ter)	ARHGEF1	no classifications from unflagged records	no classifications from unflagged records
633650	NM_004706.4(ARHGEF1):c.1624-1G>T	ARHGEF1	no classifications from unflagged records	no classifications from unflagged records
2664735	NM_001113378.2(FANCI):c.3355G>T (p.Ala1119Ser)	FANCI	Uncertain significance	criteria provided, multiple submitters, no conflicts
317294	NM_001113378.2(FANCI):c.3400A>G (p.Ile1134Val)	FANCI	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
ARHGEF1	Moderate	Autosomal recessive	immunodeficiency 62	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARHGEF1	Orphanet:696942	Childhood-onset common variable immunodeficiency due to ARHGEF1 deficiency
FANCI	Orphanet:84	Fanconi anemia
ANK1	Orphanet:251066	8p11.2 deletion syndrome
ANK1	Orphanet:822	Hereditary spherocytosis

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
ARHGEF1	HGNC:681	ENSG00000076928	Q92888	Rho guanine nucleotide exchange factor 1	gencc,clinvar
FANCI	HGNC:25568	ENSG00000140525	Q9NVI1	Fanconi anemia group I protein	clinvar
ANK1	HGNC:492	ENSG00000029534	P16157	Ankyrin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARHGEF1	Rho guanine nucleotide exchange factor 1	Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits.
FANCI	Fanconi anemia group I protein	Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA r…
ANK1	Ankyrin-1	Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.0

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
Scaffold/PPI	2	11.5×	0.019
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARHGEF1	Scaffold/PPI	no		DH_dom, PH_domain, PH-like_dom_sf
FANCI	Other/Unknown	no		FANCI, FANCI_S1-cap, FANCI_S1
ANK1	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt

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	1
lymph node	1
small intestine Peyer’s patch	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1
ventricular zone	1
body of tongue	1
skeletal muscle tissue of rectus abdominis	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARHGEF1	264	ubiquitous	marker	granulocyte, lymph node, small intestine Peyer’s patch
FANCI	221	ubiquitous	marker	ventricular zone, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
ANK1	226	broad	marker	skeletal muscle tissue of rectus abdominis, triceps brachii, body of tongue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANK1	5,705
FANCI	2,312
ARHGEF1	2,018

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANK1	P16157	21
FANCI	Q9NVI1	8
ARHGEF1	Q92888	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. 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
NrCAM interactions	1	543.8×	0.025	ANK1
Neurofascin interactions	1	475.8×	0.025	ANK1
CHL1 interactions	1	423.0×	0.025	ANK1
Interaction between L1 and Ankyrins	1	122.8×	0.051	ANK1
Fanconi Anemia Pathway	1	92.8×	0.051	FANCI
Cell death signalling via NRAGE, NRIF and NADE	1	73.2×	0.051	ARHGEF1
p75 NTR receptor-mediated signalling	1	62.4×	0.051	ARHGEF1
NRAGE signals death through JNK	1	61.4×	0.051	ARHGEF1
TP53 Regulates Transcription of DNA Repair Genes	1	60.4×	0.051	FANCI
RHOB GTPase cycle	1	51.4×	0.051	ARHGEF1
RHOC GTPase cycle	1	48.8×	0.051	ARHGEF1
Death Receptor Signaling	1	46.4×	0.051	ARHGEF1
G alpha (12/13) signalling events	1	45.9×	0.051	ARHGEF1
ER to Golgi Anterograde Transport	1	44.3×	0.051	ANK1
L1CAM interactions	1	40.1×	0.053	ANK1
COPI-mediated anterograde transport	1	36.6×	0.054	ANK1
Transport to the Golgi and subsequent modification	1	34.3×	0.054	ANK1
RHOA GTPase cycle	1	24.9×	0.071	ARHGEF1
Asparagine N-linked glycosylation	1	20.0×	0.079	ANK1
RHO GTPase cycle	1	20.0×	0.079	ARHGEF1
Axon guidance	1	15.1×	0.095	ANK1
GPCR downstream signalling	1	14.5×	0.095	ARHGEF1
Nervous system development	1	14.3×	0.095	ANK1
Signaling by GPCR	1	13.4×	0.097	ARHGEF1
Membrane Trafficking	1	12.4×	0.099	ANK1
Vesicle-mediated transport	1	11.6×	0.099	ANK1
Signaling by Rho GTPases	1	11.4×	0.099	ARHGEF1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	11.2×	0.099	ARHGEF1
Post-translational protein modification	1	6.4×	0.164	ANK1
Developmental Biology	1	4.8×	0.206	ANK1

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
maintenance of epithelial cell apical/basal polarity	1	802.5×	0.007	ANK1
Rho-activating G protein-coupled receptor signaling pathway	1	802.5×	0.007	ARHGEF1
interstrand cross-link repair	1	144.0×	0.028	FANCI
Rho protein signal transduction	1	82.6×	0.030	ARHGEF1
positive regulation of protein ubiquitination	1	71.1×	0.030	FANCI
exocytosis	1	50.6×	0.030	ANK1
regulation of small GTPase mediated signal transduction	1	48.0×	0.030	ARHGEF1
endoplasmic reticulum to Golgi vesicle-mediated transport	1	45.3×	0.030	ANK1
cytoskeleton organization	1	44.2×	0.030	ANK1
protein localization to plasma membrane	1	36.2×	0.033	ANK1
G protein-coupled receptor signaling pathway	1	12.1×	0.088	ARHGEF1
signal transduction	1	5.3×	0.176	ANK1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ARHGEF1	0	0
FANCI	0	0
ANK1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ARHGEF1	11	Binding:11
FANCI	1	Binding:1

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

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	0
E	Difficult family or no structure, no drug	3	ARHGEF1, FANCI, ANK1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ARHGEF1	11	—
FANCI	1	—
ANK1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.