Gastrointestinal defects and immunodeficiency syndrome 2

Summary

Gastrointestinal defects and immunodeficiency syndrome 2 (MONDO:0030669) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gastrointestinal defects and immunodeficiency syndrome 2
Mondo ID	MONDO:0030669
OMIM	619708
UMLS	C5676901
MedGen	1811526
GARD	0027133
Is cancer (heuristic)	no

Also known as: gastrointestinal defects and immunodeficiency syndrome 2 · GIDID2 · multiple intestinal atresia with or without leukopenia

Data availability: 7 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › gastrointestinal defect and immunodeficiency syndrome › gastrointestinal defects and immunodeficiency syndrome 2

Related subtypes (1): gastrointestinal defects and immunodeficiency syndrome 1

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

7 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1335865	NM_058004.4(PI4KA):c.4867T>G (p.Tyr1623Asp)	PI4KA	Pathogenic	no assertion criteria provided
1676320	NM_058004.4(PI4KA):c.1852C>T (p.Arg618Ter)	PI4KA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3587850	NM_058004.4(PI4KA):c.2988-2A>G	PI4KA	Likely pathogenic	criteria provided, single submitter
4294426	NM_058004.4(PI4KA):c.3290_3302del (p.His1097fs)	PI4KA	Likely pathogenic	criteria provided, single submitter
4845912	NM_058004.4(PI4KA):c.4160+1G>A	PI4KA	Likely pathogenic	criteria provided, single submitter
3242216	NM_058004.4(PI4KA):c.3757G>A (p.Ala1253Thr)	PI4KA	Uncertain significance	criteria provided, single submitter
623974	NM_058004.4(PI4KA):c.5596G>A (p.Asp1866Asn)	PI4KA	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PI4KA	Orphanet:436252	Combined immunodeficiency-multiple intestinal atresia
PI4KA	Orphanet:631079	Autosomal recessive spastic paraplegia type 84
PI4KA	Orphanet:98889	Bilateral perisylvian polymicrogyria

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PI4KA	HGNC:8983	ENSG00000241973	P42356	Phosphatidylinositol 4-kinase alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PI4KA	Phosphatidylinositol 4-kinase alpha	Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PI4KA	Kinase	yes		PI3/4_kinase_cat_dom, PI3K_accessory_dom, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 9	1
right frontal lobe	1
superior frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PI4KA	143	ubiquitous	marker	superior frontal gyrus, right frontal lobe, Brodmann (1909) area 9

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PI4KA	1,755

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PI4KA	P42356	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of PIPs at the ER membrane	1	2284.0×	9e-04	PI4KA
Synthesis of PIPs at the Golgi membrane	1	634.4×	0.002	PI4KA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
reorganization of cellular membranes to establish viral sites of replication	1	16852.0×	4e-04	PI4KA
host-mediated perturbation of viral process	1	1872.4×	0.002	PI4KA
phosphatidylinositol-mediated signaling	1	702.2×	0.003	PI4KA
phosphatidylinositol phosphate biosynthetic process	1	481.5×	0.003	PI4KA
phosphatidylinositol biosynthetic process	1	366.4×	0.003	PI4KA
signal transduction	1	16.1×	0.062	PI4KA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
PI4KA	ADENOSINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PI4KA	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ADENOSINE	4	PI4KA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PI4KA	86	Binding:83, Functional:2, ADMET:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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)
ADENOSINE	4	PI4KA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PI4KA
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.