Primary immunodeficiency syndrome due to p14 deficiency

Summary

Primary immunodeficiency syndrome due to p14 deficiency (MONDO:0012559) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 7

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0001875	Decreased total neutrophil count	Very frequent (80-99%)
HP:0002721	Immunodeficiency	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0005599	Hypopigmentation of hair	Very frequent (80-99%)
HP:0006538	Recurrent bronchopulmonary infections	Very frequent (80-99%)
HP:0007443	Partial albinism	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	primary immunodeficiency syndrome due to p14 deficiency
Mondo ID	MONDO:0012559
MeSH	C563663
OMIM	610798
Orphanet	90023
ICD-11	813140844
SNOMED CT	718717004
UMLS	C1835829
MedGen	372135
GARD	0016783
Is cancer (heuristic)	no

Also known as: primary immunodeficiency syndrome due to LAMTOR2 deficiency · primary immunodeficiency syndrome with short stature

Data availability: 3 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › leukopenia › agranulocytosis › neutropenia › constitutional neutropenia › primary immunodeficiency syndrome due to p14 deficiency

Related subtypes (12): cyclic hematopoiesis, Chediak-Higashi syndrome, Cohen syndrome, glycogen storage disease Ib, Lichtenstein syndrome, Barth syndrome, poikiloderma with neutropenia, Griscelli syndrome type 2, Hermansky-Pudlak syndrome 2, neutropenia-monocytopenia-deafness syndrome, severe congenital neutropenia, WHIM 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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
992528	NM_014017.4(LAMTOR2):c.231+7A>G	LAMTOR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000497	NM_014017.4(LAMTOR2):c.47C>T (p.Thr16Ile)	LAMTOR2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1239	NM_014017.4(LAMTOR2):c.*23C>A	LAMTOR2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
LAMTOR2	Moderate	Autosomal recessive	primary immunodeficiency syndrome due to p14 deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAMTOR2	Orphanet:90023	Primary immunodeficiency syndrome due to P14/LAMTOR2 deficiency

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
LAMTOR2	HGNC:29796	ENSG00000116586	Q9Y2Q5	Ragulator complex protein LAMTOR2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LAMTOR2	Ragulator complex protein LAMTOR2	As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LAMTOR2	Other/Unknown	no		Roadblock/LAMTOR2_dom, LAMTOR2-like

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
granulocyte	1
mucosa of transverse colon	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAMTOR2	267	ubiquitous	marker	mucosa of transverse colon, granulocyte, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMTOR2	1,781

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LAMTOR2	Q9Y2Q5	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. 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
mTORC1-mediated signalling	1	475.8×	0.018	LAMTOR2
Energy dependent regulation of mTOR by LKB1-AMPK	1	393.8×	0.018	LAMTOR2
MAP2K and MAPK activation	1	285.5×	0.018	LAMTOR2
MTOR signalling	1	265.6×	0.018	LAMTOR2
PTEN Regulation	1	228.4×	0.018	LAMTOR2
Amino acids regulate mTORC1	1	200.3×	0.018	LAMTOR2
Regulation of PTEN gene transcription	1	178.4×	0.018	LAMTOR2
Cellular response to starvation	1	165.5×	0.018	LAMTOR2
Autophagy	1	148.3×	0.018	LAMTOR2
MAPK1/MAPK3 signaling	1	131.3×	0.018	LAMTOR2
TP53 Regulates Metabolic Genes	1	129.8×	0.018	LAMTOR2
Macroautophagy	1	115.3×	0.019	LAMTOR2
MAPK family signaling cascades	1	102.9×	0.019	LAMTOR2
Intracellular signaling by second messengers	1	91.4×	0.020	LAMTOR2
PIP3 activates AKT signaling	1	66.8×	0.025	LAMTOR2
Transcriptional Regulation by TP53	1	62.1×	0.025	LAMTOR2
RAF/MAP kinase cascade	1	61.1×	0.025	LAMTOR2
Cellular responses to stress	1	36.8×	0.039	LAMTOR2
Cellular responses to stimuli	1	31.5×	0.043	LAMTOR2
Innate Immune System	1	25.5×	0.051	LAMTOR2
Neutrophil degranulation	1	23.1×	0.052	LAMTOR2
RNA Polymerase II Transcription	1	22.5×	0.052	LAMTOR2
Gene expression (Transcription)	1	17.8×	0.063	LAMTOR2
Generic Transcription Pathway	1	15.1×	0.072	LAMTOR2
Immune System	1	13.0×	0.080	LAMTOR2
Signal Transduction	1	10.2×	0.098	LAMTOR2

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
regulation of cell-substrate junction organization	1	16852.0×	6e-04	LAMTOR2
protein localization to cell junction	1	1872.4×	0.003	LAMTOR2
fibroblast migration	1	842.6×	0.003	LAMTOR2
TORC1 signaling	1	802.5×	0.003	LAMTOR2
positive regulation of TOR signaling	1	495.6×	0.004	LAMTOR2
cellular response to amino acid stimulus	1	306.4×	0.005	LAMTOR2
positive regulation of TORC1 signaling	1	295.6×	0.005	LAMTOR2
regulation of cell growth	1	221.7×	0.006	LAMTOR2
intracellular protein localization	1	104.7×	0.011	LAMTOR2
positive regulation of MAPK cascade	1	80.6×	0.012	LAMTOR2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LAMTOR2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	1	LAMTOR2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LAMTOR2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.