Rajab interstitial lung disease with brain calcifications

Summary

Rajab interstitial lung disease with brain calcifications (MONDO:0100214) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Rajab interstitial lung disease with brain calcifications
Mondo ID	MONDO:0100214
OMIM	613658
UMLS	C3150910
MedGen	462260
GARD	0026084
Is cancer (heuristic)	no

Data availability: 8 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited interstitial lung disease › Rajab interstitial lung disease with brain calcifications

Related subtypes (12): pulmonary fibrosis and/or bone marrow failure, telomere-related, hypersensitivity pneumonitis, familial, alveolar capillary dysplasia with misalignment of pulmonary veins, Niemann-Pick disease type B, interstitial lung disease due to ABCA3 deficiency, lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome, Hermansky-Pudlak syndrome with pulmonary fibrosis, familial hypocalciuric hypercalcemia, SFTPC-related interstitial lung disease, interstitial lung disease 1, Lane Hamilton syndrome, interstitial lung disease 2

Subtypes (2): Rajab interstitial lung disease with brain calcifications 1, Rajab interstitial lung disease with brain calcifications 2

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

8 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 pathogenic/likely pathogenic, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
487456	NM_005687.5(FARSB):c.1486delinsAA (p.His496fs)	FARSB	Pathogenic	criteria provided, single submitter
545501	NM_005687.5(FARSB):c.848+1G>A	FARSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545642	NM_005687.5(FARSB):c.1381A>C (p.Thr461Pro)	FARSB	Pathogenic	criteria provided, single submitter
545664	NM_005687.5(FARSB):c.1202G>A (p.Arg401Gln)	FARSB	Pathogenic	criteria provided, single submitter
545694	NM_005687.5(FARSB):c.755T>C (p.Phe252Ser)	FARSB	Pathogenic	no assertion criteria provided
559418	NM_005687.5(FARSB):c.853G>A (p.Glu285Lys)	FARSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545502	NM_005687.5(FARSB):c.914G>A (p.Arg305Gln)	FARSB	Likely pathogenic	criteria provided, single submitter
487455	NM_005687.5(FARSB):c.767C>T (p.Thr256Met)	FARSB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FARSB	Orphanet:178506	Interstitial lung disease-brain calcification syndrome

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
FARSB	HGNC:17800	ENSG00000116120	Q9NSD9	Phenylalanine–tRNA ligase beta subunit	clinvar

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FARSB	Enzyme (other)	yes	6.1.1.20	Phe-tRNA-synth_IIc_bsu_arc_euk, B3/B4_tRNA-bd, tRNA_synthase_B5-dom

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
cardiac muscle of right atrium	1
gingival epithelium	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FARSB	264	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FARSB	3,392

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FARSB	Q9NSD9	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Cytosolic tRNA aminoacylation	1	439.2×	0.007	FARSB
tRNA Aminoacylation	1	285.5×	0.007	FARSB
Translation	1	62.1×	0.021	FARSB
Metabolism of proteins	1	12.4×	0.081	FARSB

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
phenylalanyl-tRNA aminoacylation	1	4213.0×	7e-04	FARSB
protein heterotetramerization	1	1053.2×	0.001	FARSB
translation	1	102.8×	0.010	FARSB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FARSB	3	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	FARSB
TANDUTINIB	2	FARSB
PHA-793887	1	FARSB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FARSB	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FARSB	6.1.1.20	phenylalanine-tRNA ligase

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

3 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)
MOLIBRESIB	2	FARSB
TANDUTINIB	2	FARSB
PHA-793887	1	FARSB

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	1	FARSB
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.