Rajab interstitial lung disease with brain calcifications 2

Summary

Rajab interstitial lung disease with brain calcifications 2 (MONDO:0100220) is a disease caused by FARSA (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: FARSA (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Rajab interstitial lung disease with brain calcifications 2
Mondo ID	MONDO:0100220
OMIM	619013
UMLS	C5436603
MedGen	1770895
GARD	0018298
Is cancer (heuristic)	no

Also known as: RAJAB INTERSTITIAL LUNG DISEASE WITH BRAIN CALCIFICATIONS 2 · RILDBC2

Data availability: 8 ClinVar variants · 3 GenCC gene-disease records.

Disease family

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 › Rajab interstitial lung disease with brain calcifications 2

Related subtypes (1): Rajab interstitial lung disease with brain calcifications 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

8 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685812	NM_004461.3(FARSA):c.812G>A (p.Arg271His)	FARSA	Pathogenic	criteria provided, single submitter
977639	NM_004461.3(FARSA):c.766T>C (p.Phe256Leu)	FARSA	Pathogenic	criteria provided, single submitter
977640	NM_004461.3(FARSA):c.1230C>A (p.Asn410Lys)	FARSA	Pathogenic	no assertion criteria provided
3068592	NM_004461.3(FARSA):c.1040C>T (p.Pro347Leu)	FARSA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1803090	NM_004461.3(FARSA):c.1211G>A (p.Arg404His)	FARSA	Uncertain significance	criteria provided, single submitter
1803091	NM_004461.3(FARSA):c.733G>A (p.Glu245Lys)	FARSA	Uncertain significance	criteria provided, single submitter
3068268	NM_004461.3(FARSA):c.916G>A (p.Gly306Ser)	FARSA	Uncertain significance	criteria provided, multiple submitters, no conflicts
3068613	NM_004461.3(FARSA):c.244C>T (p.Arg82Ter)	FARSA	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
FARSA	Strong	Autosomal recessive	Rajab interstitial lung disease with brain calcifications 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FARSA	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
FARSA	HGNC:3592	ENSG00000179115	Q9Y285	Phenylalanine–tRNA ligase alpha subunit	gencc,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)
FARSA	Enzyme (other)	yes	6.1.1.20	Phenylalanyl-tRNA_Synthase, Phe-tRNA-synth_IIc_asu, aa-tRNA-synth_II

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
endometrium epithelium	1
mucosa of transverse colon	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FARSA	278	ubiquitous	marker	prefrontal cortex, mucosa of transverse colon, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FARSA	2,822

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FARSA	Q9Y285	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	FARSA
tRNA Aminoacylation	1	285.5×	0.007	FARSA
Translation	1	62.1×	0.021	FARSA
Metabolism of proteins	1	12.4×	0.081	FARSA

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×	5e-04	FARSA
protein heterotetramerization	1	1053.2×	9e-04	FARSA

Therapeutics

Drug target analysis

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

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
FARSA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FARSA	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FARSA	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

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	FARSA
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
FARSA	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05514470	Not specified	WITHDRAWN	Impact of Mutations in Aminoacyl tRNA Synthetases on Protein Translation and Cellular Stress