Interstitial lung disease 1

Summary

Interstitial lung disease 1 (MONDO:0030608) is a disease caused by SFTPA1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SFTPA1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	interstitial lung disease 1
Mondo ID	MONDO:0030608
OMIM	619611
DOID	DOID:0060941
UMLS	C5562021
MedGen	1794231
GARD	0027931
Is cancer (heuristic)	no

Also known as: ILD1 · interstitial lung disease 1

Data availability: 14 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited interstitial lung disease › interstitial lung disease 1

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, Rajab interstitial lung disease with brain calcifications, Lane Hamilton syndrome, interstitial lung disease 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

14 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 4 pathogenic, 1 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322016	NM_005411.5(SFTPA1):c.631T>C (p.Trp211Arg)	SFTPA1	Pathogenic	no assertion criteria provided
1322018	NM_005411.5(SFTPA1):c.673G>A (p.Val225Met)	SFTPA1	Pathogenic	no assertion criteria provided
1325403	NM_005411.5(SFTPA1):c.532G>A (p.Val178Met)	SFTPA1	Pathogenic	no assertion criteria provided
1325404	NM_005411.5(SFTPA1):c.622T>C (p.Tyr208His)	SFTPA1	Pathogenic	no assertion criteria provided
2344111	NM_005411.5(SFTPA1):c.482G>A (p.Arg161His)	SFTPA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705350	NM_005411.5(SFTPA1):c.633G>T (p.Trp211Cys)	SFTPA1	Uncertain significance	criteria provided, single submitter
2349806	NM_005411.5(SFTPA1):c.440C>G (p.Thr147Ser)	SFTPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2396751	NM_005411.5(SFTPA1):c.542A>T (p.Tyr181Phe)	SFTPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892420	NM_005411.5(SFTPA1):c.14C>T (p.Pro5Leu)	SFTPA1	Uncertain significance	criteria provided, single submitter
3892421	NM_005411.5(SFTPA1):c.332T>C (p.Leu111Pro)	SFTPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892422	NM_005411.5(SFTPA1):c.509A>G (p.Glu170Gly)	SFTPA1	Uncertain significance	criteria provided, single submitter
4292904	NM_005411.5(SFTPA1):c.368G>T (p.Gly123Val)	SFTPA1	Uncertain significance	criteria provided, single submitter
517516	NM_005411.5(SFTPA1):c.724C>T (p.Arg242Ter)	SFTPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
165198	NM_005411.5(SFTPA1):c.271C>G (p.Pro91Ala)	SFTPA1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
SFTPA1	Strong	Semidominant	interstitial lung disease 1

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SFTPA1	Orphanet:2032	Idiopathic pulmonary fibrosis

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
SFTPA1	HGNC:10798	ENSG00000122852	Q8IWL2	Pulmonary surfactant-associated protein A1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SFTPA1	Pulmonary surfactant-associated protein A1	In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration.

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)
SFTPA1	Other/Unknown	no		C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold

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
lung	1
right lung	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SFTPA1	111	tissue_specific	marker	right lung, upper lobe of left lung, lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SFTPA1	12

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SFTPA1	Q8IWL2	83.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Diseases associated with surfactant metabolism	1	2855.0×	0.003	SFTPA1
Defective CSF2RB causes SMDP5	1	1631.4×	0.003	SFTPA1
Defective CSF2RA causes SMDP4	1	1631.4×	0.003	SFTPA1
Signal regulatory protein family interactions	1	671.8×	0.006	SFTPA1
Regulation of TLR by endogenous ligand	1	496.5×	0.006	SFTPA1
Surfactant metabolism	1	368.4×	0.007	SFTPA1
Toll Like Receptor 2 (TLR2) Cascade	1	173.0×	0.012	SFTPA1
Toll Like Receptor TLR1:TLR2 Cascade	1	167.9×	0.012	SFTPA1
Cell-Cell communication	1	137.6×	0.012	SFTPA1
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.012	SFTPA1
Toll-like Receptor Cascades	1	124.1×	0.012	SFTPA1
Diseases of metabolism	1	80.4×	0.017	SFTPA1
Innate Immune System	1	25.5×	0.048	SFTPA1
Disease	1	13.1×	0.081	SFTPA1
Immune System	1	13.0×	0.081	SFTPA1
Metabolism of proteins	1	12.4×	0.081	SFTPA1

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
opsonization	1	1532.0×	0.001	SFTPA1
respiratory gaseous exchange by respiratory system	1	624.1×	0.002	SFTPA1

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
SFTPA1	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	SFTPA1

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)
SFTPA1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.