ILLD
MCID: INT271
MIFTS: 41

Interstitial Lung and Liver Disease (ILLD)

Categories: Genetic diseases, Liver diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Interstitial Lung and Liver Disease

MalaCards integrated aliases for Interstitial Lung and Liver Disease:

Name: Interstitial Lung and Liver Disease 57 58 72 36 29 6
Pulmonary Alveolar Proteinosis, Reunion Island 57 72
Infantile Liver Failure Syndrome 2 72 70
Illd 57 72
Severe Early-Onset Pulmonary Alveolar Proteinosis Due to Mars Deficiency 58
Hereditary Pulmonary Alveolar Proteinosis with Hepatic Involvement 58
Infantile Liver Failure Syndrome 2, Formerly; Ilfs2, Formerly 57
Pulmonary Alveolar Proteinosis, Reunion Island Type 58
Infantile Liver Failure Syndrome 2, Formerly 57
Lung and Liver Disease, Interstitial 39
Pap, Reunion Island Type 58
Ilfs2, Formerly 57
Ilfs2 72

Characteristics:

Orphanet epidemiological data:

58

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
onset in infancy or early childhood
early death from respiratory failure may occur
anemia, hypothyroidism, aminoaciduria, and lactic acidosis all occurred in 1 patient


HPO:

31
interstitial lung and liver disease:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity progressive


Classifications:

Orphanet: 58  
Rare hepatic diseases
Rare respiratory diseases


Summaries for Interstitial Lung and Liver Disease

KEGG : 36 Interstitial lung and liver disease (ILLD) is an autosomal recessive severe childhood form of pulmonary alveolar proteinosis. The main symptom is respiratory insufficiency, often leading to death in childhood or adolescence as a result of lung fibrosis. In addition to lung fibrosis, non-life-threatening liver involvement might be present, as indicated by elevated enzymes, steatosis, fibrosis, or cirrhosis. The mutations in MARS associated with ILLD have been reported.

MalaCards based summary : Interstitial Lung and Liver Disease, also known as pulmonary alveolar proteinosis, reunion island, is related to charcot-marie-tooth disease and charcot-marie-tooth disease, axonal, type 2u. An important gene associated with Interstitial Lung and Liver Disease is MARS1 (Methionyl-TRNA Synthetase 1), and among its related pathways/superpathways is tRNA Aminoacylation. The drugs Abatacept and rituximab have been mentioned in the context of this disorder. Affiliated tissues include liver, lung and retina, and related phenotypes are cirrhosis and failure to thrive

OMIM® : 57 Interstitial lung and liver disease is an autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood. Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis (summary by Hadchouel et al., 2015). (615486) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Interstitial lung and liver disease: An autosomal recessive, life-threatening disorder characterized by respiratory insufficiency and progressive liver disease with onset in infancy or early childhood. Clinical features include failure to thrive, hypotonia, intermittent lactic acidosis, aminoaciduria, hypothyroidism, interstitial lung disease, pulmonary alveolar proteinosis, anemia, and liver canalicular cholestasis, steatosis, and iron deposition.

Related Diseases for Interstitial Lung and Liver Disease

Diseases related to Interstitial Lung and Liver Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 16)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease 29.1 MIR6758 MARS1 ARHGAP9
2 charcot-marie-tooth disease, axonal, type 2u 29.0 MIR6758 MARS1 ARHGAP9
3 infantile liver failure syndrome 2 11.9
4 interstitial lung disease 10.3
5 liver disease 10.3
6 lung disease 10.3
7 infantile liver failure syndrome 10.2
8 neuroblastoma 10.2
9 tooth disease 10.2
10 nephrolithiasis, calcium oxalate 10.0
11 deficiency anemia 10.0
12 non-alcoholic fatty liver disease 10.0
13 cholestasis 10.0
14 hypothyroidism 10.0
15 thrombocytosis 10.0
16 nephrolithiasis 10.0

Graphical network of the top 20 diseases related to Interstitial Lung and Liver Disease:



Diseases related to Interstitial Lung and Liver Disease

Symptoms & Phenotypes for Interstitial Lung and Liver Disease

Human phenotypes related to Interstitial Lung and Liver Disease:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 cirrhosis 31 occasional (7.5%) HP:0001394
2 failure to thrive 31 HP:0001508
3 hypothyroidism 31 HP:0000821
4 respiratory insufficiency 31 HP:0002093
5 hepatomegaly 31 HP:0002240
6 aminoaciduria 31 HP:0003355
7 anemia 31 HP:0001903
8 hepatic steatosis 31 HP:0001397
9 elevated hepatic transaminase 31 HP:0002910
10 dyspnea 31 HP:0002094
11 cough 31 HP:0012735
12 decreased liver function 31 HP:0001410
13 acidosis 31 HP:0001941
14 clubbing 31 HP:0001217
15 abnormal pulmonary interstitial morphology 31 HP:0006530
16 intraalveolar phospholipid accumulation 31 HP:0006517

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Growth Other:
failure to thrive

Abdomen Liver:
hepatomegaly
fibrosis
steatosis
liver dysfunction
cirrhosis (in some patients)

Laboratory Abnormalities:
abnormal liver enzymes
aminoaciduria (patient a)
lactic acidosis, intermittent (patient a)

Endocrine Features:
hypothyroidism (patient a)

Respiratory:
respiratory insufficiency
dyspnea
cough

Skeletal Hands:
digital clubbing

Respiratory Lung:
interstitial lung disease
lung fibrosis
lung biopsy shows pulmonary alveolar proteinosis

Hematology:
anemia (patient a)

Clinical features from OMIM®:

615486 (Updated 05-Apr-2021)

Drugs & Therapeutics for Interstitial Lung and Liver Disease

Drugs for Interstitial Lung and Liver Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Abatacept Approved 332348-12-6 10237
2
rituximab Approved 174722-31-7 10201696
3 Antirheumatic Agents
4 Antineoplastic Agents, Immunological
5 Immunosuppressive Agents
6 Immunologic Factors

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Retrospective Chart Review of Children With Primary Immunodeficiencies (PID) Who Received Targeted Therapy of Interstitial Lymphocytic Lung Disease (ILLD) With Abatacept or Rituximab. Recruiting NCT04572620 Rituximab;Abatacept

Search NIH Clinical Center for Interstitial Lung and Liver Disease

Genetic Tests for Interstitial Lung and Liver Disease

Genetic tests related to Interstitial Lung and Liver Disease:

# Genetic test Affiliating Genes
1 Interstitial Lung and Liver Disease 29 MARS1

Anatomical Context for Interstitial Lung and Liver Disease

MalaCards organs/tissues related to Interstitial Lung and Liver Disease:

40
Liver, Lung, Retina

Publications for Interstitial Lung and Liver Disease

Articles related to Interstitial Lung and Liver Disease:

(show all 11)
# Title Authors PMID Year
1
Biallelic Mutations of Methionyl-tRNA Synthetase Cause a Specific Type of Pulmonary Alveolar Proteinosis Prevalent on Réunion Island. 57 6
25913036 2015
2
Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype. 57 6
24103465 2013
3
The diagnostic utility of genome sequencing in a pediatric cohort with suspected mitochondrial disease. 6
32313153 2020
4
Recurrent elevated liver transaminases and acute liver failure in two siblings with novel bi-allelic mutations of NBAS. 6
28576691 2017
5
NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina. 6
26286438 2015
6
Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy. 6
26073778 2015
7
Symptomatic leg length discrepancy after total hip arthroplasty is associated with new onset of lower back pain. 61
33316448 2021
8
Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants. 61
32833345 2020
9
MARS variant associated with both recessive interstitial lung and liver disease and dominant Charcot-Marie-Tooth disease. 61
29655802 2018
10
Novel methionyl-tRNA synthetase gene variants/phenotypes in interstitial lung and liver disease: A case report and review of literature. 61
30271085 2018
11
Mutations in methionyl-tRNA synthetase gene in a Chinese family with interstitial lung and liver disease, postnatal growth failure and anemia. 61
28148924 2017

Variations for Interstitial Lung and Liver Disease

ClinVar genetic disease variations for Interstitial Lung and Liver Disease:

6 (show top 50) (show all 145)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MARS1 NM_004990.4(MARS1):c.1568T>C (p.Ile523Thr) SNV Pathogenic 68464 rs201555303 GRCh37: 12:57905819-57905819
GRCh38: 12:57512036-57512036
2 NBAS NM_015909.4(NBAS):c.558_560del (p.Ile187del) Deletion Pathogenic 204580 rs796065037 GRCh37: 2:15676629-15676631
GRCh38: 2:15536505-15536507
3 NBAS NM_015909.4(NBAS):c.2708T>G (p.Leu903Arg) SNV Pathogenic 204582 rs368196005 GRCh37: 2:15557706-15557706
GRCh38: 2:15417582-15417582
4 NBAS NM_015909.4(NBAS):c.603_605del (p.Leu202del) Deletion Pathogenic 204583 rs796065038 GRCh37: 2:15676584-15676586
GRCh38: 2:15536460-15536462
5 NBAS NM_015909.4(NBAS):c.3164T>C (p.Leu1055Pro) SNV Pathogenic 204584 rs796052121 GRCh37: 2:15534444-15534444
GRCh38: 2:15394320-15394320
6 NBAS NM_015909.4(NBAS):c.1749G>A (p.Trp583Ter) SNV Pathogenic 424842 rs770446752 GRCh37: 2:15608634-15608634
GRCh38: 2:15468510-15468510
7 NBAS NM_015909.4(NBAS):c.1501C>T (p.Arg501Ter) SNV Pathogenic 617878 rs759960319 GRCh37: 2:15614289-15614289
GRCh38: 2:15474165-15474165
8 NBAS NM_015909.4(NBAS):c.6840G>A (p.Thr2280=) SNV Pathogenic 617879 rs776597537 GRCh37: 2:15319112-15319112
GRCh38: 2:15178988-15178988
9 NBAS NM_015909.4(NBAS):c.6433-2A>G SNV Pathogenic 975151 GRCh37: 2:15330529-15330529
GRCh38: 2:15190405-15190405
10 MARS1 NM_004990.4(MARS1):c.1108T>C (p.Phe370Leu) SNV Pathogenic 68463 rs140467171 GRCh37: 12:57894120-57894120
GRCh38: 12:57500337-57500337
11 NBAS NM_015909.4(NBAS):c.686dup (p.Ser230fs) Duplication Pathogenic 204581 rs759315662 GRCh37: 2:15674726-15674727
GRCh38: 2:15534602-15534603
12 MARS1 NM_004990.4(MARS1):c.1814A>T (p.Asp605Val) SNV Pathogenic 189365 rs756021768 GRCh37: 12:57906594-57906594
GRCh38: 12:57512811-57512811
13 MARS1 NM_004990.4(MARS1):c.1031A>G (p.Tyr344Cys) SNV Pathogenic 192373 rs766466297 GRCh37: 12:57892346-57892346
GRCh38: 12:57498563-57498563
14 MARS1 NM_004990.4(MARS1):c.1177G>A (p.Ala393Thr) SNV Pathogenic 189364 rs141340466 GRCh37: 12:57894189-57894189
GRCh38: 12:57500406-57500406
15 NBAS NM_015909.4(NBAS):c.5262del (p.Phe1754fs) Deletion Pathogenic 1032709 GRCh37: 2:15417102-15417102
GRCh38: 2:15276978-15276978
16 MARS1 NM_004990.4(MARS1):c.1852C>T (p.Arg618Cys) SNV Likely pathogenic 156025 rs587777718 GRCh37: 12:57906632-57906632
GRCh38: 12:57512849-57512849
17 FARSB NM_005687.5(FARSB):c.767C>T (p.Thr256Met) SNV Likely pathogenic 487455 rs753710639 GRCh37: 2:223496342-223496342
GRCh38: 2:222631623-222631623
18 FARSB NM_005687.5(FARSB):c.1486delinsAA (p.His496fs) Indel Likely pathogenic 487456 rs1553549333 GRCh37: 2:223464779-223464779
GRCh38: 2:222600060-222600060
19 NBAS NM_015909.4(NBAS):c.1741C>T (p.Arg581Ter) SNV Likely pathogenic 976858 GRCh37: 2:15608642-15608642
GRCh38: 2:15468518-15468518
20 NBAS NM_015909.4(NBAS):c.335+1G>A SNV Likely pathogenic 801651 rs1573008071 GRCh37: 2:15693549-15693549
GRCh38: 2:15553425-15553425
21 NBAS NM_015909.4(NBAS):c.2617C>T (p.Arg873Trp) SNV Likely pathogenic 869407 GRCh37: 2:15557797-15557797
GRCh38: 2:15417673-15417673
22 NBAS NM_015909.4(NBAS):c.2423+404G>C SNV Likely pathogenic 869408 GRCh37: 2:15567431-15567431
GRCh38: 2:15427307-15427307
23 NBAS NM_015909.4(NBAS):c.2411A>G (p.Glu804Gly) SNV Likely pathogenic 873540 GRCh37: 2:15567847-15567847
GRCh38: 2:15427723-15427723
24 NBAS NM_015909.4(NBAS):c.5467A>T (p.Ile1823Phe) SNV Likely pathogenic 801649 rs201084909 GRCh37: 2:15415865-15415865
GRCh38: 2:15275741-15275741
25 NBAS NM_015909.4(NBAS):c.5465A>C (p.Asn1822Thr) SNV Likely pathogenic 801650 rs199717686 GRCh37: 2:15415867-15415867
GRCh38: 2:15275743-15275743
26 NBAS NM_015909.4(NBAS):c.680A>C (p.His227Pro) SNV Likely pathogenic 424843 rs748880753 GRCh37: 2:15674733-15674733
GRCh38: 2:15534609-15534609
27 MARS1 NM_004990.4(MARS1):c.920A>G (p.Tyr307Cys) SNV Likely pathogenic 496635 rs758523839 GRCh37: 12:57892235-57892235
GRCh38: 12:57498452-57498452
28 NBAS NM_015909.4(NBAS):c.409C>T (p.Arg137Trp) SNV Conflicting interpretations of pathogenicity 218416 rs368085185 GRCh37: 2:15679451-15679451
GRCh38: 2:15539327-15539327
29 ARHGAP9 , MARS1 NM_004990.4(MARS1):c.97del (p.Thr32_Val33insTer) Deletion Uncertain significance 933333 GRCh37: 12:57881970-57881970
GRCh38: 12:57488187-57488187
30 MARS1 NM_004990.4(MARS1):c.2408A>C (p.Gln803Pro) SNV Uncertain significance 1029913 GRCh37: 12:57909719-57909719
GRCh38: 12:57515936-57515936
31 NBAS NM_015909.4(NBAS):c.270G>C (p.Trp90Cys) SNV Uncertain significance 1031942 GRCh37: 2:15694202-15694202
GRCh38: 2:15554078-15554078
32 MARS1 NM_004990.4(MARS1):c.1294-19C>G SNV Uncertain significance 1032278 GRCh37: 12:57897989-57897989
GRCh38: 12:57504206-57504206
33 NBAS NM_015909.4(NBAS):c.4280C>T (p.Ala1427Val) SNV Uncertain significance 1032708 GRCh37: 2:15470789-15470789
GRCh38: 2:15330665-15330665
34 ARHGAP9 , MARS1 NM_004990.4(MARS1):c.95C>G (p.Thr32Ser) SNV Uncertain significance 475435 rs11540809 GRCh37: 12:57881968-57881968
GRCh38: 12:57488185-57488185
35 MARS1 NM_004990.4(MARS1):c.749T>C (p.Leu250Pro) SNV Uncertain significance 542169 rs139033078 GRCh37: 12:57884406-57884406
GRCh38: 12:57490623-57490623
36 MARS1 NM_004990.4(MARS1):c.2470A>C (p.Thr824Pro) SNV Uncertain significance 542176 rs200404964 GRCh37: 12:57910034-57910034
GRCh38: 12:57516251-57516251
37 MARS1 NM_004990.4(MARS1):c.1813G>A (p.Asp605Asn) SNV Uncertain significance 568199 rs139600659 GRCh37: 12:57906593-57906593
GRCh38: 12:57512810-57512810
38 MARS1 NM_004990.4(MARS1):c.692A>T (p.Glu231Val) SNV Uncertain significance 842917 GRCh37: 12:57884349-57884349
GRCh38: 12:57490566-57490566
39 MARS1 NM_004990.4(MARS1):c.1177G>A (p.Ala393Thr) SNV Uncertain significance 242615 rs141340466 GRCh37: 12:57894189-57894189
GRCh38: 12:57500406-57500406
40 MARS1 NM_004990.4(MARS1):c.746C>T (p.Pro249Leu) SNV Uncertain significance 549700 rs146146070 GRCh37: 12:57884403-57884403
GRCh38: 12:57490620-57490620
41 MARS1 NM_004990.4(MARS1):c.2556+1G>A SNV Uncertain significance 957064 GRCh37: 12:57910121-57910121
GRCh38: 12:57516338-57516338
42 MARS1 NM_004990.4(MARS1):c.331G>C (p.Glu111Gln) SNV Uncertain significance 917043 GRCh37: 12:57883258-57883258
GRCh38: 12:57489475-57489475
43 NBAS NM_015909.4(NBAS):c.6237-10T>C SNV Uncertain significance 1032710 GRCh37: 2:15359102-15359102
GRCh38: 2:15218978-15218978
44 NBAS NM_015909.4(NBAS):c.6970C>T (p.Arg2324Cys) SNV Uncertain significance 1032711 GRCh37: 2:15307318-15307318
GRCh38: 2:15167194-15167194
45 MARS1 NM_004990.4(MARS1):c.1636-7C>G SNV Uncertain significance 1037334 GRCh37: 12:57906012-57906012
GRCh38: 12:57512229-57512229
46 MARS1 NM_004990.4(MARS1):c.643G>A (p.Ala215Thr) SNV Uncertain significance 1042089 GRCh37: 12:57884142-57884142
GRCh38: 12:57490359-57490359
47 MARS1 NM_004990.4(MARS1):c.2521C>G (p.Gln841Glu) SNV Uncertain significance 1046005 GRCh37: 12:57910085-57910085
GRCh38: 12:57516302-57516302
48 MARS1 NM_004990.4(MARS1):c.2384T>C (p.Ile795Thr) SNV Uncertain significance 1019872 GRCh37: 12:57909112-57909112
GRCh38: 12:57515329-57515329
49 MARS1 NM_004990.4(MARS1):c.1448G>A (p.Arg483His) SNV Uncertain significance 917036 GRCh37: 12:57905560-57905560
GRCh38: 12:57511777-57511777
50 MARS1 NM_004990.4(MARS1):c.1514dup (p.Pro506fs) Duplication Uncertain significance 1023524 GRCh37: 12:57905625-57905626
GRCh38: 12:57511842-57511843

UniProtKB/Swiss-Prot genetic disease variations for Interstitial Lung and Liver Disease:

72
# Symbol AA change Variation ID SNP ID
1 MARS1 p.Phe370Leu VAR_070872 rs140467171
2 MARS1 p.Ile523Thr VAR_070873 rs201555303
3 MARS1 p.Tyr344Cys VAR_075361 rs766466297
4 MARS1 p.Ala393Thr VAR_075362 rs141340466
5 MARS1 p.Ser567Leu VAR_075363 rs143592405
6 MARS1 p.Asp605Val VAR_075364 rs756021768

Expression for Interstitial Lung and Liver Disease

Search GEO for disease gene expression data for Interstitial Lung and Liver Disease.

Pathways for Interstitial Lung and Liver Disease

Pathways related to Interstitial Lung and Liver Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.04 MIR6758 MARS1 FARSB

GO Terms for Interstitial Lung and Liver Disease

Biological processes related to Interstitial Lung and Liver Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation GO:0006412 8.96 MARS1 FARSB
2 tRNA aminoacylation for protein translation GO:0006418 8.62 MARS1 FARSB

Molecular functions related to Interstitial Lung and Liver Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ligase activity GO:0016874 8.96 MARS1 FARSB
2 aminoacyl-tRNA ligase activity GO:0004812 8.62 MARS1 FARSB

Sources for Interstitial Lung and Liver Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....