ILLD
MCID: INT271
MIFTS: 37

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 56 58 73 36 29 6
Pulmonary Alveolar Proteinosis, Reunion Island 56 73
Infantile Liver Failure Syndrome 2 73 71
Illd 56 73
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 56
Pulmonary Alveolar Proteinosis, Reunion Island Type 58
Infantile Liver Failure Syndrome 2, Formerly 56
Lung and Liver Disease, Interstitial 39
Pap, Reunion Island Type 58
Ilfs2, Formerly 56
Ilfs2 73

Characteristics:

Orphanet epidemiological data:

58

OMIM:

56
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. Affiliated tissues include liver and lung, and related phenotypes are cirrhosis and hepatomegaly

OMIM : 56 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)

UniProtKB/Swiss-Prot : 73 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 14)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease 28.6 MIR6758 MARS1 ARHGAP9
2 charcot-marie-tooth disease, axonal, type 2u 28.5 MIR6758 MARS1 ARHGAP9
3 infantile liver failure syndrome 2 12.9
4 interstitial lung disease 10.1
5 liver disease 10.1
6 lung disease 10.1
7 neuroblastoma 10.1
8 tooth disease 10.0
9 nephrolithiasis, calcium oxalate 9.9
10 cholestasis 9.9
11 hypothyroidism 9.9
12 thrombocytosis 9.9
13 nephrolithiasis 9.9
14 hereditary spastic paraplegia 9.5 MARS1 ARHGAP9

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 hepatomegaly 31 HP:0002240
3 hypothyroidism 31 HP:0000821
4 failure to thrive 31 HP:0001508
5 aminoaciduria 31 HP:0003355
6 dyspnea 31 HP:0002094
7 anemia 31 HP:0001903
8 cough 31 HP:0012735
9 hepatic steatosis 31 HP:0001397
10 elevated hepatic transaminase 31 HP:0002910
11 respiratory insufficiency 31 HP:0002093
12 interstitial pulmonary abnormality 31 HP:0006530
13 decreased liver function 31 HP:0001410
14 clubbing 31 HP:0001217
15 acidosis 31 HP:0001941
16 alveolar proteinosis 31 HP:0006517

Symptoms via clinical synopsis from OMIM:

56
Abdomen Liver:
hepatomegaly
fibrosis
steatosis
liver dysfunction
cirrhosis (in some patients)

Respiratory:
dyspnea
cough
respiratory insufficiency

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

Endocrine Features:
hypothyroidism (patient a)

Growth Other:
failure to thrive

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

Drugs & Therapeutics for Interstitial Lung and Liver Disease

Search Clinical Trials , 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

Publications for Interstitial Lung and Liver Disease

Articles related to Interstitial Lung and Liver Disease:

# Title Authors PMID Year
1
Biallelic Mutations of Methionyl-tRNA Synthetase Cause a Specific Type of Pulmonary Alveolar Proteinosis Prevalent on Réunion Island. 6 56
25913036 2015
2
Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype. 56 6
24103465 2013
3
Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy. 6
26073778 2015
4
MARS variant associated with both recessive interstitial lung and liver disease and dominant Charcot-Marie-Tooth disease. 61
29655802 2018
5
Novel methionyl-tRNA synthetase gene variants/phenotypes in interstitial lung and liver disease: A case report and review of literature. 61
30271085 2018
6
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 114) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NBAS NM_015909.4(NBAS):c.1749G>A (p.Trp583Ter)SNV Pathogenic 424842 rs770446752 2:15608634-15608634 2:15468510-15468510
2 FARSB NM_005687.5(FARSB):c.1486delinsAA (p.His496fs)indel Pathogenic 487456 rs1553549333 2:223464779-223464779 2:222600060-222600060
3 NBAS NM_015909.4(NBAS):c.1501C>T (p.Arg501Ter)SNV Pathogenic 617878 rs759960319 2:15614289-15614289 2:15474165-15474165
4 NBAS NM_015909.4(NBAS):c.6840G>A (p.Thr2280=)SNV Pathogenic 617879 rs776597537 2:15319112-15319112 2:15178988-15178988
5 MARS1 NM_004990.4(MARS1):c.1568T>C (p.Ile523Thr)SNV Pathogenic 68464 rs201555303 12:57905819-57905819 12:57512036-57512036
6 MARS1 NM_004990.4(MARS1):c.1814A>T (p.Asp605Val)SNV Pathogenic 189365 rs756021768 12:57906594-57906594 12:57512811-57512811
7 NBAS NM_015909.4(NBAS):c.558_560del (p.Ile187del)deletion Pathogenic 204580 rs796065037 2:15676629-15676631 2:15536505-15536507
8 NBAS NM_015909.4(NBAS):c.686dup (p.Ser230fs)duplication Pathogenic 204581 rs759315662 2:15674726-15674727 2:15534602-15534603
9 NBAS NM_015909.4(NBAS):c.2708T>G (p.Leu903Arg)SNV Pathogenic 204582 rs368196005 2:15557706-15557706 2:15417582-15417582
10 NBAS NM_015909.4(NBAS):c.603_605del (p.Leu202del)deletion Pathogenic 204583 rs796065038 2:15676584-15676586 2:15536460-15536462
11 NBAS NM_015909.4(NBAS):c.409C>T (p.Arg137Trp)SNV Pathogenic 218416 rs368085185 2:15679451-15679451 2:15539327-15539327
12 MARS1 NM_004990.4(MARS1):c.1031A>G (p.Tyr344Cys)SNV Pathogenic 192373 rs766466297 12:57892346-57892346 12:57498563-57498563
13 FARSB NM_005687.5(FARSB):c.767C>T (p.Thr256Met)SNV Pathogenic/Likely pathogenic 487455 rs753710639 2:223496342-223496342 2:222631623-222631623
14 NBAS NM_015909.4(NBAS):c.3164T>C (p.Leu1055Pro)SNV Likely pathogenic 204584 rs796052121 2:15534444-15534444 2:15394320-15394320
15 NBAS NM_015909.4(NBAS):c.2617C>T (p.Arg873Trp)SNV Likely pathogenic 869407 2:15557797-15557797 2:15417673-15417673
16 NBAS NM_015909.4(NBAS):c.2423+404G>CSNV Likely pathogenic 869408 2:15567431-15567431 2:15427307-15427307
17 NBAS NM_015909.4(NBAS):c.2411A>G (p.Glu804Gly)SNV Likely pathogenic 873540 2:15567847-15567847 2:15427723-15427723
18 NBAS NM_015909.4(NBAS):c.5467A>T (p.Ile1823Phe)SNV Likely pathogenic 801649 2:15415865-15415865 2:15275741-15275741
19 NBAS NM_015909.4(NBAS):c.5465A>C (p.Asn1822Thr)SNV Likely pathogenic 801650 2:15415867-15415867 2:15275743-15275743
20 NBAS NM_015909.4(NBAS):c.335+1G>ASNV Likely pathogenic 801651 2:15693549-15693549 2:15553425-15553425
21 MARS1 NM_004990.4(MARS1):c.920A>G (p.Tyr307Cys)SNV Likely pathogenic 496635 rs758523839 12:57892235-57892235 12:57498452-57498452
22 NBAS NM_015909.4(NBAS):c.680A>C (p.His227Pro)SNV Likely pathogenic 424843 rs748880753 2:15674733-15674733 2:15534609-15534609
23 MARS1 NM_004990.4(MARS1):c.747G>A (p.Pro249=)SNV Conflicting interpretations of pathogenicity 444298 rs200490364 12:57884404-57884404 12:57490621-57490621
24 MARS1 NM_004990.4(MARS1):c.617C>T (p.Pro206Leu)SNV Conflicting interpretations of pathogenicity 542171 rs138776588 12:57884116-57884116 12:57490333-57490333
25 MARS1 NM_004990.4(MARS1):c.1108T>C (p.Phe370Leu)SNV Conflicting interpretations of pathogenicity 68463 rs140467171 12:57894120-57894120 12:57500337-57500337
26 MARS1 NM_004990.4(MARS1):c.2180G>A (p.Arg727Gln)SNV Conflicting interpretations of pathogenicity 380553 rs113808165 12:57908817-57908817 12:57515034-57515034
27 MARS1 NM_004990.4(MARS1):c.2391A>C (p.Thr797=)SNV Conflicting interpretations of pathogenicity 389593 rs140573721 12:57909119-57909119 12:57515336-57515336
28 MARS1 NM_004990.4(MARS1):c.1177G>A (p.Ala393Thr)SNV Uncertain significance 242615 rs141340466 12:57894189-57894189 12:57500406-57500406
29 NBAS NM_015909.4(NBAS):c.4721C>T (p.Ala1574Val)SNV Uncertain significance 264645 rs1553367826 2:15448416-15448416 2:15308292-15308292
30 MARS1 NM_004990.4(MARS1):c.2631_2635dup (p.Leu879fs)duplication Uncertain significance 542170 rs1172463219 12:57910291-57910292 12:57516508-57516509
31 MARS1 NM_004990.4(MARS1):c.2666A>G (p.Lys889Arg)SNV Uncertain significance 542175 rs779548081 12:57910327-57910327 12:57516544-57516544
32 MARS1 NM_004990.4(MARS1):c.1852C>T (p.Arg618Cys)SNV Uncertain significance 156025 rs587777718 12:57906632-57906632 12:57512849-57512849
33 MARS1 NM_004990.4(MARS1):c.1673C>A (p.Pro558His)SNV Uncertain significance 542172 rs771808261 12:57906056-57906056 12:57512273-57512273
34 MARS1 NM_004990.4(MARS1):c.2294C>T (p.Ala765Val)SNV Uncertain significance 542173 rs559255944 12:57909022-57909022 12:57515239-57515239
35 MARS1 NM_004990.4(MARS1):c.2470A>C (p.Thr824Pro)SNV Uncertain significance 542176 rs200404964 12:57910034-57910034 12:57516251-57516251
36 MARS1 NM_004990.4(MARS1):c.749T>C (p.Leu250Pro)SNV Uncertain significance 542169 rs139033078 12:57884406-57884406 12:57490623-57490623
37 MARS1 NM_004990.4(MARS1):c.1181G>A (p.Arg394His)SNV Uncertain significance 542177 rs769544594 12:57894193-57894193 12:57500410-57500410
38 MARS1 NM_004990.4(MARS1):c.365C>A (p.Thr122Asn)SNV Uncertain significance 475424 rs201007223 12:57883292-57883292 12:57489509-57489509
39 MARS1 NM_004990.4(MARS1):c.550C>T (p.Arg184Ter)SNV Uncertain significance 475427 rs753083306 12:57884049-57884049 12:57490266-57490266
40 MARS1 NM_004990.4(MARS1):c.661G>A (p.Glu221Lys)SNV Uncertain significance 420243 rs200334446 12:57884160-57884160 12:57490377-57490377
41 MARS1 NM_004990.4(MARS1):c.699T>G (p.Ile233Met)SNV Uncertain significance 449718 rs201597392 12:57884356-57884356 12:57490573-57490573
42 MARS1 NM_004990.4(MARS1):c.95C>G (p.Thr32Ser)SNV Uncertain significance 475435 rs11540809 12:57881968-57881968 12:57488185-57488185
43 MARS1 NM_004990.4(MARS1):c.1091+2dupduplication Uncertain significance 430002 rs754216322 12:57892407-57892408 12:57498624-57498625
44 MARS1 NM_004990.4(MARS1):c.2053G>A (p.Val685Ile)SNV Uncertain significance 475418 rs558631075 12:57908588-57908588 12:57514805-57514805
45 MARS1 NM_004990.4(MARS1):c.906_919delinsCTC (p.Gln302fs)indel Uncertain significance 475434 rs1555166943 12:57892221-57892234 12:57498438-57498451
46 MARS1 NM_004990.4(MARS1):c.2033A>G (p.Asp678Gly)SNV Uncertain significance 475417 rs1205620243 12:57908568-57908568 12:57514785-57514785
47 MARS1 NM_004990.4(MARS1):c.2116C>T (p.Arg706Cys)SNV Uncertain significance 475419 rs148501787 12:57908753-57908753 12:57514970-57514970
48 MARS1 NM_004990.4(MARS1):c.1148C>G (p.Thr383Ser)SNV Uncertain significance 802866 12:57894160-57894160 12:57500377-57500377
49 MARS1 NM_004990.4(MARS1):c.1244G>T (p.Gly415Val)SNV Uncertain significance 802867 12:57894256-57894256 12:57500473-57500473
50 MARS1 NM_004990.4(MARS1):c.330G>T (p.Gly110=)SNV Uncertain significance 853107 12:57883257-57883257 12:57489474-57489474

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

73
# 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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