MCID: HRD171
MIFTS: 38

Hereditary Pulmonary Alveolar Proteinosis

Categories: Blood diseases, Immune diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Hereditary Pulmonary Alveolar Proteinosis

MalaCards integrated aliases for Hereditary Pulmonary Alveolar Proteinosis:

Name: Hereditary Pulmonary Alveolar Proteinosis 58
Pulmonary Alveolar Proteinosis, Congenital 70
Congenital Pulmonary Alveolar Proteinosis 58
Congenital Pap 58

Characteristics:

Orphanet epidemiological data:

58
hereditary pulmonary alveolar proteinosis
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal;

Classifications:

Orphanet: 58  
Rare respiratory diseases
Rare immunological diseases


External Ids:

ICD10 via Orphanet 33 J84.0
UMLS via Orphanet 71 C2931035
Orphanet 58 ORPHA264675
UMLS 70 C2931035

Summaries for Hereditary Pulmonary Alveolar Proteinosis

MalaCards based summary : Hereditary Pulmonary Alveolar Proteinosis, also known as pulmonary alveolar proteinosis, congenital, is related to pulmonary alveolar proteinosis and congenital pulmonary alveolar proteinosis. An important gene associated with Hereditary Pulmonary Alveolar Proteinosis is CSF2RB (Colony Stimulating Factor 2 Receptor Subunit Beta), and among its related pathways/superpathways are PEDF Induced Signaling and Akt Signaling. The drugs Sargramostim and Molgramostim have been mentioned in the context of this disorder. Related phenotypes are failure to thrive in infancy and respiratory failure requiring assisted ventilation

Related Diseases for Hereditary Pulmonary Alveolar Proteinosis

Graphical network of the top 20 diseases related to Hereditary Pulmonary Alveolar Proteinosis:



Diseases related to Hereditary Pulmonary Alveolar Proteinosis

Symptoms & Phenotypes for Hereditary Pulmonary Alveolar Proteinosis

Human phenotypes related to Hereditary Pulmonary Alveolar Proteinosis:

58 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0001531
2 respiratory failure requiring assisted ventilation 58 31 frequent (33%) Frequent (79-30%) HP:0004887
3 respiratory distress 58 31 frequent (33%) Frequent (79-30%) HP:0002098
4 hypoxemia 58 31 frequent (33%) Frequent (79-30%) HP:0012418
5 restrictive ventilatory defect 58 31 frequent (33%) Frequent (79-30%) HP:0002091
6 crazy paving pattern on pulmonary hrct 58 31 frequent (33%) Frequent (79-30%) HP:0025391
7 cough 58 31 occasional (7.5%) Occasional (29-5%) HP:0012735
8 tachycardia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001649
9 tachypnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002789
10 foam cells 58 31 occasional (7.5%) Occasional (29-5%) HP:0003651
11 autoimmune antibody positivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0030057
12 crackles 58 31 occasional (7.5%) Occasional (29-5%) HP:0030830
13 elevated carcinoembryonic antigen level 58 31 occasional (7.5%) Occasional (29-5%) HP:0031029
14 acute infectious pneumonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011949
15 abnormality of circulating protein level 58 Very frequent (99-80%)

GenomeRNAi Phenotypes related to Hereditary Pulmonary Alveolar Proteinosis according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased viability with SS1P at EC90 GR00376-A-1 8.62 CSF2RA CSF2RB

Drugs & Therapeutics for Hereditary Pulmonary Alveolar Proteinosis

Drugs for Hereditary Pulmonary Alveolar Proteinosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Sargramostim Approved, Investigational Phase 2 123774-72-1, 83869-56-1
2
Molgramostim Investigational Phase 2 99283-10-0
3 Immunologic Factors Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Hereditary Pulmonary Alveolar Proteinosis (PAP) Completed NCT01511068 Phase 2 Leukine

Search NIH Clinical Center for Hereditary Pulmonary Alveolar Proteinosis

Genetic Tests for Hereditary Pulmonary Alveolar Proteinosis

Anatomical Context for Hereditary Pulmonary Alveolar Proteinosis

Publications for Hereditary Pulmonary Alveolar Proteinosis

Articles related to Hereditary Pulmonary Alveolar Proteinosis:

(show all 26)
# Title Authors PMID Year
1
Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB. 6 61
21075760 2011
2
Hereditary pulmonary alveolar proteinosis caused by recessive CSF2RB mutations. 6 61
21205713 2011
3
Characterization of CSF2RA mutation related juvenile pulmonary alveolar proteinosis. 6
25425184 2014
4
Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1. 6
18955567 2008
5
Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. 6
18955570 2008
6
Nonmyeloablative hematopoietic stem cell transplantation in a patient with hereditary pulmonary alveolar proteinosis. 61
33232559 2021
7
Hereditary pulmonary alveolar proteinosis as collateral damage from a large chromosomal deletion. 61
33629535 2021
8
Effective hematopoietic stem cell-based gene therapy in a murine model of hereditary pulmonary alveolar proteinosis. 61
31289207 2020
9
Long-Term Safety and Efficacy of Gene-Pulmonary Macrophage Transplantation Therapy of PAP in Csf2ra-/- Mice. 61
31326401 2019
10
iPSC-Derived Macrophages Effectively Treat Pulmonary Alveolar Proteinosis in Csf2rb-Deficient Mice. 61
30100408 2018
11
Pulmonary Transplantation of Human Induced Pluripotent Stem Cell-derived Macrophages Ameliorates Pulmonary Alveolar Proteinosis. 61
29652170 2018
12
Function and Safety of Lentivirus-Mediated Gene Transfer for CSF2RA-Deficiency. 61
28854814 2017
13
TALEN-mediated functional correction of human iPSC-derived macrophages in context of hereditary pulmonary alveolar proteinosis. 61
29123113 2017
14
Whole-Genome Sequencing of a Family with Hereditary Pulmonary Alveolar Proteinosis Identifies a Rare Structural Variant Involving CSF2RA/CRLF2/IL3RA Gene Disruption. 61
28233860 2017
15
Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile. 61
28212655 2017
16
Murine iPSC-Derived Macrophages as a Tool for Disease Modeling of Hereditary Pulmonary Alveolar Proteinosis due to Csf2rb Deficiency. 61
27453007 2016
17
Recurrence of pulmonary alveolar proteinosis after bilateral lung transplantation in a patient with a nonsense mutation in CSF2RB. 61
27595063 2016
18
Pulmonary alveolar proteinosis in a cat. 61
26646313 2015
19
Hereditary interstitial lung diseases manifesting in early childhood in Japan. 61
25105258 2014
20
A standardized blood test for the routine clinical diagnosis of impaired GM-CSF signaling using flow cytometry. 61
25068538 2014
21
Pulmonary macrophage transplantation therapy. 61
25274301 2014
22
Pulmonary transplantation of macrophage progenitors as effective and long-lasting therapy for hereditary pulmonary alveolar proteinosis. 61
25143363 2014
23
Gene correction of human induced pluripotent stem cells repairs the cellular phenotype in pulmonary alveolar proteinosis. 61
24279725 2014
24
Hereditary pulmonary alveolar proteinosis. Could it be triggered by Mycoplasma pneumoniae pneumonia? 61
23206404 2013
25
Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. 61
20622029 2010
26
Diagnostic accuracy of thin-section CT and chest radiography of pediatric interstitial lung disease. 61
10658741 2000

Variations for Hereditary Pulmonary Alveolar Proteinosis

ClinVar genetic disease variations for Hereditary Pulmonary Alveolar Proteinosis:

6 (show top 50) (show all 101)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CSF2RA and overlap with 1 gene(s) NG_012280.1:g.(22122_24720)_(45680_?)del Deletion Pathogenic 10354 GRCh37:
GRCh38: X:1285921-1309479
2 CSF2RA NM_172245.4(CSF2RA):c.586G>A (p.Gly196Arg) SNV Pathogenic 10355 rs137852353 GRCh37: Y:1359342-1359342
GRCh38: X:1290449-1290449
3 CSF2RB CSF2RB, 1-BP DEL, 631C Deletion Pathogenic 29744 GRCh37:
GRCh38:
4 CSF2RB NM_000395.3(CSF2RB):c.812C>T (p.Ser271Leu) SNV Pathogenic 161978 rs672601313 GRCh37: 22:37326510-37326510
GRCh38: 22:36930468-36930468
5 CSF2RA NM_172245.4(CSF2RA):c.368_377del (p.Asn123fs) Deletion Pathogenic 839421 GRCh37: X:1407676-1407685
GRCh38: X:1288783-1288792
6 CSF2RA NM_172245.4(CSF2RA):c.610C>T (p.Gln204Ter) SNV Pathogenic 847249 GRCh37: X:1409366-1409366
GRCh38: X:1290473-1290473
7 CSF2RA NM_172245.4(CSF2RA):c.595C>T (p.Arg199Ter) SNV Pathogenic 856809 GRCh37: X:1409351-1409351
GRCh38: X:1290458-1290458
8 CSF2RB NM_000395.3(CSF2RB):c.2124del (p.Ser709fs) Deletion Pathogenic 402566 rs568607741 GRCh37: 22:37333973-37333973
GRCh38: 22:36937931-36937931
9 CSF2RB NM_000395.3(CSF2RB):c.927dup (p.Val310fs) Duplication Pathogenic 1028728 GRCh37: 22:37326784-37326785
GRCh38: 22:36930742-36930743
10 CSF2RA NM_172245.4(CSF2RA):c.926G>A (p.Trp309Ter) SNV Pathogenic 1033074 GRCh37: X:1419499-1419499
GRCh38: X:1300606-1300606
11 CSF2RA NM_172245.4(CSF2RA):c.780+3C>T SNV Uncertain significance 1043764 GRCh37: X:1413357-1413357
GRCh38: X:1294464-1294464
12 CSF2RA NM_172245.4(CSF2RA):c.1129A>C (p.Ile377Leu) SNV Uncertain significance 1044720 GRCh37: X:1428298-1428298
GRCh38: X:1309405-1309405
13 CSF2RB NM_000395.3(CSF2RB):c.1874C>T (p.Ser625Phe) SNV Uncertain significance 796279 rs560156832 GRCh37: 22:37333724-37333724
GRCh38: 22:36937682-36937682
14 CSF2RA NM_172245.4(CSF2RA):c.780+4G>A SNV Uncertain significance 840750 GRCh37: X:1413358-1413358
GRCh38: X:1294465-1294465
15 CSF2RA NM_172245.4(CSF2RA):c.625C>G (p.Leu209Val) SNV Uncertain significance 939982 GRCh37: X:1409381-1409381
GRCh38: X:1290488-1290488
16 CSF2RA NM_172245.4(CSF2RA):c.21C>A (p.Ser7Arg) SNV Uncertain significance 948700 GRCh37: X:1401617-1401617
GRCh38: X:1282724-1282724
17 CSF2RA NM_172245.4(CSF2RA):c.428C>T (p.Thr143Met) SNV Uncertain significance 951233 GRCh37: X:1407736-1407736
GRCh38: X:1288843-1288843
18 CSF2RA NM_172245.4(CSF2RA):c.436C>T (p.Arg146Cys) SNV Uncertain significance 957960 GRCh37: X:1407744-1407744
GRCh38: X:1288851-1288851
19 CSF2RA NM_172245.4(CSF2RA):c.208G>A (p.Val70Met) SNV Uncertain significance 958885 GRCh37: X:1404802-1404802
GRCh38: X:1285909-1285909
20 CSF2RA NM_172245.4(CSF2RA):c.952G>A (p.Asp318Asn) SNV Uncertain significance 965748 GRCh37: X:1422821-1422821
GRCh38: X:1303928-1303928
21 CSF2RA NM_172245.4(CSF2RA):c.131C>T (p.Thr44Met) SNV Uncertain significance 971904 GRCh37: X:1404725-1404725
GRCh38: X:1285832-1285832
22 CSF2RA NM_172245.4(CSF2RA):c.953A>T (p.Asp318Val) SNV Uncertain significance 469627 rs374398870 GRCh37: Y:1372822-1372822
GRCh38: X:1303929-1303929
23 CSF2RA NM_172245.4(CSF2RA):c.668A>G (p.Asn223Ser) SNV Uncertain significance 537341 rs768648388 GRCh37: Y:1363242-1363242
GRCh38: X:1294349-1294349
24 CSF2RA NM_172245.4(CSF2RA):c.191A>G (p.Asp64Gly) SNV Uncertain significance 573103 rs150743648 GRCh37: X:1404785-1404785
GRCh38: X:1285892-1285892
25 CSF2RA NM_172245.4(CSF2RA):c.1006C>G (p.Leu336Val) SNV Uncertain significance 575181 rs143480669 GRCh37: X:1422875-1422875
GRCh38: Y:1303982-1303982
26 CSF2RA NM_172245.4(CSF2RA):c.1016G>T (p.Gly339Val) SNV Uncertain significance 581694 rs760207183 GRCh37: Y:1372885-1372885
GRCh38: X:1303992-1303992
27 CSF2RA NM_006140.5(CSF2RA):c.912G>C (p.Leu304Phe) SNV Uncertain significance 641107 rs764261104 GRCh37: X:1419485-1419485
GRCh38: Y:1300592-1300592
28 CSF2RA NM_172245.4(CSF2RA):c.596G>A (p.Arg199Gln) SNV Uncertain significance 643496 rs144461826 GRCh37: X:1409352-1409352
GRCh38: Y:1290459-1290459
29 CSF2RA NM_172245.4(CSF2RA):c.163A>G (p.Thr55Ala) SNV Uncertain significance 644683 rs759542097 GRCh37: X:1404757-1404757
GRCh38: Y:1285864-1285864
30 CSF2RA NM_172245.4(CSF2RA):c.1055T>G (p.Ile352Arg) SNV Uncertain significance 646177 rs1310278957 GRCh37: X:1424350-1424350
GRCh38: Y:1305457-1305457
31 CSF2RA NM_172245.4(CSF2RA):c.1061G>A (p.Arg354Gln) SNV Uncertain significance 646249 rs144555820 GRCh37: X:1424356-1424356
GRCh38: Y:1305463-1305463
32 CSF2RA NM_172245.4(CSF2RA):c.1156G>A (p.Gly386Arg) SNV Uncertain significance 646651 rs772019564 GRCh37: X:1428325-1428325
GRCh38: Y:1309432-1309432
33 CSF2RA NM_172245.4(CSF2RA):c.337A>T (p.Asn113Tyr) SNV Uncertain significance 647316 rs1603428019 GRCh37: X:1407529-1407529
GRCh38: Y:1288636-1288636
34 CSF2RA NM_172245.4(CSF2RA):c.69G>T (p.Glu23Asp) SNV Uncertain significance 648823 rs1603424196 GRCh37: X:1401665-1401665
GRCh38: Y:1282772-1282772
35 CSF2RA NM_172245.4(CSF2RA):c.352G>T (p.Gly118Cys) SNV Uncertain significance 649317 rs756668034 GRCh37: X:1407660-1407660
GRCh38: Y:1288767-1288767
36 CSF2RA NM_172245.4(CSF2RA):c.565C>T (p.Arg189Cys) SNV Uncertain significance 657444 rs141694686 GRCh37: X:1409321-1409321
GRCh38: Y:1290428-1290428
37 CSF2RA NM_172245.4(CSF2RA):c.496C>T (p.Pro166Ser) SNV Uncertain significance 657884 rs1603429177 GRCh37: X:1409252-1409252
GRCh38: Y:1290359-1290359
38 CSF2RA NM_172245.4(CSF2RA):c.1168C>G (p.Arg390Gly) SNV Uncertain significance 661286 rs150603886 GRCh37: X:1428337-1428337
GRCh38: Y:1309444-1309444
39 CSF2RA NM_172245.4(CSF2RA):c.1034T>C (p.Leu345Pro) SNV Uncertain significance 661944 rs138753301 GRCh37: X:1422903-1422903
GRCh38: Y:1304010-1304010
40 CSF2RB NM_000395.3(CSF2RB):c.1267G>A (p.Gly423Arg) SNV Uncertain significance 619290 rs370411972 GRCh37: 22:37329988-37329988
GRCh38: 22:36933946-36933946
41 CSF2RB NM_000395.3(CSF2RB):c.2119G>A (p.Val707Met) SNV Uncertain significance 689449 rs1601595049 GRCh37: 22:37333969-37333969
GRCh38: 22:36937927-36937927
42 CSF2RB NM_000395.3(CSF2RB):c.1597G>A (p.Glu533Lys) SNV Uncertain significance 694631 rs1601594289 GRCh37: 22:37333447-37333447
GRCh38: 22:36937405-36937405
43 CSF2RA NM_172245.4(CSF2RA):c.706C>T (p.Arg236Trp) SNV Uncertain significance 569285 rs200071635 GRCh37: X:1413280-1413280
GRCh38: X:1294387-1294387
44 CSF2RA NM_172245.4(CSF2RA):c.676G>A (p.Val226Ile) SNV Uncertain significance 571570 rs181719822 GRCh37: Y:1363250-1363250
GRCh38: X:1294357-1294357
45 CSF2RA NM_172245.4(CSF2RA):c.530G>A (p.Gly177Glu) SNV Uncertain significance 577632 rs142203271 GRCh37: X:1409286-1409286
GRCh38: X:1290393-1290393
46 CSF2RA NM_172245.4(CSF2RA):c.242G>A (p.Cys81Tyr) SNV Uncertain significance 836286 GRCh37: X:1407434-1407434
GRCh38: X:1288541-1288541
47 CSF2RA NM_172245.4(CSF2RA):c.789G>C (p.Gln263His) SNV Uncertain significance 843537 GRCh37: X:1414328-1414328
GRCh38: X:1295435-1295435
48 CSF2RA NM_172245.4(CSF2RA):c.1064T>C (p.Leu355Pro) SNV Uncertain significance 845330 GRCh37: X:1424359-1424359
GRCh38: X:1305466-1305466
49 CSF2RA NM_172245.4(CSF2RA):c.343+5G>A SNV Uncertain significance 845492 GRCh37: X:1407540-1407540
GRCh38: X:1288647-1288647
50 CSF2RA NM_172245.4(CSF2RA):c.1070C>T (p.Pro357Leu) SNV Uncertain significance 945785 GRCh37: X:1424365-1424365
GRCh38: X:1305472-1305472

Expression for Hereditary Pulmonary Alveolar Proteinosis

Search GEO for disease gene expression data for Hereditary Pulmonary Alveolar Proteinosis.

Pathways for Hereditary Pulmonary Alveolar Proteinosis

Pathways related to Hereditary Pulmonary Alveolar Proteinosis according to GeneCards Suite gene sharing:

(show all 16)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.07 IL3RA CSF2RB CSF2RA CRLF2
2
Show member pathways
12.88 IL3RA CSF2RB CSF2RA
3
Show member pathways
12.83 IL3RA CSF2RB CSF2RA
4
Show member pathways
12.78 IL3RA CSF2RB CSF2RA
5
Show member pathways
12.75 IL3RA CSF2RB CSF2RA
6 12.31 IL3RA CSF2RB CSF2RA
7
Show member pathways
11.87 IL3RA CSF2RB
8
Show member pathways
11.7 IL3RA CSF2RB
9 11.47 IL3RA CSF2RA
10
Show member pathways
11.43 CSF2RB CSF2RA
11
Show member pathways
11.32 IL3RA CSF2RB CSF2RA
12
Show member pathways
11.32 IL3RA CSF2RB CSF2RA CRLF2
13
Show member pathways
11.28 IL3RA CSF2RB
14 11.05 IL3RA CSF2RB
15
Show member pathways
10.96 CSF2RB CSF2RA
16
Show member pathways
10.55 CSF2RB CSF2RA

GO Terms for Hereditary Pulmonary Alveolar Proteinosis

Cellular components related to Hereditary Pulmonary Alveolar Proteinosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 external side of plasma membrane GO:0009897 9.13 IL3RA CSF2RA CRLF2
2 receptor complex GO:0043235 8.8 IL3RA CSF2RA CRLF2

Biological processes related to Hereditary Pulmonary Alveolar Proteinosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 MAPK cascade GO:0000165 9.43 IL3RA CSF2RB CSF2RA
2 cellular protein metabolic process GO:0044267 9.32 CSF2RB CSF2RA
3 cellular response to interleukin-3 GO:0036016 9.16 IL3RA CSF2RB
4 interleukin-3-mediated signaling pathway GO:0038156 8.96 IL3RA CSF2RB
5 cytokine-mediated signaling pathway GO:0019221 8.92 IL3RA CSF2RB CSF2RA CRLF2

Molecular functions related to Hereditary Pulmonary Alveolar Proteinosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor activity GO:0038023 9.26 CSF2RB CSF2RA
2 interleukin-3 receptor activity GO:0004912 9.16 IL3RA CSF2RB
3 cytokine binding GO:0019955 9.13 IL3RA CSF2RA CRLF2
4 cytokine receptor activity GO:0004896 8.92 IL3RA CSF2RB CSF2RA CRLF2

Sources for Hereditary Pulmonary Alveolar Proteinosis

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
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