FLG (filaggrin)

Gene

• Entrez ID: 2312
• Gene name: Filaggrin
• Gene symbol: FLG
• Synonyms: ATOD2, FLG-1, FLG1
• Chromosome: 1
• Chromosome location: 1q21.3
• Summary: The protein encoded by this gene is an intermediate filament-associated protein that aggregates keratin intermediate filaments in mammalian epidermis. It is initially synthesized as a polyprotein precursor, profilaggrin (consisting of multiple filaggrin u

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs3120649	G>A,C,T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs121909626	G>C,T	Pathogenic, risk-factor	Stop gained, coding sequence variant
rs138726443	G>A,C,T	Pathogenic	Stop gained, missense variant, synonymous variant, coding sequence variant
rs140980397	G>A,C,T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs141784184	G>A,T	Likely-pathogenic	Coding sequence variant, stop gained, missense variant
rs146466242	T>A,C	Likely-pathogenic, uncertain-significance	Stop gained, missense variant, coding sequence variant
rs146686141	G>A,C,T	Pathogenic	Stop gained, missense variant, coding sequence variant, synonymous variant
rs147145234	G>T	Pathogenic	Stop gained, coding sequence variant
rs148606936	G>A,C,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs149105551	G>A,C,T	Pathogenic	Stop gained, missense variant, coding sequence variant, synonymous variant
rs149484917	G>C,T	Pathogenic	Stop gained, coding sequence variant
rs150597413	G>A,C,T	Likely-pathogenic, pathogenic	Stop gained, missense variant, coding sequence variant
rs180768115	G>C,T	Likely-pathogenic	Stop gained, coding sequence variant
rs199895224	C>A,G	Pathogenic	Stop gained, missense variant, coding sequence variant
rs200002200	G>A	Pathogenic	Stop gained, coding sequence variant
rs201356558	G>A,C	Pathogenic	Missense variant, coding sequence variant, stop gained
rs372754256	G>C	Pathogenic	Coding sequence variant, stop gained
rs374588791	C>A,T	Pathogenic	Coding sequence variant, missense variant, stop gained
rs397507563	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs528722713	G>A	Pathogenic	Coding sequence variant, stop gained
rs528961889	G>A,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained
rs535289422	G>A,C	Pathogenic	Missense variant, stop gained, coding sequence variant
rs542799026	G>C	Pathogenic	Coding sequence variant, stop gained
rs546871592	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs564628353	G>A	Pathogenic	Coding sequence variant, stop gained
rs567795279	T>A	Pathogenic	Coding sequence variant, stop gained
rs573388805	G>A,C	Pathogenic	Stop gained, missense variant, coding sequence variant
rs578184315	GGATGATG>-	Pathogenic	Stop gained, coding sequence variant
rs747301529	C>A	Pathogenic	Stop gained, coding sequence variant
rs748135905	C>A,T	Pathogenic	Stop gained, coding sequence variant, missense variant
rs749083759	G>A,C	Pathogenic	Coding sequence variant, stop gained, missense variant
rs754328064	G>A	Pathogenic	Coding sequence variant, stop gained
rs754727774	G>A,C,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained, missense variant
rs754812742	G>A,T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs755823797	GACT>-	Pathogenic	Frameshift variant, coding sequence variant
rs756998312	G>A,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs757726987	T>A	Pathogenic	Coding sequence variant, stop gained
rs760831749	GT>-	Pathogenic	Frameshift variant, coding sequence variant
rs761212672	G>T	Pathogenic	Coding sequence variant, stop gained
rs761519693	GACT>-	Pathogenic	Frameshift variant, coding sequence variant
rs764094665	T>A	Pathogenic	Stop gained, coding sequence variant
rs769826402	TCTG>-	Pathogenic	Coding sequence variant, frameshift variant
rs771027814	TG>-	Pathogenic	Coding sequence variant, frameshift variant
rs774129089	G>C	Pathogenic	Coding sequence variant, stop gained
rs774362740	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs775716153	->TGAGT	Pathogenic	Coding sequence variant, frameshift variant
rs777848510	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs778545248	C>A,G	Pathogenic	Coding sequence variant, stop gained, missense variant
rs781161516	->G	Pathogenic	Coding sequence variant, frameshift variant
rs972579811	G>A	Pathogenic	Coding sequence variant, stop gained
rs1057517973	CT>-	Pathogenic	Coding sequence variant, frameshift variant
rs1057518212	G>C,T	Pathogenic	Stop gained, coding sequence variant
rs1064793675	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1064795983	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1064796105	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1203718709	G>C	Pathogenic	Stop gained, coding sequence variant
rs1246063885	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs1370544496	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1388479165	G>C,T	Pathogenic	Stop gained, coding sequence variant
rs1423603720	G>A	Pathogenic	Stop gained, coding sequence variant
rs1425411066	G>C,T	Pathogenic	Stop gained, coding sequence variant
rs1553211362	G>A	Pathogenic	Coding sequence variant, stop gained
rs1553213136	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs1570893617	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1570897758	T>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022464	hsa-miR-124-3p	Microarray	18668037
MIRT2229918	hsa-miR-122	CLIP-seq
MIRT2229919	hsa-miR-2110	CLIP-seq
MIRT2229920	hsa-miR-3150a-3p	CLIP-seq
MIRT2229921	hsa-miR-3175	CLIP-seq
MIRT2229922	hsa-miR-4260	CLIP-seq
MIRT2229923	hsa-miR-4659a-3p	CLIP-seq
MIRT2229924	hsa-miR-4659b-3p	CLIP-seq
MIRT2229925	hsa-miR-4775	CLIP-seq
MIRT2229926	hsa-miR-939	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
HOPX	Activation	21256618

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001533	Component	Cornified envelope	IBA	21873635
GO:0001533	Component	Cornified envelope	IDA	7543090
GO:0005198	Function	Structural molecule activity	NAS	2740331
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	23629652
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005829	Component	Cytosol	TAS
GO:0005882	Component	Intermediate filament	NAS	2740331
GO:0007275	Process	Multicellular organism development	NAS	2740331
GO:0018149	Process	Peptide cross-linking	IDA	7543090
GO:0030216	Process	Keratinocyte differentiation	TAS	17704059
GO:0030280	Function	Structural constituent of skin epidermis	IDA	7543090
GO:0036457	Component	Keratohyalin granule	IBA	21873635
GO:0036457	Component	Keratohyalin granule	IDA	1429717, 12850301
GO:0036464	Component	Cytoplasmic ribonucleoprotein granule	IDA
GO:0046914	Function	Transition metal ion binding	IEA
GO:0061436	Process	Establishment of skin barrier	IBA	21873635
GO:0061436	Process	Establishment of skin barrier	IEP	23403047
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	28344315
GO:0070268	Process	Cornification	TAS

Other IDs

• MIM: 135940
• HGNC: 3748
• e!Ensembl: ENSG00000143631

Protein

• UniProt ID: P20930
• Protein name: Filaggrin
• Protein function: Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis.
• PDB: 4PCW
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01023	S_100	4 → 46	S-100/ICaBP type calcium binding domain	Domain
  PF03516	Filaggrin	257 → 306	Filaggrin	Repeat
  PF03516	Filaggrin	373 → 428	Filaggrin	Repeat
  PF03516	Filaggrin	574 → 630	Filaggrin	Repeat
  PF03516	Filaggrin	697 → 753	Filaggrin	Repeat
  PF03516	Filaggrin	899 → 955	Filaggrin	Repeat
  PF03516	Filaggrin	1022 → 1077	Filaggrin	Repeat
  PF03516	Filaggrin	1223 → 1279	Filaggrin	Repeat
  PF03516	Filaggrin	1346 → 1401	Filaggrin	Repeat
  PF03516	Filaggrin	1547 → 1603	Filaggrin	Repeat
  PF03516	Filaggrin	1670 → 1725	Filaggrin	Repeat
  PF03516	Filaggrin	1871 → 1927	Filaggrin	Repeat
  PF03516	Filaggrin	1994 → 2050	Filaggrin	Repeat
  PF03516	Filaggrin	2196 → 2252	Filaggrin	Repeat
  PF03516	Filaggrin	2319 → 2374	Filaggrin	Repeat
  PF03516	Filaggrin	2520 → 2576	Filaggrin	Repeat
  PF03516	Filaggrin	2643 → 2698	Filaggrin	Repeat
  PF03516	Filaggrin	2844 → 2900	Filaggrin	Repeat
  PF03516	Filaggrin	2967 → 3022	Filaggrin	Repeat
  PF03516	Filaggrin	3168 → 3224	Filaggrin	Repeat
  PF03516	Filaggrin	3291 → 3346	Filaggrin	Repeat
  PF03516	Filaggrin	3492 → 3548	Filaggrin	Repeat
  PF03516	Filaggrin	3615 → 3670	Filaggrin	Repeat
  PF03516	Filaggrin	3816 → 3872	Filaggrin	Repeat

• Sequence:

  MSTLLENIFAIINLFKQYSKKDKNTDTLSKKELKELLEKEFRQILKNPDDPDMVDVFMDH
  LDIDHNKKIDFTEFLLMVFKLAQAYYESTRKENLPISGHKHRKHSHHDKHEDNKQEENKE
  NRKRPSSLERRNNRKGNKGRSKSPRETGGKRHESSSEKKERKGYSPTHREEEYGKNHHNS
  SKKEKNKTENTRLGDNRKRLSERLEEKEDNEEGVYDYENTGRMTQKWIQSGHIATYYTIQ
  DEAYDTTDSLLEENKIYERSRSSDGKSSSQVNRSRHENTSQVPLQESRTRKRRGSRVSQD
  RDSEGHSEDSERHSGSASRNHHGSAWEQSRDGSRHPRSHDEDRASHGHSADSSRQSGTRH
  AETSSRGQTASSHEQARSSPGERHGSGHQQSADSSRHSATGRGQASSAVSDRGHRGSSGS
  QASDSEGHSENSDTQSVSGHGKAGLRQQSHQESTRGRSGERSGRSGSSLYQVSTHEQPDS
  AHGRTGTSTGGRQGSHHEQARDSSRHSASQEGQDTIRGHPGSSRGGRQGSHHEQSVNRSG
  HSGSHHSHTTSQGRSDASHGQSGSRSASRQTRNEEQSGDGTRHSGSRHHEASSQADSSRH
  SQVGQGQSSGPRTSRNQGSSVSQDSDSQGHSEDSERWSGSASRNHHGSAQEQSRDGSRHP
  RSHHEDRAGHGHSADSSRKSGTRHTQNSSSGQAASSHEQARSSAGERHGSRHQLQSADSS
  RHSGTGHGQASSAVRDSGHRGSSGSQATDSEGHSEDSDTQSVSGHGQAGHHQQSHQESAR
  DRSGERSRRSGSFLYQVSTHKQSESSHGWTGPSTGVRQGSHHEQARDNSRHSASQDGQDT
  IRGHPGSSRRGRQGSHHEQSVDRSGHSGSHHSHTTSQGRSDASRGQSGSRSASRTTRNEE
  QSRDGSRHSGSRHHEASSHADISRHSQAGQGQSEGSRTSRRQGSSVSQDSDSEGHSEDSE
  RWSGSASRNHRGSAQEQSRHGSRHPRSHHEDRAGHGHSADSSRQSGTPHAETSSGGQAAS
  SHEQARSSPGERHGSRHQQSADSSRHSGIPRRQASSAVRDSGHWGSSGSQASDSEGHSEE
  SDTQSVSGHGQDGPHQQSHQESARDWSGGRSGRSGSFIYQVSTHEQSESAHGRTRTSTGR
  RQGSHHEQARDSSRHSASQEGQDTIRAHPGSRRGGRQGSHHEQSVDRSGHSGSHHSHTTS
  QGRSDASHGQSGSRSASRQTRKDKQSGDGSRHSGSRHHEAASWADSSRHSQVGQEQSSGS
  RTSRHQGSSVSQDSDSERHSDDSERLSGSASRNHHGSSREQSRDGSRHPGFHQEDRASHG
  HSADSSRQSGTHHTESSSHGQAVSSHEQARSSPGERHGSRHQQSADSSRHSGIGHRQASS
  AVRDSGHRGSSGSQVTNSEGHSEDSDTQSVSAHGQAGPHQQSHKESARGQSGESSGRSRS
  FLYQVSSHEQSESTHGQTAPSTGGRQGSRHEQARNSSRHSASQDGQDTIRGHPGSSRGGR
  QGSYHEQSVDRSGHSGYHHSHTTPQGRSDASHGQSGPRSASRQTRNEEQSGDGSRHSGSR
  HHEPSTRAGSSRHSQVGQGESAGSKTSRRQGSSVSQDRDSEGHSEDSERRSESASRNHYG
  SAREQSRHGSRNPRSHQEDRASHGHSAESSRQSGTRHAETSSGGQAASSQEQARSSPGER
  HGSRHQQSADSSTDSGTGRRQDSSVVGDSGNRGSSGSQASDSEGHSEESDTQSVSAHGQA
  GPHQQSHQESTRGQSGERSGRSGSFLYQVSTHEQSESAHGRTGPSTGGRQRSRHEQARDS
  SRHSASQEGQDTIRGHPGSSRGGRQGSHYEQSVDSSGHSGSHHSHTTSQERSDVSRGQSG
  SRSVSRQTRNEKQSGDGSRHSGSRHHEASSRADSSRHSQVGQGQSSGPRTSRNQGSSVSQ
  DSDSQGHSEDSERWSGSASRNHLGSAWEQSRDGSRHPGSHHEDRAGHGHSADSSRQSGTR
  HTESSSRGQAASSHEQARSSAGERHGSHHQLQSADSSRHSGIGHGQASSAVRDSGHRGYS
  GSQASDSEGHSEDSDTQSVSAQGKAGPHQQSHKESARGQSGESSGRSGSFLYQVSTHEQS
  ESTHGQSAPSTGGRQGSHYDQAQDSSRHSASQEGQDTIRGHPGPSRGGRQGSHQEQSVDR
  SGHSGSHHSHTTSQGRSDASRGQSGSRSASRKTYDKEQSGDGSRHSGSHHHEASSWADSS
  RHSLVGQGQSSGPRTSRPRGSSVSQDSDSEGHSEDSERRSGSASRNHHGSAQEQSRDGSR
  HPRSHHEDRAGHGHSAESSRQSGTHHAENSSGGQAASSHEQARSSAGERHGSHHQQSADS
  SRHSGIGHGQASSAVRDSGHRGSSGSQASDSEGHSEDSDTQSVSAHGQAGPHQQSHQEST
  RGRSAGRSGRSGSFLYQVSTHEQSESAHGRTGTSTGGRQGSHHKQARDSSRHSTSQEGQD
  TIHGHPGSSSGGRQGSHYEQLVDRSGHSGSHHSHTTSQGRSDASHGHSGSRSASRQTRND
  EQSGDGSRHSGSRHHEASSRADSSGHSQVGQGQSEGPRTSRNWGSSFSQDSDSQGHSEDS
  ERWSGSASRNHHGSAQEQLRDGSRHPRSHQEDRAGHGHSADSSRQSGTRHTQTSSGGQAA
  SSHEQARSSAGERHGSHHQQSADSSRHSGIGHGQASSAVRDSGHRGYSGSQASDNEGHSE
  DSDTQSVSAHGQAGSHQQSHQESARGRSGETSGHSGSFLYQVSTHEQSESSHGWTGPSTR
  GRQGSRHEQAQDSSRHSASQDGQDTIRGHPGSSRGGRQGYHHEHSVDSSGHSGSHHSHTT
  SQGRSDASRGQSGSRSASRTTRNEEQSGDGSRHSGSRHHEASTHADISRHSQAVQGQSEG
  SRRSRRQGSSVSQDSDSEGHSEDSERWSGSASRNHHGSAQEQLRDGSRHPRSHQEDRAGH
  GHSADSSRQSGTRHTQTSSGGQAASSHEQARSSAGERHGSHHQQSADSSRHSGIGHGQAS
  SAVRDSGHRGYSGSQASDNEGHSEDSDTQSVSAHGQAGSHQQSHQESARGRSGETSGHSG
  SFLYQVSTHEQSESSHGWTGPSTRGRQGSRHEQAQDSSRHSASQYGQDTIRGHPGSSRGG
  RQGYHHEHSVDSSGHSGSHHSHTTSQGRSDASRGQSGSRSASRTTRNEEQSGDSSRHSVS
  RHHEASTHADISRHSQAVQGQSEGSRRSRRQGSSVSQDSDSEGHSEDSERWSGSASRNHR
  GSVQEQSRHGSRHPRSHHEDRAGHGHSADRSRQSGTRHAETSSGGQAASSHEQARSSPGE
  RHGSRHQQSADSSRHSGIPRGQASSAVRDSRHWGSSGSQASDSEGHSEESDTQSVSGHGQ
  AGPHQQSHQESARDRSGGRSGRSGSFLYQVSTHEQSESAHGRTRTSTGRRQGSHHEQARD
  SSRHSASQEGQDTIRGHPGSSRRGRQGSHYEQSVDRSGHSGSHHSHTTSQGRSDASRGQS
  GSRSASRQTRNDEQSGDGSRHSWSHHHEASTQADSSRHSQSGQGQSAGPRTSRNQGSSVS
  QDSDSQGHSEDSERWSGSASRNHRGSAQEQSRDGSRHPTSHHEDRAGHGHSAESSRQSGT
  HHAENSSGGQAASSHEQARSSAGERHGSHHQQSADSSRHSGIGHGQASSAVRDSGHRGSS
  GSQASDSEGHSEDSDTQSVSAHGQAGPHQQSHQESTRGRSAGRSGRSGSFLYQVSTHEQS
  ESAHGRAGPSTGGRQGSRHEQARDSSRHSASQEGQDTIRGHPGSRRGGRQGSYHEQSVDR
  SGHSGSHHSHTTSQGRSDASHGQSGSRSASRETRNEEQSGDGSRHSGSRHHEASTQADSS
  RHSQSGQGESAGSRRSRRQGSSVSQDSDSEAYPEDSERRSESASRNHHGSSREQSRDGSR
  HPGSSHRDTASHVQSSPVQSDSSTAKEHGHFSSLSQDSAYHSGIQSRGSPHSSSSYHYQS
  EGTERQKGQSGLVWRHGSYGSADYDYGESGFRHSQHGSVSYNSNPVVFKERSDICKASAF
  GKDHPRYYATYINKDPGLCGHSSDISKQLGFSQSQRYYYYE

• Sequence length: 4061

Pathways

Reactome:

Formation of the cornified envelope

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Asthma	Asthma, Childhood asthma	rs324981, rs121912630, rs150116809, rs4950928, rs708494, rs1581842283	31619474, 30929738, 31036433, 30552067, 31036433
Autism	Autistic Disorder	rs121964908, rs121912597, rs2710102, rs7794745, rs142990298, rs62643608, rs181327458, rs797046134, rs869312704, rs1555013332, rs876657679, rs1057518999, rs1057518658, rs771827120, rs1555187899, rs773080572, rs753871454, rs1684130791, rs1684180699, rs1553510219, rs1684182454, rs1559060428, rs1553510677, rs1576352885, rs1574152522, rs1574152672, rs1696658542, rs1751123722, rs1750373491, rs1751075634	16444271
Dermatitis	Dermatitis, Dermatitis, Atopic, Contact Dermatitis, Dermatitis, Atopic, 2, Inflammatory dermatosis	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	31330126, 16550169, 23348739, 17030239, 19349982, 16815158, 16444271, 23042114, 24061166, 25724174, 16444271, 17030239, 16444271, 16815158, 16550169
Developmental delay	Global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Ichthyosis	Ichthyoses	rs199766569, rs587776996, rs587777262, rs863223405, rs370031870, rs1569044747, rs200806519
Ichthyosis vulgaris	Ichthyosis Vulgaris, NON RARE IN EUROPE: Autosomal dominant ichthyosis vulgaris	rs61816761, rs121909626, rs150597413, rs397507563, rs138726443, rs797045090, rs147145234, rs761212672, rs535289422, rs754812742, rs201356558, rs760831749, rs374588791, rs144419479, rs200002200, rs142991475, rs148606936, rs114733570, rs149484917, rs774362740, rs777181377, rs528722713, rs1060499587, rs578184315, rs140980397, rs200519781, rs749083759, rs761519693, rs183942200, rs146686141, rs746683647, rs372754256, rs1214424848, rs542799026, rs567795279, rs180768115, rs1570897758, rs769826402, rs564628353, rs775716153, rs745915174, rs1570913142, rs143418984	17030239, 17417636, 19733298, 18200065, 16550169, 21923666, 27279822, 24061166, 22403702, 19874431, 19501237, 17291859, 16815158, 23947670, 21514438, 22220561, 21428977, 27363669, 18325573, 16444271, 20573035, 19538357, 19839980
Myopia	Myopia	rs387907109, rs146936371, rs587776903, rs786205127, rs398122836, rs199624584, rs587777625, rs786205216, rs758872875, rs764211125, rs1135402746, rs765658563, rs1555941129, rs1555941116, rs199923805, rs782555528, rs1554862601, rs1586620121, rs1387950081, rs2051026773, rs1422332023
Nystagmus	Nystagmus	rs137852207, rs137852208, rs1928435502, rs137852209, rs137852210, rs1929191668, rs137852211, rs137852212, rs2124209414, rs387906720, rs387906721, rs1602791884, rs786205896

Unknown
Disease name	Disease term	dbSNP ID	References
Cerebellar hypoplasia	Cerebellar Hypoplasia
Cutis marmorata	Cutis marmorata
Dysmorphic features	Dysmorphic features		16444271, 22542183, 17417636, 24267886, 21173567, 20790920
Eczema	Eczema, Eczema, Infantile		30595370, 17417636, 16444271, 16550169, 24061166, 23348739, 19349982, 23042114
Hypospadias	Hypospadias
Movement disorders	Movement Disorders		16444271, 20790920, 22542183, 24267886, 17417636, 21173567
Osteopenia	Osteopenia
Respiratory tract diseases	Respiratory Tract Diseases		30595370