SFTPC

surfactant protein C, the group of BRICHOS domain containing

Basic information

Region (hg38): 8:22156913-22164479

Previous symbols: [ "SFTP2" ]

Links

ENSG00000168484

∙ NCBI:6440 ∙ OMIM:178620 ∙ HGNC:10802 ∙ Uniprot:P11686 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

surfactant metabolism dysfunction, pulmonary, 2 (Strong), mode of inheritance: AD
surfactant metabolism dysfunction, pulmonary, 2 (Definitive), mode of inheritance: AD
chronic respiratory distress with surfactant metabolism deficiency (Supportive), mode of inheritance: AD
SFTPC- related interstitial lung disease (Supportive), mode of inheritance: AD
surfactant metabolism dysfunction, pulmonary, 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Surfactant metabolism dysfunction, pulmonary, 2	AD	Pulmonary	There have been reports of individuals who received benefit from medical treatment, including hydroxychloroquine, whole-lung lavage, systemic corticosteroids, azathioprine; Lung transplantation may be indicated in individuals with severe and/or refractory disease	Pulmonary	11207353; 11445799; 11893657; 11991887; 15039969; 15293602; 15647591; 19443464

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SFTPC gene.

not_provided (77 variants)
Hereditary_pulmonary_alveolar_proteinosis (66 variants)
Surfactant_metabolism_dysfunction,_pulmonary,_2 (48 variants)
Interstitial_lung_disease_2 (25 variants)
SFTPC-related_disorder (11 variants)
not_specified (8 variants)
Pulmonary_fibrosis (5 variants)
Pulmonary_Surfactant_Metabolism_Dysfunction,_Dominant (3 variants)
Surfactant_metabolism_dysfunction,_pulmonary,_1 (1 variants)
Inborn_genetic_diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SFTPC gene is commonly pathogenic or not. These statistics are base on transcript: NM_001317778.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	2 clinvar	19 clinvar	2 clinvar	24
missense	7 clinvar	12 clinvar	66 clinvar	10 clinvar	1 clinvar	96
nonsense		2 clinvar	1 clinvar			3
start loss						0
frameshift	2 clinvar	2 clinvar	3 clinvar			7
splice donor/acceptor (+/-2bp)	4 clinvar	1 clinvar				5
Total	13	18	72	29	3

Highest pathogenic variant AF is 0.00000309874

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SFTPC	protein_coding	protein_coding	ENST00000318561	5	7567

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000753	0.781	124781	0	16	124797	0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.849	90	116	0.778	0.00000713	1254
Missense in Polyphen		26	45.123	0.5762		523
Synonymous	-1.02	57	48.0	1.19	0.00000311	420
Loss of Function	1.04	6	9.44	0.636	5.40e-7	102

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000167	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.0000354	0.0000353
Middle Eastern	0.000167	0.000167
South Asian	0.000197	0.000196
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

Function: FUNCTION: Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air- liquid interface in the peripheral air spaces.;
Disease: DISEASE: Pulmonary surfactant metabolism dysfunction 2 (SMDP2) [MIM:610913]: A rare disease associated with progressive respiratory insufficiency and lung disease with a variable clinical course, due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress. {ECO:0000269|PubMed:11991887, ECO:0000269|PubMed:15039969, ECO:0000269|PubMed:15293602, ECO:0000269|PubMed:15557112, ECO:0000269|PubMed:15572558}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Respiratory distress syndrome in premature infants (RDS) [MIM:267450]: A lung disease affecting usually premature newborn infants. It is characterized by deficient gas exchange, diffuse atelectasis, high-permeability lung edema and fibrin-rich alveolar deposits called 'hyaline membranes'. {ECO:0000269|PubMed:14735158}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.;
Pathway: Surfactant metabolism;Lung fibrosis;Surfactant metabolism;Metabolism of proteins (Consensus)

Recessive Scores

pRec: 0.234

Intolerance Scores

loftool: 0.122
rvis_EVS: 0.22
rvis_percentile_EVS: 68.13

Haploinsufficiency Scores

pHI: 0.257
hipred: N
hipred_score: 0.290
ghis: 0.415

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.516

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

Gene name: Sftpc
Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; immune system phenotype; vision/eye phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: respiratory gaseous exchange;cellular protein metabolic process
Cellular component: extracellular region;extracellular space;endoplasmic reticulum membrane;lamellar body;clathrin-coated endocytic vesicle;multivesicular body lumen
Molecular function: protein binding;identical protein binding