SFTPC

surfactant protein C, the group of BRICHOS domain containing

Basic information

Region (hg38): 8:22156912-22164479

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
• interstitial lung disease due to SP-C deficiency (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 (59 variants)
• Surfactant metabolism dysfunction, pulmonary, 2 (56 variants)
• Hereditary pulmonary alveolar proteinosis (45 variants)
• Interstitial lung disease 2 (42 variants)
• Pulmonary Surfactant Metabolism Dysfunction, Dominant (14 variants)
• not specified (12 variants)
• Osteogenesis Imperfecta, Recessive (9 variants)
• SFTPC-related condition (3 variants)
• Inborn genetic diseases (2 variants)
• Pulmonary fibrosis (2 variants)
• 14 conditions (1 variants)
• Usher syndrome type 2A (1 variants)
• Neonatal acute respiratory distress due to SP-B deficiency (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	15	2	19
missense	3	7	37	3	1	51
nonsense			1			1
start loss						0
frameshift	2	2				4
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	1				2
splice region		1	1	2		4
non coding			3	10	19	32
Total	6	10	46	28	22

Variants in SFTPC

This is a list of pathogenic ClinVar variants found in the SFTPC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-22161558-G-A			Benign (Jul 09, 2018)
8-22161695-G-C		Pulmonary Surfactant Metabolism Dysfunction, Dominant • Osteogenesis Imperfecta, Recessive • Interstitial lung disease 2 • Surfactant metabolism dysfunction, pulmonary, 2	Benign/Likely benign (Jul 15, 2018)
8-22161737-C-G		Interstitial lung disease 2 • Surfactant metabolism dysfunction, pulmonary, 2	Benign (Jan 13, 2018)
8-22161738-C-T		Interstitial lung disease 2 • Surfactant metabolism dysfunction, pulmonary, 2	Benign (Jan 12, 2018)
8-22161762-C-T		Surfactant metabolism dysfunction, pulmonary, 2 • Interstitial lung disease 2	Likely benign (Jan 12, 2018)
8-22161772-T-TAA		Interstitial lung disease 2 • Pulmonary Surfactant Metabolism Dysfunction, Dominant	Likely benign (Jun 14, 2016)
8-22161802-AGAG-A		Pulmonary Surfactant Metabolism Dysfunction, Dominant • Interstitial lung disease 2	Uncertain significance (Jun 14, 2016)
8-22161819-C-G		SFTPC-related disorder	Likely benign (Aug 13, 2019)
8-22161838-G-A		Surfactant metabolism dysfunction, pulmonary, 1	Uncertain significance (Jun 28, 2019)
8-22161852-C-G		Pulmonary Surfactant Metabolism Dysfunction, Dominant • Interstitial lung disease 2 • Surfactant metabolism dysfunction, pulmonary, 2 • Hereditary pulmonary alveolar proteinosis	Benign/Likely benign (Jan 09, 2024)
8-22161866-C-T		SFTPC-related disorder	Uncertain significance (Jan 23, 2024)
8-22161867-G-A		Hereditary pulmonary alveolar proteinosis	Likely benign (Apr 21, 2020)
8-22161869-C-T		Hereditary pulmonary alveolar proteinosis	Uncertain significance (Dec 13, 2021)
8-22161870-G-A		Surfactant metabolism dysfunction, pulmonary, 2 • Interstitial lung disease 2 • Hereditary pulmonary alveolar proteinosis	Conflicting classifications of pathogenicity (Jan 25, 2024)
8-22161884-C-T		not specified	Likely benign (Feb 21, 2013)
8-22161887-G-A			Likely benign (Jul 24, 2021)
8-22161905-G-A			Benign (Jul 09, 2018)
8-22161907-G-A			Benign (May 09, 2020)
8-22162299-G-A			Benign (Jul 09, 2018)
8-22162327-A-G			Benign (Oct 19, 2018)
8-22162380-G-A			Benign (Jul 09, 2018)
8-22162487-C-T			Benign (Oct 27, 2018)
8-22162553-T-C		Surfactant metabolism dysfunction, pulmonary, 2	Benign (Jul 15, 2021)
8-22162566-C-T			Likely benign (May 08, 2022)
8-22162567-G-A		Pulmonary Surfactant Metabolism Dysfunction, Dominant • Interstitial lung disease 2 • not specified • Surfactant metabolism dysfunction, pulmonary, 2 • Hereditary pulmonary alveolar proteinosis	Benign/Likely benign (Nov 18, 2023)

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