SFTPD

Summary

SFTPD (surfactant protein D, HGNC:10803) is a protein-coding gene on chromosome 10q22.3, encoding Pulmonary surfactant-associated protein D (P35247). Contributes to the lung’s defense against inhaled microorganisms, organic antigens and toxins.

The protein encoded by this gene is part of the innate immune response, protecting the lungs against inhaled microorganisms and chemicals. The encoded protein may also be involved in surfactant metabolism.

Source: NCBI Gene 6441 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 53 total
• Druggable target: yes
• MANE Select transcript: NM_003019

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10803
Approved symbol	SFTPD
Name	surfactant protein D
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	SP-D, COLEC7
Ensembl gene	ENSG00000133661
Ensembl biotype	protein_coding
OMIM	178635
Entrez	6441

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 31 protein_coding, 2 retained_intron

ENST00000372292, ENST00000444384, ENST00000678361, ENST00000679234, ENST00000865181, ENST00000865182, ENST00000865183, ENST00000865184, ENST00000865185, ENST00000865186, ENST00000865187, ENST00000865188, ENST00000865189, ENST00000865190, ENST00000865191, ENST00000865192, ENST00000946699, ENST00000946700, ENST00000946701, ENST00000946702, ENST00000946703, ENST00000946704, ENST00000946705, ENST00000946706, ENST00000946707, ENST00000946708, ENST00000946709, ENST00000946710, ENST00000946711, ENST00000946712, ENST00000946713, ENST00000946714, ENST00000946715

RefSeq mRNA: 1 — MANE Select: NM_003019 NM_003019

CCDS: CCDS7362

Canonical transcript exons

ENST00000372292 — 8 exons

Exon	Start	End
ENSE00000909267	79941954	79942070
ENSE00000909268	79942388	79942504
ENSE00001388162	79942763	79942879
ENSE00001457451	79949066	79949105
ENSE00001708197	79940705	79940788
ENSE00001920473	79937740	79938228
ENSE00002173050	79941398	79941514
ENSE00003507171	79946461	79946662

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 99.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7318 / max 378.0285, expressed in 38 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110317	0.6747	22
110318	0.0571	13

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.54	gold quality
visceral pleura	UBERON:0002401	98.95	gold quality
upper lobe of lung	UBERON:0008948	96.46	gold quality
upper lobe of left lung	UBERON:0008952	96.24	gold quality
lung	UBERON:0002048	95.02	gold quality
right lung	UBERON:0002167	93.59	gold quality
adult organism	UBERON:0007023	89.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.63	gold quality
germinal epithelium of ovary	UBERON:0001304	77.94	gold quality
pleura	UBERON:0000977	77.87	gold quality
cervix squamous epithelium	UBERON:0006922	77.13	gold quality
tongue squamous epithelium	UBERON:0006919	75.08	gold quality
body of pancreas	UBERON:0001150	73.03	gold quality
skin of leg	UBERON:0001511	72.80	gold quality
left lobe of thyroid gland	UBERON:0001120	72.46	gold quality
endometrium epithelium	UBERON:0004811	72.45	gold quality
thyroid gland	UBERON:0002046	71.85	gold quality
granulocyte	CL:0000094	71.47	gold quality
right lobe of thyroid gland	UBERON:0001119	71.47	gold quality
skin of abdomen	UBERON:0001416	70.80	gold quality
gingival epithelium	UBERON:0001949	70.79	gold quality
squamous epithelium	UBERON:0006914	70.73	silver quality
nucleus accumbens	UBERON:0001882	70.24	gold quality
amniotic fluid	UBERON:0000173	70.12	gold quality
zone of skin	UBERON:0000014	70.03	gold quality
cingulate cortex	UBERON:0003027	69.94	gold quality
type B pancreatic cell	CL:0000169	69.90	gold quality
anterior cingulate cortex	UBERON:0009835	69.77	gold quality
pancreas	UBERON:0001264	69.71	gold quality
caudate nucleus	UBERON:0001873	69.61	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	3075.02
E-MTAB-6653	yes	2621.55
E-MTAB-6308	yes	2389.81
E-HCAD-1	yes	1868.93
E-HCAD-15	yes	1650.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPD, CEBPG, FOSL1, FOXA1, JUNB, JUND, NFATC3, NKX2-1, RB1, TTF1

miRNA regulators (miRDB)

2 targeting SFTPD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-3190-5P	98.87	64.89	1345

Literature-anchored findings (GeneRIF, showing 40)

• SP-D (surfactant protein D) may therefore play a significant role in the innate immune response to H. pylori infection (PMID:11854236)
• Surfactant protein D gene regulation. Interactions among the conserved CCAAT/enhancer-binding protein elements (PMID:11912209)
• binds Mycoplasma pneumoniae by high affinity interactions with lipids (PMID:11916969)
• Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection. (PMID:12032263)
• Intrapulmonary administration of a truncated 60-kDa fragment of human recombinant SP-D into SP-D-deficient mice reduces the number of apoptotic and necrotic alveolar macrophages and partially corrects the lipid accumulation. (PMID:12218102)
• SP-D preferentially inhibits the adhesion of the O3-serotype of Klebsiella pneumoniae to lung epithelial cells. (PMID:12218146)
• SP-D enhances phagocytosis of apoptotic cells by human and murine alveolar macrophages in vitro, independent of the apoptotic cell type. (PMID:12244199)
• SP-D mRNA might be a valuable marker to detect circulating tumor cells in the peripheral blood of lung cancer patients. (PMID:12479105)
• Pseudomonas aeruginosa elastase degrades this protein in human lung. (PMID:12654643)
• aggregation of Pneumocystis carinii by SP-D was shown to be responsible for the impaired phagocytosis of the organisms by alveolar macrophages (PMID:12654779)
• carbohydrate recognition domains of SP-D interact with the dermatan sulfate moiety of decorin via lectin activity and the core protein of decorin binds the collagen-like region of SP-D (PMID:12730206)
• Limited proteolysis of SFTPD causes a loss of its calcium-dependent lectin functions. (PMID:12853121)
• SP-D has roles in ligand binding and immune cell recognition because of its multivalent ligand binding and recognition sites (PMID:12888356)
• A recombinant trimeric fragment of surfactant protein D chemically cross-linked to the Fab’ of anti-Fc alpha receptor monoclonal antibody markedly enhances the uptake of influenza A virus, Candida albicans, and Escherichia coli by neutrophils in vitro. (PMID:15067073)
• Degradation of pulmonary surfactant protein D by Pseudomonas aeruginosa elastase abrogates innate immune function (PMID:15123664)
• surfactant proteins A and D and mannose-binding lectin play roles in inflammation caused by DNA in lungs and other tissues (PMID:15145932)
• surfactant protein D gene transcription is regulated by NFAT and thyroid transcription factor-1 (PMID:15173172)
• serum SP-D levels may serve as a good diagnostic indicator of acute respiratory distress syndrome in patients with sepsis (PMID:15244040)
• Data describe a proteome analysis of surfactant proteins SP-A and SP-D in bronchoalveolar lavage fluid from patients with cystic fibrosis, chronic bronchitis and pulmonary alveolar proteinosis. (PMID:15274124)
• SP-D, SP-A, and gp340 showed cooperative antiviral interactions (PMID:15608147)
• Polymorphic variation in the N-terminal domain of the SP-D molecule influences oligomerization, function, and the concentration of the molecule in serum. (PMID:15661913)
• Identification of specific haplotype of SPTPD gene that indicates its negative association with SP-D levels in the serum. (PMID:15700120)
• analysis of ligand specificity of human surfactant protein D (PMID:15711012)
• The ability of SP-D to increase neutrophil uptake of influenza A virus can be dissociated from enhancement of oxidant responses (PMID:15951332)
• SP-D binds various classes of immunoglobins, including IgG, IgM, IgE and secretory IgA, but not serum IgA. (PMID:16061223)
• role in Aspergillus mediated allergies and infections (PMID:16114131)
• Serum SP-D concentrations in children are genetically determined and that a single nucleotide polymorphism (SNP) located in the NH(2)-terminal region (Met11Thr) of the mature protein is associated with serum SP-D levels. (PMID:16361352)
• Decreased levels of SP-A and SP-D have been measured in bronchoalveolar lavage fluid of these patients, as well as patients with acute pneumonia but no chronic lung disease. (review) (PMID:16406431)
• functional amino acid variants in SFTPD do not play a major role in the genetic pre-disposition to bronchial asthma in children. (PMID:16426259)
• The ligand binding of homologous human, rat, and mouse trimeric trimeric neck plus carbohydrate recognition domain (neck+CRD) fusion proteins, each with identical N-terminal tags remote from the ligand-binding surface, was compared. (PMID:16514117)
• Phe-335, which is evolutionarily conserved in all known SP-Ds, plays important, if not critical, roles in SP-D function (PMID:16636058)
• In vitro interactions during the early phase of host defense against influenza A virus suggest a complex interplay between SP-D and human neutrophil defensins at sites of active inflammation. (PMID:16709857)
• Human SP-D binds the extracellular domains of TLR2 and TLR4 through its carbohydrate recognition domain by a mechanism different from its binding to phosphatidylinositol and lipopolysaccharide. (PMID:16834340)
• broncho-alveolar lavage fluid with high levels of bile acids also had significantly lower SP-A, SP-D, dipalmitoylphosphatidylcholine (PMID:16889547)
• SP-A, SP-B, and SP-D are expressed in human nasal mucosa and cultured normal human nasal epithelial cells. (PMID:17209137)
• A two-marker haplotype of SP-A and SP-D associates with protection from respiratory distress syndrome in premature infants; also, three- and four-marker haplotypes containing one or both markers associate with protection against RDS. (PMID:17524024)
• Surfactant protein D levels are increased in lung fluid from AIDS patients but not in patients with early HIV infection. (PMID:17567900)
• Serum surfactant-protein D (SP-D) concentrations increased in silica-exposed miners and may associate with pathogenesis of and be a useful biomarker for early diagnosis of silicosis. (PMID:17693780)
• the degradation and consequent inactivation of SP-A and SP-D may be a novel mechanism to account for the potent allergenicity of these common dust mite allergens. (PMID:17848554)
• Both SP-A and KL-6 were detected in intimate relationship to the stage of regeneration of alveolar epithelial cells and were expressed before SP-D. (PMID:17874049)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sftpd	ENSMUSG00000021795
rattus_norvegicus	Sftpd	ENSRNOG00000056001

Paralogs (4): COLEC11 (ENSG00000118004), SFTPA1 (ENSG00000122852), COLEC10 (ENSG00000184374), SFTPA2 (ENSG00000185303)

Protein

Protein identifiers

Pulmonary surfactant-associated protein D — P35247 (reviewed: P35247)

Alternative names: Collectin-7, Lung surfactant protein D

All UniProt accessions (2): P35247, Q5T0M2

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to the lung’s defense against inhaled microorganisms, organic antigens and toxins. Interacts with compounds such as bacterial lipopolysaccharides, oligosaccharides and fatty acids and modulates leukocyte action in immune response. May participate in the extracellular reorganization or turnover of pulmonary surfactant. Binds strongly maltose residues and to a lesser extent other alpha-glucosyl moieties.

Subunit / interactions. Oligomeric complex of 4 set of homotrimers.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Surface film.

Tissue specificity. Expressed in lung, brain, pancreas and adipose tissue (mainly mature adipocytes).

Post-translational modifications. The N-terminus is blocked. Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates. S-nitrosylation at Cys-35 and Cys-40 alters the quaternary structure which results in a pro-inflammatory chemoattractive signaling activity with macrophages.

Miscellaneous. Pulmonary surfactant consists of 90% lipid and 10% protein. There are 4 surfactant-associated proteins: 2 collagenous, carbohydrate-binding glycoproteins (SP-A and SP-D) and 2 small hydrophobic proteins (SP-B and SP-C).

Similarity. Belongs to the SFTPD family.

RefSeq proteins (1): NP_003010* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR008160	Collagen	Repeat
IPR015097	Surfac_D-trimer	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR033990	Collectin_CTLD	Domain
IPR051077	Ca-dependent_lectin	Family

Pfam: PF00059, PF01391, PF09006

UniProt features (48 total): strand 9, modified residue 8, compositionally biased region 6, sequence conflict 6, sequence variant 5, helix 4, domain 2, disulfide bond 2, signal peptide 1, chain 1, glycosylation site 1, turn 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1PWB	X-RAY DIFFRACTION	1.4
1PW9	X-RAY DIFFRACTION	1.6
2RIE	X-RAY DIFFRACTION	1.6
3IKN	X-RAY DIFFRACTION	1.6
9QW3	X-RAY DIFFRACTION	1.63
3IKR	X-RAY DIFFRACTION	1.65
5OXS	X-RAY DIFFRACTION	1.65
2OS9	X-RAY DIFFRACTION	1.7
4E52	X-RAY DIFFRACTION	1.7
3IKP	X-RAY DIFFRACTION	1.75
5OXR	X-RAY DIFFRACTION	1.75
9QVU	X-RAY DIFFRACTION	1.75
2ORJ	X-RAY DIFFRACTION	1.8
2RIA	X-RAY DIFFRACTION	1.8
2RIB	X-RAY DIFFRACTION	1.8
2RIC	X-RAY DIFFRACTION	1.8
2RID	X-RAY DIFFRACTION	1.8
3DBZ	X-RAY DIFFRACTION	1.8
3G81	X-RAY DIFFRACTION	1.8
9QW4	X-RAY DIFFRACTION	1.85
2ORK	X-RAY DIFFRACTION	1.89
2GGU	X-RAY DIFFRACTION	1.9
2GGX	X-RAY DIFFRACTION	1.9
3G83	X-RAY DIFFRACTION	1.9
9QW2	X-RAY DIFFRACTION	1.92
4M17	X-RAY DIFFRACTION	2.1
3IKQ	X-RAY DIFFRACTION	2.25
1B08	X-RAY DIFFRACTION	2.3
3G84	X-RAY DIFFRACTION	2.3
4M18	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35247-F1	67.60	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 35, 40, 78, 87, 96, 99, 171, 177

Disulfide bonds (2): 281–373, 351–365

Glycosylation sites (1): 90

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-391160	Signal regulatory protein family interactions
R-HSA-5683826	Surfactant metabolism
R-HSA-5686938	Regulation of TLR by endogenous ligand
R-HSA-5688849	Defective CSF2RB causes SMDP5
R-HSA-5688890	Defective CSF2RA causes SMDP4
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-1280218	Adaptive Immune System
R-HSA-1500931	Cell-Cell communication
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-392499	Metabolism of proteins
R-HSA-5663205	Infectious disease
R-HSA-5668914	Diseases of metabolism
R-HSA-5687613	Diseases associated with surfactant metabolism
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9692914	SARS-CoV-1-host interactions
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 182 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOCC_COLLAGEN_TRIMER, MODULE_45, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (14): regulation of cytokine production (GO:0001817), receptor-mediated endocytosis (GO:0006898), respiratory gaseous exchange by respiratory system (GO:0007585), negative regulation of interleukin-2 production (GO:0032703), negative regulation of T cell proliferation (GO:0042130), defense response to bacterium (GO:0042742), surfactant homeostasis (GO:0043129), innate immune response (GO:0045087), macrophage chemotaxis (GO:0048246), lung alveolus development (GO:0048286), positive regulation of phagocytosis (GO:0050766), reactive oxygen species metabolic process (GO:0072593), immune system process (GO:0002376), regulation of immune system process (GO:0002682)

GO Molecular Function (3): carbohydrate binding (GO:0030246), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (10): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), multivesicular body (GO:0005771), endoplasmic reticulum membrane (GO:0005789), endocytic vesicle (GO:0030139), clathrin-coated endocytic vesicle (GO:0045334), cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Toll-like Receptor Cascades	3
Diseases associated with surfactant metabolism	2
Immune System	2
Disease	2
Toll Like Receptor 2 (TLR2) Cascade	1
Adaptive Immune System	1
Cell-Cell communication	1
Metabolism of proteins	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
endocytosis	1
multicellular organismal process	1
negative regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
T cell proliferation	1
regulation of T cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
defense response	1
response to bacterium	1
multicellular organismal-level chemical homeostasis	1
immune response	1
defense response to symbiont	1
leukocyte chemotaxis	1
macrophage migration	1
lung development	1
anatomical structure development	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
metabolic process	1
biological_process	1
immune system process	1
regulation of biological process	1
protein binding	1
protein-containing complex	1
lytic vacuole	1
late endosome	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasmic vesicle	1
clathrin-coated vesicle	1
endocytic vesicle	1

Protein interactions and networks

STRING

1325 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SFTPD	DMBT1	Q9UGM3	965
SFTPD	LAIR1	Q6GTX8	959
SFTPD	SFTPB	P07988	947
SFTPD	SFTPC	P11686	944
SFTPD	SIRPA	P78324	936
SFTPD	LRP1	Q07954	890
SFTPD	CALR	P27797	864
SFTPD	MUC1	P13931	790
SFTPD	LAIR2	Q6ISS4	731
SFTPD	SCGB1A1	P11684	720
SFTPD	DCN	P07585	719
SFTPD	CXCL8	P10145	702
SFTPD	CRP	P02741	654
SFTPD	MPO	P05164	624
SFTPD	DEFA1	P11479	619

IntAct

12 interactions, top by confidence:

A	B	Type	Score
SFTPD	UPK1A	psi-mi:“MI:0407”(direct interaction)	0.540
UPK1A	SFTPD	psi-mi:“MI:0915”(physical association)	0.540
SFTPD	S	psi-mi:“MI:0407”(direct interaction)	0.540
S	SFTPD	psi-mi:“MI:0407”(direct interaction)	0.540
S	SFTPD	psi-mi:“MI:0915”(physical association)	0.540
SFTPD	DMBT1	psi-mi:“MI:0407”(direct interaction)	0.440
SFTPD	MASP1	psi-mi:“MI:0407”(direct interaction)	0.440
SFTPD	S	psi-mi:“MI:0407”(direct interaction)	0.440
SFTPD	ACE2	psi-mi:“MI:0407”(direct interaction)	0.440
ACE2	SFTPD	psi-mi:“MI:0407”(direct interaction)	0.440
UPK1A	fimH	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (13): DNAJC2 (Co-fractionation), DCN (Reconstituted Complex), SFTPD (Reconstituted Complex), SFTPD (Reconstituted Complex), SFTPD (Co-purification), SFTPD (Co-purification), SFTPD (Reconstituted Complex), SFTPD (Reconstituted Complex), SFTPD (Reconstituted Complex), S (Reconstituted Complex), SFTPD (Reconstituted Complex), SFTPD (Reconstituted Complex), SFTPD (Reconstituted Complex)

ESM2 similar proteins: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, P02745, P02746, P02747, P08125, P0C862, P12106, P14106, P20849, P23206, P23805, P31720, P31721, P31722, P35246, P35247, P35248, P42916, P50404, P83371, P98085, P98086, Q02105, Q05306, Q05722, Q0II24, Q0VF58, Q14993, Q15848, Q1PBC5, Q2KIV9, Q3Y5Z3, Q4ZJM7, Q4ZJN1, Q5E9E3, Q60994, Q641F3

Diamond homologs: A1XRN2, B1A4M7, B1A4N2, B1A4N8, B1A4P2, B1A4P6, B1A4P7, B1A4P8, B1A4P9, B1A4Q0, B1A4Q2, B1A4Q3, B1A4Q5, B1A4Q6, B1A4Q8, B1A4Q9, B1A4R0, B1A4R4, B2D1Y0, C0STK6, P0DQP8, P12842, P21755, P21756, P35242, P35247, P35248, P50404, P81077, P82142, Q1PBC5, Q6RXL1, Q8AXS4, Q8AYA2, Q95L88, Q9N1X4, Q9TT06, P06908, P23805, P35246

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CEBPA	“up-regulates quantity by expression”	SFTPD	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	SFTPD	“transcriptional regulation”
CEBPG	“up-regulates quantity by expression”	SFTPD	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

53 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	3
Benign	13

Top pathogenic / likely-pathogenic (0)

SpliceAI

863 predictions. Top by Δscore:

Variant	Effect	Δscore
10:79941513:CC:C	acceptor_gain	1.0000
10:79941514:CC:C	acceptor_gain	1.0000
10:79946529:T:A	donor_gain	1.0000
10:79938224:CTCAA:C	acceptor_gain	0.9900
10:79938226:CAA:C	acceptor_gain	0.9900
10:79938229:C:CC	acceptor_gain	0.9900
10:79940699:ACTC:A	donor_loss	0.9900
10:79940700:CTCA:C	donor_loss	0.9900
10:79940701:TCA:T	donor_loss	0.9900
10:79940702:CA:C	donor_loss	0.9900
10:79940704:C:CA	donor_loss	0.9900
10:79940786:CAT:C	acceptor_gain	0.9900
10:79940788:TCTG:T	acceptor_loss	0.9900
10:79940789:CT:C	acceptor_loss	0.9900
10:79940790:T:A	acceptor_loss	0.9900
10:79941392:CCTTA:C	donor_loss	0.9900
10:79941393:CTTAC:C	donor_loss	0.9900
10:79941394:TTA:T	donor_loss	0.9900
10:79941396:ACC:A	donor_loss	0.9900
10:79941415:C:CA	donor_gain	0.9900
10:79941511:GACC:G	acceptor_gain	0.9900
10:79941515:C:CC	acceptor_gain	0.9900
10:79941515:C:T	acceptor_gain	0.9900
10:79941515:CT:C	acceptor_loss	0.9900
10:79941516:T:C	acceptor_loss	0.9900
10:79946534:TGAGC:T	donor_gain	0.9900
10:79946545:TG:T	donor_gain	0.9900
10:79949064:A:AC	donor_gain	0.9900
10:79949065:C:CC	donor_gain	0.9900
10:79949065:CAG:C	donor_gain	0.9900

AlphaMissense

2384 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:79937900:C:A	W360C	0.999
10:79937900:C:G	W360C	0.999
10:79937969:C:A	W337C	0.998
10:79937969:C:G	W337C	0.998
10:79937902:A:G	W360R	0.997
10:79937902:A:T	W360R	0.997
10:79938137:G:C	C281W	0.995
10:79938138:C:G	C281S	0.995
10:79938139:A:T	C281S	0.995
10:79937928:C:G	C351S	0.994
10:79937929:A:T	C351S	0.994
10:79938008:G:C	F324L	0.994
10:79938008:G:T	F324L	0.994
10:79938010:A:G	F324L	0.994
10:79938186:A:C	F265C	0.993
10:79937862:C:G	C373S	0.992
10:79937863:A:G	C373R	0.992
10:79937863:A:T	C373S	0.992
10:79938009:A:C	F324C	0.992
10:79938138:C:T	C281Y	0.992
10:79937929:A:G	C351R	0.991
10:79938139:A:G	C281R	0.991
10:79937895:T:A	D362V	0.990
10:79937862:C:T	C373Y	0.989
10:79937971:A:G	W337R	0.989
10:79937971:A:T	W337R	0.989
10:79937861:G:C	C373W	0.988
10:79937901:C:G	W360S	0.988
10:79937927:A:C	C351W	0.987
10:79937928:C:T	C351Y	0.987

dbSNP variants (sampled 300 via entrez): RS1000082417 (10:79965225 T>C), RS1000270857 (10:79944550 T>C), RS1000316962 (10:79956724 G>A,T), RS1000372115 (10:79950977 TAA>T,TA), RS1000425731 (10:79950647 C>T), RS1000643978 (10:79978238 T>C), RS1000760969 (10:79952192 T>C), RS1000781451 (10:79948166 C>T), RS1000992887 (10:79955324 G>T), RS1001012149 (10:79945878 T>C), RS1001012994 (10:79975032 C>G), RS1001063975 (10:79948398 C>T), RS1001244966 (10:79969394 A>C), RS1001309384 (10:79981355 T>C), RS1001362795 (10:79981006 T>C)

Disease associations

OMIM: gene MIM:178635 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001737_24	Chronic obstructive pulmonary disease-related biomarkers	5.000000e-09
GCST001737_4	Chronic obstructive pulmonary disease-related biomarkers	2.000000e-27
GCST002318_32	Rheumatoid arthritis	9.000000e-09
GCST004147_30	Chronic obstructive pulmonary disease	2.000000e-08
GCST006959_10	Rheumatoid arthritis	8.000000e-08
GCST006959_124	Rheumatoid arthritis	1.000000e-06
GCST007431_159	Lung function (FEV1/FVC)	2.000000e-15
GCST007692_66	Chronic obstructive pulmonary disease	2.000000e-08
GCST011766_26	Chronic obstructive pulmonary disease	9.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005081	surfactant protein D measurement
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2176857 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression	3
sodium arsenite	increases expression	2
Air Pollutants	increases abundance, increases expression	2
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beryllium sulfate	increases expression	1
tetrabromobisphenol A	decreases expression	1
didecyldimethylammonium	increases expression	1
nickel monoxide	increases expression	1
CGP 52608	increases reaction, affects binding	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Aspirin	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Carbon Monoxide	increases abundance, increases expression	1
Glucose	decreases expression	1
Methylmercury Compounds	decreases expression	1
Nitrogen Dioxide	increases expression, increases abundance	1
Paraquat	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2185433	Binding	Displacement of biotinylated-TM PAA from human SP-D at 50 mM after 3 hrs by colorimetry	Target Selectivity of FimH Antagonists. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.