BPIFA1

Summary

BPIFA1 (BPI fold containing family A member 1, HGNC:15749) is a protein-coding gene on chromosome 20q11.21, encoding BPI fold-containing family A member 1 (Q9NP55). Lipid-binding protein which shows high specificity for the surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC).

This gene is the human homolog of murine plunc, and like the mouse gene, is specifically expressed in the upper airways and nasopharyngeal regions. The encoded antimicrobial protein displays antibacterial activity against Gram-negative bacteria. It is thought to be involved in inflammatory responses to irritants in the upper airways and may also serve as a potential molecular marker for detection of micrometastasis in non-small-cell lung cancer. Multiple transcript variants resulting from alternative splicing in the 3’ UTR have been detected, but the full-length nature of only three are known.

Source: NCBI Gene 51297 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_130852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15749
Approved symbol	BPIFA1
Name	BPI fold containing family A member 1
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	LUNX, bA49G10.5, SPLUNC1
Ensembl gene	ENSG00000198183
Ensembl biotype	protein_coding
OMIM	607412
Entrez	51297

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000354297, ENST00000375413, ENST00000375422, ENST00000863454, ENST00000955588, ENST00000955589

RefSeq mRNA: 3 — MANE Select: NM_130852 NM_001243193, NM_016583, NM_130852

CCDS: CCDS13217

Canonical transcript exons

ENST00000354297 — 9 exons

Exon	Start	End
ENSE00001048863	33237697	33237871
ENSE00001048866	33242056	33242119
ENSE00001048867	33238055	33238214
ENSE00001048868	33242487	33242561
ENSE00001048869	33240233	33240385
ENSE00001048870	33241385	33241469
ENSE00001048871	33239803	33239910
ENSE00001418677	33243107	33243306
ENSE00003846766	33235996	33236050

Expression profiles

Bgee: expression breadth broad, 67 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9012 / max 970.0789, expressed in 20 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184131	0.8838	20
209080	0.0174	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	99.96	gold quality
nasal cavity epithelium	UBERON:0005384	99.93	gold quality
nasal cavity mucosa	UBERON:0001826	99.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.60	gold quality
trachea	UBERON:0003126	99.41	gold quality
bronchus	UBERON:0002185	89.50	gold quality
epithelium of bronchus	UBERON:0002031	89.13	gold quality
bronchial epithelial cell	CL:0002328	86.53	gold quality
type B pancreatic cell	CL:0000169	80.57	gold quality
tongue	UBERON:0001723	80.47	gold quality
olfactory bulb	UBERON:0002264	80.45	gold quality
superior surface of tongue	UBERON:0007371	77.90	gold quality
body of tongue	UBERON:0011876	77.20	gold quality
diaphragm	UBERON:0001103	75.79	gold quality
tibialis anterior	UBERON:0001385	71.65	silver quality
epithelium of nasopharynx	UBERON:0001951	70.64	gold quality
adenohypophysis	UBERON:0002196	69.78	gold quality
thymus	UBERON:0002370	68.49	gold quality
adult organism	UBERON:0007023	67.12	gold quality
cervix squamous epithelium	UBERON:0006922	66.87	gold quality
CA1 field of hippocampus	UBERON:0003881	63.90	gold quality
hair follicle	UBERON:0002073	62.87	gold quality
left ventricle myocardium	UBERON:0006566	62.72	gold quality
cardiac muscle of right atrium	UBERON:0003379	62.22	gold quality
pharyngeal mucosa	UBERON:0000355	62.10	silver quality
ileal mucosa	UBERON:0000331	61.82	silver quality
quadriceps femoris	UBERON:0001377	61.03	gold quality
cerebellar vermis	UBERON:0004720	60.31	gold quality
pancreatic ductal cell	CL:0002079	59.94	silver quality
vastus lateralis	UBERON:0001379	59.41	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, JUN

miRNA regulators (miRDB)

22 targeting BPIFA1, 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-497-5P	99.92	71.83	2674
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-3194-5P	96.80	64.90	1027

Literature-anchored findings (GeneRIF, showing 40)

• members of the PLUNC family may function in the innate immune response in regions of the mouth, nose and lungs, which are sites of significant bacterial exposure (PMID:11971875)
• results provide the cloning and characterization of a tissue-specific novel gene and its possible relationship with airway diseases (PMID:12409287)
• There were three splicing variants in NASG 3’UTR. Its abnormal expression may be an important molecular event in NPC and lung cancer. (PMID:12753706)
• SPLUNC1 is found to be down-expressed in 34 of 48 nasopharyngeal carcinoma biopsies. (PMID:12874788)
• This study showed that plunc gene product is expressed both in vivo and in vitro, detailed a method for its purification and provided basic information on its biochemical properties in secretions. (PMID:12920053)
• PLUNC proteins mediate host defense functions in the oral, nasal and respiratory epithelia [review]. (PMID:15313462)
• SPLUNC1 protein is expressed at not only the serous glands and epithelium of the upper respiratory tract and digestive tract, but also in the oculi of embryos. (PMID:16195890)
• This research sheds new light on the mechanism of SPLUNC1 involvement in the host upper respiratory tract defense system. (PMID:16364440)
• SPLUNC1 is specifically and significantly increased in the epithelial cells of small airways of lungs from patients with cystic fibrosis. (PMID:17988392)
• This study shows that SPLUNC1 not only has the role of antibacteria and antivirus, but also inhibits the potential oncogenicity of epstein barr virus in respiratory epithelium. (PMID:18049866)
• PLUNC is a novel marker that distinguishes gastric hepatoid adenocarcinoma from primary hepatocellular carcinoma (PMID:18204429)
• Immunoblots performed on polymorphonuclear cell lysates and subcellular fractions indicate that PLUNC is present in the specific granules of the neutrophil. (PMID:18245229)
• LunX mRNA is the most specific gene marker for lung cancer and has potential diagnostic utility when measured in the peripheral blood and pleural fluid. (PMID:18513434)
• mRNA expression of LUNX, CK19 and CEA genes in the regional lymph nodes of NSCLC was significantly higher than that in those of benign lung diseases. (PMID:18646695)
• Expression of Cu/ZnSOD and PLUNC in in chronic sinusitis was higher than in normal tissue, and expression in nasal polyp tissue was lower than in normal tissue. (PMID:19119597)
• SPLUNC1 is secreted onto mucosal surfaces as a soluble volume sensor whose concentration and dilution can regulate ENaC activity and mucosal volumes, including that of airway surface liquid. (PMID:19541605)
• Data suggest that the PLUNC protein contributes to the surfactant properties of airway secretions, and that this activity may interfere with biofilm formation by an airway pathogen. (PMID:20161732)
• SPLUNC1 potently reduced surface levels of the epithelial sodium channel (ENaC)in bronchial epithelial cells and Xenopus laevis oocytes. (PMID:20519934)
• LUNX gene sequences from +3770 to +3959 bp and +14553 to +14652 bp possess the capacity to enhance gene transcription. (PMID:20855242)
• data have provided the first in vivo evidence that cSPLUNC1 functions to maintain homeostasis of the upper airway and, thereby, is critical for protection of the middle ear (PMID:20949060)
• The LUNX mRNA expression in the lymph nodes was closely related to the pathological type, cancer cell differentiation and clinical stage of non-small cell lung cancer. (PMID:21200090)
• PLUNC transgene is associated with enhanced bacterial killing and decreased inflammation after exposure with a major human airway pathogen, the Gram-negative bacterium Pseudomonas aeruginosa, both in vitro and in vivo. (PMID:21632717)
• PLUNC is a multifunctional protein, which plays a novel role in airway defences at the air/liquid interface (PMID:21787339)
• BPIFA1 protein displays bacteriocidal activity against Gram-negative bacteria. (PMID:21787346)
• RSV-positive boys had significantly less 25 kDa SPLUNC1 than RSV-negative boys while there were no significant differences among girls (PMID:21805676)
• genetic polymorphisms of SPLUNC1 protein confer risk of nasopharyngeal carcinoma in a Malaysian Chinese population (PMID:22213098)
• Reduced expression of antimicrobial PLUNC proteins in nasal polyp tissues of patients with chronic rhinosinusitis (PMID:22676062)
• P. aeruginosa treated with recombinant human SPLUNC1 protein showed decreased growth in vitro. (PMID:23132494)
• Sinusitis with positive P. aeruginosa bacterial culture is associated with decreased SPLUNC1 sinus mucosa expression. Repeated sinus surgeries are more frequently needed for these patients. (PMID:23371910)
• SPLUNC1 regulates NPC cell proliferation, differentiation and apoptosis through miR-141, which in turn regulates PTEN and p27 expression, and is negatively regulated by LMP1 (PMID:23472073)
• SPLUNC1 is a crucial component of mucosal innate immune defense against pulmonary infection. (PMID:23499554)
• In patients with chronic rhinosinusitis with nasal polyps, decreased PLUNC expression is associated with multibacterial colonization, specifically those mediated by Staphyloccocus aureus and Pseudomonas aeruginosa. (PMID:23644997)
• Data indicate that SPLUNC1 is an important component of mucosal innate immune defense against pulmonary inhaled particles. (PMID:23721177)
• SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections. (PMID:23741370)
• The changes in Lunx mRNA levels after chemotherapy can predict the prognosis of patients with MPEs caused by pulmonary carcinoma. (PMID:23759037)
• High LUNX mRNA expression correlated with lung cancer stage and distant metastases. (PMID:23810363)
• Short palate lung and nasal epithelial clone 1, the most abundant gene in airway epithelia, is the extracellular pH-sensitive factor that inhibits ENaC in normal but not cystic fibrosis airways. (PMID:24043776)
• the epithelial sodium channel inhibitory domain of SPLUNC1 may be cleaved away from the main molecule by neutrophil elastase (PMID:24124190)
• Our results indicate that BPIFA1 is a novel target for autoantibodies in cystic fibrosis. (PMID:24269518)
• SPLUNC1 is differentially modulated in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps. (PMID:24342548)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bpifa1	ENSMUSG00000027483
mus_musculus	Bpifa5	ENSMUSG00000027484
rattus_norvegicus	Bpifa1	ENSRNOG00000013859
rattus_norvegicus	Bpifa5	ENSRNOG00000013908
caenorhabditis_elegans		WBGENE00015544

Paralogs (12): BPIFB2 (ENSG00000078898), CETP (ENSG00000087237), PLTP (ENSG00000100979), BPI (ENSG00000101425), BPIFB1 (ENSG00000125999), LBP (ENSG00000129988), BPIFA2 (ENSG00000131050), BPIFA3 (ENSG00000131059), BPIFB6 (ENSG00000167104), BPIFC (ENSG00000184459), BPIFB3 (ENSG00000186190), BPIFB4 (ENSG00000186191)

Protein

Protein identifiers

BPI fold-containing family A member 1 — Q9NP55 (reviewed: Q9NP55)

Alternative names: Lung-specific protein X, Nasopharyngeal carcinoma-related protein, Palate lung and nasal epithelium clone protein, Secretory protein in upper respiratory tracts, Short PLUNC1, Tracheal epithelium-enriched protein, Von Ebner protein Hl

All UniProt accessions (1): Q9NP55

UniProt curated annotations — full annotation on UniProt →

Function. Lipid-binding protein which shows high specificity for the surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC). Plays a role in the innate immune responses of the upper airways. Reduces the surface tension in secretions from airway epithelia and inhibits the formation of biofilm by pathogenic Gram-negative bacteria, such as P.aeruginosa and K.pneumoniae. Negatively regulates proteolytic cleavage of SCNN1G, an event that is required for activation of the epithelial sodium channel (ENaC), and thereby contributes to airway surface liquid homeostasis and proper clearance of mucus. Plays a role in the airway inflammatory response after exposure to irritants. May attract macrophages and neutrophils.

Subunit / interactions. Monomer. Interacts (via N-terminus) with SCNN1B, a subunit of the heterotrimeric epithelial sodium channel (ENaC); this inhibits proteolytic activation of ENaC.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in lung, upper airways and nasopharyngeal regions, including trachea and nasal epithelium (at protein level). Specifically expressed in the secretory ducts and submucosal glands of tracheobronchial tissues (at protein level). Also expressed in the eye where it is detected in lacrimal gland, eyelid, conjunctiva and cornea (at protein level). Specifically localizes to epithelial cell layers in cornea, eyelid (basal epithelium) and conjunctiva (at protein level). Detected within acinar cells and ducts in the lacrimal and Meibomian glands (at protein level). In lung, shows highest expression in the trachea and progressive decrease from proximal (bronchial) to distal (bronchiolar) airways. Also expressed in lung cancers and some other types of cancer.

Post-translational modifications. May be N-glycosylated.

Induction. Up-regulated in response to all-trans retinoic acid (ATRA). Up-regulated in tear fluid of patients suffering from dry eye disease. Up-regulated in response to the pro-inflammatory cytokines IL1B and TNF, and the bacteria E.coli and P.aeruginosa.

Similarity. Belongs to the BPI/LBP/Plunc superfamily. Plunc family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NP55-1	1	yes
Q9NP55-2	2

RefSeq proteins (3): NP_001230122, NP_057667, NP_570913* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017942	Lipid-bd_serum_glycop_N	Domain
IPR017943	Bactericidal_perm-incr_a/b_dom	Homologous_superfamily
IPR051902	BPI_fold-superfamily_member	Family

Pfam: PF01273

UniProt features (34 total): strand 10, mutagenesis site 9, helix 7, turn 2, signal peptide 1, chain 1, sequence conflict 1, region of interest 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4KEG	X-RAY DIFFRACTION	2.5
4N4X	X-RAY DIFFRACTION	2.5
5I7J	X-RAY DIFFRACTION	2.54
5I7K	X-RAY DIFFRACTION	2.55
5I7L	X-RAY DIFFRACTION	2.6
4KGH	X-RAY DIFFRACTION	2.81
4KGO	X-RAY DIFFRACTION	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP55-F1	79.06	0.49

Functional residue map

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

Disulfide bonds (1): 180–224

Mutagenesis-validated functional residues (9):

Position	Phenotype
203–204	no effect on surfactant activity; when associated with 191-a–a-195.
214	forms an artificial disulfide bond. reduced surfactant activity; when associated with c-76.
224	no effect on surfactant activity; when associated with a-180.
253	forms an artificial disulfide bond. negligible effect on surfactant activity; when associated with c-48.
48	forms an artificial disulfide bond. negligible effect on surfactant activity; when associated with c-253.
76	forms an artificial disulfide bond. reduced surfactant activity; when associated with c-214.
87–92	impaired surfactant activity and lipopolysaccharide (lps) binding. reduced bacteriostatic activity.
180	no effect on surfactant activity; when associated with a-224.
191–195	no effect on surfactant activity; when associated with 203-a-a-204.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6803157	Antimicrobial peptides
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 97 (showing top): FREAC2_01, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, MODULE_255, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_317, HNF1_Q6, FOXD3_01, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, FREAC3_01, GOBP_REGULATION_OF_BIOLOGICAL_PROCESS_INVOLVED_IN_SYMBIOTIC_INTERACTION, GOBP_CELL_AGGREGATION, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTRASPECIES_INTERACTION_BETWEEN_ORGANISMS

GO Biological Process (11): immune response in nasopharyngeal-associated lymphoid tissue (GO:0002395), antibacterial humoral response (GO:0019731), surfactant homeostasis (GO:0043129), innate immune response (GO:0045087), multicellular organismal-level water homeostasis (GO:0050891), defense response to virus (GO:0051607), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), negative regulation of single-species biofilm formation in or on host organism (GO:1900229), regulation of sodium ion transmembrane transport (GO:1902305), immune system process (GO:0002376), defense response to bacterium (GO:0042742)

GO Molecular Function (2): lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antimicrobial humoral response	2
multicellular organismal-level chemical homeostasis	2
defense response	2
binding	2
immune response in gut-associated lymphoid tissue	1
defense response to bacterium	1
immune response	1
defense response to symbiont	1
regulation of body fluid levels	1
response to virus	1
single-species biofilm formation in or on host organism	1
negative regulation of single-species biofilm formation	1
regulation of single-species biofilm formation in or on host organism	1
regulation of sodium ion transport	1
sodium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
biological_process	1
response to bacterium	1
cellular anatomical structure	1

Protein interactions and networks

STRING

932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPIFA1	PLTP	P55058	836
BPIFA1	COX7B2	Q8TF08	825
BPIFA1	CETP	P11597	759
BPIFA1	BPIFB4	P59827	742
BPIFA1	LTF	P02788	724
BPIFA1	BPI	P17213	720
BPIFA1	MUC5AC	P98088	664
BPIFA1	BPIFB2	Q8N4F0	663
BPIFA1	BPIFB6	Q8NFQ5	647
BPIFA1	MECOM	Q03112	635
BPIFA1	MUC5B	Q9HC84	597
BPIFA1	BPIFB3	P59826	583
BPIFA1	ELANE	P08246	576
BPIFA1	LBP	P18428	571
BPIFA1	TNFRSF19	Q9NS68	547

IntAct

205 interactions, top by confidence:

A	B	Type	Score
GFAP	NEFL	psi-mi:“MI:0914”(association)	0.850
HNRNPCL1	HNRNPC	psi-mi:“MI:0914”(association)	0.670
UBQLN1	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
TLE5	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
ELK3	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
TFG	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	RSPH14	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	ALKBH4	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	INIP	psi-mi:“MI:0915”(physical association)	0.560
NUP54	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
HCK	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	PEF1	psi-mi:“MI:0915”(physical association)	0.560
NPAS2	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
HNF1B	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
EML2	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
INCA1	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
CRYBA2	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
KRT3	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
HSFY1	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
PITX1	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	TCF7L2	psi-mi:“MI:0915”(physical association)	0.560
PPIH	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
PSMB1	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560
TEPSIN	BPIFA1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (111): BPIFA1 (Two-hybrid), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFB3 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), BPIFA1 (Two-hybrid)

ESM2 similar proteins: A0A0N6WHT4, A0A0R4IVV0, A0JPN3, A2BGH0, D4A1W8, E9Q414, F6KSY2, G3HIK4, O08601, P04114, P07743, P11597, P22687, P25914, P47896, P55058, P55065, P55158, P59826, P59827, P79124, P79125, P82615, P97361, Q05701, Q05704, Q28685, Q5XW65, Q61114, Q62165, Q63313, Q63471, Q7TMA5, Q80ZU7, Q865V1, Q86YQ2, Q8BU51, Q8C186, Q8C1E1, Q8K4I4

Diamond homologs: P97361, Q5XW65, Q8K4I4, Q8SPU5, Q9CQX3, Q9D9J8, Q9NP55, Q8TDL5, Q8SPF8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1324 predictions. Top by Δscore:

Variant	Effect	Δscore
20:33238343:GAC:G	donor_gain	1.0000
20:33242482:TTTA:T	acceptor_loss	1.0000
20:33242484:TA:T	acceptor_loss	1.0000
20:33242485:A:AG	acceptor_gain	1.0000
20:33242486:G:A	acceptor_loss	1.0000
20:33242486:G:GG	acceptor_gain	1.0000
20:33242486:GA:G	acceptor_gain	1.0000
20:33242486:GAC:G	acceptor_gain	1.0000
20:33242486:GACAT:G	acceptor_gain	1.0000
20:33237857:G:GT	donor_gain	0.9900
20:33238136:G:GT	donor_gain	0.9900
20:33238215:G:GG	donor_gain	0.9900
20:33241465:GCAAC:G	donor_gain	0.9900
20:33241470:G:GG	donor_gain	0.9900
20:33242116:GTTA:G	donor_gain	0.9900
20:33242472:T:A	acceptor_gain	0.9900
20:33242476:T:TA	acceptor_gain	0.9900
20:33242486:GACA:G	acceptor_gain	0.9900
20:33236047:CCAGG:C	donor_loss	0.9800
20:33236051:G:GA	donor_loss	0.9800
20:33236052:T:G	donor_loss	0.9800
20:33237688:T:TA	acceptor_gain	0.9800
20:33237745:G:A	acceptor_gain	0.9800
20:33242468:T:A	acceptor_gain	0.9800
20:33237689:G:A	acceptor_gain	0.9700
20:33237743:ACG:A	acceptor_gain	0.9700
20:33237744:C:CA	acceptor_gain	0.9700
20:33237744:C:G	acceptor_gain	0.9700
20:33237868:AATGG:A	donor_loss	0.9700
20:33237869:ATGGT:A	donor_loss	0.9700

AlphaMissense

1624 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:33242059:T:C	C224R	0.965
20:33239874:T:A	V131D	0.951
20:33240342:T:C	C180R	0.950
20:33242059:T:A	C224S	0.945
20:33242060:G:C	C224S	0.945
20:33240285:G:C	A161P	0.943
20:33242060:G:A	C224Y	0.943
20:33240342:T:A	C180S	0.942
20:33240343:G:C	C180S	0.942
20:33240343:G:A	C180Y	0.936
20:33240344:C:G	C180W	0.935
20:33242061:C:G	C224W	0.932
20:33239849:A:C	S123R	0.921
20:33239851:C:A	S123R	0.921
20:33239851:C:G	S123R	0.921
20:33238070:T:C	L59P	0.915
20:33239880:T:C	I133T	0.914
20:33239865:G:C	R128P	0.913
20:33240274:T:C	L157P	0.913
20:33242069:T:A	V227D	0.913
20:33241459:T:A	V219D	0.912
20:33239868:T:C	L129P	0.908
20:33240292:T:G	I163S	0.908
20:33238058:T:A	L55H	0.905
20:33238070:T:A	L59Q	0.905
20:33240292:T:C	I163T	0.902
20:33239898:T:A	L139H	0.901
20:33237863:T:C	L51S	0.899
20:33240370:T:C	I189T	0.899
20:33239886:T:A	L135H	0.898

dbSNP variants (sampled 300 via entrez): RS1000171397 (20:33234828 T>C), RS1000432932 (20:33243454 T>A), RS1000706868 (20:33236379 C>G), RS1000739193 (20:33241827 T>A,G), RS1001462224 (20:33238577 T>A), RS1001885216 (20:33239098 C>T), RS1002910272 (20:33241477 G>A,C), RS1002944834 (20:33235595 T>C), RS1003413846 (20:33234743 G>A), RS1003685819 (20:33234454 T>A,C), RS1003916595 (20:33242964 T>A,C), RS1004458368 (20:33240061 T>C), RS1004471405 (20:33242720 A>G), RS1004592634 (20:33234359 A>G,T), RS1004798046 (20:33238881 C>T)

Disease associations

OMIM: gene MIM:607412 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002361_14	Smooth-surface caries	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	3
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	affects expression	1
Estradiol	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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