CD207

Summary

CD207 (CD207 molecule, HGNC:17935) is a protein-coding gene on chromosome 2p13.3, encoding C-type lectin domain family 4 member K (Q9UJ71). Calcium-dependent lectin displaying mannose-binding specificity.

The protein encoded by this gene is expressed only in Langerhans cells which are immature dendritic cells of the epidermis and mucosa. It is localized in the Birbeck granules, organelles present in the cytoplasm of Langerhans cells and consisting of superimposed and zippered membranes. It is a C-type lectin with mannose binding specificity, and it has been proposed that mannose binding by this protein leads to internalization of antigen into Birbeck granules and providing access to a nonclassical antigen-processing pathway. Mutations in this gene result in Birbeck granules deficiency or loss of sugar binding activity.

Source: NCBI Gene 50489 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Birbeck granule deficiency (No Known Disease Relationship, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 67 total
• Druggable target: yes
• MANE Select transcript: NM_015717

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17935
Approved symbol	CD207
Name	CD207 molecule
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Langerin, CLEC4K
Ensembl gene	ENSG00000116031
Ensembl biotype	protein_coding
OMIM	604862
Entrez	50489

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000410009

RefSeq mRNA: 1 — MANE Select: NM_015717 NM_015717

CCDS: CCDS74520

Canonical transcript exons

ENST00000410009 — 6 exons

Exon	Start	End
ENSE00000760756	70831701	70831819
ENSE00000760757	70832900	70833051
ENSE00000760758	70833646	70834020
ENSE00001588982	70835491	70835607
ENSE00001589135	70835704	70835816
ENSE00001949188	70830211	70831200

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 93.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.1793 / max 3220.5457, expressed in 35 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29048	3.1793	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	93.84	gold quality
skin of hip	UBERON:0001554	92.46	gold quality
skin of abdomen	UBERON:0001416	84.01	gold quality
zone of skin	UBERON:0000014	83.37	gold quality
skin of leg	UBERON:0001511	82.57	gold quality
upper arm skin	UBERON:0004263	82.32	gold quality
mammalian vulva	UBERON:0000997	78.38	gold quality
nipple	UBERON:0002030	77.76	gold quality
epithelium of esophagus	UBERON:0001976	76.71	gold quality
esophagus squamous epithelium	UBERON:0006920	76.04	gold quality
oral cavity	UBERON:0000167	70.70	gold quality
squamous epithelium	UBERON:0006914	69.98	gold quality
gingiva	UBERON:0001828	69.69	gold quality
gingival epithelium	UBERON:0001949	69.12	gold quality
esophagus mucosa	UBERON:0002469	67.83	gold quality
rectum	UBERON:0001052	67.26	gold quality
palpebral conjunctiva	UBERON:0001812	66.66	gold quality
penis	UBERON:0000989	66.58	gold quality
gall bladder	UBERON:0002110	66.48	gold quality
ileal mucosa	UBERON:0000331	65.16	silver quality
pharyngeal mucosa	UBERON:0000355	62.63	gold quality
cervix epithelium	UBERON:0004801	62.45	gold quality
lower esophagus mucosa	UBERON:0035834	62.29	gold quality
mucosa of transverse colon	UBERON:0004991	60.96	gold quality
duodenum	UBERON:0002114	59.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.24	gold quality
hair follicle	UBERON:0002073	59.19	silver quality
esophagus	UBERON:0001043	58.34	gold quality
smooth muscle tissue	UBERON:0001135	57.58	gold quality
vagina	UBERON:0000996	57.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	72.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT5A

miRNA regulators (miRDB)

42 targeting CD207, 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-4533	100.00	69.48	2758
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-670-3P	99.03	68.88	2404

Literature-anchored findings (GeneRIF, showing 40)

• langerin was expressed by Langerhans cells (PMID:12352970)
• Langerin is a potent langerhans cells -specific regulator of membrane superimposition and zippering, representing a key molecule to trace Langerhans cells [Review]. (PMID:14610287)
• CD1a and langerin have roles in antigen presentation to T cells (PMID:14991068)
• The Langerin-positive cells strictly colonized the epidermis and no cells were found in the dermis. (PMID:15222130)
• Expression of mutated Langerin in human fibroblasts induces tubular-like structures that are negative for Birbeck granules-specific antibodies and do not resemble the characteristic structural features of Birbeck granules. (PMID:15816828)
• Electron microscopy analysis demonstrated a colocalization of human papillomavirus 16 virus-like particles and langerin, which is expressed only by Langerhans cells (PMID:15831940)
• The effects of the amino acid changes on the activity of langerin were examined by expressing each of the polymorphic forms. (PMID:16567809)
• Langerin prevents HIV-1 transmission by Langernhans cells. (PMID:17334373)
• Langerin transgenic mice have substantially reduced numbers of epidermal langerhans cells, demonstrating that TGFbeta1 acts directly on these cells. (PMID:17938236)
• The carbohydrate-recognition domain of human Langerin was crystallized followed by X-ray analyses to resolutions of 2.5A for apo-Langerin and to 1.6A and 2.1A for the complexes with mannose and maltose, respectively. (PMID:18061677)
• overproduction, purification and crystallization of the langerin carbohydrate binding domain is reported (PMID:18259063)
• Immunohistochemical evaluation of langerin expression may have utility in substantiating a diagnosis of Langerhans cell histiocytosis and separating this disorder from other non-Langerhans cell histiocytic proliferations. (PMID:18277880)
• Transgenic langerin effectively mediates antigen presentation in vivo by targeting its receptor in appropriate mouse dendritic cell subsets of draining lymph nodes and spleen; peptide major histocompatibility I and II complexes persist for days. (PMID:18322168)
• Data show that the expression of CD1a and CD207 is markedly down-regulated in CA epidermis. (PMID:19426597)
• In a transgenic mouse model, the langerin-expressing subset of CD8alpha-positive dendritic cells is crucially involved in priming and differentiation of responses to cross-presented antigen. (PMID:19923446)
• Langerin mediates diverse functions on Langerhans cells through dual recognition of sulfated as well as mannosylated glycans by its uniquely evolved C-type carbohydrate-recognition domain (PMID:20026605)
• Langerin is the major fungal pathogen receptor on human Langerhans cells that recognizes pathogenic and commensal fungi. (PMID:20097424)
• Trimeric structure of langerin. (PMID:20181944)
• Activation of CD8-positive T cells following intradermal plasmid DNA immunization depends on directly transfected langerin-positive dermal dendritic cells and dermal DCs. (PMID:20713888)
• Crystal structures of the carbohydrate-recognition domain from langerin bound to oligomannoses, blood group B antigen, and a fragment of beta-glucan reveal binding to mannose, fucose, and glucose by Ca(2+) coordination of hydroxyl groups. (PMID:21112338)
• Unlike selective Langerhans cell deficiency, ablation of all langerin-positive dendritic cells abrogates activation of IFN-gamma-producing and cytolytic CD8-positive T cells following gene gun vaccination. (PMID:21187444)
• This study involves a comprehensive comparison of the glycan specificities of both the carbohydrate-recognition domains (CRDs) of DC-SIGN and Langerin. (PMID:21540232)
• measles virus receptor on Langergans cells (PMID:21739428)
• A langerin-cre recombinase transgenic knockin mouse strain is generated that efficiently targets Langerhans cells and other langerin-positive dendritic cells, in particular, in the dermis and the lung. (PMID:21998450)
• binding properties of langerin (PMID:23226363)
• Altered langerin function in individuals with the linked N288D and K313I polymorphisms may affect susceptibility to infection by microorganisms. (PMID:24217250)
• This study shows that mutations in the Langerin gene are present in the analysed populations at different genotypic and allelic frequencies and further studies should be conducted to verify the role of these mutations in HIV-1 susceptibility. (PMID:24676666)
• Both phases of HIV transfer from eLCs to T cells were inhibited when eLCs were pretreated with a mAb to langerin CRD or when HIV was pretreated with a soluble langerin trimeric extracellular domain or by a CRD homolog. (PMID:25070850)
• However, the superoxide dismutase C (SodC) protein of the Mycobacterium leprae cell wall was identified as a langerin-reactive ligand. (PMID:25422308)
• Langerin is not expressed by freshly isolated CD1c(+) blood DCs but is rapidly induced on CD1c(+) DCs by serum or TGF-beta via an ALK-3-dependent pathway. (PMID:25516751)
• The authors not only show that langerin and caveolin-1 co-localize at the cell membrane and in vesicles but that caveolin-1 mediated HIV-1 uptake is an intrinsic restriction mechanism present in human Langerhans cells that prevents HIV-1 infection. (PMID:25551286)
• Cell-sorting experiments demonstrated that IDO1 expression is found in a subset of CD1a(+)CD14(-)langerin(+) cells, expressing CD103 (PMID:25584868)
• The impact of two carbohydrate recognition domains mutations, W264R and F241L, on langerin structure, function, and Birbeck granules assembly. (PMID:25650933)
• Langerin binds heparin (HEP)-like oligosaccharides in two different binding sites depending on the ligand size. (PMID:25747117)
• Data suggest that Langerin (CD207)-mediated binding of Yersinia pestis to antigen-presenting cells (APCs) may promote its dissemination and infection. (PMID:25829141)
• the data provide evidence that human Langerhans cells are able to cross-present antigens after langerin-mediated internalization. (PMID:26456691)
• This study is the first to demonstrate that langerin represents an authentic receptor that binds and internalizes influenza A virus to facilitate infection. (PMID:26468543)
• We suggest that CD207 gene polymorphisms rs13421115 and rs17718987 increase the risk of development of end-stage renal disease. (PMID:27234728)
• Kinetic and Structural Studies of Interactions between Glycosaminoglycans and Langerin (PMID:27447199)
• Bacterial Polysaccharide Specificity of the Pattern Recognition Receptor Langerin Is Highly Species-dependent (PMID:27903635)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
danio_rerio	asgr1c.2	ENSDARG00000046092
danio_rerio	asgrl1	ENSDARG00000046142
danio_rerio	si:dkey-61f9.1	ENSDARG00000070414
danio_rerio	asgr1a	ENSDARG00000095963
danio_rerio	si:cabz01007816.2	ENSDARG00000102537
danio_rerio	asgr1b	ENSDARG00000103480
danio_rerio	si:ch211-283g2.5	ENSDARG00000108953
danio_rerio		ENSDARG00000111755
danio_rerio		ENSDARG00000112842
mus_musculus	Cd207	ENSMUSG00000034783
rattus_norvegicus	Cd207	ENSRNOG00000013222
drosophila_melanogaster	tfc	FBGN0035199
drosophila_melanogaster	CG14866	FBGN0038315
drosophila_melanogaster	lectin-46Cb	FBGN0040092
drosophila_melanogaster	lectin-46Ca	FBGN0040093
drosophila_melanogaster	lectin-33A	FBGN0040096
drosophila_melanogaster	CG34033	FBGN0054033
caenorhabditis_elegans	clec-87	WBGENE00007709
caenorhabditis_elegans	clec-91	WBGENE00014117
caenorhabditis_elegans		WBGENE00016088
caenorhabditis_elegans		WBGENE00018692
caenorhabditis_elegans		WBGENE00019606

Paralogs (14): CD209 (ENSG00000090659), FCER2 (ENSG00000104921), CLEC4M (ENSG00000104938), CLEC4A (ENSG00000111729), CLEC10A (ENSG00000132514), ASGR1 (ENSG00000141505), CLEC4F (ENSG00000152672), ASGR2 (ENSG00000161944), CLEC4E (ENSG00000166523), CLEC4D (ENSG00000166527), CLEC4G (ENSG00000182566), CLEC17A (ENSG00000187912), CLEC4C (ENSG00000198178), CLEC6A (ENSG00000205846)

Protein

Protein identifiers

C-type lectin domain family 4 member K — Q9UJ71 (reviewed: Q9UJ71)

Alternative names: Langerin

All UniProt accessions (1): Q9UJ71

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells. Major receptor on primary Langerhans cells for Candida species, Saccharomyces species, and Malassezia furfur. Protects against human immunodeficiency virus-1 (HIV-1) infection. Binds to high-mannose structures present on the envelope glycoprotein which is followed by subsequent targeting of the virus to the Birbeck granules leading to its rapid degradation.

Subunit / interactions. Homotrimer.

Subcellular location. Membrane.

Tissue specificity. Exclusively expressed by Langerhans cells. Expressed in astrocytoma and malignant ependymoma, but not in normal brain tissues.

Disease relevance. Birbeck granule deficiency (BIRGD) [MIM:613393] A condition characterized by the absence of Birbeck granules in epidermal Langerhans cells. Despite the lack of Birbeck granules, Langerhans cells are present in normal numbers and have normal morphologic characteristics and antigen-presenting capacity. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-type lectin domain mediates dual recognition of both sulfated and mannosylated glycans.

RefSeq proteins (1): NP_056532* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR033989	CD209-like_CTLD	Domain
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00059

UniProt features (37 total): strand 8, sequence variant 7, helix 6, mutagenesis site 4, glycosylation site 3, topological domain 2, disulfide bond 2, chain 1, transmembrane region 1, turn 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
4AK8	X-RAY DIFFRACTION	1.4
3C22	X-RAY DIFFRACTION	1.5
3P7G	X-RAY DIFFRACTION	1.5
7YTQ	X-RAY DIFFRACTION	1.6
3P5G	X-RAY DIFFRACTION	1.6
3P5H	X-RAY DIFFRACTION	1.61
3P5E	X-RAY DIFFRACTION	1.7
4N32	X-RAY DIFFRACTION	1.75
4N34	X-RAY DIFFRACTION	1.75
3P5F	X-RAY DIFFRACTION	1.75
3P5I	X-RAY DIFFRACTION	1.8
3P5D	X-RAY DIFFRACTION	1.8
5G6U	X-RAY DIFFRACTION	1.84
4N33	X-RAY DIFFRACTION	1.85
4N35	X-RAY DIFFRACTION	1.85
4N36	X-RAY DIFFRACTION	1.85
4N37	X-RAY DIFFRACTION	2
4N38	X-RAY DIFFRACTION	2
3KQG	X-RAY DIFFRACTION	2.3
3P7H	X-RAY DIFFRACTION	2.3
3P7F	X-RAY DIFFRACTION	2.5
7WZ8	ELECTRON MICROSCOPY	6.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJ71-F1	87.13	0.74

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 (2): 295–311, 223–319

Glycosylation sites (3): 87, 113, 180

Mutagenesis-validated functional residues (4):

Position	Phenotype
285	loss of binding to 6’-sulfo-lacnac and invertase.
287	loss of binding to 6’-sulfo-lacnac and invertase.
299	loss of binding to 6’-sulfo-lacnac.
313	loss of binding to 6’-sulfo-lacnac and 6-sulfo-glcnac.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)

MSigDB gene sets: 88 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, JAEGER_METASTASIS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOCC_CELL_SURFACE, GOCC_COATED_VESICLE, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_VIRUS, GOCC_CLATHRIN_COATED_VESICLE, GOCC_ENDOCYTIC_VESICLE, GOCC_ENDOCYTIC_VESICLE_MEMBRANE, GOCC_EARLY_ENDOSOME_MEMBRANE, GOCC_CLATHRIN_COATED_ENDOCYTIC_VESICLE, GOCC_SIDE_OF_MEMBRANE

GO Biological Process (2): immune response (GO:0006955), defense response to virus (GO:0051607)

GO Molecular Function (4): D-mannose binding (GO:0005537), carbohydrate binding (GO:0030246), pattern recognition receptor activity (GO:0038187), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endocytic vesicle (GO:0030139), clathrin-coated endocytic vesicle membrane (GO:0030669), early endosome membrane (GO:0031901), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Antigen processing-Cross presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
immune system process	1
response to stimulus	1
defense response	1
response to virus	1
monosaccharide binding	1
signaling receptor activity	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cytoplasmic vesicle	1
clathrin-coated vesicle membrane	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1
early endosome	1
endosome membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD207	CD1A	P06126	937
CD207	CD1E	P15812	930
CD207	CD1B	P29016	923
CD207	ITIH4	Q14624	921
CD207	CD1C	P29017	919
CD207	CD1D	P15813	907
CD207	ITGAX	P20702	838
CD207	LY75	O60449	784
CD207	CD4	P01730	752
CD207	LAMP3	Q9UQV4	750
CD207	ITGAE	P38570	728
CD207	CD86	P42081	728
CD207	CLEC7A	Q9BXN2	727
CD207	ITGAM	P11215	657
CD207	CD68	P34810	646

IntAct

43 interactions, top by confidence:

A	B	Type	Score
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
CD207	GRAMD2B	psi-mi:“MI:0915”(physical association)	0.720
GRAMD2B	CD207	psi-mi:“MI:0915”(physical association)	0.720
CD207	CREB3	psi-mi:“MI:0915”(physical association)	0.560
SCD	CD207	psi-mi:“MI:0915”(physical association)	0.560
ZCCHC12	CD207	psi-mi:“MI:0915”(physical association)	0.560
CD207	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
SEC22A	CD207	psi-mi:“MI:0915”(physical association)	0.560
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
S	CD207	psi-mi:“MI:0407”(direct interaction)	0.440
CD207	UBA52	psi-mi:“MI:0915”(physical association)	0.400
PDE4DIP	A2ML1	psi-mi:“MI:0914”(association)	0.350
SUSD3	IGLL5	psi-mi:“MI:0914”(association)	0.350
KLHL11	PIPSL	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
RIPPLY3	A2ML1	psi-mi:“MI:0914”(association)	0.350
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350
SCARA3	DEGS1	psi-mi:“MI:0914”(association)	0.350
CLEC4F	ITGAV	psi-mi:“MI:0914”(association)	0.350
C18orf21	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
ATP6AP2	KLK10	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): CD207 (Affinity Capture-MS), CD207 (Affinity Capture-MS), CREB3 (Two-hybrid), GRAMD3 (Two-hybrid), CD207 (Affinity Capture-MS), CD207 (Affinity Capture-MS), CD207 (Affinity Capture-MS), CD207 (Affinity Capture-MS), CD207 (Two-hybrid), SEC22A (Two-hybrid), ERGIC3 (Two-hybrid), GRAMD3 (Two-hybrid), ZCCHC12 (Two-hybrid), CD207 (Proximity Label-MS), CD207 (Reconstituted Complex)

ESM2 similar proteins: A4KWA1, D4AD02, O70156, O70215, P20937, P21854, P21855, P26715, P26717, P27471, P27811, P27812, P27814, P60883, Q149M0, Q2HXU8, Q2NL33, Q504P2, Q5QGZ9, Q60651, Q60652, Q60653, Q60654, Q60660, Q60682, Q64329, Q6QLQ4, Q6UXN8, Q6WRU0, Q80ZC8, Q8BRU4, Q8BWY2, Q8CJC7, Q8HY02, Q8HY04, Q8HY06, Q8MI05, Q8NC01, Q8VBX4, Q8VD98

Diamond homologs: A4KWA1, A4KWA5, A4KWA6, A4KWA8, O89335, P02706, P08290, P0C7M8, P0C7M9, P14371, P24721, P26715, P26717, P34927, P37217, Q07108, Q07444, Q0H8B9, Q0ZCA7, Q5M9I1, Q60660, Q6EIG7, Q6QLQ4, Q6UVW9, Q6UXN8, Q80XD9, Q8BWY2, Q8C1T8, Q8HY02, Q8HY10, Q8HY11, Q8HY12, Q8IUN9, Q8MIS5, Q8N1N0, Q8VI21, Q8WTT0, Q90WJ8, Q91V08, Q92478

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	5
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

1240 predictions. Top by Δscore:

Variant	Effect	Δscore
2:70831695:GCTT:G	donor_loss	1.0000
2:70831696:CTTA:C	donor_loss	1.0000
2:70831699:A:AT	donor_loss	1.0000
2:70831709:TTGG:T	donor_gain	1.0000
2:70831817:CTC:C	acceptor_gain	1.0000
2:70832898:ACC:A	donor_loss	1.0000
2:70832899:C:CG	donor_loss	1.0000
2:70832899:CCTG:C	donor_gain	1.0000
2:70833644:A:AC	donor_gain	1.0000
2:70833645:C:CC	donor_gain	1.0000
2:70833645:CT:C	donor_gain	1.0000
2:70834019:ATC:A	acceptor_loss	1.0000
2:70834020:TC:T	acceptor_loss	1.0000
2:70834021:C:CG	acceptor_loss	1.0000
2:70835489:A:AC	donor_gain	1.0000
2:70835490:C:CC	donor_gain	1.0000
2:70830856:T:A	donor_gain	0.9900
2:70831699:A:AC	donor_gain	0.9900
2:70831699:AC:A	donor_gain	0.9900
2:70831700:C:CC	donor_gain	0.9900
2:70831700:CC:C	donor_gain	0.9900
2:70831700:CCT:C	donor_gain	0.9900
2:70831700:CCTCA:C	donor_gain	0.9900
2:70831815:AACTC:A	acceptor_gain	0.9900
2:70831818:TC:T	acceptor_gain	0.9900
2:70831819:CC:C	acceptor_gain	0.9900
2:70831820:C:CC	acceptor_gain	0.9900
2:70831820:CTGTA:C	acceptor_loss	0.9900
2:70833049:CAT:C	acceptor_gain	0.9900
2:70833052:C:CC	acceptor_gain	0.9900

AlphaMissense

2152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:70831119:C:A	W306C	0.986
2:70831119:C:G	W306C	0.986
2:70831739:C:A	W266C	0.985
2:70831739:C:G	W266C	0.985
2:70832948:A:C	C223W	0.985
2:70832949:C:T	C223Y	0.985
2:70831153:C:G	C295S	0.984
2:70831154:A:T	C295S	0.984
2:70831121:A:G	W306R	0.982
2:70831121:A:T	W306R	0.982
2:70832962:C:G	A219P	0.982
2:70831194:C:A	W281C	0.980
2:70831194:C:G	W281C	0.980
2:70832949:C:G	C223S	0.980
2:70832950:A:T	C223S	0.980
2:70832969:C:A	W216C	0.977
2:70832969:C:G	W216C	0.977
2:70831081:C:G	C319S	0.975
2:70831082:A:T	C319S	0.975
2:70831086:G:C	F317L	0.975
2:70831086:G:T	F317L	0.975
2:70831088:A:G	F317L	0.975
2:70831105:C:T	C311Y	0.975
2:70831153:C:T	C295Y	0.975
2:70831105:C:G	C311S	0.974
2:70831106:A:T	C311S	0.974
2:70831741:A:G	W266R	0.974
2:70831741:A:T	W266R	0.974
2:70832950:A:G	C223R	0.973
2:70831081:C:T	C319Y	0.971

dbSNP variants (sampled 300 via entrez): RS1000314217 (2:70827690 C>A), RS1000644102 (2:70828605 G>A,C), RS1000678255 (2:70828873 C>G,T), RS1001263790 (2:70831871 A>G,T), RS1001317550 (2:70826465 C>A,T), RS1001695245 (2:70832143 A>G), RS1002423877 (2:70836674 C>T), RS1002489450 (2:70836966 T>C,G), RS1003091892 (2:70834625 C>T), RS1003163812 (2:70834746 A>G), RS1003663913 (2:70825128 A>G), RS1004011327 (2:70830786 C>T), RS1004539733 (2:70832179 C>T), RS1004643645 (2:70826795 T>G), RS1004716051 (2:70825457 T>A,C)

Disease associations

OMIM: gene MIM:604862 | disease phenotypes: MIM:613393

GenCC curated gene-disease

Disease	Classification	Inheritance
Birbeck granule deficiency	No Known Disease Relationship	Autosomal dominant

Mondo (1): Birbeck granule deficiency (MONDO:0013251)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002380_1	Erythema nodosum in inflammatory bowel disease	3.000000e-06
GCST002481_1	Acne (severe)	5.000000e-06
GCST003184_12	Atopic dermatitis	2.000000e-07
GCST003184_4	Atopic dermatitis	9.000000e-09
GCST010397_16	Gut microbiota (bacterial taxa, rank normal transformation method)	1.000000e-06
GCST012020_38	Serum metabolite levels	1.000000e-11
GCST012310_21	Schizophrenia x sex interaction	9.000000e-06
GCST012311_30	Schizophrenia x sex interaction	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2176853 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
decabromobiphenyl ether	affects expression	1
nickel sulfate	decreases expression, increases reaction	1
CGP 52608	affects binding, increases reaction	1
pyrazolanthrone	decreases expression, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2185428	Binding	Displacement of biotinylated-TM PAA from human langerin after 3 hrs by colorimetry	Target Selectivity of FimH Antagonists. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7BL	Abeomics CHO-K1 Langerin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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