TAPBPL

Summary

TAPBPL (TAP binding protein like, HGNC:30683) is a protein-coding gene on chromosome 12p13.31, encoding Tapasin-related protein (Q9BX59). Component of the antigen processing and presentation pathway, which binds to MHC class I coupled with beta2-microglobulin/B2M.

Tapasin, or TAPBP (MIM 601962), is a member of the variable-constant Ig superfamily that links major histocompatibility complex (MHC) class I molecules to the transporter associated with antigen processing (TAP; see MIM 170260) in the endoplasmic reticulum (ER). The TAPBP gene is located near the MHC complex on chromosome 6p21.3. TAPBPL is a member of the Ig superfamily that is localized on chromosome 12p13.3, a region somewhat paralogous to the MHC.

Source: NCBI Gene 55080 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 205 total — 6 pathogenic, 4 likely-pathogenic
• MANE Select transcript: NM_018009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30683
Approved symbol	TAPBPL
Name	TAP binding protein like
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	TAPBP-R, FLJ10143, TAPBPR
Ensembl gene	ENSG00000139192
Ensembl biotype	protein_coding
OMIM	607081
Entrez	55080

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000266556, ENST00000539384, ENST00000542160, ENST00000543567, ENST00000544021, ENST00000544289, ENST00000544826, ENST00000545700, ENST00000853206, ENST00000853207, ENST00000853208, ENST00000853209, ENST00000954550, ENST00000954551, ENST00000954552, ENST00000954553

RefSeq mRNA: 2 — MANE Select: NM_018009 NM_001351355, NM_018009

CCDS: CCDS8546

Canonical transcript exons

ENST00000266556 — 7 exons

Exon	Start	End
ENSE00001044376	6462034	6462316
ENSE00002226446	6452042	6452312
ENSE00003585709	6460855	6460938
ENSE00003604042	6453447	6453716
ENSE00003632538	6457406	6457744
ENSE00003646096	6458645	6458947
ENSE00003676432	6453067	6453297

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 95.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7828 / max 156.5765, expressed in 1570 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123673	8.4527	1555
123674	1.1012	414
123676	0.1222	55
123677	0.0996	57
123675	0.0071	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.39	gold quality
left lobe of thyroid gland	UBERON:0001120	93.85	gold quality
right lobe of thyroid gland	UBERON:0001119	93.61	gold quality
thyroid gland	UBERON:0002046	93.39	gold quality
right uterine tube	UBERON:0001302	93.36	gold quality
mucosa of transverse colon	UBERON:0004991	93.25	gold quality
metanephros cortex	UBERON:0010533	93.11	gold quality
transverse colon	UBERON:0001157	92.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.34	gold quality
spleen	UBERON:0002106	91.99	gold quality
right lobe of liver	UBERON:0001114	91.76	gold quality
small intestine	UBERON:0002108	91.70	gold quality
gall bladder	UBERON:0002110	91.69	gold quality
leukocyte	CL:0000738	91.47	gold quality
monocyte	CL:0000576	91.45	gold quality
apex of heart	UBERON:0002098	91.45	gold quality
minor salivary gland	UBERON:0001830	91.40	gold quality
rectum	UBERON:0001052	91.39	gold quality
mononuclear cell	CL:0000842	91.38	gold quality
saliva-secreting gland	UBERON:0001044	91.26	gold quality
lymph node	UBERON:0000029	91.11	gold quality
blood	UBERON:0000178	90.91	gold quality
adenohypophysis	UBERON:0002196	90.52	gold quality
trachea	UBERON:0003126	90.14	gold quality
body of stomach	UBERON:0001161	90.10	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.03	gold quality
intestine	UBERON:0000160	89.98	gold quality
colon	UBERON:0001155	89.88	gold quality
large intestine	UBERON:0000059	89.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting TAPBPL, 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-6740-5P	100.00	65.64	932
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-630	97.50	66.38	921
HSA-MIR-4474-5P	94.23	67.95	568

Literature-anchored findings (GeneRIF, showing 22)

• HLA-I, TAP1, CNX, LMP7, Erp57, Tapasin and ERAP1 were down-regulated in 68%, 44%, 48%, 40%, 52%, 32% and 20% of esophageal squamous cell carcinoma lesions then, respectively. (PMID:21362330)
• The function of the tapasin-related protein, TAPBPR, was investigated. (PMID:23401559)
• the data indicate that TAPBPR and tapasin bind in a similar orientation to the same face of MHC class I. (PMID:24163410)
• The longer TAPBPR protein interacted with MHC class I but was attenuated in its ability to down-regulate surface expression of MHC class I. (PMID:24444341)
• TAPBPR is a new player in the MHC class I presentation pathway. (Review) (PMID:25720504)
• It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system. (PMID:26439010)
• These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing. (PMID:26869717)
• The authors identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle that is known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. The results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with p (PMID:28425917)
• this study reports the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein-related), a tapasin homolog. (PMID:29025991)
• this study presents the x-ray structure of the TAPBPR-MHC I complex, which delineates the central step of catalysis. (PMID:29025996)
• The results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. (PMID:29988068)
• The ability of TAPBPR to interact with MHC class I molecules outside of the ER. (PMID:30077416)
• soluble TAPBPR, consisting of the luminal domain alone, added to intact cells, also functions as an effective peptide editor on surface MHC I molecules. (PMID:30213851)
• Data suggest therapeutic potential of TAP binding protein like tapasin-related protein (TAPBPR) manipulation to increase tumour immunogenicity. (PMID:30484775)
• Distinct Polymorphisms in HLA Class I Molecules Govern Their Susceptibility to Peptide Editing by TAPBPR. (PMID:31693900)
• A loop structure allows TAPBPR to exert its dual function as MHC I chaperone and peptide editor. (PMID:32167472)
• The Ins and Outs of TAPBPR. (PMID:32814254)
• TAPBPR promotes antigen loading on MHC-I molecules using a peptide trap. (PMID:34039964)
• Why TAPBPR? Implications of an additional player in MHC class I peptide presentation. (PMID:34052734)
• The role of MHC I protein dynamics in tapasin and TAPBPR-assisted immunopeptidome editing. (PMID:34265495)
• Get into the groove! The influence of TAPBPR on cargo selection. (PMID:37295041)
• The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. (PMID:37345806)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tapbpl	ENSDARG00000058351
mus_musculus	Tapbpl	ENSMUSG00000038213
rattus_norvegicus	Tapbpl	ENSRNOG00000077779

Paralogs (2): NCR3LG1 (ENSG00000188211), TAPBP (ENSG00000231925)

Protein

Protein identifiers

Tapasin-related protein — Q9BX59 (reviewed: Q9BX59)

Alternative names: TAP-binding protein-like, TAP-binding protein-related protein, Tapasin-like

All UniProt accessions (2): Q9BX59, G3V1T3

UniProt curated annotations — full annotation on UniProt →

Function. Component of the antigen processing and presentation pathway, which binds to MHC class I coupled with beta2-microglobulin/B2M. Association between TAPBPR and MHC class I occurs in the absence of a functional peptide-loading complex (PLC).

Subunit / interactions. Interacts with peptide-free HLA-A*02-B2M complexes or those loaded with low affinity peptides, likely facilitating peptide exchange onto higher affinity peptides. Interacts with MR1 in a ligand-independent way; this interaction may stabilize MR1 pool and facilitate ligand loading and dissociation.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Microsome membrane. Golgi apparatus membrane.

Induction. By interferon gamma.

Miscellaneous. Has reduced cell surface expression, and does not down-regulate MHC class I surface expression as efficiently as isoform alpha. Does not interact with MHC class I. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9BX59-1	alpha	yes
Q9BX59-2	beta
Q9BX59-3	gamma
Q9BX59-4	delta
Q9BX59-5	epsilon
Q9BX59-6	eta
Q9BX59-7	zeta

RefSeq proteins (2): NP_001338284, NP_060479* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003006	Ig/MHC_CS	Conserved_site
IPR003597	Ig_C1-set	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050380	Immune_Resp_Modulators	Family

Pfam: PF07654, PF07686

UniProt features (69 total): strand 32, splice variant 8, sequence variant 6, mutagenesis site 6, helix 4, turn 3, topological domain 2, domain 2, disulfide bond 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9C96	ELECTRON MICROSCOPY	3
5WER	X-RAY DIFFRACTION	3.41
7RNO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BX59-F1	79.28	0.48

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): 212–283, 321–382

Mutagenesis-validated functional residues (6):

Position	Phenotype
115	no effect on cell surface expression of mr1-metabolite antigen complex.
226	loss of mr1 expression at the cell surface; when associated with glu-228; ser-230 and ser-293.
228	loss of mr1 expression at the cell surface; when associated with glu-226; ser-230 and ser-293.
230	loss of mr1 expression at the cell surface; when associated with glu-226; ser-228 and ser-293.
282	decreases cell surface expression of mr1-metabolite antigen complex.
293	loss of mr1 expression at the cell surface; when associated with glu-226; ser-228 and ser-230.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): GOBP_REGULATION_OF_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GCANCTGNY_MYOD_Q6, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_REGULATION_OF_ANTIGEN_PROCESSING_AND_PRESENTATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN_VIA_MHC_CLASS_I, IRF1_Q6, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, IRF_Q6, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, KORKOLA_TERATOMA_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT

GO Biological Process (3): peptide antigen assembly with MHC class I protein complex (GO:0002502), negative regulation of antigen processing and presentation of peptide antigen via MHC class I (GO:0002590), immune system process (GO:0002376)

GO Molecular Function (3): MHC class I protein complex binding (GO:0023024), TAP complex binding (GO:0062061), protein binding (GO:0005515)

GO Cellular Component (7): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), MHC class I peptide loading complex (GO:0042824), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antigen processing and presentation of peptide antigen via MHC class I	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
MHC class I protein complex assembly	1
peptide antigen assembly with MHC protein complex	1
negative regulation of antigen processing and presentation of peptide antigen	1
regulation of antigen processing and presentation of peptide antigen via MHC class I	1
biological_process	1
MHC protein complex binding	1
protein-containing complex binding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
membrane	1
cell periphery	1
endoplasmic reticulum membrane	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

378 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAPBPL	VAMP1	P23763	760
TAPBPL	UGGT2	Q9NYU1	639
TAPBPL	TAPBP	O15533	622
TAPBPL	ERAP1	Q9NZ08	602
TAPBPL	PDIA3	P30101	571
TAPBPL	CD27	P26842	547
TAPBPL	UGGT1	Q9NYU2	543
TAPBPL	ERAP2	Q6P179	511
TAPBPL	MVB12B	Q9H7P6	448
TAPBPL	HLA-A	P01891	447
TAPBPL	CALR	P27797	446
TAPBPL	HLA-B	P01889	431
TAPBPL	FN1	P02751	381
TAPBPL	C12orf57	Q99622	373
TAPBPL	CANX	P27824	368
TAPBPL	B2M	P01884	368

IntAct

52 interactions, top by confidence:

A	B	Type	Score
TAPBPL	HLA-A	psi-mi:“MI:0915”(physical association)	0.720
HLA-A	TAPBPL	psi-mi:“MI:0915”(physical association)	0.720
HLA-A	TAPBP	psi-mi:“MI:0914”(association)	0.690
CYSRT1	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
KRT31	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
KRT35	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
PM20D2	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
KRT34	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
TCF4	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
TEPSIN	TAPBPL	psi-mi:“MI:0915”(physical association)	0.560
HLA-A	C	psi-mi:“MI:0915”(physical association)	0.400
HLA-A	SMC2	psi-mi:“MI:0915”(physical association)	0.400
HLA-A	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.400
TAPBPL	HLA-A	psi-mi:“MI:0915”(physical association)	0.400
TAPBPL	HLA-B	psi-mi:“MI:0915”(physical association)	0.400
HLA-B	gag	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (21): TAPBPL (Two-hybrid), TAPBPL (Two-hybrid), TAPBPL (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), TAPBPL (Two-hybrid), TAPBPL (Two-hybrid), PM20D2 (Two-hybrid), ENTHD2 (Two-hybrid), KRTAP10-8 (Two-hybrid), TCF4 (Two-hybrid), KRT35 (Two-hybrid), CYSRT1 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid)

ESM2 similar proteins: A2APT9, A5PJC7, A5PKB7, D7PDD4, O08672, O94761, O94989, P33076, P51617, P79621, Q16671, Q2LGB3, Q3T0Y9, Q496M5, Q49LS3, Q53GL7, Q5FVN6, Q5FWH6, Q5R866, Q5R8H1, Q5RA67, Q5VTJ3, Q60837, Q6P9H5, Q6UX68, Q75NR7, Q7Z6P3, Q86UT6, Q8BTN6, Q8BWA8, Q8BWF2, Q8CIE4, Q8IUD6, Q8IW93, Q8IYJ3, Q8K349, Q8K3L6, Q8K558, Q8NAG6, Q8R2S1

Diamond homologs: O15533, O73895, Q5R8H1, Q5TJE4, Q6PZD2, Q8VD31, Q9BX59, Q9R233, A2AJ76, P01889, P01893, P01894, P01898, P01901, P01902, P03991, P04223, P04439, P06140, P06339, P10321, P13747, P13748, P13749, P13750, P13751, P14427, P14428, P14429, P14430, P15978, P16209, P16210, P16211, P16215, P16391, P17693, P18466, P28068, P30375

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	4
Uncertain significance	99
Likely benign	50
Benign	16

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1459195	NM_014231.5(VAMP1):c.59del (p.Gly20fs)	Pathogenic
1806955	NM_014231.5(VAMP1):c.340+2T>A	Pathogenic
240888	NM_014231.5(VAMP1):c.340+2T>G	Pathogenic
4796977	NM_014231.5(VAMP1):c.118C>T (p.Gln40Ter)	Pathogenic
619002	NM_014231.5(VAMP1):c.51_64del (p.Gly18fs)	Pathogenic
619005	NM_014231.5(VAMP1):c.128_129del (p.Glu43fs)	Pathogenic
2575084	NM_014231.5(VAMP1):c.152dup (p.Asn51fs)	Likely pathogenic
4771265	NM_014231.5(VAMP1):c.129+2T>G	Likely pathogenic
493108	NM_014231.5(VAMP1):c.230C>A (p.Ser77Ter)	Likely pathogenic
619004	NM_014231.5(VAMP1):c.129+1G>A	Likely pathogenic

SpliceAI

2082 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6453293:CTCAG:C	donor_loss	1.0000
12:6453294:TCAGG:T	donor_loss	1.0000
12:6453295:CAGG:C	donor_loss	1.0000
12:6453296:AG:A	donor_loss	1.0000
12:6453297:G:GT	donor_loss	1.0000
12:6453298:GT:G	donor_loss	1.0000
12:6453299:T:A	donor_loss	1.0000
12:6460935:CAAGG:C	donor_loss	1.0000
12:6460936:AAGG:A	donor_loss	1.0000
12:6460937:AGGTA:A	donor_loss	1.0000
12:6460938:GGTA:G	donor_loss	1.0000
12:6460939:GTAA:G	donor_loss	1.0000
12:6460940:T:G	donor_loss	1.0000
12:6464942:C:CC	acceptor_gain	1.0000
12:6465837:TTCAC:T	donor_loss	1.0000
12:6465839:CA:C	donor_loss	1.0000
12:6465840:A:C	donor_loss	1.0000
12:6465841:C:T	donor_loss	1.0000
12:6465865:T:TA	donor_gain	1.0000
12:6465866:C:A	donor_gain	1.0000
12:6465874:G:C	donor_gain	1.0000
12:6465997:CCAC:C	acceptor_gain	1.0000
12:6465998:CAC:C	acceptor_gain	1.0000
12:6465998:CACC:C	acceptor_gain	1.0000
12:6466001:C:CC	acceptor_gain	1.0000
12:6466222:TACCT:T	donor_loss	1.0000
12:6466223:AC:A	donor_loss	1.0000
12:6466223:ACCT:A	donor_gain	1.0000
12:6466224:CC:C	donor_loss	1.0000
12:6466224:CCTC:C	donor_gain	1.0000

AlphaMissense

3008 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6458743:T:A	W335R	0.993
12:6458743:T:C	W335R	0.993
12:6458745:G:C	W335C	0.993
12:6458745:G:T	W335C	0.993
12:6457519:T:A	W227R	0.989
12:6457519:T:C	W227R	0.989
12:6458702:G:A	C321Y	0.988
12:6457521:G:C	W227C	0.987
12:6457521:G:T	W227C	0.987
12:6458701:T:A	C321S	0.987
12:6458702:G:C	C321S	0.987
12:6458884:T:A	C382S	0.986
12:6458885:G:C	C382S	0.986
12:6460887:A:C	S414R	0.986
12:6460889:C:A	S414R	0.986
12:6460889:C:G	S414R	0.986
12:6457689:C:G	C283W	0.985
12:6458701:T:C	C321R	0.984
12:6457688:G:A	C283Y	0.983
12:6458884:T:C	C382R	0.983
12:6458703:C:G	C321W	0.982
12:6457687:T:C	C283R	0.981
12:6458885:G:A	C382Y	0.978
12:6458886:C:G	C382W	0.978
12:6457675:G:T	G279W	0.977
12:6457687:T:A	C283S	0.977
12:6457688:G:C	C283S	0.977
12:6457681:T:G	Y281D	0.974
12:6458878:T:G	Y380D	0.973
12:6458702:G:T	C321F	0.972

dbSNP variants (sampled 300 via entrez): RS1000101316 (12:6465083 T>C), RS1000146139 (12:6462405 C>A), RS1000236213 (12:6469446 G>T), RS1000438311 (12:6455540 C>T), RS1000984180 (12:6467187 T>C), RS1001210441 (12:6456502 T>C), RS1001493116 (12:6456160 T>G), RS1001518143 (12:6469168 A>G), RS1001525542 (12:6456477 C>T), RS1001593270 (12:6462682 C>G,T), RS1001685370 (12:6469380 C>G), RS1001716393 (12:6469029 G>A,C), RS1001721549 (12:6449811 T>C), RS1001839764 (12:6454967 G>A), RS1001942115 (12:6461474 G>A)

Disease associations

OMIM: gene MIM:607081 | disease phenotypes: MIM:108600, MIM:618323, MIM:601462, MIM:616362

GenCC curated gene-disease

Mondo (4): spastic ataxia 1 (MONDO:0007164), myasthenic syndrome, congenital, 25, presynaptic (MONDO:0032675), congenital myasthenic syndrome (MONDO:0018940), Houge-Janssens syndrome 2 (MONDO:0014605)

Orphanet (3): Autosomal dominant spastic ataxia type 1 (Orphanet:251282), Congenital myasthenic syndrome (Orphanet:590), Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome (Orphanet:457284)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_403	Blood protein levels	0.000000e+00

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
C566993	Ataxia, Spastic, 1, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	3
Smoke	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
sotorasib	affects cotreatment, increases expression	1
propionaldehyde	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
licochalcone B	increases expression	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiodarone	increases expression	1
Arsenic	increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01203592	PHASE1	COMPLETED	Efficacy of Albuterol in the Treatment of Congenital Myasthenic Syndromes
NCT06436742	PHASE1	RECRUITING	A Phase 1b Study to Investigate Safety and Tolerability of ARGX-119 in Adult Participants With DOK7-Congenital Myasthenic Syndromes (CMS)
NCT07226726	PHASE1	RECRUITING	Patients With Congenital Myasthenic Syndrome Will be Treated With Mesenchymal Stem Cell Exosome Solution
NCT00872950	Not specified	APPROVED_FOR_MARKETING	3,4-Diaminopyridine Use in Lambert-Eaton Myasthenic Syndrome(LEMS) and Congenital Myasthenic Syndromes (CMS)
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information
NCT01474980	Not specified	COMPLETED	Pregnancy Outcomes in Congenital Myasthenie Syndrome
NCT02012933	Not specified	NO_LONGER_AVAILABLE	3,4-Diaminopyridine for Lambert-Eaton Myasthenic Syndrome (LEMS) and Congenital Myasthenia (CM)
NCT02189720	Not specified	APPROVED_FOR_MARKETING	Expanded Access Study Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS),Congenital Myasthenic Syndrome
NCT03062631	Not specified	NO_LONGER_AVAILABLE	Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia
NCT05408702	Not specified	COMPLETED	Exercise in Autoimmune Myasthenia Gravis and Myasthenic Syndromes
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06078553	Not specified	RECRUITING	A Natural History Study in Participants With Congenital Myasthenic Syndromes (CMS) Due to Mutations in DOK7, MUSK, AGRN, or LRP4