TRAPPC2

Summary

TRAPPC2 (trafficking protein particle complex subunit 2, HGNC:23068) is a protein-coding gene on chromosome Xp22.2, encoding Trafficking protein particle complex subunit 2 (P0DI81). Prevents transcriptional repression and induction of cell death by ENO1. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is thought to be part of a large multi-subunit complex involved in the targeting and fusion of endoplasmic reticulum-to-Golgi transport vesicles with their acceptor compartment. In addition, the encoded protein can bind c-myc promoter-binding protein 1 and block its transcriptional repression capability. Mutations in this gene are a cause of spondyloepiphyseal dysplasia tarda (SEDT). A processed pseudogene of this gene is located on chromosome 19, and other pseudogenes are found on chromosomes 8 and Y. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 6399 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepiphyseal dysplasia tarda, X-linked (Definitive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 73 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 64
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001011658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23068
Approved symbol	TRAPPC2
Name	trafficking protein particle complex subunit 2
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	TRS20, SEDT, MIP-2A, ZNF547L, hYP38334
Ensembl gene	ENSG00000196459
Ensembl biotype	protein_coding
OMIM	300202
Entrez	6399

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 retained_intron

ENST00000359680, ENST00000380578, ENST00000380579, ENST00000458511, ENST00000517553, ENST00000518847, ENST00000519382, ENST00000519885, ENST00000683569, ENST00000683983, ENST00000937066, ENST00000937067, ENST00000937068, ENST00000941739, ENST00000941740, ENST00000941741

RefSeq mRNA: 3 — MANE Select: NM_001011658 NM_001011658, NM_001128835, NM_014563

CCDS: CCDS48082, CCDS48083

Canonical transcript exons

ENST00000380579 — 6 exons

Exon	Start	End
ENSE00001353934	13712245	13714505
ENSE00001485533	13734525	13734620
ENSE00001485559	13734044	13734185
ENSE00001769112	13716004	13716089
ENSE00003491382	13716534	13716678
ENSE00003496691	13719871	13719982

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 89.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.6908 / max 172.2434, expressed in 1756 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198463	7.6031	1741
198461	0.7977	293
198460	0.2612	86
198462	0.0288	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	89.67	gold quality
cerebellar vermis	UBERON:0004720	87.64	gold quality
cerebellar cortex	UBERON:0002129	85.73	gold quality
cerebellar hemisphere	UBERON:0002245	85.68	gold quality
cerebellum	UBERON:0002037	85.63	gold quality
thymus	UBERON:0002370	84.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.64	gold quality
epithelium of nasopharynx	UBERON:0001951	84.62	gold quality
ganglionic eminence	UBERON:0004023	84.52	gold quality
blood	UBERON:0000178	84.50	gold quality
lymph node	UBERON:0000029	83.97	gold quality
superficial temporal artery	UBERON:0001614	83.94	gold quality
esophagus squamous epithelium	UBERON:0006920	83.90	gold quality
urethra	UBERON:0000057	83.72	gold quality
body of uterus	UBERON:0009853	83.63	gold quality
endometrium	UBERON:0001295	83.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.38	gold quality
ovary	UBERON:0000992	83.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.24	gold quality
myometrium	UBERON:0001296	83.23	gold quality
oocyte	CL:0000023	83.21	gold quality
lower esophagus mucosa	UBERON:0035834	83.20	gold quality
granulocyte	CL:0000094	83.07	gold quality
postcentral gyrus	UBERON:0002581	83.00	gold quality
uterus	UBERON:0000995	82.92	gold quality
leukocyte	CL:0000738	82.91	gold quality
nucleus accumbens	UBERON:0001882	82.88	gold quality
calcaneal tendon	UBERON:0003701	82.86	gold quality
tonsil	UBERON:0002372	82.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting TRAPPC2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 26)

• A novel mutation produces a truncated protein, which may be useful in determining carboxy-terminal function (PMID:12030902)
• SEDL mutations are not a common cause of early primary osteoarthritis in men. (PMID:12123495)
• The mutation IVS2 -2A–>C of SEDL gene was firstly determined in the world. The change of the splice acceptor in SEDL intron 2 may cause skipping of exon 3 which is responsible for the X-linked spondyloepiphyseal dysplasia tarda. (PMID:12579492)
• A previously unreported deletion of T in exon 5 of SEDL gene (293delT) was observed in 2 spondyloepiphyseal dysplasia probands in a Chinese family; seven individuals in the family carry the mutation resulting in frameshift and a putative truncated protein (PMID:12650905)
• 3 new SEDL mutations were found: 1 in the non-canonical 5’ splice site of intron 4 (IVS4+4T>C), a deletion in exon 6 [333-336del(GAAT) & a 1.335-kb deletion (in5/ex6del). (PMID:12919139)
• Sedl protein may participate in the ER-to-Golgi transport as part of a novel highly conserved multiprotein TRAPP complex (PMID:12939648)
• Six novel SEDL mutations found in European X-linked spondyloepiphyseal dysplasia tarda patients. (PMID:15221797)
• The 13 bp deletion mutation consisting of IVS5-2-1delAG and 322-332del TTTTCAATGAA was identified in SEDL patients, but not detected in unrelated normal male individuals. (PMID:15300622)
• Data show that mutation of acceptor splice site of the SEDL gene in X-linked spondyloepiphyseal dysplasia tarda causes the activation of cryptic splice site. (PMID:15952107)
• SEDL gene mutation in a Chinese family with X-linked spondyloepiphyseal dysplasia tarda (SEDL) (PMID:18247296)
• A novel missense mutation (H80R) was identified for SEDL gene in the large Chinese SEDT pedigree. (PMID:18393234)
• results illustrate how disruption of the AT donor site in a rare AT-AC intron, leading to a canonical GT donor site, resulted in a multitude of aberrant transcripts, thus impairing exon definition of the SEDL gene. (PMID:19002213)
• A novel RNA-splicing mutation in TRAPPC2 gene causing x-linked spondyloepiphyseal dysplasia tarda in a large Chinese family. (PMID:19417549)
• Identification of the novel insertion mutation (c.370-371insA) in this X-linked spondyloepiphyseal dysplasia tarda family is predicted to result in frameshifts and generate a premature stop codon (PMID:19766614)
• The results suggest that nucleus-localized Sedlin may play a role in regulation of transcriptional activities of the MRG family of transcription factors via binding to PAM14. (PMID:20108251)
• SEDLIN is present in the nucleus, forms homodimers and that SEDT-associated mutations cause a loss of interaction with the transcription factors MBP1, PITX1 and SF1. (PMID:20498720)
• Data indicate SPATA4 interacts with the C2 portion of the TRAPP complex. (PMID:21827752)
• Data show that a disease-causing mutation of TRAPPC2, D47Y, failed to interact with either TRAPPC9 or TRAPPC8, suggesting that aspartate 47 in TRAPPC2 is at or near the site of interaction with TRAPPC9 or TRAPPC8. (PMID:21858081)
• Sedlin bound and promoted efficient cycling of Sar1, a guanosine triphosphatase that can constrict membranes, and thus allowed nascent carriers to grow and incorporate procollagen prefibrils. (PMID:23019651)
• a novel hemizygous mutation, c.341-(11_9)delAAT, in an intron of TRAPPC caused spondyloepiphyseal dysplasia tarda (PMID:23656395)
• Studies indicate that splice site mutation that leads to aberrant splicing often causes genetic skeletal system disease, like COL1A1, SEDL and LRP. (PMID:23800666)
• A novel splicing mutation in the SEDL gene causes spondyloepiphyseal dysplasia tarda in a large Chinese pedigree. (PMID:23876379)
• identification of the novel nonsense mutation (c.61G>T) in the SEDT family enables carrier detection, genetic counseling, and prenatal diagnosis. (PMID:24841781)
• Data suggest that c.267_271delAAGAC frameshift mutation of the exon 5 of the spondyloepiphyseal dysplasia, late protein (SEDL) gene probably underlies the disease in the family. (PMID:25297591)
• c.93+5G>A mutation in the TRAPPC2 gene is associated with X-linked spondyloepiphyseal dysplasia in a Chinese family. (PMID:26252088)
• Novel loss-of-function variants of TRAPPC2 manifesting X-linked spondyloepiphyseal dysplasia tarda: report of two cases (PMID:31053099)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trappc2	ENSMUSG00000079317

Paralogs (2): TRAPPC2L (ENSG00000167515), TRAPPC2B (ENSG00000256060)

Protein

Protein identifiers

Trafficking protein particle complex subunit 2 — P0DI81 (reviewed: P0DI81)

Alternative names: Sedlin

All UniProt accessions (4): E5RFG0, F5H785, P0DI81, Q6IBE5

UniProt curated annotations — full annotation on UniProt →

Function. Prevents transcriptional repression and induction of cell death by ENO1. May play a role in vesicular transport from endoplasmic reticulum to Golgi.

Subunit / interactions. Can homodimerize. Component of the multisubunit TRAPP (transport protein particle) complex, which includes TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12. Interacts with ENO1, PITX1 and SF1.

Subcellular location. Cytoplasm. Perinuclear region. Endoplasmic reticulum-Golgi intermediate compartment. Nucleus.

Tissue specificity. Expressed in brain, heart, kidney, liver, lung, pancreas, placenta, skeletal muscle, fetal cartilage, fibroblasts, placenta and lymphocytes.

Disease relevance. Spondyloepiphyseal dysplasia tarda (SEDT) [MIM:313400] X-linked recessive disorder of endochondral bone formation. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. A paralogous gene encoding an identical protein appears to have arisen by retrotransposition of a cDNA from this locus and to have acquired a promoter and non-coding 5’ UTR from the ZNF547 gene.

Similarity. Belongs to the TRAPP small subunits family. Sedlin subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P0DI81-1	1, Major	yes
P0DI81-2	2
P0DI81-3	3

RefSeq proteins (3): NP_001011658, NP_001122307, NP_055378 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006722	Sedlin	Family
IPR011012	Longin-like_dom_sf	Homologous_superfamily

Pfam: PF04628

UniProt features (9 total): sequence variant 4, splice variant 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DI81-F1	92.44	0.83

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 (1): 119

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 314 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_VESICLE_LOCALIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_VESICLE_ORGANIZATION, MODULE_493, GOBP_VESICLE_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_MEMBRANE_ORGANIZATION, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_ORGANELLE_LOCALIZATION

GO Biological Process (6): skeletal system development (GO:0001501), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), vesicle coat assembly (GO:0006901), COPII vesicle coat assembly (GO:0048208), obsolete vesicle tethering (GO:0099022), vesicle-mediated transport (GO:0016192)

GO Molecular Function (2): transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), cytosol (GO:0005829), TRAPP complex (GO:0030008), perinuclear region of cytoplasm (GO:0048471), TRAPPII protein complex (GO:1990071), TRAPPIII protein complex (GO:1990072)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
Golgi apparatus	2
TRAPP complex	2
system development	1
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
vesicle budding from membrane	1
vesicle organization	1
vesicle coat assembly	1
protein-containing complex assembly	1
COPII-coated vesicle budding	1
transport	1
cellular process	1
protein binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
vesicle tethering complex	1
intracellular protein-containing complex	1
endosome	1

Protein interactions and networks

STRING

958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAPPC2	TRAPPC1	Q9Y5R8	998
TRAPPC2	TRAPPC4	Q9Y296	998
TRAPPC2	TRAPPC6A	O75865	997
TRAPPC2	TRAPPC3	O43617	997
TRAPPC2	TRAPPC5	Q8IUR0	997
TRAPPC2	TRAPPC8	Q9Y2L5	993
TRAPPC2	YKT6	O15498	928
TRAPPC2	TRAPPC10	P48553	921
TRAPPC2	TRAPPC9	Q96Q05	899
TRAPPC2	SEC22B	O75396	899
TRAPPC2	TRAPPC12	Q8WVT3	866
TRAPPC2	MIA3	Q5JRA6	857
TRAPPC2	TRAPPC11	Q7Z392	852
TRAPPC2	TRAPPC2L	Q9UL33	852
TRAPPC2	TRAPPC6B	Q86SZ2	845

IntAct

24 interactions, top by confidence:

A	B	Type	Score
RAB3IP	TRAPPC3	psi-mi:“MI:0914”(association)	0.700
RAB3IP	TRAPPC3	psi-mi:“MI:0915”(physical association)	0.700
TRIM42	TRAPPC2	psi-mi:“MI:0915”(physical association)	0.560
KCTD1	TRAPPC2	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC2	EPS15L1	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC2	TRIM42	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC2	KCTD1	psi-mi:“MI:0915”(physical association)	0.560
EPS15L1	TRAPPC2	psi-mi:“MI:0915”(physical association)	0.560
RAB3IP	TRAPPC2	psi-mi:“MI:0914”(association)	0.560
TRAPPC2	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
TRAPPC2	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
TRAPPC2	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
REPS1	TRAPPC2	psi-mi:“MI:0915”(physical association)	0.000
TRAPPC2	ABRA	psi-mi:“MI:0915”(physical association)	0.000
TRAPPC2	EIF3C	psi-mi:“MI:0915”(physical association)	0.000
ENO1	TRAPPC2	psi-mi:“MI:0915”(physical association)	0.000
TRAPPC2	ENO3	psi-mi:“MI:0915”(physical association)	0.000
TRAPPC2	HLA-E	psi-mi:“MI:0915”(physical association)	0.000
TRAPPC2	PYGM	psi-mi:“MI:0915”(physical association)	0.000
ZBTB38	TRAPPC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (238): PITX1 (Affinity Capture-Western), NR5A1 (Affinity Capture-Western), TRAPPC2 (Affinity Capture-Western), TRAPPC2 (Two-hybrid), TRAPPC2 (Two-hybrid), TRAPPC2 (Two-hybrid), TRAPPC2 (Affinity Capture-Western), MBL2 (Affinity Capture-Western), TRAPPC2 (Affinity Capture-MS), TRAPPC2 (Affinity Capture-MS), TRAPPC2 (Affinity Capture-MS), TRAPPC2 (Affinity Capture-MS), TRAPPC2 (Affinity Capture-MS), TRAPPC2 (Affinity Capture-MS), TRAPPC2 (Affinity Capture-MS)

ESM2 similar proteins: A7RJI7, B0G185, D3ZVF4, E2QV03, F1SRI0, O02173, O13732, O17901, O23685, O43041, O74891, P0DI81, P0DI82, P35181, P35604, P38334, P53600, P56377, P61923, P61924, P61966, P61967, Q03630, Q08CN0, Q0VD30, Q1JQ98, Q28HU2, Q28IG8, Q3T0F2, Q3ZBS3, Q4S4I5, Q54CU7, Q54RV6, Q54UU1, Q5R5F2, Q5RES6, Q5ZKP4, Q5ZLN2, Q74ZD2, Q7T102

Diamond homologs: A7RVK7, D3ZVF4, E2QV03, F1SRI0, O02173, P0DI81, P0DI82, P38334, Q08CN0, Q28IG8, Q3T0F2, Q54RV6, Q5RES6, Q5ZKP4, Q9CQP2, Q9USZ5, Q9VUZ1, B5FXJ6, Q54CU7, A6H7F7, B2RYU6, Q5M8X5, Q9JME7, Q9UL33, B5XGE7, Q5RBK9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TRAPPC2	“form complex”	“TRAPP III complex, TRAPPC2 variant”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	34
Likely benign	11
Benign	20

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
11514	NM_001011658.4(TRAPPC2):c.391C>T (p.Gln131Ter)	Pathogenic
11515	NM_001011658.4(TRAPPC2):c.329C>A (p.Ser110Ter)	Pathogenic
11517	NM_001011658.4(TRAPPC2):c.387del (p.Val130fs)	Pathogenic
1457497	NM_001011658.4(TRAPPC2):c.329C>G (p.Ser110Ter)	Pathogenic
1457801	NM_001011658.4(TRAPPC2):c.364C>T (p.Arg122Ter)	Pathogenic
1701592	NM_001011658.4(TRAPPC2):c.382A>T (p.Arg128Ter)	Likely pathogenic
3384073	NM_001011658.4(TRAPPC2):c.391_392del (p.Gln131fs)	Likely pathogenic

SpliceAI

1091 predictions. Top by Δscore:

Variant	Effect	Δscore
X:13714501:GAAAA:G	acceptor_gain	1.0000
X:13714506:C:CC	acceptor_gain	1.0000
X:13719865:A:AC	donor_gain	1.0000
X:13719866:C:CC	donor_gain	1.0000
X:13719866:CGTA:C	donor_gain	1.0000
X:13719869:A:AC	donor_gain	1.0000
X:13719870:C:CC	donor_gain	1.0000
X:13719870:CT:C	donor_gain	1.0000
X:13734522:TACC:T	donor_loss	1.0000
X:13734523:ACC:A	donor_loss	1.0000
X:13734524:C:CT	donor_loss	1.0000
X:13714355:T:TA	donor_gain	0.9900
X:13714503:AAA:A	acceptor_gain	0.9900
X:13714503:AAAC:A	acceptor_loss	0.9900
X:13714504:AA:A	acceptor_gain	0.9900
X:13714504:AACTA:A	acceptor_loss	0.9900
X:13714505:ACT:A	acceptor_loss	0.9900
X:13714506:CTA:C	acceptor_loss	0.9900
X:13714507:T:G	acceptor_loss	0.9900
X:13716116:T:C	acceptor_gain	0.9900
X:13716122:A:AC	acceptor_gain	0.9900
X:13716562:C:CT	donor_gain	0.9900
X:13716562:CCA:C	donor_gain	0.9900
X:13716576:TGTCC:T	donor_gain	0.9900
X:13716675:CGTC:C	acceptor_gain	0.9900
X:13716676:GTCC:G	acceptor_loss	0.9900
X:13716679:C:CC	acceptor_gain	0.9900
X:13716689:G:C	acceptor_gain	0.9900
X:13716689:G:GC	acceptor_gain	0.9900
X:13719867:GTA:G	donor_loss	0.9900

AlphaMissense

960 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:13716551:G:T	A74E	1.000
X:13716571:G:C	F67L	1.000
X:13716571:G:T	F67L	1.000
X:13716573:A:G	F67L	1.000
X:13716631:G:C	D47E	1.000
X:13716631:G:T	D47E	1.000
X:13716632:T:A	D47V	1.000
X:13716635:A:G	L46P	1.000
X:13716638:G:T	A45D	1.000
X:13716639:C:G	A45P	1.000
X:13716641:G:T	A44D	1.000
X:13716642:C:G	A44P	1.000
X:13716647:G:T	A42D	1.000
X:13714441:A:T	V130D	0.999
X:13716071:A:G	L86P	0.999
X:13716071:A:T	L86H	0.999
X:13716545:A:T	V76D	0.999
X:13716552:C:G	A74P	0.999
X:13716555:A:G	S73P	0.999
X:13716557:A:T	V72E	0.999
X:13716572:A:G	F67S	0.999
X:13716578:T:A	D65V	0.999
X:13716579:C:G	D65H	0.999
X:13716587:T:A	K62I	0.999
X:13716629:A:G	L48P	0.999
X:13716632:T:C	D47G	0.999
X:13716632:T:G	D47A	0.999
X:13716633:C:G	D47H	0.999
X:13716633:C:T	D47N	0.999
X:13716635:A:T	L46H	0.999

dbSNP variants (sampled 300 via entrez): RS1000055734 (X:13731388 C>A,T), RS1000128856 (X:13728836 G>A,T), RS1000304188 (X:13714109 C>T), RS1000426915 (X:13731013 C>A), RS1000515379 (X:13734774 C>A,G,T), RS1000624212 (X:13724498 A>G), RS1000671048 (X:13716368 A>G), RS1000676484 (X:13723817 G>A), RS1000979351 (X:13724964 G>A,C,T), RS1001700813 (X:13733266 G>A), RS1001731861 (X:13733674 A>G), RS1001772545 (X:13735552 C>T), RS1002034318 (X:13734876 G>A,C), RS1002092464 (X:13713240 A>G), RS1002247561 (X:13726604 A>G)

Disease associations

OMIM: gene MIM:300202 | disease phenotypes: MIM:313400

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepiphyseal dysplasia tarda, X-linked	Definitive	X-linked
spondyloepiphyseal dysplasia tarda	Supportive	Autosomal dominant

Mondo (2): spondyloepiphyseal dysplasia tarda (MONDO:0019667), spondyloepiphyseal dysplasia tarda, X-linked (MONDO:0010737)

Orphanet (1): Spondyloepiphyseal dysplasia tarda (Orphanet:93284)

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000175	Cleft palate
HP:0000470	Short neck
HP:0000541	Retinal detachment
HP:0000914	Shield chest
HP:0000926	Platyspondyly
HP:0001376	Limitation of joint mobility
HP:0001386	Joint swelling
HP:0001419	X-linked recessive inheritance
HP:0001508	Failure to thrive
HP:0001552	Barrel-shaped chest
HP:0002650	Scoliosis
HP:0002654	Multiple epiphyseal dysplasia
HP:0002655	Spondyloepiphyseal dysplasia
HP:0002751	Kyphoscoliosis
HP:0002763	Abnormal cartilage morphology
HP:0002808	Kyphosis
HP:0002812	Coxa vara
HP:0002829	Arthralgia
HP:0002866	Hypoplastic iliac wing
HP:0002938	Lumbar hyperlordosis
HP:0002942	Thoracic kyphosis
HP:0002945	Intervertebral space narrowing
HP:0002960	Autoimmunity
HP:0002996	Limited elbow movement
HP:0003043	Abnormal shoulder morphology
HP:0003051	Enlarged metaphyses
HP:0003088	Premature osteoarthritis
HP:0003090	Hypoplasia of the capital femoral epiphysis
HP:0003311	Hypoplasia of the odontoid process
HP:0003365	Arthralgia of the hip

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	3
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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