EXOC6B

Summary

EXOC6B (exocyst complex component 6B, HGNC:17085) is a protein-coding gene on chromosome 2p13.2, encoding Exocyst complex component 6B (Q9Y2D4). Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.

This gene encodes a protein which is a part of the evolutionarily conserved exocyst, a multimeric protein complex necessary for exocytosis, which in turn, is crucial for cell growth, polarity and migration. Disruption of this gene may be associated with phenotypes exhibiting multiple symptoms including intellectual disability and developmental delay (DD).

Source: NCBI Gene 23233 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepimetaphyseal dysplasia with joint laxity, type 3 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 355 total — 8 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 26
• MANE Select transcript: NM_015189

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17085
Approved symbol	EXOC6B
Name	exocyst complex component 6B
Location	2p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0919
Ensembl gene	ENSG00000144036
Ensembl biotype	protein_coding
OMIM	607880
Entrez	23233

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 17 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000272427, ENST00000410104, ENST00000410112, ENST00000464347, ENST00000471335, ENST00000485398, ENST00000490919, ENST00000492257, ENST00000634650, ENST00000862930, ENST00000862931, ENST00000862932, ENST00000862933, ENST00000862934, ENST00000862935, ENST00000862936, ENST00000862937, ENST00000971148, ENST00000971149, ENST00000971150, ENST00000971151, ENST00000971152, ENST00000971153

RefSeq mRNA: 6 — MANE Select: NM_015189 NM_001321729, NM_001321730, NM_001321731, NM_001321733, NM_001321734, NM_015189

CCDS: CCDS46333, CCDS82468

Canonical transcript exons

ENST00000272427 — 22 exons

Exon	Start	End
ENSE00000000137	72825798	72826033
ENSE00001070608	72379729	72379870
ENSE00001122411	72480616	72480750
ENSE00001675180	72741304	72741469
ENSE00001952405	72175984	72179461
ENSE00003463493	72499901	72499972
ENSE00003479739	72498454	72498551
ENSE00003480917	72513132	72513252
ENSE00003483582	72515043	72515126
ENSE00003520282	72559453	72559521
ENSE00003523316	72334947	72335020
ENSE00003525855	72718103	72718307
ENSE00003536755	72575492	72575668
ENSE00003552269	72492318	72492429
ENSE00003568204	72514634	72514680
ENSE00003570399	72495430	72495539
ENSE00003593937	72496454	72496559
ENSE00003612181	72733071	72733118
ENSE00003622831	72465160	72465339
ENSE00003639418	72731155	72731245
ENSE00003659181	72184075	72184187
ENSE00003661317	72731007	72731052

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 95.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0348 / max 244.0114, expressed in 1723 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29102	12.8287	1716
29101	0.9999	486
29098	0.4833	231
29099	0.2245	106
29100	0.1882	72
29089	0.1587	26
29088	0.0568	16
29086	0.0374	14
29087	0.0363	14
29090	0.0212	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.92	gold quality
medial globus pallidus	UBERON:0002477	92.58	gold quality
globus pallidus	UBERON:0001875	92.34	gold quality
corpus callosum	UBERON:0002336	92.21	gold quality
sural nerve	UBERON:0015488	91.93	gold quality
lateral globus pallidus	UBERON:0002476	91.57	gold quality
tendon	UBERON:0000043	91.31	gold quality
substantia nigra pars compacta	UBERON:0001965	91.31	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.21	gold quality
cortical plate	UBERON:0005343	90.69	gold quality
heart left ventricle	UBERON:0002084	90.33	gold quality
cardiac ventricle	UBERON:0002082	90.27	gold quality
right atrium auricular region	UBERON:0006631	89.61	gold quality
apex of heart	UBERON:0002098	89.43	gold quality
upper leg skin	UBERON:0004262	89.18	gold quality
skin of abdomen	UBERON:0001416	88.88	gold quality
heart	UBERON:0000948	88.75	gold quality
heart right ventricle	UBERON:0002080	88.27	gold quality
skin of leg	UBERON:0001511	88.15	gold quality
cardiac atrium	UBERON:0002081	87.82	gold quality
inferior vagus X ganglion	UBERON:0005363	87.60	gold quality
superior vestibular nucleus	UBERON:0007227	87.55	gold quality
postcentral gyrus	UBERON:0002581	87.43	gold quality
subthalamic nucleus	UBERON:0001906	87.34	gold quality
colonic epithelium	UBERON:0000397	87.17	gold quality
nucleus accumbens	UBERON:0001882	87.06	gold quality
parietal lobe	UBERON:0001872	87.03	gold quality
pons	UBERON:0000988	86.90	gold quality
prefrontal cortex	UBERON:0000451	86.80	gold quality
ganglionic eminence	UBERON:0004023	86.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.87
E-MTAB-11268	no	3828.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

136 targeting EXOC6B, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6857-5P	99.87	65.32	985
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 7)

• TNS3-EXOC6B and EXOC6B-TNS3 fusion transcripts are detected in a premature male newborn with a complex multisystemic phenotype associated with a balanced translocation. (PMID:18424204)
• Data suggest that the Rabin8-Rab8-Sec15 interaction may couple the activation of Rab8 to the recruitment of the Rab8 effector and is involved in the regulation of vesicular trafficking for primary cilium formation. (PMID:22433857)
• We report a 2p13.2 microdeletion in 2 subjects encompasing 2 genes, EXOC6B and CYP26B12 with clinical effects on cognitive function, and craniofacial and skeletal development. (PMID:23837398)
• EXOC6B and the exocyst complex might play an important role in the molecular pathogenesis of intellectual disability. (PMID:25256811)
• Homozygous nonsense variant in EXOC6B identified in two brothers with spondyloepimetaphyseal dysplasia and multiple joint dislocations syndrome. (PMID:26669664)
• CircEXOC6B Suppresses the Proliferation and Motility and Sensitizes Ovarian Cancer Cells to Paclitaxel Through miR-376c-3p/FOXO3 Axis. (PMID:33006481)
• Biallelic loss-of-function variants in EXOC6B are associated with impaired primary ciliogenesis and cause spondylo-epi-metaphyseal dysplasia with joint laxity type 3. (PMID:36150098)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Exoc6b	ENSMUSG00000033769
rattus_norvegicus	Exoc6b	ENSRNOG00000059615

Paralogs (1): EXOC6 (ENSG00000138190)

Protein

Protein identifiers

Exocyst complex component 6B — Q9Y2D4 (reviewed: Q9Y2D4)

Alternative names: Exocyst complex component Sec15B, SEC15-like protein 2

All UniProt accessions (4): Q9Y2D4, A0A0U1RRB6, F8W6R7, J3QT38

UniProt curated annotations — full annotation on UniProt →

Function. Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.

Subunit / interactions. The exocyst complex is composed of SEC3, SEC5, SEC6, SEC8, SEC10, SEC15, EXO70 and EXO84.

Disease relevance. Spondyloepimetaphyseal dysplasia with joint laxity, 3 (SEMDJL3) [MIM:618395] An autosomal recessive bone disease characterized by multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SEC15 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2D4-1	1	yes
Q9Y2D4-2	2

RefSeq proteins (6): NP_001308658, NP_001308659, NP_001308660, NP_001308662, NP_001308663, NP_056004* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007225	EXOC6/Sec15	Family
IPR042044	EXOC6PINT-1/Sec15/Tip20_C_dom2	Homologous_superfamily
IPR042045	EXOC6/Sec15_C_dom1	Homologous_superfamily
IPR046361	EXOC6/Sec15_C	Domain
IPR048359	EXOC6_Sec15_N	Domain

Pfam: PF04091, PF20651

UniProt features (6 total): splice variant 2, chain 1, region of interest 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2D4-F1	80.08	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 252 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, BEIER_GLIOMA_STEM_CELL_DN, GOBP_MEMBRANE_DOCKING, GOBP_EXOCYTOSIS, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, MODULE_205, GOBP_VESICLE_DOCKING_INVOLVED_IN_EXOCYTOSIS, WANG_LMO4_TARGETS_DN, GOBP_CYTOKINESIS, GOBP_SECRETION, CORRE_MULTIPLE_MYELOMA_UP

GO Biological Process (8): mitotic cytokinesis (GO:0000281), intracellular protein transport (GO:0006886), exocytosis (GO:0006887), Golgi to plasma membrane transport (GO:0006893), obsolete vesicle docking involved in exocytosis (GO:0006904), membrane fission (GO:0090148), obsolete vesicle tethering involved in exocytosis (GO:0090522), protein transport (GO:0015031)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): exocyst (GO:0000145), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
protein transport	1
intracellular transport	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
post-Golgi vesicle-mediated transport	1
vesicle-mediated transport to the plasma membrane	1
membrane organization	1
transport	1
establishment of protein localization	1
binding	1
cell cortex	1
vesicle tethering complex	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXOC6B	RALA	P11233	804
EXOC6B	EXOC5	O00471	800
EXOC6B	EXOC4	Q96A65	771
EXOC6B	EXOC3	O60645	769
EXOC6B	CYP26B1	Q9NR63	636
EXOC6B	EXOC1	Q9NV70	616
EXOC6B	EXOC2	Q96KP1	572
EXOC6B	EXOC8	Q8IYI6	572
EXOC6B	EXOC7	Q9UPT5	557
EXOC6B	N4BP2L2	Q92802	482
EXOC6B	TNS3	Q68CZ2	467
EXOC6B	DYSF	O75923	461
EXOC6B	RAB11FIP2	Q7L804	450
EXOC6B	SNX32	Q86XE0	449
EXOC6B	PTGR3	Q8N4Q0	436

IntAct

65 interactions, top by confidence:

A	B	Type	Score
EXOC6B	EXOC5	psi-mi:“MI:0914”(association)	0.790
EXOC5	EXOC6B	psi-mi:“MI:0915”(physical association)	0.790
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
EXOC8	EXOC5	psi-mi:“MI:0914”(association)	0.730
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.730
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
SHTN1	EXOC6B	psi-mi:“MI:0915”(physical association)	0.560
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CA14	EXOC5	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
KXD1	TRAK2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
EXOC4	EXOC5	psi-mi:“MI:0914”(association)	0.510
EXOC5	ZNF609	psi-mi:“MI:0914”(association)	0.510
EXOC7	EXOC5	psi-mi:“MI:0914”(association)	0.510
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
	NBAS	psi-mi:“MI:0914”(association)	0.350
LURAP1	CIBAR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Co-fractionation), EXOC6B (Co-fractionation), EXOC8 (Co-fractionation), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS), EXOC6B (Affinity Capture-MS)

ESM2 similar proteins: A2A432, A6H5Z3, A9X1D0, B0VX69, B1MTJ4, B2KI88, B5FW36, C1FXW2, E2R766, E2RBS6, F1LSG8, O43242, O54923, O55047, O70133, P60762, Q13098, Q13619, Q13620, Q29425, Q2KJ46, Q3TCH7, Q4V860, Q5NVP9, Q5R5J4, Q5RAN1, Q5RB36, Q5VIR6, Q5ZKV9, Q5ZLD7, Q5ZML9, Q6AYU1, Q6NRT5, Q6NZH6, Q86TU7, Q8CCB4, Q8CI71, Q8K4Q0, Q8N122, Q8R3S6

Diamond homologs: A6H5Z3, E2R766, O54923, Q18286, Q8R313, Q8TAG9, Q9VDE6, Q9Y2D4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EXOC6B	“form complex”	“Exocyst_EXOC6B variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
VxPx cargo-targeting to cilium	8	94.4×	1e-12
Insulin processing	8	83.0×	2e-12
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	28.1×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking involved in exocytosis	8	103.7×	1e-12
Golgi to plasma membrane transport	6	64.8×	3e-08
membrane fission	8	63.2×	6e-11
mitotic cytokinesis	8	39.9×	2e-09
exocytosis	8	23.4×	1e-07
protein transport	8	6.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	9
Uncertain significance	156
Likely benign	125
Benign	30

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1335877	NM_015189.3(EXOC6B):c.401T>G (p.Leu134Ter)	Pathogenic
1704251	NM_015189.1:c.2122+15447_2197-59588del	Pathogenic
2714435	NM_015189.3(EXOC6B):c.1411C>T (p.Gln471Ter)	Pathogenic
3669490	NM_015189.3(EXOC6B):c.2041C>T (p.Gln681Ter)	Pathogenic
3775346	NM_015189.3(EXOC6B):c.2127del (p.Phe709fs)	Pathogenic
4279380	GRCh37/hg19 2p13.2(chr2:72679204-72789317)x1	Pathogenic
625845	NM_015189.3(EXOC6B):c.906T>A (p.Tyr302Ter)	Pathogenic
625846	NG_050967.1:g.291668_510915del	Pathogenic
1378529	NM_015189.3(EXOC6B):c.1047-2A>C	Likely pathogenic
1500492	NM_015189.3(EXOC6B):c.670-2A>G	Likely pathogenic
2125741	NM_015189.3(EXOC6B):c.2309+1169G>T	Likely pathogenic
3250437	NM_015189.3(EXOC6B):c.933del (p.Phe311fs)	Likely pathogenic
3335928	NM_015189.3(EXOC6B):c.2122+1G>A	Likely pathogenic
421388	NM_015189.3(EXOC6B):c.1299T>G (p.Tyr433Ter)	Likely pathogenic
4723494	NM_015189.3(EXOC6B):c.915+2T>G	Likely pathogenic
4849342	NM_015189.3(EXOC6B):c.2122C>T (p.Gln708Ter)	Likely pathogenic
562543	GRCh37/hg19 2p13.2(chr2:72503642-72716038)x1	Likely pathogenic

SpliceAI

5152 predictions. Top by Δscore:

Variant	Effect	Δscore
2:72184073:A:AC	donor_gain	1.0000
2:72184074:C:CT	donor_gain	1.0000
2:72184074:CTT:C	donor_gain	1.0000
2:72334943:TTA:T	donor_loss	1.0000
2:72334944:TA:T	donor_loss	1.0000
2:72334945:A:AC	donor_gain	1.0000
2:72334946:C:A	donor_loss	1.0000
2:72334946:C:CA	donor_gain	1.0000
2:72334946:CT:C	donor_gain	1.0000
2:72334946:CTT:C	donor_gain	1.0000
2:72334946:CTTG:C	donor_gain	1.0000
2:72334946:CTTGT:C	donor_gain	1.0000
2:72335016:AAACT:A	acceptor_gain	1.0000
2:72335017:AACT:A	acceptor_gain	1.0000
2:72335018:ACT:A	acceptor_gain	1.0000
2:72335019:CT:C	acceptor_gain	1.0000
2:72335019:CTC:C	acceptor_gain	1.0000
2:72335020:TC:T	acceptor_loss	1.0000
2:72335020:TCT:T	acceptor_gain	1.0000
2:72335021:C:CA	acceptor_loss	1.0000
2:72335021:C:CC	acceptor_gain	1.0000
2:72335022:T:C	acceptor_loss	1.0000
2:72379723:TCTTA:T	donor_loss	1.0000
2:72379724:CTTA:C	donor_loss	1.0000
2:72379725:TTACG:T	donor_loss	1.0000
2:72379726:TACGT:T	donor_loss	1.0000
2:72379727:A:AC	donor_gain	1.0000
2:72379727:ACGTT:A	donor_gain	1.0000
2:72379728:C:CA	donor_gain	1.0000
2:72379728:C:T	donor_loss	1.0000

AlphaMissense

5390 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:72179366:A:G	L802P	1.000
2:72184093:G:T	A764D	1.000
2:72184118:A:C	Y756D	1.000
2:72184151:A:C	Y745D	1.000
2:72184160:A:G	W742R	1.000
2:72184160:A:T	W742R	1.000
2:72184177:A:G	L736P	1.000
2:72465194:A:G	L649P	1.000
2:72465206:A:G	L645P	1.000
2:72492403:C:G	R527P	1.000
2:72514634:C:T	G349D	1.000
2:72514635:C:G	G349R	1.000
2:72515085:C:A	R319S	1.000
2:72515085:C:G	R319S	1.000
2:72515086:C:A	R319M	1.000
2:72515086:C:G	R319T	1.000
2:72559484:A:T	V295D	1.000
2:72718122:C:T	G217E	1.000
2:72718155:A:G	L206P	1.000
2:72718157:A:C	F205L	1.000
2:72718157:A:T	F205L	1.000
2:72718159:A:G	F205L	1.000
2:72718167:A:G	L202P	1.000
2:72718275:A:G	L166P	1.000
2:72718293:A:G	L160P	1.000
2:72718296:G:T	A159E	1.000
2:72731031:A:G	L147P	1.000
2:72741308:A:G	L92P	1.000
2:72741338:A:G	L82P	1.000
2:72741351:A:G	S78P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002759 (2:72558535 C>G), RS1000007664 (2:72375892 C>T), RS1000008888 (2:72413829 G>A), RS1000010997 (2:72784089 A>T), RS1000012101 (2:72510864 A>C), RS1000017002 (2:72627033 A>T), RS1000025972 (2:72514098 A>G), RS1000031731 (2:72459689 C>G,T), RS1000041372 (2:72281188 C>A,T), RS1000042068 (2:72330274 T>G), RS1000043378 (2:72602879 T>C), RS1000051272 (2:72735747 G>A), RS1000056649 (2:72558713 G>A), RS1000057286 (2:72272012 C>G), RS1000062694 (2:72414196 G>A)

Disease associations

OMIM: gene MIM:607880 | disease phenotypes: MIM:618395, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia with joint laxity, type 3	Strong	Autosomal recessive
spondyloepimetaphyseal dysplasia with joint laxity	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia with joint laxity, type 3	Definitive	AR

Mondo (3): spondyloepimetaphyseal dysplasia with joint laxity, type 3 (MONDO:0032724), schizophrenia (MONDO:0005090), spondyloepimetaphyseal dysplasia with joint laxity (MONDO:0019675)

Orphanet (3): EXOC6B-related spondyloepimetaphyseal dysplasia with joint laxity (Orphanet:642085), Non-syndromic anorectal malformation (Orphanet:557), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

26 total (27 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000268	Dolichocephaly
HP:0000470	Short neck
HP:0000883	Thin ribs
HP:0000926	Platyspondyly
HP:0001182	Tapered finger
HP:0001216	Delayed ossification of carpal bones
HP:0001382	Joint hypermobility
HP:0001498	Carpal bone hypoplasia
HP:0001513	Obesity
HP:0001763	Pes planus
HP:0002650	Scoliosis
HP:0002651	Spondyloepimetaphyseal dysplasia
HP:0002827	Hip dislocation
HP:0002999	Patellar dislocation
HP:0003022	Hypoplasia of the ulna
HP:0003025	Metaphyseal irregularity
HP:0003083	Dislocated radial head
HP:0003301	Irregular vertebral endplates
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0004976	Knee dislocation
HP:0008450	Narrow vertebral interpedicular distance
HP:0012095	Multiple joint dislocation
HP:0031936	Delayed ability to walk
HP:0100864	Short femoral neck
HP:0100753	Schizophrenia

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST006627_73	Diastolic blood pressure	3.000000e-09
GCST007094_72	Diastolic blood pressure	2.000000e-09
GCST007099_71	Systolic blood pressure	4.000000e-06
GCST008839_372	Height	7.000000e-38
GCST010725_60	Malaria	7.000000e-06
GCST010725_79	Malaria	5.000000e-06
GCST012020_585	Serum metabolite levels	3.000000e-12
GCST012021_33	Serum metabolite levels	3.000000e-12
GCST90000025_755	Appendicular lean mass	6.000000e-10
GCST90026412_12	Severe autoimmune type 2 diabetes	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562968	Spondyloepimetaphyseal Dysplasia With Joint Laxity (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, decreases expression (+1 more)	4
Valproic Acid	decreases expression, increases expression	3
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	decreases expression	1
Diethylstilbestrol	increases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Ketoconazole	increases expression	1
Lead	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Potassium Dichromate	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety