CPLX1

Summary

CPLX1 (complexin 1, HGNC:2309) is a protein-coding gene on chromosome 4p16.3, encoding Complexin-1 (O14810). Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles.

Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release.

Source: NCBI Gene 10815 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 63 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 93 total — 2 likely-pathogenic
• Phenotypes (HPO): 186
• MANE Select transcript: NM_006651

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2309
Approved symbol	CPLX1
Name	complexin 1
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	CPX-I
Ensembl gene	ENSG00000168993
Ensembl biotype	protein_coding
OMIM	605032
Entrez	10815

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000304062, ENST00000504062, ENST00000505203, ENST00000506404, ENST00000892263, ENST00000892264, ENST00000892265, ENST00000892266, ENST00000892267, ENST00000944762

RefSeq mRNA: 1 — MANE Select: NM_006651 NM_006651

CCDS: CCDS46995

Canonical transcript exons

ENST00000304062 — 4 exons

Exon	Start	End
ENSE00001293910	826046	826129
ENSE00002068152	784957	786698
ENSE00003373475	824492	824601
ENSE00003616973	792433	792608

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 99.72.

FANTOM5 (CAGE): breadth broad, TPM avg 10.5687 / max 701.2164, expressed in 601 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51019	6.9332	411
51018	2.4362	175
51008	0.5382	182
51020	0.1492	73
203085	0.1007	61
51012	0.0843	40
51011	0.0797	33
51017	0.0779	44
51009	0.0673	41
51013	0.0493	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.72	gold quality
lateral globus pallidus	UBERON:0002476	99.00	gold quality
postcentral gyrus	UBERON:0002581	98.87	gold quality
parietal lobe	UBERON:0001872	98.83	gold quality
pons	UBERON:0000988	98.64	gold quality
superior frontal gyrus	UBERON:0002661	98.60	gold quality
right frontal lobe	UBERON:0002810	98.48	gold quality
putamen	UBERON:0001874	98.47	gold quality
primary visual cortex	UBERON:0002436	98.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.24	gold quality
caudate nucleus	UBERON:0001873	98.00	gold quality
occipital lobe	UBERON:0002021	97.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.94	gold quality
cerebellar cortex	UBERON:0002129	97.90	gold quality
cerebellar hemisphere	UBERON:0002245	97.89	gold quality
cerebellum	UBERON:0002037	97.83	gold quality
cerebellar vermis	UBERON:0004720	97.83	gold quality
nucleus accumbens	UBERON:0001882	97.69	gold quality
anterior cingulate cortex	UBERON:0009835	97.46	gold quality
frontal cortex	UBERON:0001870	97.07	gold quality
entorhinal cortex	UBERON:0002728	96.81	gold quality
neocortex	UBERON:0001950	96.31	gold quality
prefrontal cortex	UBERON:0000451	96.08	gold quality
cerebral cortex	UBERON:0000956	95.93	gold quality
temporal lobe	UBERON:0001871	95.49	gold quality
middle temporal gyrus	UBERON:0002771	95.38	gold quality
substantia nigra pars compacta	UBERON:0001965	95.13	gold quality
medulla oblongata	UBERON:0001896	95.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	10.36
E-ANND-3	yes	4.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting CPLX1, 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-4283	100.00	66.42	2097
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-5580-5P	99.38	66.96	1139

Literature-anchored findings (GeneRIF, showing 16)

• role in synaptic vesicle exocytosis (PMID:12058476)
• altered immunoreactivity of this protein in prefrontal cortex in severe mental illness (PMID:12082566)
• description of what may represent a basic principle of the coupling mechanism in SNARE dependent exocytosis: a reversible clamping protein, complexin, that can freeze the SNAREpin, an assembled fusion-competent intermediate en route to fusion (PMID:16794037)
• CX1 level increased progressively across development (PMID:18240322)
• The crystal structure of complexin bound to a prefusion SNAREpin mimetic shows that the accessory helix extends away from the SNAREpin in an ‘open’ conformation, binding another SNAREpin and inhibiting its assembly, to clamp fusion. (PMID:21785412)
• The ‘central helix’ of complexin is anchored to one SNARE complex, while its ‘accessory helix’ extends away at ~45 degrees and bridges to a second complex, occupying the vacant v-SNARE binding site to inhibit fusion. (PMID:21785414)
• Together with synaptotagmin 1, complexin synchronizes and stimulates rapid fusion of accumulated docked vesicles in response to physiological Ca(2+) concentrations. (PMID:22705946)
• Data support the the trans insertion model for complexin clamping. (PMID:25831964)
• Studies indicate the role of the small regulatory factor complexin in Ca(2+)-dependent vesicle fusion and exocytosis. (PMID:26245303)
• Study showed for the first time that neuro-Behcet’s disease and Behcet’s disease patients are inclined to display the GG genotype of the CPLX1 rs936551 polymorphism and to exhibit increased CPLX1 expression levels (PMID:26577184)
• Collectively these results demonstrate that CPX-1 is a secreted collagen-binding glycoprotein and provide a foundation for future studies investigating the function of CPX-1. (PMID:26603934)
• This study demonstrated that complexin-I influence cognitive function in early and late stages of Alzheimer’s disease. (PMID:27866231)
• data define CPLX1 as a PD risk factor and provide functional insights into the role and regulation of blood SNCA levels. The new blood biomarkers of PARK4 in this Turkish family might become useful for PD prediction (PMID:28108469)
• Homozygous CPLX1 variants were identified in three patients with severe infantile myoclonic epilepsy and ID. (PMID:28422131)
• Findings do not support microRNA137 (MIR137) and complexin 1 (CPLX1) conferring susceptibility to schizophrenia in Han Chinese. (PMID:29118371)
• Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis. (PMID:32401194)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cplx2a	ENSDARG00000018997
danio_rerio	CPLX1	ENSDARG00000111920
mus_musculus	Cplx1	ENSMUSG00000033615
rattus_norvegicus	Cplx1	ENSRNOG00000090522
drosophila_melanogaster	cpx	FBGN0041605
caenorhabditis_elegans		WBGENE00010520
caenorhabditis_elegans	cpx-1	WBGENE00022271

Paralogs (3): CPLX2 (ENSG00000145920), CPLX4 (ENSG00000166569), CPLX3 (ENSG00000213578)

Protein

Protein identifiers

Complexin-1 — O14810 (reviewed: O14810)

Alternative names: Complexin I, Synaphin-2

All UniProt accessions (3): D6RAG3, D6RI11, O14810

UniProt curated annotations — full annotation on UniProt →

Function. Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles. Organizes the SNAREs into a cross-linked zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion, thereby preventing SNAREs from releasing neurotransmitters until an action potential arrives at the synapse. Also involved in glucose-induced secretion of insulin by pancreatic beta-cells. Essential for motor behavior.

Subunit / interactions. Binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A.

Subcellular location. Cytoplasm. Cytosol. Perikaryon. Presynapse.

Tissue specificity. Nervous system. In hippocampus and cerebellum, expressed mainly by inhibitory neurons. Overexpressed in substantia nigra from patients with Parkinson disease.

Disease relevance. Developmental and epileptic encephalopathy 63 (DEE63) [MIM:617976] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE63 is an autosomal recessive disease with onset in infancy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the complexin/synaphin family.

RefSeq proteins (1): NP_006642* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008849	Synaphin	Family

Pfam: PF05835

UniProt features (10 total): region of interest 3, sequence variant 3, chain 1, coiled-coil region 1, compositionally biased region 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3RK3	X-RAY DIFFRACTION	3.5
3RL0	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14810-F1	72.31	0.22

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-181429	Serotonin Neurotransmitter Release Cycle
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-210500	Glutamate Neurotransmitter Release Cycle
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle
R-HSA-888590	GABA synthesis, release, reuptake and degradation

MSigDB gene sets: 541 (showing top): GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_VESICLE_ORGANIZATION, GOBP_INSULIN_SECRETION, AAGCCAT_MIR135A_MIR135B, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS, GOBP_VESICLE_FUSION_TO_PLASMA_MEMBRANE

GO Biological Process (9): exocytosis (GO:0006887), chemical synaptic transmission (GO:0007268), synaptic vesicle exocytosis (GO:0016079), regulation of exocytosis (GO:0017157), insulin secretion (GO:0030073), regulation of synaptic vesicle fusion to presynaptic active zone membrane (GO:0031630), modulation of chemical synaptic transmission (GO:0050804), regulation of exocytic insertion of neurotransmitter receptor to postsynaptic membrane (GO:0099145), neurotransmitter transport (GO:0006836)

GO Molecular Function (4): SNARE binding (GO:0000149), syntaxin-1 binding (GO:0017075), protein binding (GO:0005515), syntaxin binding (GO:0019905)

GO Cellular Component (17): cytosol (GO:0005829), dendrite (GO:0030425), SNARE complex (GO:0031201), terminal bouton (GO:0043195), perikaryon (GO:0043204), calyx of Held (GO:0044305), synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex (GO:0070032), synaptobrevin 2-SNAP-25-syntaxin-3-complexin complex (GO:0070554), Schaffer collateral - CA1 synapse (GO:0098685), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), protein-containing complex (GO:0032991), cell projection (GO:0042995), neuronal cell body (GO:0043025), synapse (GO:0045202), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotransmitter release cycle	6

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
synapse	4
presynapse	2
cytoplasm	2
axon terminus	2
SNARE complex	2
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
anterograde trans-synaptic signaling	1
neurotransmitter secretion	1
regulated exocytosis	1
establishment of localization in cell	1
vesicle-mediated transport in synapse	1
synaptic vesicle cycle	1
signal release from synapse	1
exocytosis	1
regulation of vesicle-mediated transport	1
regulation of secretion by cell	1
protein secretion	1
peptide hormone secretion	1
regulation of vesicle fusion	1
synaptic vesicle fusion to presynaptic active zone membrane	1
regulation of synaptic vesicle membrane organization	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
regulation of exocytosis	1
regulation of protein transport	1
regulation of biological quality	1
exocytic insertion of neurotransmitter receptor to postsynaptic membrane	1
regulation of receptor localization to synapse	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
transport	1
protein binding	1
syntaxin binding	1
binding	1
SNARE binding	1
neuron projection	1
dendritic tree	1

Protein interactions and networks

STRING

1826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPLX1	SYT1	P21579	985
CPLX1	STX1A	Q16623	934
CPLX1	VAMP2	P19065	928
CPLX1	SNAP25	P13795	910
CPLX1	SYT4	Q9H2B2	839
CPLX1	SYT7	O43581	838
CPLX1	SYT2	Q8N9I0	731
CPLX1	GAK	O14976	676
CPLX1	CPLX3	Q8WVH0	665
CPLX1	SYN2	Q92777	660
CPLX1	CPLX4	Q7Z7G2	641
CPLX1	NSF	P46459	632
CPLX1	STXBP1	P61764	614
CPLX1	RNF212	Q495C1	607
CPLX1	UNC13B	O14795	512

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CPLX1	SNAP25	psi-mi:“MI:0407”(direct interaction)	0.730
CPLX1	Stx1a	psi-mi:“MI:0915”(physical association)	0.660
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
CPLX1	VAMP3	psi-mi:“MI:0914”(association)	0.530
CPLX2	CPLX1	psi-mi:“MI:0914”(association)	0.530
CPLX1	OPRM1	psi-mi:“MI:0915”(physical association)	0.370
CPLX1	AGTRAP	psi-mi:“MI:0915”(physical association)	0.370
CPLX1	CMTM5	psi-mi:“MI:0915”(physical association)	0.370
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
CPLX1	HSPA8	psi-mi:“MI:0914”(association)	0.350
RXRB	CPLX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): CPLX2 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), CPLX1 (Affinity Capture-MS), CPLX1 (Affinity Capture-Western), CPLX1 (Two-hybrid), CPLX1 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), CPLX1 (Co-crystal Structure), SNAP25 (Co-crystal Structure), VAMP2 (Co-crystal Structure), SNAP25 (Reconstituted Complex), STX1A (Reconstituted Complex), CPLX2 (Affinity Capture-MS), CPLX1 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS)

ESM2 similar proteins: B2GUV7, B4NSP6, B5XG19, G0S8G9, O02108, O14810, O42105, O42106, O60841, P36188, P63040, P63041, P84086, P84087, P84088, Q05D44, Q08310, Q0IIE0, Q0IIL7, Q13442, Q14320, Q20334, Q22472, Q24276, Q27371, Q28BK4, Q299F9, Q2VPH1, Q3E772, Q3UHX2, Q4KLV7, Q4R4N1, Q568K9, Q5RDE1, Q60PP8, Q60ZR7, Q62785, Q6PUV4, Q7PYQ5, Q7Z7G2

Diamond homologs: O14810, O42105, O42106, P63040, P63041, P84086, P84087, P84088, Q0IIL7, Q4R4N1, Q60PP8, Q6PUV4, Q9GUM7, Q8I6U3, Q8IPM8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	46
Likely benign	35
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1705441	NM_006651.4(CPLX1):c.66_75del (p.Asp23fs)	Likely pathogenic
402136	NM_006651.4(CPLX1):c.322G>T (p.Glu108Ter)	Likely pathogenic

SpliceAI

1672 predictions. Top by Δscore:

Variant	Effect	Δscore
4:786694:CCGTA:C	acceptor_gain	1.0000
4:786695:CGTA:C	acceptor_gain	1.0000
4:786695:CGTAC:C	acceptor_gain	1.0000
4:786697:TA:T	acceptor_gain	1.0000
4:786698:ACTGC:A	acceptor_loss	1.0000
4:786699:C:CC	acceptor_gain	1.0000
4:786699:CTGCG:C	acceptor_loss	1.0000
4:801767:C:CC	acceptor_gain	1.0000
4:826048:T:A	donor_gain	1.0000
4:792428:CGCA:C	donor_loss	0.9900
4:792429:GCACC:G	donor_loss	0.9900
4:792430:CACCT:C	donor_loss	0.9900
4:792431:A:C	donor_loss	0.9900
4:792432:CCT:C	donor_loss	0.9900
4:801764:TGA:T	acceptor_gain	0.9900
4:822919:G:C	donor_gain	0.9900
4:824493:T:TA	donor_gain	0.9900
4:824601:CCTGG:C	acceptor_loss	0.9900
4:824602:CTGGG:C	acceptor_loss	0.9900
4:826049:C:A	donor_gain	0.9900
4:786696:GTA:G	acceptor_gain	0.9800
4:792427:GCGCA:G	donor_loss	0.9800
4:792606:CCC:C	acceptor_gain	0.9800
4:792607:CC:C	acceptor_gain	0.9800
4:792607:CCC:C	acceptor_gain	0.9800
4:792608:CC:C	acceptor_gain	0.9800
4:792610:T:C	acceptor_loss	0.9800
4:801560:CCA:C	donor_gain	0.9800
4:801762:CATGA:C	acceptor_gain	0.9800
4:824486:TCCTA:T	donor_loss	0.9800

AlphaMissense

885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:824514:A:C	F3L	0.997
4:824514:A:T	F3L	0.997
4:824516:A:G	F3L	0.997
4:792440:C:G	R67P	0.995
4:792453:G:T	R63S	0.994
4:792465:G:T	R59S	0.993
4:824515:A:C	F3C	0.993
4:786547:A:T	V120D	0.992
4:792497:C:G	R48P	0.992
4:786691:A:G	I72T	0.991
4:792464:C:G	R59P	0.991
4:824500:G:T	A8D	0.991
4:786691:A:C	I72S	0.990
4:792443:A:C	I66S	0.990
4:792443:A:G	I66T	0.989
4:792522:C:G	A40P	0.988
4:824505:C:A	K6N	0.988
4:824505:C:G	K6N	0.988
4:792443:A:T	I66N	0.987
4:792441:G:C	R67G	0.986
4:824494:C:T	G10E	0.986
4:786691:A:T	I72N	0.984
4:792452:C:G	R63P	0.984
4:792498:G:T	R48S	0.984
4:792471:C:G	A57P	0.983
4:792518:A:G	L41P	0.983
4:792433:C:A	K69N	0.982
4:792433:C:G	K69N	0.982
4:786535:A:G	L124P	0.981
4:786698:A:C	Y70D	0.979

dbSNP variants (sampled 300 via entrez): RS1000057244 (4:816207 C>T), RS1000080660 (4:810346 G>A,T), RS1000094746 (4:810240 G>A,C), RS1000118786 (4:797234 T>C,G), RS1000123879 (4:792719 C>T), RS1000173550 (4:802666 G>A), RS1000243664 (4:787061 G>A), RS1000321548 (4:795163 G>A), RS1000331103 (4:791060 CG>C), RS1000338043 (4:825611 G>A), RS1000338204 (4:826989 G>A), RS1000428431 (4:816511 C>T), RS10004297 (4:799975 C>T), RS10004482 (4:802433 G>A,C,T), RS10004503 (4:800141 C>A,G,T)

Disease associations

OMIM: gene MIM:605032 | disease phenotypes: MIM:617976, MIM:194190

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 63	Strong	Autosomal recessive
familial infantile myoclonic epilepsy	Supportive	Autosomal recessive

Mondo (3): developmental and epileptic encephalopathy, 63 (MONDO:0033372), Wolf-Hirschhorn syndrome (MONDO:0008684), familial infantile myoclonic epilepsy (MONDO:0011506)

Orphanet (1): Wolf-Hirschhorn syndrome (Orphanet:280)

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000077	Abnormality of the kidney
HP:0000078	Abnormality of the genital system
HP:0000079	Abnormality of the urinary system
HP:0000119	Abnormality of the genitourinary system
HP:0000151	Aplasia of the uterus
HP:0000153	Abnormality of the mouth
HP:0000159	Abnormal lip morphology
HP:0000175	Cleft palate
HP:0000188	Short upper lip
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000288	Abnormality of the philtrum
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000384	Preauricular skin tag

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006979_316	Heel bone mineral density	2.000000e-09
GCST012073_14	Behcet’s disease	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D054877	Wolf-Hirschhorn Syndrome	C16.131.077.944; C16.131.260.985; C16.320.180.985

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Cyclosporine	decreases expression, increases expression	2
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cylindrospermopsin	increases expression	1
MRK 003	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1
Azacitidine	increases expression	1
Cadmium	increases abundance, increases expression	1
Bucladesine	affects cotreatment, increases expression	1
Estradiol	increases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Medroxyprogesterone Acetate	affects cotreatment, increases expression	1
Asbestos, Serpentine	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D0H2	KAIMRCi003-A	Induced pluripotent stem cell	Female
CVCL_D0H3	KAIMRCi003-B	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford