PLXNA3

Summary

PLXNA3 (plexin A3, HGNC:9101) is a protein-coding gene on chromosome Xq28, encoding Plexin-A3 (P51805). Coreceptor for SEMA3A and SEMA3F.

This gene encodes a member of the plexin class of proteins. The encoded protein is a class 3 semaphorin receptor, and may be involved in cytoskeletal remodeling and as well as apoptosis. Studies of a similar gene in zebrafish suggest that it is important for axon pathfinding in the developing nervous system. This gene may be associated with tumor progression.

Source: NCBI Gene 55558 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypogonadotropic hypogonadism (Strong, GenCC)
• Clinical variants (ClinVar): 954 total — 1 pathogenic
• Phenotypes (HPO): 2
• MANE Select transcript: NM_017514

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9101
Approved symbol	PLXNA3
Name	plexin A3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	SEX, XAP-6, 6.3, Plxn3
Ensembl gene	ENSG00000130827
Ensembl biotype	protein_coding
OMIM	300022
Entrez	55558

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 4 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron

ENST00000369682, ENST00000467463, ENST00000478236, ENST00000480645, ENST00000482598, ENST00000491066, ENST00000493546, ENST00000495040, ENST00000497802, ENST00000937806, ENST00000955276, ENST00000955277

RefSeq mRNA: 1 — MANE Select: NM_017514 NM_017514

CCDS: CCDS14752

Canonical transcript exons

ENST00000369682 — 33 exons

Exon	Start	End
ENSE00000897919	154461099	154461638
ENSE00000897923	154462128	154462310
ENSE00000897928	154463391	154463519
ENSE00000897940	154463590	154463690
ENSE00000897945	154463951	154464074
ENSE00000897950	154464157	154464313
ENSE00000897954	154464402	154464501
ENSE00000897958	154464754	154464868
ENSE00000897961	154465018	154465218
ENSE00000897965	154465424	154465520
ENSE00000897968	154465657	154465847
ENSE00000897972	154465935	154466080
ENSE00000897976	154466150	154466270
ENSE00000897988	154467057	154467150
ENSE00000897991	154467232	154467471
ENSE00000897993	154467545	154467688
ENSE00000897995	154467767	154468001
ENSE00000897997	154468082	154468224
ENSE00000897999	154468303	154468559
ENSE00000898005	154469056	154469215
ENSE00001450630	154472590	154477779
ENSE00001450662	154460157	154460777
ENSE00001597708	154468823	154468969
ENSE00001664343	154470442	154470611
ENSE00001696603	154468663	154468729
ENSE00001780245	154471105	154471317
ENSE00001945795	154458281	154458428
ENSE00003517443	154469379	154469482
ENSE00003521830	154466376	154466512
ENSE00003572722	154469688	154469784
ENSE00003574877	154466623	154466793
ENSE00003638396	154469977	154470167
ENSE00003694523	154471488	154471638

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9799 / max 142.7259, expressed in 1748 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198188	9.9799	1748

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	98.06	gold quality
stromal cell of endometrium	CL:0002255	97.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.52	gold quality
ganglionic eminence	UBERON:0004023	97.21	gold quality
left ovary	UBERON:0002119	96.91	gold quality
cerebellar hemisphere	UBERON:0002245	96.89	gold quality
pituitary gland	UBERON:0000007	96.88	gold quality
right ovary	UBERON:0002118	96.84	gold quality
cortical plate	UBERON:0005343	96.83	gold quality
cerebellar cortex	UBERON:0002129	96.66	gold quality
tibial nerve	UBERON:0001323	96.37	gold quality
right coronary artery	UBERON:0001625	95.91	gold quality
right uterine tube	UBERON:0001302	95.80	gold quality
sural nerve	UBERON:0015488	95.63	gold quality
descending thoracic aorta	UBERON:0002345	94.97	gold quality
minor salivary gland	UBERON:0001830	94.71	gold quality
endocervix	UBERON:0000458	94.56	gold quality
ascending aorta	UBERON:0001496	94.43	gold quality
thoracic aorta	UBERON:0001515	94.41	gold quality
right lobe of thyroid gland	UBERON:0001119	94.35	gold quality
body of uterus	UBERON:0009853	94.29	gold quality
cerebellum	UBERON:0002037	94.21	gold quality
left lobe of thyroid gland	UBERON:0001120	93.90	gold quality
left coronary artery	UBERON:0001626	93.71	gold quality
ovary	UBERON:0000992	93.67	gold quality
aorta	UBERON:0000947	93.29	gold quality
olfactory bulb	UBERON:0002264	93.25	gold quality
ventricular zone	UBERON:0003053	93.06	gold quality
coronary artery	UBERON:0001621	93.02	gold quality
ectocervix	UBERON:0012249	93.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.55
E-MTAB-6386	no	1209.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting PLXNA3, 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-5193	100.00	67.26	1744
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-583	98.71	67.44	1791

Literature-anchored findings (GeneRIF, showing 5)

• Data show that the expression of Sema3A receptors (neuropilin-1 (NRP-1), NRP-2, plexin A1, plexin A2, and plexin A3) significantly increased during M-CSF-mediated differentiation of monocytes into macrophages. (PMID:19480842)
• in vitro analysis on PLXNA3 also suggest that this gene may have some form of growth suppressive role in breast cancer, in addition to a similar role for the gene previously reported in ovarian cancer. (PMID:21925246)
• Data indicate that plexin A1-4 (PLXNA1-4) mediation of neuroanatomical traits can be detected using in vivo neuroimaging techniques. (PMID:25518740)
• Exome analysis of Kuwaiti multiple sclerosis patients revealed a missense variant (rs5945430) in Plexin A3 (PLXNA3) gene (Xq28) associated with male-specific MS severity and disability. (PMID:28536997)
• Semaphorin-Plexin Signaling: From Axonal Guidance to a New X-Linked Intellectual Disability Syndrome. (PMID:34740135)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plxna3	ENSDARG00000007172
mus_musculus	Plxna3	ENSMUSG00000031398
rattus_norvegicus	Plxna3	ENSRNOG00000060464

Paralogs (8): PLXND1 (ENSG00000004399), PLXNA2 (ENSG00000076356), PLXNA1 (ENSG00000114554), PLXNC1 (ENSG00000136040), PLXNB1 (ENSG00000164050), PLXNB2 (ENSG00000196576), PLXNB3 (ENSG00000198753), PLXNA4 (ENSG00000221866)

Protein

Protein identifiers

Plexin-A3 — P51805 (reviewed: P51805)

Alternative names: Plexin-4, Semaphorin receptor SEX

All UniProt accessions (1): P51805

UniProt curated annotations — full annotation on UniProt →

Function. Coreceptor for SEMA3A and SEMA3F. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Regulates the migration of sympathetic neurons, but not of neural crest precursors. Required for normal dendrite spine morphology in pyramidal neurons. May play a role in regulating semaphorin-mediated programmed cell death in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.

Subunit / interactions. Interacts with CBFA2T3/MTG16.

Subcellular location. Cell membrane.

Similarity. Belongs to the plexin family.

RefSeq proteins (1): NP_059984* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR002165	Plexin_repeat	Repeat
IPR002909	IPT_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR013548	Plexin_cytoplasmic_RasGAP_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR031148	Plexin	Family
IPR036352	Semap_dom_sf	Homologous_superfamily
IPR041019	TIG1_plexin	Domain
IPR041362	TIG2_plexin	Domain
IPR046800	Plexin_RBD	Domain

Pfam: PF01403, PF01437, PF01833, PF08337, PF17960, PF18020, PF20170, PF24479

UniProt features (36 total): glycosylation site 10, disulfide bond 10, domain 5, sequence variant 4, topological domain 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51805-F1	84.77	0.43

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): 1596

Disulfide bonds (10): 77–86, 112–120, 266–387, 282–338, 356–375, 491–508, 497–539, 500–517, 511–523, 574–594

Glycosylation sites (10): 59, 548, 637, 738, 746, 1009, 1036, 1073, 1115, 1162

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-399954	Sema3A PAK dependent Axon repulsion
R-HSA-399955	SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
R-HSA-399956	CRMPs in Sema3A signaling

MSigDB gene sets: 234 (showing top): GOBP_FOREBRAIN_NEURON_DEVELOPMENT, LOPEZ_MESOTHELIOMA_SURVIVAL_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_NEURON_PROJECTION_EXTENSION_INVOLVED_IN_NEURON_PROJECTION_GUIDANCE, GOZGIT_ESR1_TARGETS_DN, GOBP_GROWTH, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_NEUROGENESIS, GOBP_CRANIAL_NERVE_MORPHOGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (24): axon guidance (GO:0007411), synapse assembly (GO:0007416), motor neuron axon guidance (GO:0008045), facial nerve structural organization (GO:0021612), olfactory nerve formation (GO:0021628), trigeminal nerve structural organization (GO:0021637), hippocampus development (GO:0021766), branchiomotor neuron axon guidance (GO:0021785), gonadotrophin-releasing hormone neuronal migration to the hypothalamus (GO:0021828), pyramidal neuron development (GO:0021860), regulation of cell migration (GO:0030334), negative regulation of axon extension involved in axon guidance (GO:0048843), axon extension involved in axon guidance (GO:0048846), negative chemotaxis (GO:0050919), positive regulation of cytoskeleton organization (GO:0051495), semaphorin-plexin signaling pathway (GO:0071526), neuron projection guidance (GO:0097485), cell surface receptor signaling pathway (GO:0007166), telencephalon development (GO:0021537), axon extension (GO:0048675), regulation of axon extension involved in axon guidance (GO:0048841), regulation of axonogenesis (GO:0050770), regulation of chemotaxis (GO:0050920), neuron projection extension (GO:1990138)

GO Molecular Function (3): semaphorin receptor activity (GO:0017154), protein binding (GO:0005515), signaling receptor activity (GO:0038023)

GO Cellular Component (3): semaphorin receptor complex (GO:0002116), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Semaphorin interactions	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axonogenesis	2
axon guidance	2
cranial nerve structural organization	2
anatomical structure development	2
neuron projection guidance	1
nervous system development	1
cell junction assembly	1
synapse organization	1
facial nerve morphogenesis	1
cranial nerve formation	1
olfactory nerve morphogenesis	1
trigeminal nerve morphogenesis	1
pallium development	1
limbic system development	1
motor neuron axon guidance	1
neuron migration	1
hypothalamic tangential migration using cell-axon interactions	1
hypothalamus gonadotrophin-releasing hormone neuron development	1
pyramidal neuron differentiation	1
forebrain neuron development	1
cell migration	1
regulation of cell motility	1
negative regulation of axon extension	1
regulation of axon extension involved in axon guidance	1
axon extension involved in axon guidance	1
negative regulation of chemotaxis	1
axon extension	1
chemotaxis	1
cytoskeleton organization	1
positive regulation of organelle organization	1
regulation of cytoskeleton organization	1
cell surface receptor signaling pathway	1
neuron projection development	1
neuron projection morphogenesis	1
signal transduction	1
forebrain development	1
neuron projection extension	1
transmembrane signaling receptor activity	1
semaphorin-plexin signaling pathway	1
binding	1

Protein interactions and networks

STRING

916 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLXNA3	SEMA3F	Q13275	999
PLXNA3	SEMA3A	Q14563	999
PLXNA3	NRP1	O14786	996
PLXNA3	NRP2	O60462	993
PLXNA3	SEMA3B	Q13214	956
PLXNA3	SEMA6A	Q9H2E6	924
PLXNA3	SEMA3C	Q99985	870
PLXNA3	SEMA3E	O15041	858
PLXNA3	SEMA3D	O95025	813
PLXNA3	SEMA3G	Q9NS98	809
PLXNA3	SEMA5A	Q13591	809
PLXNA3	MICAL1	Q8TDZ2	796
PLXNA3	SEMA6B	Q9H3T3	748
PLXNA3	SEMA6C	Q9H3T2	706
PLXNA3	SEMA6D	Q8NFY4	682

IntAct

121 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
OAZ1	AZIN1	psi-mi:“MI:0914”(association)	0.640
SCGB1D1	MANBA	psi-mi:“MI:0914”(association)	0.640
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
PLXNA3	CBFA2T3	psi-mi:“MI:0915”(physical association)	0.520
	PLXNA3	psi-mi:“MI:0407”(direct interaction)	0.410
CSNK2B	PLXNA3	psi-mi:“MI:0915”(physical association)	0.370
PLXNA3	MAPK8IP2	psi-mi:“MI:0915”(physical association)	0.370
PPP2CB	PLXNA3	psi-mi:“MI:0915”(physical association)	0.370
SMN1	PLXNA3	psi-mi:“MI:0915”(physical association)	0.370
PLXNA3	TK1	psi-mi:“MI:0915”(physical association)	0.370
Tuba3a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Nedd1		psi-mi:“MI:0914”(association)	0.350
Kif4	UMPS	psi-mi:“MI:0914”(association)	0.350
Ect2	STX18	psi-mi:“MI:0914”(association)	0.350
Kif1c	ABLIM1	psi-mi:“MI:0914”(association)	0.350
KLC4	PUF60	psi-mi:“MI:0914”(association)	0.350
SMC6	IFT88	psi-mi:“MI:0914”(association)	0.350
Kctd5		psi-mi:“MI:0914”(association)	0.350
PARD6A		psi-mi:“MI:0914”(association)	0.350
Mad2l1bp	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Med22	MED7	psi-mi:“MI:0914”(association)	0.350
Gspt1	MRPL27	psi-mi:“MI:0914”(association)	0.350

BioGRID (125): PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Y0, A1KZ92, A2AJ76, B0S5N4, D3YXG0, D3ZPX4, F1MMS9, O00187, O55005, O60500, O75093, O88279, O88280, P11627, P17852, P26006, P32004, P51805, P57110, P59511, P70208, P85171, Q05695, Q0PMG2, Q13219, Q3UH53, Q4KMG0, Q62470, Q62918, Q7Z5N4, Q80TR4, Q8AV58, Q8AXZ4, Q8CIY2, Q8HZK2, Q8HZK3, Q8NDA2, Q8R4K8, Q8TE57, Q91WP0

Diamond homologs: B0S5N4, B2RXS4, D3ZLH5, D3ZPX4, O15031, O43157, O60486, O75051, P51805, P70206, P70207, P70208, Q3UH93, Q6BEA0, Q80UG2, Q8CJH3, Q9HCM2, Q9NTN9, Q9QY40, Q9QZC2, Q9UIW2, Q9ULL4, Q9V4A7, Q9WUH7, Q9Y4D7, Q09YN5, Q80ZA4, Q60519, Q9P283, O42236, Q13591, Q9C0C4, Q62190, Q626H5, Q9H2E6, O95754, Q64151, Q9Z123, Q9Z143, Q90665

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	435
Likely benign	328
Benign	30

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253438	GRCh37/hg19 Xp22.33-q28(chrX:176426-155250222)x3	Pathogenic

SpliceAI

5722 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154458425:ACAGG:A	donor_loss	1.0000
X:154458426:CAGG:C	donor_loss	1.0000
X:154458427:AGGTA:A	donor_loss	1.0000
X:154458428:GGTA:G	donor_loss	1.0000
X:154458429:G:T	donor_loss	1.0000
X:154458430:T:A	donor_loss	1.0000
X:154460156:GGCCT:G	acceptor_gain	1.0000
X:154460773:GTCTC:G	donor_gain	1.0000
X:154460778:GTGC:G	donor_gain	1.0000
X:154460780:GC:G	donor_gain	1.0000
X:154461618:G:GT	donor_gain	1.0000
X:154461634:ACACC:A	donor_gain	1.0000
X:154461636:ACC:A	donor_gain	1.0000
X:154461637:CC:C	donor_gain	1.0000
X:154461639:G:GG	donor_gain	1.0000
X:154462123:A:AG	acceptor_gain	1.0000
X:154462124:C:G	acceptor_gain	1.0000
X:154462126:A:AG	acceptor_gain	1.0000
X:154462127:G:GG	acceptor_gain	1.0000
X:154462307:G:GT	donor_gain	1.0000
X:154462308:A:T	donor_gain	1.0000
X:154463505:C:G	donor_gain	1.0000
X:154463507:GA:G	donor_gain	1.0000
X:154463509:G:GG	donor_gain	1.0000
X:154464075:GTGAG:G	donor_loss	1.0000
X:154464153:CCA:C	acceptor_loss	1.0000
X:154464154:CA:C	acceptor_loss	1.0000
X:154464155:A:AG	acceptor_gain	1.0000
X:154464155:AGCT:A	acceptor_gain	1.0000
X:154464156:G:GG	acceptor_gain	1.0000

AlphaMissense

12214 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154461283:C:T	S260F	1.000
X:154461629:C:G	C375W	1.000
X:154464793:G:C	W656C	1.000
X:154464793:G:T	W656C	1.000
X:154465204:T:A	C744S	1.000
X:154465205:G:C	C744S	1.000
X:154465480:G:C	W767C	1.000
X:154465480:G:T	W767C	1.000
X:154465736:G:C	W807C	1.000
X:154465736:G:T	W807C	1.000
X:154467265:T:A	C1079S	1.000
X:154467266:G:C	C1079S	1.000
X:154467645:T:C	L1181P	1.000
X:154467948:T:C	L1256P	1.000
X:154467969:T:C	L1263P	1.000
X:154467994:C:G	C1271W	1.000
X:154468084:T:C	F1275L	1.000
X:154468085:T:G	F1275C	1.000
X:154468086:T:A	F1275L	1.000
X:154468086:T:G	F1275L	1.000
X:154468094:T:C	L1278P	1.000
X:154468508:T:C	L1390P	1.000
X:154468559:G:C	R1407T	1.000
X:154468559:G:T	R1407M	1.000
X:154468689:T:C	L1416P	1.000
X:154468938:T:A	L1468H	1.000
X:154468938:T:C	L1468P	1.000
X:154470073:T:C	L1631P	1.000
X:154470141:T:G	Y1654D	1.000
X:154470145:T:A	L1655Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000612271 (X:154470910 C>T), RS1000735586 (X:154464302 C>G,T), RS10011 (X:154477866 C>A,T), RS1001425182 (X:154476133 C>G), RS1001999944 (X:154463287 G>C), RS1002250042 (X:154459922 C>T), RS1002426504 (X:154477651 C>G), RS1002685438 (X:154461567 T>G), RS1002695209 (X:154469277 G>A), RS1002843383 (X:154466027 G>A,T), RS1003069296 (X:154473098 C>G), RS1003080659 (X:154473342 G>A), RS1003953952 (X:154458622 C>T), RS1004506554 (X:154458676 C>G,T), RS1004665620 (X:154462493 G>A)

Disease associations

OMIM: gene MIM:300022 | disease phenotypes: MIM:209850, MIM:147950

GenCC curated gene-disease

Disease	Classification	Inheritance
hypogonadotropic hypogonadism	Strong	X-linked

Mondo (6): disorder of sexual differentiation (MONDO:0002145), childhood-onset schizophrenia (MONDO:0957430), autism (MONDO:0005260), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), hypogonadotropic hypogonadism (MONDO:0018555)

Orphanet (4): Difference of sex development (Orphanet:90771), Childhood-onset schizophrenia (Orphanet:641496), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000717	Autism
HP:0000044	Hypogonadotropic hypogonadism

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis, increases expression	3
Acetaminophen	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
trichostatin A	affects expression	1
arsenite	decreases reaction, affects binding	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
jinfukang	increases expression	1
NSC 689534	increases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Atrazine	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Methylnitronitrosoguanidine	increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Sulindac	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00328926	PHASE4	TERMINATED	Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	PHASE4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	PHASE4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	PHASE4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	PHASE4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	PHASE4	TERMINATED	A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00467870	PHASE3	COMPLETED	Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men
NCT00962637	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal™ Treatment in Men With Secondary Hypogonadism