SEMA3B

Summary

SEMA3B (semaphorin 3B, HGNC:10724) is a protein-coding gene on chromosome 3p21.31, encoding Semaphorin-3B (Q13214). Inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons.

The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 7869 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 237 total
• MANE Select transcript: NM_001290060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10724
Approved symbol	SEMA3B
Name	semaphorin 3B
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	SemA, semaV, LUCA-1, sema5
Ensembl gene	ENSG00000012171
Ensembl biotype	protein_coding
OMIM	601281
Entrez	7869

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 21 protein_coding, 7 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000416295, ENST00000418576, ENST00000419007, ENST00000433753, ENST00000434030, ENST00000439487, ENST00000441915, ENST00000456210, ENST00000456560, ENST00000611067, ENST00000612509, ENST00000616701, ENST00000618865, ENST00000619119, ENST00000621029, ENST00000852511, ENST00000852512, ENST00000852513, ENST00000852514, ENST00000852515, ENST00000852516, ENST00000942593, ENST00000942594, ENST00000942595, ENST00000942596, ENST00000942597, ENST00000942598, ENST00000942599, ENST00000942600

RefSeq mRNA: 6 — MANE Select: NM_001290060 NM_001005914, NM_001290060, NM_001290061, NM_001290062, NM_001290063, NM_004636

CCDS: CCDS74941, CCDS77743, CCDS77744, CCDS77745

Canonical transcript exons

ENST00000616701 — 17 exons

Exon	Start	End
ENSE00003715161	50275705	50275844
ENSE00003717487	50273298	50273443
ENSE00003724529	50273535	50273646
ENSE00003725065	50274843	50274934
ENSE00003726826	50275560	50275615
ENSE00003727500	50276302	50277546
ENSE00003729047	50269147	50269349
ENSE00003729900	50274363	50274582
ENSE00003731682	50271088	50271181
ENSE00003735946	50270433	50270495
ENSE00003736844	50270890	50271009
ENSE00003737129	50273759	50273828
ENSE00003739142	50273913	50274057
ENSE00003744933	50275012	50275053
ENSE00003746224	50270127	50270284
ENSE00003751997	50275302	50275459
ENSE00003752428	50271361	50271480

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.1020 / max 1290.8933, expressed in 1129 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36719	18.3188	1029
36715	2.0137	469
36721	0.5058	136
36714	0.4705	173
36716	0.4267	216
36718	0.1438	72
36720	0.1214	63
36717	0.0616	20
202760	0.0397	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	99.18	gold quality
right adrenal gland	UBERON:0001233	98.82	gold quality
left adrenal gland	UBERON:0001234	98.67	gold quality
left adrenal gland cortex	UBERON:0035825	98.67	gold quality
right adrenal gland cortex	UBERON:0035827	98.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.60	gold quality
adrenal cortex	UBERON:0001235	98.59	gold quality
sural nerve	UBERON:0015488	98.53	gold quality
spinal cord	UBERON:0002240	97.92	gold quality
middle frontal gyrus	UBERON:0002702	97.85	gold quality
trigeminal ganglion	UBERON:0001675	97.33	gold quality
olfactory bulb	UBERON:0002264	96.77	gold quality
cranial nerve II	UBERON:0000941	96.49	gold quality
dorsal root ganglion	UBERON:0000044	96.42	gold quality
inferior vagus X ganglion	UBERON:0005363	96.31	gold quality
metanephros cortex	UBERON:0010533	96.23	gold quality
endocervix	UBERON:0000458	96.21	gold quality
body of stomach	UBERON:0001161	96.17	gold quality
left uterine tube	UBERON:0001303	96.17	gold quality
right lung	UBERON:0002167	96.01	gold quality
adrenal gland	UBERON:0002369	95.97	gold quality
putamen	UBERON:0001874	95.74	gold quality
mucosa of transverse colon	UBERON:0004991	95.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.26	gold quality
inferior olivary complex	UBERON:0002127	94.97	gold quality
body of uterus	UBERON:0009853	94.93	gold quality
lateral globus pallidus	UBERON:0002476	94.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.64	gold quality
upper lobe of left lung	UBERON:0008952	94.53	gold quality
small intestine	UBERON:0002108	94.46	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	37.95
E-MTAB-8410	yes	26.46
E-GEOD-135922	yes	23.62
E-HCAD-10	yes	21.02
E-CURD-46	yes	14.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

14 targeting SEMA3B, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-1266-3P	96.23	66.36	778
HSA-MIR-6854-3P	90.99	65.18	155

Literature-anchored findings (GeneRIF, showing 36)

• Human Semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. (PMID:11809707)
• Identification of semaphorin 3B as a direct target of p53. (PMID:11922394)
• SEMA3B gene alterations may play a important role in the malignant transformation of NSCLC via a two-hit mechanism, including epigenetic changes and allelic loss, for tumor suppressor gene inactivation. (PMID:12810670)
• VEGF165, produced by tumor cells, acts as an autocrine survival factor and that SEMA3B mediates its tumor-suppressing effects, at least in part, by blocking this VEGF autocrine activity. (PMID:15273288)
• Heterozygous or homozygous variant genotype confers a >40% reduced relative risk of lung cancer in Latino Americans controlling for other lung cancer risk factors. (PMID:15831529)
• Higher level of SEMA3B expression was found in differentiated tumors with favorable histopathology (n = 19) than in tumors with unfavorable histology. (PMID:17452250)
• A putative role for SEMA3B as an osteoblast protein that regulates bone mass and skeletal homeostasis. (PMID:18356290)
• SEMA3B exerts unexpected functions in cancer progression by fostering a prometastatic environment through elevated IL-8 secretion. (PMID:18458115)
• Repulsion of human umbilical vascular endothelial cells by sema3B-m was mediated primarily by the neuropilin-1 receptor but sema3B-m was also able to transduce signals via neuropilin-2 (PMID:18757406)
• SEMA3B is a potential tumor suppressor that induces apoptosis in SEMA3B-inactivated tumor cells through the Np-1 receptor by inactivating the Akt signaling pathway. (PMID:18922901)
• IGFBP-6 is the effector of tumor suppressor activity of SEMA3B. (PMID:18985860)
• SEMA3B plays role in inhibiting of growth of renal, ovarian and colorectal cancer cells. (PMID:19548530)
• These data indicate that polymorphisms in SEMA3B are associated with prostate cancer risk and poor prognosis in Hispanic and nonHispanic white men (PMID:19683737)
• that methylation of promoter CpG-island contributed into inactivation of SEMA3B gene-suppressor in RCC. (PMID:20088387)
• semaphorin-3B and semaphorin-3F have roles in ovarian cancer (PMID:20124444)
• Three candidate tumor-suppressor genes, SEMA3B, AXUD1 and GNAT1 may be involved in oral squamous cell carcinoma. (PMID:23292452)
• Loss of Sema3B expression is associated with biochemical recurrence of patients with low- and intermediate-risk prostate cancer. (PMID:23906303)
• The transcriptional activity of RHOA, SEMA3B, and CKAP2 genes was assessed in blood samples of leukaemia patients and healthy donors. (PMID:24280143)
• CpG methylation of SEMA3B epigenetically regulates SEMA3B expression during development of gastric cancer. (PMID:24402303)
• although plexin-A4 overexpression restored Sema3A signaling in plexin-A1-silenced cells, it failed to restore Sema3B signaling in plexin-A2-silenced cells. (PMID:25335892)
• SEMA3B mRNA and protein is not altered in severe early onset preeclamptic placentas. (PMID:25454475)
• Aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression. (PMID:25961819)
• Maternal SEMA 3B level increased in preeclampsia before the onset of manifestations, indicating that SEMA 3B plays a role in the pathogenesis of preeclampsia (PMID:26828533)
• As the clinical pathological glioma grade increased, SEMA3B expression decreased. (PMID:27050958)
• By upregulating p53 and p21 expression and inhibiting Akt (Ser473) phosphorylation, SEMA3B could induce cell cycle arrest at G1/S phase. (PMID:27349960)
• data provide new insights into the role of SEMA3B in mammary gland and provides a new branch of GATA3 signaling that is pivotal for inhibition of breast cancer progression and metastasis (PMID:28581515)
• Advanced peri-implantitis lesions showed higher levels of gene expression for Sem3A and Sem4D and lower levels of Sem4A in comparison to tissues obtained from a healthy dental implant. (PMID:29763494)
• Low SEMA3B expression is associated with gastric cardia adenocarcinoma. (PMID:30656427)
• miR-374b promotes glioma process in vitro through suppressing SEMA3B via targeting GATA3 (PMID:30868892)
• the findings suggest that SEMA3B and SEMA3B-AS1 may act as tumor suppressors and may serve as potential targets for antitumor therapy. (PMID:30915595)
• our research revealed the regulation of EFEMP1 on cell proliferation and apoptosis in HCC. EFEMP1 may suppress the growth of HCC cells by promoting SEMA3B. (PMID:30972979)
• Analysis of the SEMA3B expression profile shows the complexity of neoplastic transformation, which confirms the different expression of SEMA3B in endometrial cancer cells and endothelial cells. (PMID:31217417)
• Semaphorin 3B-associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients. (PMID:32534052)
• Central Role of Semaphorin 3B in a Serum-Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis. (PMID:35001548)
• Semaphorin3B promotes an anti-inflammatory and pro-resolving phenotype in macrophages from rheumatoid arthritis patients in a MerTK-dependent manner. (PMID:38283352)
• SEMA3B inhibits TGFbeta-induced extracellular matrix protein production and its reduced levels are associated with a decline in lung function in IPF. (PMID:38646784)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sema3b	ENSDARG00000011672
mus_musculus	Sema3b	ENSMUSG00000057969
rattus_norvegicus	Sema3b	ENSRNOG00000016512

Paralogs (19): SEMA3F (ENSG00000001617), SEMA3G (ENSG00000010319), SEMA3A (ENSG00000075213), SEMA3C (ENSG00000075223), SEMA5B (ENSG00000082684), SEMA6A (ENSG00000092421), SEMA4G (ENSG00000095539), SEMA5A (ENSG00000112902), SEMA4F (ENSG00000135622), SEMA6D (ENSG00000137872), SEMA7A (ENSG00000138623), SEMA6C (ENSG00000143434), SEMA3D (ENSG00000153993), SEMA6B (ENSG00000167680), SEMA4C (ENSG00000168758), SEMA3E (ENSG00000170381), SEMA4B (ENSG00000185033), SEMA4D (ENSG00000187764), SEMA4A (ENSG00000196189)

Protein

Protein identifiers

Semaphorin-3B — Q13214 (reviewed: Q13214)

Alternative names: Sema A(V), Semaphorin-V

All UniProt accessions (4): Q13214, A0A087WZE0, A0A0C4DGV8, B4DEK9

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons.

Subcellular location. Secreted. Endoplasmic reticulum.

Tissue specificity. Expressed abundantly but differentially in a variety of neural and nonneural tissues.

Similarity. Belongs to the semaphorin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13214-1	1	yes
Q13214-2	2

RefSeq proteins (9): NP_001005914, NP_001276989, NP_001276990, NP_001276991, NP_001276992, NP_001422885, NP_001422886, NP_001422887, NP_004627 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR027231	Semaphorin	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036352	Semap_dom_sf	Homologous_superfamily

Pfam: PF00047, PF01403

UniProt features (21 total): disulfide bond 6, sequence variant 3, glycosylation site 3, sequence conflict 2, domain 2, signal peptide 1, chain 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13214-F1	85.84	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (6): 131–140, 269–380, 293–340, 516–534, 644–710, 102–113

Glycosylation sites (3): 82, 124, 427

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 195 (showing top): RNGTGGGC_UNKNOWN, MODULE_92, BENPORATH_ES_WITH_H3K27ME3, PAX4_01, MACLACHLAN_BRCA1_TARGETS_DN, MODULE_418, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, KYNG_DNA_DAMAGE_DN, GOBP_NEUROGENESIS, NAGASHIMA_NRG1_SIGNALING_UP, GGGTGGRR_PAX4_03, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_CELL_CELL_SIGNALING, NFKB_Q6

GO Biological Process (7): neural crest cell migration (GO:0001755), cell-cell signaling (GO:0007267), axon guidance (GO:0007411), positive regulation of cell migration (GO:0030335), negative chemotaxis (GO:0050919), chemorepulsion of axon (GO:0061643), semaphorin-plexin signaling pathway (GO:0071526)

GO Molecular Function (4): semaphorin receptor binding (GO:0030215), neuropilin binding (GO:0038191), chemorepellent activity (GO:0045499), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative chemotaxis	2
signaling receptor binding	2
neural crest cell development	1
mesenchymal cell migration	1
cell communication	1
signaling	1
axonogenesis	1
neuron projection guidance	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
chemotaxis	1
axon guidance	1
cellular response to chemical stimulus	1
cell surface receptor signaling pathway	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
external encapsulating structure	1

Protein interactions and networks

STRING

1000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMA3B	NRP1	O14786	992
SEMA3B	NRP2	O60462	973
SEMA3B	PLXNA3	P51805	956
SEMA3B	PLXNA4	Q9HCM2	849
SEMA3B	PLXNA2	O75051	815
SEMA3B	PLXNB1	O43157	811
SEMA3B	PLXNA1	Q9UIW2	807
SEMA3B	PLXNC1	O60486	787
SEMA3B	PLXNB3	Q9ULL4	728
SEMA3B	HGF	P14210	723
SEMA3B	THSD7A	Q9UPZ6	713
SEMA3B	PLXND1	Q9Y4D7	685
SEMA3B	NRCAM	Q92823	682
SEMA3B	PLA2R1	Q13018	671
SEMA3B	GNAT1	P11488	598

IntAct

49 interactions, top by confidence:

A	B	Type	Score
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PAK6	SEMA3B	psi-mi:“MI:0915”(physical association)	0.370
KLK1	CRLF1	psi-mi:“MI:0914”(association)	0.350
MFAP4	CRLF1	psi-mi:“MI:0914”(association)	0.350
SEMA3B	HSPA5	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
EDN3	POTEF	psi-mi:“MI:0914”(association)	0.350
IGLL5	POTEF	psi-mi:“MI:0914”(association)	0.350
PI15		psi-mi:“MI:0914”(association)	0.350
ISLR		psi-mi:“MI:0914”(association)	0.350
NAAA	HAX1	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
FMOD	QSOX1	psi-mi:“MI:0914”(association)	0.350
ALPI	RTCA	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
TRGV3	MANBA	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350
CBLN4	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): SEMA3B (Affinity Capture-MS), SEMA3B (Affinity Capture-MS), SEMA3B (Affinity Capture-MS), SEMA3B (Affinity Capture-MS), SEMA3B (Affinity Capture-MS), SEMA3B (Affinity Capture-RNA), SEMA3B (Affinity Capture-RNA), TRIP13 (Two-hybrid), CARD10 (Two-hybrid), PICK1 (Two-hybrid), NAA10 (Two-hybrid), MDFI (Two-hybrid), BOLL (Two-hybrid), HSF2BP (Two-hybrid), RBPMS2 (Two-hybrid)

ESM2 similar proteins: A2AJ76, B0S5N4, B2RXS4, D3ZLH5, D3ZPX4, F1MMS9, O15031, O75326, O75578, O95754, P08514, P08648, P11688, P17852, P26006, P38570, P51805, P53711, P60882, P70206, P70208, Q13214, Q13683, Q27977, Q3UH93, Q4LFA9, Q5STE3, Q60519, Q61738, Q62177, Q62179, Q62470, Q63258, Q64151, Q7Z7M0, Q8NDA2, Q9C0C4, Q9NPR2, Q9NS98, Q9NTN9

Diamond homologs: A7MB70, D3ZTD8, O08665, O09126, O15041, O35464, O42236, O42237, O88632, O95025, O95754, P70275, Q13214, Q13275, Q13591, Q14563, Q17330, Q24322, Q24323, Q26473, Q26972, Q4LFA9, Q5EA85, Q5R7F5, Q5RE75, Q60519, Q62177, Q62178, Q62179, Q62181, Q62217, Q63548, Q64151, Q76KF0, Q8BH34, Q8NFY4, Q90607, Q90663, Q90665, Q92854

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SEMA3B	“up-regulates activity”	PLXNA4	binding
SEMA3B	“up-regulates activity”	PLXNA2	binding
SEMA3B	“up-regulates activity”	NRP1	binding
SEMA3B	“up-regulates activity”	NRP2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	140
Likely benign	68
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3116 predictions. Top by Δscore:

Variant	Effect	Δscore
3:50267774:GT:G	donor_gain	1.0000
3:50267787:G:T	donor_gain	1.0000
3:50267795:G:T	donor_gain	1.0000
3:50270319:G:GT	donor_gain	1.0000
3:50270319:G:T	donor_gain	1.0000
3:50271355:CTGCA:C	acceptor_loss	1.0000
3:50271356:TGCAG:T	acceptor_loss	1.0000
3:50271357:GCAGG:G	acceptor_loss	1.0000
3:50271358:CA:C	acceptor_loss	1.0000
3:50271359:A:AT	acceptor_loss	1.0000
3:50271359:AGG:A	acceptor_gain	1.0000
3:50271360:G:GT	acceptor_loss	1.0000
3:50271360:GGG:G	acceptor_gain	1.0000
3:50271476:CAATG:C	donor_loss	1.0000
3:50271477:AATGG:A	donor_loss	1.0000
3:50271478:ATGGT:A	donor_loss	1.0000
3:50271481:GT:G	donor_loss	1.0000
3:50271482:T:G	donor_loss	1.0000
3:50273642:GCTCC:G	donor_gain	1.0000
3:50273643:C:G	donor_gain	1.0000
3:50273645:CC:C	donor_gain	1.0000
3:50273647:G:GG	donor_gain	1.0000
3:50273651:G:GG	donor_gain	1.0000
3:50273995:G:GT	donor_gain	1.0000
3:50274012:G:GG	donor_gain	1.0000
3:50274072:G:T	donor_gain	1.0000
3:50274105:GGTT:G	donor_gain	1.0000
3:50274361:A:AG	acceptor_gain	1.0000
3:50274362:G:GG	acceptor_gain	1.0000
3:50274362:GT:G	acceptor_gain	1.0000

AlphaMissense

4818 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:50273571:T:A	W283R	1.000
3:50273571:T:C	W283R	1.000
3:50270469:T:A	C102S	0.999
3:50270469:T:C	C102R	0.999
3:50270470:G:A	C102Y	0.999
3:50270470:G:C	C102S	0.999
3:50270470:G:T	C102F	0.999
3:50270471:C:G	C102W	0.999
3:50270896:T:A	C113S	0.999
3:50270897:G:C	C113S	0.999
3:50270898:C:G	C113W	0.999
3:50270965:T:C	F136L	0.999
3:50270967:C:A	F136L	0.999
3:50270967:C:G	F136L	0.999
3:50273307:T:G	F225C	0.999
3:50273438:T:A	C269S	0.999
3:50273439:G:A	C269Y	0.999
3:50273439:G:C	C269S	0.999
3:50273440:C:G	C269W	0.999
3:50273538:G:C	D272H	0.999
3:50273573:G:C	W283C	0.999
3:50273573:G:T	W283C	0.999
3:50273588:G:C	K288N	0.999
3:50273588:G:T	K288N	0.999
3:50273601:T:A	C293S	0.999
3:50273601:T:C	C293R	0.999
3:50273602:G:C	C293S	0.999
3:50273603:C:G	C293W	0.999
3:50273940:C:G	C340W	0.999
3:50274363:T:C	C380R	0.999

dbSNP variants (sampled 300 via entrez): RS1000216160 (3:50268718 C>T), RS1000553484 (3:50267125 A>C), RS1001217098 (3:50270388 C>G), RS1001601310 (3:50276479 G>A,T), RS1002088431 (3:50268449 T>C), RS1002137063 (3:50276717 C>A,G,T), RS1003012457 (3:50277890 C>T), RS1004260565 (3:50267873 A>C,T), RS1004572525 (3:50272922 G>A), RS1004731691 (3:50266679 G>T), RS1004799540 (3:50268346 T>C), RS1005000164 (3:50266375 C>A,T), RS1005110555 (3:50272646 G>A), RS1005403442 (3:50269956 G>A), RS1005680296 (3:50269540 C>T)

Disease associations

OMIM: gene MIM:601281 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007240_13	Obese vs. thin	1.000000e-06
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST90020029_1180	Waist circumference adjusted for body mass index	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007041	obese body mass index status
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression, increases reaction	8
Calcitriol	increases response to substance, increases expression, increases reaction, decreases reaction	4
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	increases expression, affects cotreatment, increases methylation	2
entinostat	increases expression, affects cotreatment	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Vehicle Emissions	decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Ozone	affects expression, increases abundance, increases expression	2
Progesterone	decreases expression, decreases reaction, increases expression, affects cotreatment	2
Raloxifene Hydrochloride	affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
VX-agent	increases expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
ferrous chloride	decreases expression	1
indeno(1,2,3-cd)pyrene	decreases expression	1
picene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
seocalcitol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
gypenoside	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
belinostat	decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice