SEMA6A

Summary

SEMA6A (semaphorin 6A, HGNC:10738) is a protein-coding gene on chromosome 5q23.1, encoding Semaphorin-6A (Q9H2E6). Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling.

Predicted to enable identical protein binding activity; signaling receptor binding activity; and transmembrane signaling receptor activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be located in axon and membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 57556 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 193 total — 1 likely-pathogenic
• MANE Select transcript: NM_020796

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10738
Approved symbol	SEMA6A
Name	semaphorin 6A
Location	5q23.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1368, SEMA6A1, SEMA, HT018
Ensembl gene	ENSG00000092421
Ensembl biotype	protein_coding
OMIM	605885
Entrez	57556

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 18 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000257414, ENST00000343348, ENST00000502996, ENST00000503402, ENST00000503865, ENST00000503962, ENST00000506114, ENST00000509665, ENST00000510024, ENST00000510263, ENST00000512156, ENST00000513137, ENST00000514316, ENST00000515009, ENST00000515129, ENST00000879671, ENST00000879672, ENST00000879673, ENST00000879674, ENST00000879675, ENST00000879676, ENST00000917979, ENST00000917980, ENST00000917981, ENST00000917982

RefSeq mRNA: 2 — MANE Select: NM_020796 NM_001300780, NM_020796

CCDS: CCDS47256, CCDS75288

Canonical transcript exons

ENST00000343348 — 19 exons

Exon	Start	End
ENSE00001547241	116443555	116447811
ENSE00001556024	116574185	116574823
ENSE00002204910	116480122	116480277
ENSE00002216709	116504845	116504982
ENSE00002253265	116482444	116482575
ENSE00002279181	116478542	116478718
ENSE00003458790	116478014	116478154
ENSE00003459948	116477846	116477926
ENSE00003482927	116475545	116475603
ENSE00003503441	116467583	116467747
ENSE00003529500	116497327	116497387
ENSE00003531329	116502210	116502327
ENSE00003553294	116488108	116488196
ENSE00003556540	116473073	116473093
ENSE00003565910	116488888	116489007
ENSE00003592572	116486749	116486966
ENSE00003616926	116495413	116495514
ENSE00003628079	116491740	116491830
ENSE00003788012	116496251	116496313

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.6889 / max 1369.6016, expressed in 929 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63058	14.4948	809
63056	8.3667	639
63057	3.3262	483
63054	1.8560	410
63061	1.7428	259
63060	0.6871	182
63055	0.4421	200
63059	0.4213	190
63051	0.2428	98
63050	0.0384	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	98.36	gold quality
adrenal tissue	UBERON:0018303	98.10	gold quality
lateral globus pallidus	UBERON:0002476	97.73	gold quality
subthalamic nucleus	UBERON:0001906	97.63	gold quality
corpus callosum	UBERON:0002336	97.50	gold quality
jejunal mucosa	UBERON:0000399	96.64	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.63	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.59	gold quality
ventral tegmental area	UBERON:0002691	96.45	gold quality
superior vestibular nucleus	UBERON:0007227	95.98	gold quality
pons	UBERON:0000988	95.96	gold quality
substantia nigra pars compacta	UBERON:0001965	95.70	gold quality
right adrenal gland cortex	UBERON:0035827	95.69	gold quality
right adrenal gland	UBERON:0001233	95.31	gold quality
adrenal cortex	UBERON:0001235	95.31	gold quality
buccal mucosa cell	CL:0002336	94.99	gold quality
adrenal gland	UBERON:0002369	94.97	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.96	gold quality
left adrenal gland cortex	UBERON:0035825	94.84	gold quality
placenta	UBERON:0001987	94.74	gold quality
left adrenal gland	UBERON:0001234	94.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.47	gold quality
medulla oblongata	UBERON:0001896	94.44	gold quality
spinal cord	UBERON:0002240	94.19	gold quality
globus pallidus	UBERON:0001875	94.00	gold quality
medial globus pallidus	UBERON:0002477	93.06	gold quality
right lung	UBERON:0002167	92.04	gold quality
ventricular zone	UBERON:0003053	91.99	gold quality
colonic mucosa	UBERON:0000317	91.56	gold quality
olfactory bulb	UBERON:0002264	91.32	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-10	yes	78.95
E-ANND-3	yes	23.93
E-HCAD-5	yes	17.60
E-HCAD-9	yes	14.42
E-GEOD-109979	no	1108.39
E-GEOD-81383	no	1098.91
E-MTAB-7008	no	554.00
E-MTAB-8271	no	314.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NANOG, POU5F1, SOX2

miRNA regulators (miRDB)

200 targeting SEMA6A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 13)

• Strong expression of SEMA6A is associated with langerhans cells of histiocytosis or dermatopathic lymphadenitis (PMID:16436660)
• NANOG-, SOX2-, and POU5F1 (OCT3/OCT4)-binding sites within intron 1 of the SEMA6A gene (PMID:17671748)
• findings suggest for SEMA6A a novel function in the cytoskeleton and a role in modulating tubulin isotype composition and microtubule dynamics (PMID:18187809)
• Data show that miR-27a/b regulated the expression of the angiogenesis inhibitor semaphorin 6A (SEMA6A) in vitro and in vivo and targeted the 3’-untranslated region of SEMA6A. (PMID:22184411)
• We identified the SEMA6A and HLA-DP loci as significant contributors to risk for granulomatosis with polyangiitis. (PMID:23740775)
• Data suggest that Sema6A and Mical1 may represent new potential therapeutic targets in BRAFV600E melanoma. (PMID:25576923)
• our findings indicated that SEMA6A may be a potential prognostic biomarker in the treatment of Glioblastoma multiforme (PMID:26014517)
• describes the experiments and methods enabling the characterization of Semaphorin 6A as a critical regulator of endothelial cell survival and vessel function (PMID:27787863)
• miR-203 induces the apoptosis of YD-38 human oral cancer cells by directly targeting SEMA6A. (PMID:28982852)
• RNA-guided epigenetic editing of Sema6a gene promoters via a dCas9-SunTag system with C11orf46 binding normalized SEMA6A expression and rescued transcallosal dysconnectivity via repressive chromatin remodeling by the SETDB1 repressor complex. (PMID:31511512)
• Semaphorin 6A Attenuates the Migration Capability of Lung Cancer Cells via the NRF2/HMOX1 Axis. (PMID:31527696)
• The A alleles of SEMA6A and POMP genes are likely the risk factors of disease development in Georgians (PMID:31687947)
• Genome-Wide CRISPR Screen Identifies Semaphorin 6A and 6B as Receptors for Paeniclostridium sordellii Toxin TcsL. (PMID:32302524)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000102165
		ENSDARG00000113719
mus_musculus	Sema6a	ENSMUSG00000019647
rattus_norvegicus	Sema6a	ENSRNOG00000004033

Paralogs (19): SEMA3F (ENSG00000001617), SEMA3G (ENSG00000010319), SEMA3B (ENSG00000012171), SEMA3A (ENSG00000075213), SEMA3C (ENSG00000075223), SEMA5B (ENSG00000082684), 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-6A — Q9H2E6 (reviewed: Q9H2E6)

Alternative names: Semaphorin VIA, Semaphorin-6A-1

All UniProt accessions (7): Q9H2E6, A0A0A0MQU6, B3KU01, D6RAG9, D6RCR0, E9PDV9, H0Y8V9

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation. (Microbial infection) Acts as a receptor for P.sordellii toxin TcsL in the in the vascular endothelium.

Subunit / interactions. Active as a homodimer or oligomer. The SEMA6A homodimer interacts with a PLXNA2 homodimer, giving rise to a heterotetramer. Interacts with EVL. (Microbial infection) Interacts with P.sordellii toxin TcsL; semaphorins SEMA6A and SEMA6B constitute the major host receptors for TcsL in the vascular endothelium.

Subcellular location. Cell membrane.

Similarity. Belongs to the semaphorin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H2E6-1	1	yes
Q9H2E6-2	2

RefSeq proteins (2): NP_001287709, NP_065847* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR002165	Plexin_repeat	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR027231	Semaphorin	Family
IPR036352	Semap_dom_sf	Homologous_superfamily

Pfam: PF01403, PF01437

UniProt features (87 total): strand 34, helix 11, turn 9, disulfide bond 8, glycosylation site 6, compositionally biased region 4, sequence variant 3, region of interest 3, modified residue 2, topological domain 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6WTS	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2E6-F1	70.49	0.49

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 (2): 698, 952

Disulfide bonds (8): 107–117, 135–144, 258–369, 283–328, 477–506, 515–533, 521–568, 525–542

Glycosylation sites (6): 33, 49, 65, 282, 434, 461

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-416700	Other semaphorin interactions
R-HSA-1266738	Developmental Biology
R-HSA-373755	Semaphorin interactions
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 357 (showing top): LI_CISPLATIN_RESISTANCE_DN, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, E2F4DP1_01, LFA1_Q6, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, REACTOME_OTHER_SEMAPHORIN_INTERACTIONS, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_NEUROGENESIS, LHX3_01, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, MORF_RAD51L3, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION

GO Biological Process (17): neural crest cell migration (GO:0001755), apoptotic process (GO:0006915), cytoskeleton organization (GO:0007010), cell surface receptor signaling pathway (GO:0007166), nervous system development (GO:0007399), axon guidance (GO:0007411), animal organ morphogenesis (GO:0009887), negative regulation of angiogenesis (GO:0016525), cellular response to vascular endothelial growth factor stimulus (GO:0035924), negative regulation of ERK1 and ERK2 cascade (GO:0070373), semaphorin-plexin signaling pathway (GO:0071526), negative regulation of cell adhesion involved in sprouting angiogenesis (GO:0106089), negative regulation of vascular endothelial growth factor signaling pathway (GO:1900747), negative regulation of sprouting angiogenesis (GO:1903671), positive regulation of neuron migration (GO:2001224), cell differentiation (GO:0030154), negative chemotaxis (GO:0050919)

GO Molecular Function (3): semaphorin receptor binding (GO:0030215), chemorepellent activity (GO:0045499), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Semaphorin interactions	1
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neural crest cell development	1
mesenchymal cell migration	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
organelle organization	1
signal transduction	1
system development	1
axonogenesis	1
neuron projection guidance	1
anatomical structure morphogenesis	1
animal organ development	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cellular response to growth factor stimulus	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
cell surface receptor signaling pathway	1
negative regulation of cell adhesion	1
cell adhesion involved in sprouting angiogenesis	1
negative regulation of sprouting angiogenesis	1
negative regulation of signal transduction	1
vascular endothelial growth factor signaling pathway	1
regulation of vascular endothelial growth factor signaling pathway	1
negative regulation of cellular response to vascular endothelial growth factor stimulus	1
sprouting angiogenesis	1
negative regulation of angiogenesis	1
regulation of sprouting angiogenesis	1
neuron migration	1
positive regulation of cell migration	1
regulation of neuron migration	1
cellular developmental process	1
chemotaxis	1
signaling receptor binding	1
receptor ligand activity	1
negative chemotaxis	1
binding	1
membrane	1

Protein interactions and networks

STRING

1244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMA6A	PLXNA4	Q9HCM2	999
SEMA6A	PLXNA2	O75051	985
SEMA6A	PLXNA3	P51805	924
SEMA6A	NRP2	O60462	922
SEMA6A	NRP1	O14786	911
SEMA6A	PLXNA1	Q9UIW2	869
SEMA6A	EVL	Q9UI08	855
SEMA6A	PLXND1	Q9Y4D7	771
SEMA6A	PLXNC1	O60486	770
SEMA6A	HGF	P14210	712
SEMA6A	RRAS	P10301	572
SEMA6A	RND1	Q92730	568
SEMA6A	KDR	P35968	560
SEMA6A	FARP1	Q9Y4F1	559
SEMA6A	PLXNB3	Q9ULL4	547

IntAct

58 interactions, top by confidence:

A	B	Type	Score
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
NCK1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
	SEMA6A	psi-mi:“MI:0407”(direct interaction)	0.440
SEMA6A	CAVIN1	psi-mi:“MI:0915”(physical association)	0.400
SEMA6A	SORBS2	psi-mi:“MI:0915”(physical association)	0.370
SEMA6A	ITSN2	psi-mi:“MI:0915”(physical association)	0.370
SEMA6A	SORBS1	psi-mi:“MI:0915”(physical association)	0.370
SEMA6A	SH3RF1	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
TMEM169	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC3A2	GET1	psi-mi:“MI:0914”(association)	0.350
CST9L	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF7	AGRN	psi-mi:“MI:0914”(association)	0.350
HFE	PODXL	psi-mi:“MI:0914”(association)	0.350
EDDM3B	PLXNB2	psi-mi:“MI:0914”(association)	0.350
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	AREL1	psi-mi:“MI:0914”(association)	0.350
SCGB1C1	LAMA5	psi-mi:“MI:0914”(association)	0.350
ITM2B	HS6ST1	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): SEMA6A (Biochemical Activity), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Proximity Label-MS), SEMA6A (Proximity Label-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), SEMA6A (Affinity Capture-RNA), SEMA6A (Proximity Label-MS)

ESM2 similar proteins: A0A8M2B818, A0A8M9PFP2, A1XQX3, A1XQY0, A1XQY3, B0S5G3, D0PRN4, F1N4M2, L7VG99, O35158, O35464, O61307, Q01083, Q14DG7, Q24322, Q3KN41, Q3UHK6, Q3UN70, Q568T5, Q58EG3, Q5R7F5, Q62765, Q62889, Q66IV1, Q76KF0, Q7T2X6, Q8BMA3, Q8N2Q7, Q8NFY4, Q8VDA1, Q90Z04, Q91713, Q96LU7, Q9DER5, Q9ER65, Q9H2E6, Q9H4D0, Q9HDB5, Q9NT68, Q9NZ94

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
RHO GTPase cycle	6	8.4×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell migration	5	14.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	150
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2571587	NM_020796.5(SEMA6A):c.1268T>C (p.Ile423Thr)	Likely pathogenic

SpliceAI

3377 predictions. Top by Δscore:

Variant	Effect	Δscore
5:116475600:CAGT:C	acceptor_gain	1.0000
5:116475605:T:C	acceptor_gain	1.0000
5:116475607:T:C	acceptor_gain	1.0000
5:116475607:T:TC	acceptor_gain	1.0000
5:116478012:A:AC	donor_gain	1.0000
5:116478013:C:CC	donor_gain	1.0000
5:116478024:T:TA	donor_gain	1.0000
5:116478025:C:A	donor_gain	1.0000
5:116480273:CTGGC:C	acceptor_gain	1.0000
5:116486744:ATTAC:A	donor_loss	1.0000
5:116486745:TTAC:T	donor_loss	1.0000
5:116486746:TACC:T	donor_loss	1.0000
5:116486747:ACC:A	donor_loss	1.0000
5:116486748:CCT:C	donor_loss	1.0000
5:116486963:CTAC:C	acceptor_gain	1.0000
5:116486964:TAC:T	acceptor_gain	1.0000
5:116486965:AC:A	acceptor_gain	1.0000
5:116486966:CC:C	acceptor_gain	1.0000
5:116486967:C:CC	acceptor_gain	1.0000
5:116488102:TCTTA:T	donor_loss	1.0000
5:116488103:CTTAC:C	donor_loss	1.0000
5:116488104:TTA:T	donor_loss	1.0000
5:116488105:TAC:T	donor_loss	1.0000
5:116488107:CCTTT:C	donor_gain	1.0000
5:116488192:TGGTT:T	acceptor_gain	1.0000
5:116488193:GGTT:G	acceptor_gain	1.0000
5:116488194:GTT:G	acceptor_gain	1.0000
5:116488195:TT:T	acceptor_gain	1.0000
5:116488196:TCT:T	acceptor_loss	1.0000
5:116488197:C:CC	acceptor_gain	1.0000

AlphaMissense

6799 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:116447706:C:T	G667D	1.000
5:116447721:C:T	G662E	1.000
5:116447722:C:G	G662R	1.000
5:116447722:C:T	G662R	1.000
5:116482479:C:A	W353C	1.000
5:116482479:C:G	W353C	1.000
5:116482481:A:G	W353R	1.000
5:116482481:A:T	W353R	1.000
5:116482554:A:C	C328W	1.000
5:116482555:C:T	C328Y	1.000
5:116482556:A:G	C328R	1.000
5:116486862:G:C	C283W	1.000
5:116486863:C:T	C283Y	1.000
5:116486864:A:G	C283R	1.000
5:116486877:C:A	K278N	1.000
5:116486877:C:G	K278N	1.000
5:116486892:C:A	W273C	1.000
5:116486892:C:G	W273C	1.000
5:116486893:C:G	W273S	1.000
5:116486894:A:G	W273R	1.000
5:116486894:A:T	W273R	1.000
5:116486905:A:G	L269P	1.000
5:116486920:C:T	G264E	1.000
5:116486921:C:G	G264R	1.000
5:116486921:C:T	G264R	1.000
5:116486923:C:T	G263E	1.000
5:116486937:A:C	C258W	1.000
5:116486941:A:T	V257D	1.000
5:116488910:C:A	K211N	1.000
5:116488910:C:G	K211N	1.000

dbSNP variants (sampled 300 via entrez): RS1000002187 (5:116456444 C>T), RS1000006151 (5:116444081 G>A), RS1000018210 (5:116567949 G>A,T), RS1000031750 (5:116456154 T>C), RS1000036227 (5:116492273 T>C), RS1000069443 (5:116573111 G>T), RS1000077665 (5:116574009 G>T), RS1000088143 (5:116569507 G>C), RS1000128505 (5:116465414 T>C), RS1000149618 (5:116574334 C>G,T), RS1000171178 (5:116534326 C>T), RS1000206935 (5:116462158 T>C), RS1000229553 (5:116540647 A>G), RS1000235409 (5:116535025 A>G,T), RS1000244210 (5:116540956 C>A)

Disease associations

OMIM: gene MIM:605885 | disease phenotypes: MIM:619613

GenCC curated gene-disease

Mondo (1): delayed puberty, self-limited (MONDO:0859205)

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000406_14	Amyotrophic lateral sclerosis	8.000000e-06
GCST001310_2	Allergic rhinitis	1.000000e-06
GCST002129_1	Periodontitis (DPAL)	6.000000e-06
GCST002129_4	Periodontitis (DPAL)	2.000000e-06
GCST002159_1	Wegener’s granulomatosis	2.000000e-08
GCST002527_5	Eosinophilic esophagitis	7.000000e-08
GCST003647_2	Body mass index	1.000000e-07
GCST007576_71	Chronotype	1.000000e-08
GCST008952_1	High chromosomal aberration frequency (chromatid type)	3.000000e-07
GCST010701_7	Cortical surface area (MOSTest)	2.000000e-08
GCST010702_80	Subcortical volume (MOSTest)	5.000000e-09
GCST010703_298	Brain morphology (MOSTest)	5.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0009862	chromatid-type aberration frequency
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3806915	SEMA6A		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	4
Valproic Acid	affects expression, decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Acetaminophen	affects expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Lead	affects splicing, decreases expression	2
Silver	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
arsenite	increases methylation	1
sodium arsenite	affects splicing, decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	decreases phosphorylation	1
enzacamene	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
mercuric bromide	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
thifluzamide	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
incobotulinumtoxinA	decreases expression	1

Clinical trials (associated diseases)

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