SEMA7A

Summary

SEMA7A (semaphorin 7A (JohnMiltonHagen blood group), HGNC:10741) is a protein-coding gene on chromosome 15q24.1, encoding Semaphorin-7A (O75326). Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses.

This gene encodes a member of the semaphorin family of proteins. The encoded preproprotein is proteolytically processed to generate the mature glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein. The encoded protein is found on activated lymphocytes and erythrocytes and may be involved in immunomodulatory and neuronal processes. The encoded protein carries the John Milton Hagen (JMH) blood group antigens. Mutations in this gene may be associated with reduced bone mineral density (BMD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 8482 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cholestasis, progressive familial intrahepatic, 11 (Moderate, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 110 total — 1 pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_003612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10741
Approved symbol	SEMA7A
Name	semaphorin 7A (JohnMiltonHagen blood group)
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	H-Sema-L, CD108
Ensembl gene	ENSG00000138623
Ensembl biotype	protein_coding
OMIM	607961
Entrez	8482

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000261918, ENST00000542748, ENST00000543145, ENST00000569617

RefSeq mRNA: 3 — MANE Select: NM_003612 NM_001146029, NM_001146030, NM_003612

CCDS: CCDS10262, CCDS53958, CCDS53959

Canonical transcript exons

ENST00000261918 — 14 exons

Exon	Start	End
ENSE00000698498	74417335	74417445
ENSE00000698500	74416575	74416714
ENSE00000931893	74411295	74411356
ENSE00000931894	74411556	74411710
ENSE00000931895	74411885	74412012
ENSE00000931896	74414547	74414745
ENSE00000931897	74414838	74414946
ENSE00000931898	74415801	74415985
ENSE00001045556	74409289	74410985
ENSE00002627195	74433741	74433958
ENSE00003535583	74417877	74417969
ENSE00003537863	74417591	74417675
ENSE00003587169	74418268	74418309
ENSE00003628566	74418801	74418952

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.9406 / max 717.7886, expressed in 1629 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150912	30.8757	1628
150910	0.0649	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	95.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.19	gold quality
primary visual cortex	UBERON:0002436	94.92	gold quality
cortical plate	UBERON:0005343	94.53	gold quality
placenta	UBERON:0001987	93.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.21	gold quality
prefrontal cortex	UBERON:0000451	91.96	gold quality
cerebellum	UBERON:0002037	91.67	gold quality
cerebellar hemisphere	UBERON:0002245	91.63	gold quality
cerebellar cortex	UBERON:0002129	91.59	gold quality
frontal cortex	UBERON:0001870	90.69	gold quality
stromal cell of endometrium	CL:0002255	89.40	gold quality
superior frontal gyrus	UBERON:0002661	89.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.05	gold quality
right frontal lobe	UBERON:0002810	89.01	gold quality
lymph node	UBERON:0000029	88.93	gold quality
tibial nerve	UBERON:0001323	88.37	gold quality
cerebral cortex	UBERON:0000956	88.12	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.96	gold quality
right testis	UBERON:0004534	87.95	gold quality
left testis	UBERON:0004533	87.80	gold quality
testis	UBERON:0000473	87.66	gold quality
substantia nigra	UBERON:0002038	87.41	gold quality
adrenal tissue	UBERON:0018303	87.41	gold quality
vermiform appendix	UBERON:0001154	85.52	gold quality
Ammon’s horn	UBERON:0001954	85.27	gold quality
ganglionic eminence	UBERON:0004023	84.10	gold quality
sural nerve	UBERON:0015488	83.96	gold quality
anterior cingulate cortex	UBERON:0009835	83.61	gold quality
corpus callosum	UBERON:0002336	83.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting SEMA7A, 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-574-5P	100.00	66.01	989
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-432-3P	100.00	67.86	705
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-4803	99.98	71.99	3117
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-205-5P	99.81	70.05	1557

Literature-anchored findings (GeneRIF, showing 40)

• Sema7A is a potent stimulator of cytokine production, chemotaxis and superoxide release in monocytes (PMID:12193228)
• SEMA 7A might be a molecule involved in the terminal innervation of the dentin-pulp complex. (PMID:15907379)
• Polymorphisms in SEMA7A may play a role in decreased bone mineral density and increased risk of vertebral fracture. (PMID:16372136)
• beta1-integrins and Plexin C1 receptors are ligands for Semaphorin 7a, and that signaling by these receptors has opposing effects on Semaphorin 7a-induced dendrite formation. (PMID:17671519)
• Sema7A binds to human melanocytes through beta1-integrins and the Plexin C1 receptor (PMID:19318806)
• Study reports the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1; both structures show two PlexinC1 molecules symmetrically bridged by Semaphorin dimers. (PMID:20727575)
• A new SEMA7A variant was identified in Native American plasma samples, and an alloantibody that recognizes the wild-type protein (PMID:20854351)
• Sema7A on keratinocytes and beta1-integrin on monocytes contribute to monocyte activation by keratinocytes within skin inflammation, inducing IL-8 (PMID:21524887)
• Sema7A markedly reduces the production rates of megakaryocytes and platelets from CD34(+) progenitor cells. (PMID:22448926)
• Semaphorin 7A protein variants differentially regulate T-cell activity. (PMID:22845496)
• We report here the expression and induction of semaphorin 7A (SEMA7A) on endothelium through hypoxia-inducible factor 1alpha during hypoxia. (PMID:22891341)
• two MTRAP monomers interact via their tandem TSR domains with the Sema domains of a Semaphorin-7A homodimer (PMID:23166499)
• SEMA7A was expressed in the liver and was increased in the course of liver fibrosis, both in mice and in humans. (PMID:23850082)
• Semaphorin 7A is a potentially important modulator of eosinophil profibrotic functions in the airway remodeling of patients with chronic asthma. (PMID:24333536)
• heterozygous missense variants in SEMA3A and SEMA7A may modify the phenotype of Kallmann syndrome but most likely are not alone sufficient to cause the disorder (PMID:24522099)
• These results suggest that SEMA7a plays a role as a CSF biomarkers associated with the conversion to clinically definite multiple sclerosis in clinically isolated syndromes patients (PMID:25406498)
• Sema3A and sema7A expression correlated with the inflammatory activity of the multiple sclerosis (MS) lesions, suggesting their involvement in the immunological process that takes place in MS. (PMID:26432853)
• This study demonstrates that Sema7A controls the assembly of actin-based protrusions that drive Dendritic cell migration in response to CCL21. (PMID:26597008)
• SEMA7A has a role in the development of lung injury (PMID:26752048)
• short hairpin-mediated silencing of SEMA7A reveals roles for semaphorin 7a in the promotion of DCIS growth, motility and invasion as well as lymphangiogenesis in the tumor microenvironment. Our studies also uncover a relationship between COX-2 and semaphorin 7a expression and suggest that semaphorin 7a promotes tumor cell invasion on collagen and lymphangiogenesis via activation of b1-integrin receptor (PMID:27065336)
• These findings indicate that Sema7A as a potent activator of T cells and monocytes in the immune response contributes to the inflammation and progression of rheumatoid arthritis (PMID:28109308)
• Our results identified FGL2, GAL, SEMA4D, SEMA7A, and IDO1 as new candidate genes that could be involved in MSCs-mediated immunomodulation. FGL2, GAL, SEMA4D, SEMA7A, and IDO1 genes appeared to be differentially transcribed in the different MSC populations. Moreover, these genes were not similarly modulated following MSCs-exposure to inflammatory signals (PMID:28336906)
• Sema7A has a significant role in atherosclerosis by mediating endothelial dysfunction in a beta1 integrin-dependent manner. (PMID:29269512)
• Semaphorin-7A promoted growth and migration of oral tongue squamous cell carcinoma by regulating transforming growth factor-beta induced epithelial mesenchymal transition. (PMID:29509252)
• SEMA7A, which is expressed on mammary cells during glandular involution, alters macrophage biology and lymphangiogenesis to drive breast cancer metastasis (PMID:30254150)
• High Serum semaphorin 7A level is associated with the risk of acute atherothrombotic stroke. (PMID:30729666)
• this study shows that semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells (PMID:31016720)
• Sema7A, a brain immune regulator, regulates seizure activity in PTZ-kindled epileptic rats. (PMID:31179640)
• Sema3A and Sema7A gene polymorphisms are not related to systemic lupus erythematosus genetic susceptibility, but may link to several clinical features of systemic lupus erythematosus. (PMID:31394943)
• The LOXL1-AS1/miR-28-5p/SEMA7A axis facilitated pancreatic cancer progression, which may be regarded as an innovative therapeutic target for PC treatment. (PMID:31732974)
• Study reports that soluble SEMA7A is elevated in plasma of patients with acute Myocardial infarction (MI), and that Semaphorin 7A holds significant impact on the extent of MI reperfusion injury. In mouse model Sema7a promotes myocardial thrombo-inflammation and tissue damage by reinforcing platelet thrombotic activity and platelet-neutrophil complexes formation through a platelet GPIb-dependent mechanism. (PMID:32161256)
• Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A. (PMID:32313230)
• Semaphorin 7A promotes endothelial to mesenchymal transition through ATF3 mediated TGF-beta2/Smad signaling. (PMID:32826874)
• Hormonal Regulation of Semaphorin 7a in ER(+) Breast Cancer Drives Therapeutic Resistance. (PMID:33122307)
• Sema7A is crucial for resolution of severe inflammation. (PMID:33637648)
• The Expression of Semaphorin 7A in Human Periapical Lesions. (PMID:34126161)
• Anoikis resistance in mammary epithelial cells is mediated by semaphorin 7a. (PMID:34561423)
• A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma. (PMID:35955933)
• Serum Sema7A is increased in patients with acute aortic dissection. (PMID:37698489)
• Semaphorin 7a aggravates TGF-beta1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma. (PMID:38022556)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000098508
mus_musculus	Sema7a	ENSMUSG00000038264
rattus_norvegicus	Sema7a	ENSRNOG00000007687

Paralogs (19): SEMA3F (ENSG00000001617), SEMA3G (ENSG00000010319), SEMA3B (ENSG00000012171), SEMA3A (ENSG00000075213), SEMA3C (ENSG00000075223), SEMA5B (ENSG00000082684), SEMA6A (ENSG00000092421), SEMA4G (ENSG00000095539), SEMA5A (ENSG00000112902), SEMA4F (ENSG00000135622), SEMA6D (ENSG00000137872), SEMA6C (ENSG00000143434), SEMA3D (ENSG00000153993), SEMA6B (ENSG00000167680), SEMA4C (ENSG00000168758), SEMA3E (ENSG00000170381), SEMA4B (ENSG00000185033), SEMA4D (ENSG00000187764), SEMA4A (ENSG00000196189)

Protein

Protein identifiers

Semaphorin-7A — O75326 (reviewed: O75326)

Alternative names: CDw108, JMH blood group antigen, John-Milton-Hargen human blood group Ag, Semaphorin-K1, Semaphorin-L

All UniProt accessions (2): O75326, F5GYX3

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK1 and MAPK3. Promotes production of pro-inflammatory cytokines by monocytes and macrophages. Plays an important role in modulating inflammation and T-cell-mediated immune responses. Promotes axon growth in the embryonic olfactory bulb. Promotes attachment, spreading and dendrite outgrowth in melanocytes.

Subunit / interactions. Interacts with ITGA1 and ITGB1. Interacts with PLXNC1.

Subcellular location. Cell membrane.

Tissue specificity. Detected in skin keratinocytes and on endothelial cells from skin blood vessels (at protein level). Expressed in fibroblasts, keratinocytes, melanocytes, placenta, testis, ovary, spleen, brain, spinal cord, lung, heart, adrenal gland, lymph nodes, thymus, intestine and kidney.

Disease relevance. Cholestasis, progressive familial intrahepatic, 11 (PFIC11) [MIM:619874] An autosomal recessive form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated in UV-irradiated fibroblasts, but not in UV-irradiated keratinocytes.

Polymorphism. Genetic variations in SEMA7A define the John Milton Hagen blood group system (JMH) [MIM:614745]. Three different JMH phenotypes have been identified based on the presence or absence of the high-frequency JMH antigen: JMH-weak, JMH-negative, and JMH-variant. The JMH-weak and -negative phenotypes can be either acquired or inherited and are characterized by a reduction or complete loss of JMH expression on red blood cells. Individuals with the JMH-variant phenotype are usually JMH-positive and have alloantibodies compatible with JMH-negative red blood cells. The JMH-variant phenotype results from rare SEMA7A missense variants.

Similarity. Belongs to the semaphorin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75326-1	1	yes
O75326-2	2

RefSeq proteins (3): NP_001139501, NP_001139502, NP_003603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR002165	Plexin_repeat	Repeat
IPR007110	Ig-like_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
IPR042824	Sema7A_sema	Domain

Pfam: PF01403, PF01437, PF13895

UniProt features (90 total): strand 43, disulfide bond 9, sequence variant 7, turn 6, glycosylation site 5, helix 5, domain 2, mutagenesis site 2, region of interest 2, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1, splice variant 1, sequence conflict 1, short sequence motif 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3NVQ	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75326-F1	89.77	0.80

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): 648, 135

Disulfide bonds (9): 120–126, 143–152, 266–366, 291–335, 493–511, 500–541, 503–518, 566–613, 587–596

Glycosylation sites (5): 105, 157, 258, 330, 602

Mutagenesis-validated functional residues (2):

Position	Phenotype
267	abolishes itgb1-dependent enhancement of axon growth; when associated with e-269.
269	abolishes itgb1-dependent enhancement of axon growth; when associated with k-267.

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: 403 (showing top): GOBP_NEURON_PROJECTION_EXTENSION, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, REACTOME_OTHER_SEMAPHORIN_INTERACTIONS, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_OSTEOBLAST_DIFFERENTIATION, KYNG_DNA_DAMAGE_DN, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GGGTGGRR_PAX4_03

GO Biological Process (19): osteoblast differentiation (GO:0001649), neural crest cell migration (GO:0001755), inflammatory response (GO:0006954), immune response (GO:0006955), integrin-mediated signaling pathway (GO:0007229), axon guidance (GO:0007411), olfactory lobe development (GO:0021988), positive regulation of cell migration (GO:0030335), positive regulation of axon extension (GO:0045773), axon extension (GO:0048675), regulation of inflammatory response (GO:0050727), negative chemotaxis (GO:0050919), positive regulation of macrophage cytokine production (GO:0060907), positive regulation of ERK1 and ERK2 cascade (GO:0070374), semaphorin-plexin signaling pathway (GO:0071526), regulation of synapse maturation (GO:0090128), nervous system development (GO:0007399), cell differentiation (GO:0030154), neuron projection development (GO:0031175)

GO Molecular Function (4): integrin binding (GO:0005178), semaphorin receptor binding (GO:0030215), chemorepellent activity (GO:0045499), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), presynapse (GO:0098793), GABA-ergic synapse (GO:0098982), extracellular matrix (GO:0031012), side of membrane (GO:0098552)

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
cellular anatomical structure	3
cell surface receptor signaling pathway	2
axonogenesis	2
signaling receptor binding	2
membrane	2
synapse	2
ossification	1
cell differentiation	1
neural crest cell development	1
mesenchymal cell migration	1
defense response	1
immune system process	1
response to stimulus	1
neuron projection guidance	1
telencephalon development	1
anatomical structure development	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
positive regulation of cell growth	1
regulation of axon extension	1
positive regulation of developmental growth	1
axon extension	1
positive regulation of axonogenesis	1
neuron projection extension	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
chemotaxis	1
macrophage cytokine production	1
regulation of macrophage cytokine production	1
positive regulation of myeloid leukocyte cytokine production involved in immune response	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
regulation of developmental process	1
regulation of synapse organization	1
synapse maturation	1
system development	1
cellular developmental process	1

Protein interactions and networks

STRING

1080 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMA7A	PLXNC1	O60486	999
SEMA7A	ITGB1	P05556	959
SEMA7A	NRP1	O14786	755
SEMA7A	PLXNA1	Q9UIW2	742
SEMA7A	PLXNB1	O43157	734
SEMA7A	PLXNA4	Q9HCM2	712
SEMA7A	ITGA1	P56199	706
SEMA7A	PLXNA3	P51805	679
SEMA7A	NRP2	O60462	604
SEMA7A	PLXND1	Q9Y4D7	586
SEMA7A	PLXNA2	O75051	547
SEMA7A	GYPC	P04921	517
SEMA7A	BSG	P35613	515
SEMA7A	CD55	P08174	500
SEMA7A	ITGA3	P26006	496

IntAct

28 interactions, top by confidence:

A	B	Type	Score
PLXNC1	SEMA7A	psi-mi:“MI:0915”(physical association)	0.720
SEMA7A	PLXNC1	psi-mi:“MI:0407”(direct interaction)	0.720
PLXNC1	SEMA7A	psi-mi:“MI:0407”(direct interaction)	0.720
SEMA7A	SGPL1	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SEMA7A	SEMA7A	psi-mi:“MI:0407”(direct interaction)	0.440
aerA	SEMA7A	psi-mi:“MI:0407”(direct interaction)	0.440
ABL1	SEMA7A	psi-mi:“MI:0915”(physical association)	0.400
SEMA7A	FYN	psi-mi:“MI:0915”(physical association)	0.400
SEMA7A	GRB2	psi-mi:“MI:0915”(physical association)	0.400
NCK1	SEMA7A	psi-mi:“MI:0915”(physical association)	0.400
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NFATC1	OBSL1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
CLEC4A	RBFOX3	psi-mi:“MI:0914”(association)	0.350
CCDC144BP	AOC2	psi-mi:“MI:0914”(association)	0.350
CLEC4A		psi-mi:“MI:0914”(association)	0.350
PTPRN	KCNK1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): SOAT1 (Affinity Capture-MS), DPY19L1 (Affinity Capture-MS), UNC93B1 (Affinity Capture-MS), TAPT1 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), SLC9A1 (Affinity Capture-MS), SLC12A9 (Affinity Capture-MS), ATP11C (Affinity Capture-MS), SEMA7A (Affinity Capture-MS), LMF2 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), SEMA7A (Affinity Capture-MS)

ESM2 similar proteins: A2BD09, B0BNI5, B5MFE9, D3Z7H8, O70624, O75326, O88632, P09531, P42917, P82350, Q0P3W2, Q0V9V5, Q0VCP3, Q13275, Q16586, Q25C36, Q28686, Q29RB4, Q2HJE5, Q2KHV9, Q2PT31, Q3UH93, Q4LFA9, Q594P2, Q64255, Q66H86, Q68BL7, Q6UWY5, Q6ZMI3, Q80WF4, Q80WL1, Q863A3, Q866N2, Q8BH02, Q8BHP7, Q8BK62, Q8BMF8, Q8IUL8, Q8IYS2, Q91X21

Diamond homologs: A7MB70, D3ZTD8, O08665, O09126, O15031, O15041, O35464, O42236, O42237, O75326, O88632, O95025, O95754, P70275, Q13214, Q13275, Q13591, Q14563, Q17330, Q24323, Q26473, Q26972, Q4LFA9, Q5EA85, Q5R7F5, Q5RE75, Q60519, Q62177, Q62178, Q62179, Q62181, Q62217, Q63548, Q64151, Q76KF0, Q80UG2, Q8BH34, Q8NFY4, Q90607, Q90663

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SEMA7A	up-regulates	PLXNC1	binding
SEMA7A	“up-regulates activity”	“A1/b1 integrin”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	66
Likely benign	16
Benign	9

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1687038	NM_003612.5(SEMA7A):c.442C>T (p.Arg148Trp)	Pathogenic

SpliceAI

2053 predictions. Top by Δscore:

Variant	Effect	Δscore
15:74410981:CTTGT:C	acceptor_gain	1.0000
15:74410982:TTGT:T	acceptor_gain	1.0000
15:74410983:TGTC:T	acceptor_loss	1.0000
15:74410984:GTCT:G	acceptor_loss	1.0000
15:74410986:C:CA	acceptor_loss	1.0000
15:74410986:C:CC	acceptor_gain	1.0000
15:74410987:T:A	acceptor_loss	1.0000
15:74410996:A:T	acceptor_gain	1.0000
15:74411352:CTGAC:C	acceptor_gain	1.0000
15:74411354:GACCT:G	acceptor_loss	1.0000
15:74411355:ACCTG:A	acceptor_loss	1.0000
15:74411356:CCT:C	acceptor_loss	1.0000
15:74411357:CTG:C	acceptor_loss	1.0000
15:74411358:T:A	acceptor_loss	1.0000
15:74411551:CGTA:C	donor_loss	1.0000
15:74411552:GTA:G	donor_loss	1.0000
15:74411554:A:AC	donor_gain	1.0000
15:74411554:ACC:A	donor_loss	1.0000
15:74411555:C:CA	donor_loss	1.0000
15:74411555:C:CC	donor_gain	1.0000
15:74411555:CCG:C	donor_gain	1.0000
15:74411555:CCGTT:C	donor_gain	1.0000
15:74411706:TTCCT:T	acceptor_gain	1.0000
15:74411707:TCCT:T	acceptor_gain	1.0000
15:74411708:CCTC:C	acceptor_gain	1.0000
15:74411709:CT:C	acceptor_gain	1.0000
15:74411710:TCTGG:T	acceptor_loss	1.0000
15:74411711:C:CC	acceptor_gain	1.0000
15:74411711:CTGGA:C	acceptor_loss	1.0000
15:74411879:GCTCA:G	donor_loss	1.0000

AlphaMissense

4355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:74414928:A:C	C335W	1.000
15:74414929:C:G	C335S	1.000
15:74414929:C:T	C335Y	1.000
15:74414930:A:G	C335R	1.000
15:74414930:A:T	C335S	1.000
15:74415944:C:A	W281C	1.000
15:74415944:C:G	W281C	1.000
15:74415946:A:G	W281R	1.000
15:74415946:A:T	W281R	1.000
15:74416579:C:G	C266S	1.000
15:74416580:A:T	C266S	1.000
15:74410894:C:A	W577C	0.999
15:74410894:C:G	W577C	0.999
15:74414744:C:G	C366S	0.999
15:74414745:A:G	C366R	0.999
15:74414745:A:T	C366S	0.999
15:74414896:A:C	F346C	0.999
15:74414896:A:G	F346S	0.999
15:74414924:A:C	Y337D	0.999
15:74414929:C:A	C335F	0.999
15:74414932:A:T	V334D	0.999
15:74414935:G:T	A333D	0.999
15:74414936:C:G	A333P	0.999
15:74415812:G:C	F325L	0.999
15:74415812:G:T	F325L	0.999
15:74415813:A:C	F325C	0.999
15:74415813:A:G	F325S	0.999
15:74415814:A:G	F325L	0.999
15:74415914:G:C	C291W	0.999
15:74415915:C:G	C291S	0.999

dbSNP variants (sampled 300 via entrez): RS1000144319 (15:74430912 T>A), RS1000284659 (15:74425281 T>A,C), RS1000311219 (15:74422055 C>G), RS1000370738 (15:74427908 C>T), RS1000550324 (15:74432568 G>A,T), RS1000621563 (15:74431070 T>G), RS1000637450 (15:74420769 C>T), RS1000891690 (15:74419544 A>G), RS1000929489 (15:74431831 C>T), RS1000987777 (15:74416287 C>G), RS1001012923 (15:74410386 C>T), RS1001172241 (15:74415318 G>C), RS1001211485 (15:74409802 G>A), RS1001263523 (15:74420871 T>G), RS1001292649 (15:74416096 A>G)

Disease associations

OMIM: gene MIM:607961 | disease phenotypes: MIM:619874

GenCC curated gene-disease

Disease	Classification	Inheritance
cholestasis, progressive familial intrahepatic, 11	Moderate	Autosomal recessive

Mondo (1): cholestasis, progressive familial intrahepatic, 11 (MONDO:0030815)

Orphanet (0):

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000989	Pruritus
HP:0002240	Hepatomegaly
HP:0003593	Infantile onset
HP:0012202	Increased serum bile acid concentration
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0033479	Abnormal circulating bilirubin concentration

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001621_17	Airflow obstruction	8.000000e-06
GCST004412_7	Craniofacial microsomia	1.000000e-23
GCST007328_63	Alcohol consumption (drinks per week)	1.000000e-09
GCST009685_19	Hypertension	8.000000e-11
GCST010241_96	Apolipoprotein A1 levels	9.000000e-13
GCST010242_347	HDL cholesterol levels	1.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Arsenic Trioxide	decreases expression	2
Estradiol	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
quinocetone	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8P7	Abcam HCT 116 SEMA7A KO	Cancer cell line	Male
CVCL_B9RK	Abcam A-549 SEMA7A KO	Cancer cell line	Male
CVCL_TK55	HAP1 SEMA7A (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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