SEMA7A

semaphorin 7A (John Milton Hagen blood group), the group of Immunoglobulin like domain containing|Semaphorins|CD molecules|MicroRNA protein coding host genes|Blood group antigens

Basic information

Region (hg38): 15:74409288-74433958

Previous symbols: [ "SEMAL" ]

Links

ENSG00000138623 ∙ NCBI:8482 ∙ OMIM:607961 ∙ HGNC:10741 ∙ Uniprot:O75326 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cholestasis, progressive familial intrahepatic 11; Blood group, John Milton Hagen	BG/AR	Gastrointestinal; Hematologic	Individuals with Cholestasis, progressive familial intrahepatic 11 may benefit from medical management (eg, with ursodeoxycholic acid or glutathione); Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	Gastrointestinal; Hematologic	17207242; 20854351; 34585848

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEMA7A gene.

• Inborn genetic diseases (20 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEMA7A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			17	4	1	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	5	2

Variants in SEMA7A

This is a list of pathogenic ClinVar variants found in the SEMA7A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-74410628-T-G		not specified	Uncertain significance (Feb 05, 2024)
15-74410662-C-A		not specified	Uncertain significance (Sep 27, 2021)
15-74410681-G-A		SEMA7A-related disorder	Benign (Oct 24, 2019)
15-74410713-C-T			Uncertain significance (Sep 01, 2023)
15-74410724-C-T		not specified	Uncertain significance (Dec 19, 2023)
15-74410893-G-A		not specified	Uncertain significance (Sep 16, 2021)
15-74411329-G-A		not specified	Likely benign (Mar 07, 2024)
15-74411560-C-T		not specified	Uncertain significance (Dec 14, 2023)
15-74411584-G-A		not specified	Uncertain significance (Jan 03, 2024)
15-74411588-T-C		SEMA7A-related disorder	Benign (Oct 17, 2019)
15-74411642-G-A		SEMA7A-related disorder	Benign (Aug 20, 2019)
15-74411888-C-G		not specified	Likely benign (Oct 12, 2022)
15-74411901-G-A		not specified	Uncertain significance (Oct 25, 2022)
15-74411925-C-T		not specified	Likely benign (Mar 22, 2022)
15-74411926-G-A		John Milton Hagen blood group system	Affects (Jan 01, 2007)
15-74411928-C-T		John Milton Hagen blood group system	Affects (Jan 01, 2007)
15-74411970-T-C		not specified	Uncertain significance (Dec 21, 2023)
15-74411983-G-A		not specified	Likely benign (Jan 11, 2023)
15-74414597-C-A		not specified	Uncertain significance (Feb 27, 2024)
15-74414602-G-A		SEMA7A-related disorder	Benign (Oct 24, 2019)
15-74414645-G-A		not specified	Uncertain significance (Jul 12, 2023)
15-74414660-A-G		not specified	Uncertain significance (Dec 03, 2021)
15-74414831-C-T		SEMA7A-related disorder	Benign (Jun 12, 2019)
15-74414851-G-A		not specified	Uncertain significance (Jun 06, 2023)
15-74414864-T-C		not specified	Likely benign (Oct 05, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEMA7A	protein_coding	protein_coding	ENST00000261918	14	25179

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.180	0.820	125719	0	23	125742	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	296	399	0.741	0.0000257	4314
Missense in Polyphen		68	127.21	0.53453		1426
Synonymous	-0.689	177	166	1.07	0.0000112	1329
Loss of Function	4.01	8	32.8	0.244	0.00000158	359

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.000300	0.000198
East Asian	0.0000547	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000106	0.0000879
Middle Eastern	0.0000547	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: 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 proinflammatory 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. {ECO:0000269|PubMed:12879062, ECO:0000269|PubMed:17377534, ECO:0000269|PubMed:17671519}.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;Other semaphorin interactions;Semaphorin interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.653
• rvis_EVS: -1.04
• rvis_percentile_EVS: 7.77

Haploinsufficiency Scores

• pHI: 0.306
• hipred: Y
• hipred_score: 0.567
• ghis: 0.661

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.350

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sema7a
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Gene ontology

• Biological process: osteoblast differentiation;neural crest cell migration;inflammatory response;immune response;integrin-mediated signaling pathway;olfactory lobe development;positive regulation of cell migration;positive regulation of axon extension;axon extension;negative regulation of axon extension involved in axon guidance;regulation of inflammatory response;negative chemotaxis;positive regulation of macrophage cytokine production;positive regulation of ERK1 and ERK2 cascade;semaphorin-plexin signaling pathway
• Cellular component: extracellular space;plasma membrane;integral component of plasma membrane;external side of plasma membrane;membrane;anchored component of membrane;collagen-containing extracellular matrix
• Molecular function: integrin binding;protein binding;semaphorin receptor binding;neuropilin binding;chemorepellent activity