SEMA6D

semaphorin 6D, the group of Semaphorins

Basic information

Region (hg38): 15:47184100-47774228

Links

ENSG00000137872 ∙ NCBI:80031 ∙ OMIM:609295 ∙ HGNC:16770 ∙ Uniprot:Q8NFY4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEMA6D gene.

• Inborn genetic diseases (36 variants)
• not provided (3 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEMA6D 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
missense			35	2	1	38
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	36	3	1

Variants in SEMA6D

This is a list of pathogenic ClinVar variants found in the SEMA6D region.

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

Position	Type	Phenotype	Significance	ClinVar
15-47760334-G-A		not specified	Uncertain significance (May 05, 2023)
15-47760391-G-A		SEMA6D-related disorder • not specified	Conflicting classifications of pathogenicity (Jul 06, 2021)
15-47760398-A-C		SEMA6D-related disorder	Benign (Jan 14, 2020)
15-47761170-C-G		not specified	Uncertain significance (Jun 11, 2021)
15-47761177-G-T		not specified	Uncertain significance (May 16, 2022)
15-47761185-G-C		not specified	Uncertain significance (Jun 18, 2021)
15-47761364-C-G		SEMA6D-related disorder	Uncertain significance (Nov 13, 2023)
15-47761372-G-A		not specified	Uncertain significance (Dec 19, 2022)
15-47761675-A-G		SEMA6D-related disorder	Likely benign (Mar 14, 2019)
15-47761692-T-C		not specified	Uncertain significance (Jun 07, 2023)
15-47762274-G-A		not specified	Uncertain significance (Feb 26, 2024)
15-47762276-A-T		SEMA6D-related disorder	Likely benign (Mar 22, 2019)
15-47763070-G-A		not specified	Uncertain significance (Sep 30, 2022)
15-47763076-T-A		not specified	Uncertain significance (Oct 02, 2023)
15-47763905-G-A		not specified	Uncertain significance (Feb 03, 2022)
15-47763920-A-G		not specified	Uncertain significance (Jul 05, 2023)
15-47763989-T-G		not specified	Uncertain significance (Apr 08, 2022)
15-47764022-A-G		SEMA6D-related disorder	Benign (Jan 14, 2020)
15-47764171-C-T		SEMA6D-related disorder	Likely benign (Aug 12, 2019)
15-47764187-G-T		not specified	Uncertain significance (Jul 06, 2022)
15-47764225-A-G		SEMA6D-related disorder	Likely benign (May 22, 2020)
15-47764236-G-T		not specified	Benign (Dec 12, 2023)
15-47764659-C-T		SEMA6D-related disorder	Likely benign (Dec 24, 2019)
15-47764739-A-T		not specified	Uncertain significance (Nov 17, 2022)
15-47764783-A-G		not specified	Uncertain significance (May 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEMA6D	protein_coding	protein_coding	ENST00000316364	18	590123

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.939	0.0605	125702	0	14	125716	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.08	528	603	0.876	0.0000334	7038
Missense in Polyphen		174	258.43	0.6733		2972
Synonymous	0.146	223	226	0.988	0.0000133	2107
Loss of Function	5.26	9	48.6	0.185	0.00000273	586

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.000141	0.000139
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.0000545	0.0000544
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Shows growth cone collapsing activity on dorsal root ganglion (DRG) neurons in vitro. May be a stop signal for the DRG neurons in their target areas, and possibly also for other neurons. May also be involved in the maintenance and remodeling of neuronal connections.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;Other semaphorin interactions;Semaphorin interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.289
• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.24

Haploinsufficiency Scores

• pHI: 0.239
• hipred: Y
• hipred_score: 0.654
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.134

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sema6d

Gene ontology

• Biological process: neural crest cell migration;positive regulation of smooth muscle cell migration;negative regulation of smooth muscle cell migration;ventricular system development;positive regulation of cell migration;negative regulation of axon extension involved in axon guidance;negative chemotaxis;semaphorin-plexin signaling pathway
• Cellular component: extracellular space;Golgi apparatus;plasma membrane;integral component of plasma membrane
• Molecular function: semaphorin receptor binding;neuropilin binding;chemorepellent activity