SEMA3D

protein-coding

semaphorin 3D, the group of Semaphorins|V-set domain containing

Gene summary

This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

MANE transcript

NM_001384900.1

Inheritance

ClinVar variants

P:1U:254B:101

Top phenotype

SEMA3D-related disorder

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr7:84,995,553-85,187,056

External References & Databases

Ensembl (ENSG00000153993)

Transcript & Mutation Effects

hg38 • Region Span ~191.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

skeletal dysplasiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0018230

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEMA3D variants in ClinVar

6 Conditions Cataloged

SEMA3D-related disorderTotal: 330

not specifiedTotal: 95

not providedTotal: 32

Progressive sensorineural hearing impairmentTotal: 1

Aganglionic megacolonTotal: 1

Hirschsprung disease, susceptibility to, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001384900.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	85 clinvar	7 clinvar	93
missense	1 clinvar		235 clinvar	8 clinvar	1 clinvar	245
nonsense			7 clinvar			7
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	1	0	254	93	8	356

Highest pathogenic variant AF is 0.0000018627385

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001384900.1	RefSeq	NP_001371829.1	17	MANE Select
ENST00000284136.11	Ensembl	ENSP00000284136.6	17	MANE Select
NM_001384901.1	RefSeq	NP_001371830.1	17	Standard
NM_001384902.1	RefSeq	NP_001371831.1	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sema3d	Danio rerio	Structure: Rohon-Beard neuron Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

sema3d

Danio rerio

Structure: Rohon-Beard neuron

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)

Biological Process

neural crest cell migration
positive regulation of cell migration
negative regulation of axon extension involved in axon guidance
negative chemotaxis
semaphorin-plexin signaling pathway

Molecular Function

semaphorin receptor binding
neuropilin binding
chemorepellent activity

Cellular Component

extracellular space
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000284136
Coding exons: 17
Length: 191303
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 41
Defined: 125748
p: 0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.755	371	414	0.896	0.0000211	5127
Missense (PolyPhen)		141	173.64	0.81202		2135
Synonymous	-0.303	151	146	1.03	0.00000752	1416
Loss of Function	3.37	20	44.2	0.452	0.00000248	529

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00018	0.00016	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00020	0.00020	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Induces the collapse and paralysis of neuronal growth cones. Could potentially act as repulsive cues toward specific neuronal populations. Binds to neuropilin (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.718
RVIS EVS: -0.26
RVIS percentile EVS: 34.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.120

Gene Damage Prediction

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