SEZ6L2

protein-coding

seizure related 6 homolog like 2, the group of Sushi domain containing

Gene summary

This gene encodes a seizure-related protein that is localized on the cell surface. The gene is located in a region of chromosome 16p11.2 that is thought to contain candidate genes for autism spectrum disorders (ASD), though there is no evidence directly implicating this gene in ASD. Increased expression of this gene has been found in lung cancers, and the protein is therefore considered to be a novel prognostic marker for lung cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001243332.2

Inheritance

—

ClinVar variants

U:131B:24

Top phenotype

Anophthalmia-microphthalmia syndrome

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr16:29,871,159-29,899,550

External References & Databases

Ensembl (ENSG00000174938)

Transcript & Mutation Effects

hg38 • Region Span ~28.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEZ6L2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 114

not providedTotal: 20

Anophthalmia-microphthalmia syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001243332.2. 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			3 clinvar	9 clinvar	7 clinvar	19
missense			116 clinvar	6 clinvar	2 clinvar	124
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	131	15	9	155

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001243332.2	RefSeq	NP_001230261.1	18	MANE Select
ENST00000617533.5	Ensembl	ENSP00000481917.1	18	MANE Select
NM_001114099.3	RefSeq	NP_001107571.1	17	Standard
NM_001114100.3	RefSeq	NP_001107572.1	16	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sez6l2	Danio rerio	Structure: post-vent region Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

sez6l2

Danio rerio

Structure: post-vent region

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

endoplasmic reticulum membrane
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000308713
Coding exons: 17
Length: 28389
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.75	452	570	0.793	0.0000349	5735
Missense (PolyPhen)		132	194.11	0.68004		2048
Synonymous	0.238	259	264	0.981	0.0000177	2000
Loss of Function	4.42	10	40.3	0.248	0.00000187	445

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000031	0.000029	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0.000069	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May contribute to specialized endoplasmic reticulum functions in neurons. {ECO:0000250}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.607
RVIS EVS: -1.12
RVIS percentile EVS: 6.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.461

Gene Damage Prediction

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