SEZ6L

protein-coding

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

Gene summary

Predicted to be involved in synapse maturation. Predicted to act upstream of or within activation of protein kinase C activity; adult locomotory behavior; and cerebellar Purkinje cell layer development. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in several cellular components, including glutamatergic synapse; neuronal cell body; and postsynaptic membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_021115.5

Inheritance

—

ClinVar variants

P:1U:172B:17

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr22:26,169,462-26,383,597

External References & Databases

Ensembl (ENSG00000100095)

Transcript & Mutation Effects

hg38 • Region Span ~214.1 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 SEZ6L variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 171

not providedTotal: 12

Prostate cancerTotal: 2

AutismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021115.5. 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	4 clinvar	4 clinvar	11
missense			167 clinvar	7 clinvar	2 clinvar	176
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	172	11	6	190

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021115.5	RefSeq	NP_066938.2	17	MANE Select
ENST00000248933.11	Ensembl	ENSP00000248933.6	17	MANE Select
NM_001184773.2	RefSeq	NP_001171702.1	17	Standard
NM_001184774.2	RefSeq	NP_001171703.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

adult locomotory behavior
cerebellar Purkinje cell layer development
synapse maturation
regulation of protein kinase C signaling

Cellular Component

endoplasmic reticulum membrane
integral component of membrane
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000248933
Coding exons: 17
Length: 214123
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125747
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	495	596	0.831	0.0000349	6598
Missense (PolyPhen)		148	249.25	0.59379		2771
Synonymous	-0.0901	273	271	1.01	0.0000188	2105
Loss of Function	4.90	10	45.7	0.219	0.00000230	526

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0	0.0	absent
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: 0.113

Intolerance Scores

LoFtool: 0.331
RVIS EVS: -2.03
RVIS percentile EVS: 1.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.295

Gene Damage Prediction

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