SEZ6

protein-coding

seizure related 6 homolog, the group of Sushi domain containing

Gene summary

The protein encoded by this gene is thought to contain five cysteine-rich motifs that are similar to sushi domains, as well as two domains similar to the amino terminal half of the CUB (for complement C1r/C1s, Uegf, Bmp1) domain. Mutations in this gene have been associated with febrile seizures. [provided by RefSeq, Jul 2016]

MANE transcript

NM_178860.5

Inheritance

ClinVar variants

U:118B:17

Top phenotype

Childhood-onset schizophrenia

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr17:28,954,901-29,006,440

External References & Databases

Ensembl (ENSG00000063015)

Transcript & Mutation Effects

hg38 • Region Span ~51.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nonsyndromic genetic hearing lossLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEZ6 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 121

not providedTotal: 12

Childhood-onset schizophreniaTotal: 1

SEZ6-related conditionTotal: 1

Nonsyndromic hearing impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178860.5. 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				1 clinvar	2 clinvar	3
missense			117 clinvar	8 clinvar	6 clinvar	131
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	118	9	8	135

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178860.5	RefSeq	NP_849191.3	17	MANE Select
ENST00000317338.17	Ensembl	ENSP00000312942.11	17	MANE Select
NM_001098635.2	RefSeq	NP_001092105.1	17	Standard
NM_001290202.2	RefSeq	NP_001277131.1	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
regulation of dendrite development
synapse maturation
excitatory postsynaptic potential

Cellular Component

endoplasmic reticulum
plasma membrane
integral component of membrane
neuronal cell body
dendritic spine

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317338
Coding exons: 17
Length: 51540
Individuals with no LoFs: 124740
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 124778
p: 0.000152

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.96	449	582	0.771	0.0000331	6347
Missense (PolyPhen)		129	224.43	0.57479		2405
Synonymous	1.20	214	238	0.901	0.0000142	2068
Loss of Function	3.78	18	45.5	0.396	0.00000248	470

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in cell-cell recognition and in neuronal membrane signaling. Seems to be important for the achievement of the necessary balance between dendrite elongation and branching during the elaboration of a complex dendritic arbor. Involved in the development of appropriate excitatory synaptic connectivity (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0903

Intolerance Scores

LoFtool: 0.936
RVIS EVS: 1.25
RVIS percentile EVS: 93.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.197

Gene Damage Prediction

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