SYVN1

protein-coding

synoviolin 1, the group of MicroRNA protein coding host genes|Ring finger proteins

Gene summary

This gene encodes a protein involved in endoplasmic reticulum (ER)-associated degradation. The encoded protein removes unfolded proteins, accumulated during ER stress, by retrograde transport to the cytosol from the ER. This protein also uses the ubiquitin-proteasome system for additional degradation of unfolded proteins. Sequence analysis identified two transcript variants that encode different isoforms. [provided by RefSeq, May 2011]

MANE transcript

NM_172230.3

Inheritance

—

ClinVar variants

U:82B:4

Top phenotype

Encephalomalacia

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr11:65,121,780-65,134,532

External References & Databases

Ensembl (ENSG00000162298)

Transcript & Mutation Effects

hg38 • Region Span ~12.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SYVN1 variants in ClinVar

11 Conditions Cataloged

not specifiedTotal: 72

EncephalomalaciaTotal: 2

not providedTotal: 2

Moderate intellectual disabilityTotal: 2

HypotoniaTotal: 2

TracheomalaciaTotal: 2

Periventricular leukomalaciaTotal: 2

HypospadiasTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172230.3. 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		1 clinvar	4
missense			74 clinvar	2 clinvar	1 clinvar	77
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	82	2	2	86

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172230.3	RefSeq	NP_757385.1	15	MANE Select
ENST00000377190.8	Ensembl	ENSP00000366395.3	15	MANE Select
NM_032431.3	RefSeq	NP_115807.1	15	Standard
ENST00000294256.12	Ensembl	ENSP00000294256.8	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
Protein processing in endoplasmic reticulum - Homo sapiens (human)
XBP1(S) activates chaperone genes
Disease
Signal Transduction

Biological Process

ubiquitin-dependent protein catabolic process
protein ubiquitination
protein N-linked glycosylation via asparagine
ubiquitin-dependent ERAD pathway
endoplasmic reticulum unfolded protein response

Molecular Function

protein binding
metal ion binding
unfolded protein binding
chaperone binding
ATPase binding

Cellular Component

Hrd1p ubiquitin ligase complex
Hrd1p ubiquitin ligase ERAD-L complex
nucleoplasm
endoplasmic reticulum
endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377190
Coding exons: 15
Length: 12753
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125748
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.18	248	365	0.679	0.0000214	3958
Missense (PolyPhen)		27	87.827	0.30742		1013
Synonymous	-0.105	139	137	1.01	0.00000752	1320
Loss of Function	4.70	1	27.7	0.0362	0.00000146	299

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000034	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130). Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130). Also promotes the degradation of normal but naturally short-lived proteins such as SGK. Protects cells from ER stress-induced apoptosis. Protects neurons from apoptosis induced by polyglutamine-expanded huntingtin (HTT) or unfolded GPR37 by promoting their degradation (PubMed:17141218). Sequesters p53/TP53 in the cytoplasm and promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation and apoptosis (PubMed:17170702). Mediates the ubiquitination and subsequent degradation of cytoplasmic NFE2L1 (By similarity). {ECO:0000250|UniProtKB:Q9DBY1, ECO:0000269|PubMed:12459480, ECO:0000269|PubMed:12646171, ECO:0000269|PubMed:12975321, ECO:0000269|PubMed:14593114, ECO:0000269|PubMed:16289116, ECO:0000269|PubMed:16847254, ECO:0000269|PubMed:17059562, ECO:0000269|PubMed:17141218, ECO:0000269|PubMed:17170702, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:26471130}.;

Recessive Scores

pRec: 0.192

Intolerance Scores

LoFtool: 0.169
RVIS EVS: -0.73
RVIS percentile EVS: 14.02

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.566

Gene Damage Prediction

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