SNAP29

protein-coding

synaptosome associated protein 29, the group of SNAREs

Gene summary

This gene, a member of the SNAP25 gene family, encodes a protein involved in multiple membrane trafficking steps. Two other members of this gene family, SNAP23 and SNAP25, encode proteins that bind a syntaxin protein and mediate synaptic vesicle membrane docking and fusion to the plasma membrane. The protein encoded by this gene binds tightly to multiple syntaxins and is localized to intracellular membrane structures rather than to the plasma membrane. While the protein is mostly membrane-bound, a significant fraction of it is found free in the cytoplasm. Use of multiple polyadenylation sites has been noted for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004782.4

Inheritance

ClinVar variants

P:24U:89B:77

Top phenotype

Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK syndrome)

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr22:20,859,007-20,891,214

External References & Databases

Ensembl (ENSG00000099940)

Transcript & Mutation Effects

hg38 • Region Span ~32.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

CEDNIK syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012290

Submitter: Labcorp Genetics (formerly Invitae)

CEDNIK syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012290

Submitter: G2P

CEDNIK syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012290

Submitter: Genomics England PanelApp

CEDNIK syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012290

Submitter: Orphanet

CEDNIK syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012290

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK syndrome)AR

Manifestation: Dermatologic; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 15968592

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SNAP29 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 185

Inborn genetic diseasesTotal: 53

CEDNIK syndromeTotal: 33

SNAP29-related disorderTotal: 12

not specifiedTotal: 9

Leukodystrophy, hypomyelinating, 2Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004782.4. 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				71 clinvar		71
missense		1 clinvar	87 clinvar	6 clinvar		94
nonsense	5 clinvar	4 clinvar	2 clinvar			11
start loss		1 clinvar				1
frameshift	5 clinvar	4 clinvar				9
splice donor/acceptor (+/-2bp)		4 clinvar				4
Total	10	14	89	77	0	190

Highest pathogenic variant AF is 0.000016120972

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004782.4	RefSeq	NP_004773.1	5	MANE Select
ENST00000215730.12	Ensembl	ENSP00000215730.6	5	MANE Select
ENST00000439214.1	Ensembl	ENSP00000411095.1	4	Standard
ENST00000880966.1	Ensembl	ENSP00000551025.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
snap29	Danio rerio	Structure: keratinocyte Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

snap29

Danio rerio

Structure: keratinocyte

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Autophagy - animal - Homo sapiens (human)
SNARE interactions in vesicular transport - Homo sapiens (human)
miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

exocytosis
vesicle targeting
vesicle fusion
protein transport
synaptic vesicle priming

Molecular Function

SNAP receptor activity
protein binding
syntaxin binding

Cellular Component

Golgi membrane
autophagosome membrane
nucleoplasm
cytoplasm
autophagosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000215730
Coding exons: 5
Length: 32236
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125748
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.872	178	148	1.20	0.00000780	1692
Missense (PolyPhen)		54	44.887	1.203		592
Synonymous	1.52	41	55.4	0.739	0.00000282	489
Loss of Function	1.91	5	12.2	0.409	6.81e-7	127

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000028	0.000026	rare
South Asian	0.00030	0.00029	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: SNAREs, soluble N-ethylmaleimide-sensitive factor- attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Plays also a role in ciliogenesis by regulating membrane fusions. {ECO:0000269|PubMed:23217709, ECO:0000269|PubMed:25686250, ECO:0000269|PubMed:25686604}.;

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.247
RVIS EVS: 0.08
RVIS percentile EVS: 60.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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